Miracle-dz/UniFAR-FTUs huggingface dataset:
SD-208, a Novel Transforming Growth Factor β Receptor I Kinase Inhibitor, Inhibits Growth and Invasiveness and Enhances Immunogenicity of Murine and Human Glioma Cells In vitro and In vivo

The cytokine transforming growth factor (TGF)-β, by virtue of its immunosuppressive and promigratory properties, has become a major target for the experimental treatment of human malignant gliomas. Here we characterize the effects of a novel TGF-β receptor (TGF-βR) I kinase inhibitor, SD-208, on the growth and immunogenicity of murine SMA-560 and human LN-308 glioma cells in vitro and the growth of and immune response to intracranial SMA-560 gliomas in syngeneic VM/Dk mice in vivo. SD-208 inhibits the growth inhibition of TGF-β–sensitive CCL64 cells mediated by recombinant TGF-β1 or TGF-β2 or of TGF-β–containing glioma cell supernatant at an EC50 of 0.1 μmol/L. SD-208 blocks autocrine and paracrine TGF-β signaling in glioma cells as detected by the phosphorylation of Smad2 or TGF-β reporter assays and strongly inhibits constitutive and TGF-β–evoked migration and invasion, but not viability or proliferation. Peripheral blood lymphocytes or purified T cells, cocultured with TGF-β–releasing LN-308 glioma cells in the presence of SD-208, exhibit enhanced lytic activity against LN-308 targets. The release of interferon γ and tumor necrosis factor α by these immune effector cells is enhanced by SD-208, whereas the release of interleukin 10 is reduced. SD-208 restores the lytic activity of polyclonal natural killer cells against glioma cells in the presence of recombinant TGF-β or of TGF-β–containing glioma cell supernatant. The oral bioavailability of SD-208 was verified by demonstrating the inhibition of TGF-β–induced Smad phosphorylation in spleen and brain. Systemic SD-208 treatment initiated 3 days after the implantation of SMA-560 cells into the brains of syngeneic VM/Dk mice prolongs their median survival from 18.6 to 25.1 days. Histologic analysis revealed no difference in blood vessel formation, proliferation, or apoptosis. However, animals responding to SD-208 showed an increased tumor infiltration by natural killer cells, CD8 T cells, and macrophages. These data define TGF-β receptor I kinase inhibitors such as SD-208 as promising novel agents for the treatment of human malignant glioma and other conditions associated with pathological TGF-β activity.
An attachment theoretical perspective for the neural representation of close others

Abstract Recent investigations in neuroscience elucidate the neural basis of close other cognitive representations, which serve functions central to our health and happiness. Yet, there are persistent barriers to this research, including disparate research methods and the absence of a common theoretical background. The present review connects neuroimaging and attachment theory within a novel social, cognitive and affective framework. We apply attachment theory to understand why we would expect cognitive representations of close others to be different from other social neural representations. Developing reliable markers of attachment is a critical step in mapping close other neural representations. We then examine existing neuroimaging literature on close other representations, highlighting the recruitment of neural systems supporting reward, motivation and distress alleviation, in addition to the mirror neuron system, default network and salience network. We then review the methodologies of past studies, revealing a diverse array of self-report measures assessing `closeness’ and social cognitive tasks that, taken together, preclude meaningful synthesis of findings. Lastly, we discuss specific behavioral measures of attachment and closeness with recommendations for the field. This attachment framework integrates brain and behavioral sciences and unites theoretical principles with empirical methods to further our understanding of how the brain represents close others.
Motivational Incongruence and Well-Being at the Workplace: Person-Job Fit, Job Burnout, and Physical Symptoms

Person–environment fit has been identified as a key prerequisite for employee well-being. We investigated to what extent a misfit between motivational needs and supplies at the workplace affects two key health outcomes: burnout and physical symptoms. Individual needs (implicit affiliation and power motives) and environment supplies (motive specific job characteristics) were assessed in an online survey of full time employees (n = 97), using a picture story exercise measuring implicit motives and a scale listing affiliation and power related job characteristics. Outcomes were assessed using the Maslach Burnout Inventory and a checklist of physical symptoms. We conducted polynomial regressions with response surface analysis. Results reveal that motivational incongruence with respect to the affiliation motive was related to high job burnout, while motivational incongruence concerning the power motive predicted increased physical symptoms. This was true for both those with a strong affiliation or power motive and low corresponding job characteristics and those with a weak affiliation or power motive and job characteristics demanding the respective motive. Results hint at potential interventions toward preventing or remedying a lack of needs-supply fit and reducing the risk of impairments of well-being.
The effects of classroom noise on the reading comprehension of adolescents.

An investigation has been carried out to examine the impact of different levels of classroom noise on adolescents' performance on reading and vocabulary-learning tasks. A total of 976 English high school pupils (564 aged 11 to 13 years and 412 aged 14 to 16 years) completed reading tasks on laptop computers while exposed to different levels of classroom noise played through headphones. The tasks consisted of reading science texts, which were followed by multiple-choice questions probing comprehension and word learning. Number of questions attempted, times taken to read the texts and to answer questions were recorded, as well as correct answers to different types of question. The study consisted of two similar experiments, the first comparing performance in classroom noise at levels of 50 and 70 dB LAeq; and the second at levels of 50 and 64 dB LAeq. The results showed that the performance of all pupils was significantly negatively affected in the 70 dB LAeq condition, for the number of questions attempted and the accuracy of answers to factual and word learning questions. It was harder to discern effects at 64 dB LAeq, this level of noise having a detrimental effect upon the older pupils only.
Exploration of Machine Learning for Hyperuricemia Prediction Models Based on Basic Health Checkup Tests

Background: Machine learning (ML) is a promising methodology for classification and prediction applications in healthcare. However, this method has not been practically established for clinical data. Hyperuricemia is a biomarker of various chronic diseases. We aimed to predict uric acid status from basic healthcare checkup test results using several ML algorithms and to evaluate the performance. Methods: We designed a prediction model for hyperuricemia using a comprehensive health checkup database designed by the classification of ML algorithms, such as discrimination analysis, K-nearest neighbor, naïve Bayes (NBC), support vector machine, decision tree, and random forest classification (RFC). The performance of each algorithm was evaluated and compared with the performance of a conventional logistic regression (CLR) algorithm by receiver operating characteristic curve analysis. Results: Of the 38,001 participants, 7705 were hyperuricemic. For the maximum sensitivity criterion, NBC showed the highest sensitivity (0.73), and RFC showed the second highest (0.66); for the maximum balanced classification rate (BCR) criterion, RFC showed the highest BCR (0.68), and NBC showed the second highest (0.66) among the various ML algorithms for predicting uric acid status. In a comparison to the performance of NBC (area under the curve (AUC) = 0.669, 95% confidence intervals (CI) = 0.669–0.675) and RFC (AUC = 0.775, 95% CI 0.770–0.780) with a CLR algorithm (AUC = 0.568, 95% CI = 0.563–0.571), NBC and RFC showed significantly better performance (p < 0.001). Conclusions: The ML model was superior to the CLR model for the prediction of hyperuricemia. Future studies are needed to determine the best-performing ML algorithms based on data set characteristics. We believe that this study will be informative for studies using ML tools in clinical research.
PTP1b Inhibition, A Promising Approach for the Treatment of Diabetes Type II.

BACKGROUND Diabetes Mellitus (DM), is a metabolic disorder characterized by high blood glucose levels. The main types of diabetes mellitus are Diabetes mellitus type I, Diabetes mellitus type II, gestational diabetes and Diabetes of other etiology. Diabetes type II, the Non Insulin Dependent Type (NIDDM) is the most common type, characterized by the impairment in activation of the intracellular mechanism leading to the insertion and usage of glucose after interaction of insulin with its receptor, known as insulin resistance. Although, a number of drugs have been developed for the treatment of diabetes type II, their ability to reduce blood glucose levels is limited, while several side effects are also observed. Furthermore, none of the market drugs targets the enhancement of the action of the intracellular part of insulin receptor or recuperation of the glucose transport mechanism in GLUT4 dependent cells. The Protein Tyrosine Phosphatase (PTP1b) is the main enzyme involved in insulin receptor desensitization and has become a drug target for the treatment of Diabetes type II. Several PTP1b inhibitors have already been found, interacting with the binding site of the enzyme, surrounding the catalytic amino acid Cys215 and the neighboring area or with the allosteric site of the enzyme, placed at a distance of 20 Å from the active site, around Phe280. However, the research continues for finding more potent inhibitors with increased cell permeability and specificity. OBJECTIVE The aim of this review is to show the attempts made in developing of Protein Tyrosine Phosphatase (PTP1b) inhibitors with high potency, selectivity and bioavailability and to sum up the indications for favorable structural characteristics of effective PTP1b inhibitors. METHODS The methods used include a literature survey and the use of Protein Structure Databanks such as PuBMed Structure and RCSB and the tools they provide. CONCLUSION The research for finding PTP1b inhibitors started with the design of molecules mimicking the Tyrosine substrate of the enzyme. The study revealed that an aromatic ring connected to a polar group, which preferably enables hydrogen bond formation, is the minimum requirement for small inhibitors binding to the active site surrounding Cys215. Molecules bearing two hydrogen bond donor/acceptor (Hb d/a) groups at a distance of 8.5-11.5 Å may form more stable complexes, interacting simultaneously with a secondary area A2. Longer molecules with two Hb d/a groups at a distance of 17 Å or 19 Å may enable additional interactions with secondary sites (B and C) that confer stability as well as specificity. An aromatic ring linked to polar or Hb d/a moieties is also required for allosteric inhibitors. A lower distance between Hb d/a moieties, around 7.5 Å may favor allosteric interaction. Permanent inhibition of the enzyme by oxidation of the catalytic Cys215 has also been referred. Moreover, covalent modification of Cys121, placed near but not inside the catalytic pocket has been associated with permanent inhibition of the enzyme.
A variable stiffness gripper based on differential drive particle jamming

Compared with rigid grippers, soft grippers show fantastic adaptability and flexibility in grasping irregularly shaped and fragile objects. However, the low stiffness of the soft actuator limits the scope of applications. Particle jamming has emerged as an important method to adjust the stiffness of soft grippers. This paper proposes a novel particle jamming mechanism based on the differential pressure drive. With the differential drive particle jamming mechanism, a soft actuator is designed, which is characterized by a dual-deformable chamber structure in which one chamber is filled with particles. The simultaneous inflation of the two chambers will result in the bending behavior without significant stiffening. However, if the air chamber is pressurized with a larger pressure, the differential pressure will cause the particles inside the particle chamber to jam each other, which increases the stiffness of the actuator significantly. Thus, the differential drive particle jamming mechanism can achieve the independent control of the stiffness and the bending angle. Both theoretical and experimental studies in this area have shown that the gripper based on the differential drive particle jamming mechanism can stiffen itself effectively, and achieve the independent control of the stiffness and the bending angle, which can be adopted in applications where both high stiffness and dexterity are required.
Comprehensive circular RNA expression profiles in a mouse model of nonalcoholic steatohepatitis

Recent studies have revealed that circular RNAs (circRNAs) are involved in the development of various liver diseases. However, the regulatory role of circRNAs in nonalcoholic steatohepatitis (NASH) has not been fully elucidated. In the present study, the circRNA profiles in a NASH mouse model were investigated, and their functions in NASH were predicted using bioinformatics analysis, with the aim of providing novel clues for delineating the mechanisms of action. A NASH mouse model was established by feeding mice with a methionine and choline-deficient diet. The liver circRNA profile was screened using a circRNA microarray, and the differentially expressed circRNAs were verified by reverse transcription-quantitative polymerase chain reaction. Subsequently, circRNA-microRNA (miRNA) interactions were predicted. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological functions of host linear transcripts of circRNA. A total of 450 circRNAs were revealed to be dysregulated, with 298 circRNAs upregulated and 152 circRNAs downregulated in the NASH model mice. circRNA_29981 was identified as a significantly differentially expressed circRNA. The results from the circRNA-miRNA pathway interaction analysis revealed that circRNA_29981 was a potential regulator of hepatic stellate cell activation. The host linear transcripts were also analyzed, and the top 10 enriched GO entries and KEGG pathways were annotated. These findings suggested that circRNAs may be important regulators of NASH. Taken together, the results of the present study demonstrated that the circRNA profile in NASH may provide potential candidates for future studies aimed at elucidating the pathogenic mechanism(s) involved in the disease.
Endogenously Generated and Visually Guided Saccades after Lesions of the Human Frontal Eye Fields

Nine patients with chronic, unilateral lesions of the dorso-lateral prefrontal cortex including the frontal eye fields (FEF) made saccades toward contralesional and ipsilesional fields. The saccades were either voluntarily directed in response to arrows in the center of a visual display, or were reflexively summoned by a peripheral visual signal. Saccade latencies were compared to those made by seven neurologic control patients with chronic, unilateral lesions of dorsolateral prefrontal cortex sparing the FEF, and by 13 normal control subjects. In both the normal and neurologic control subjects, reflexive saccades had shorter Latencies than voluntary saccades. In the FEF lesion patients, voluntary saccades had longer latencies toward the contralesional field than toward the ipsilesional field. The opposite pattern was found for reflexive saccades: latencies of saccades to targets in the contralesional field were shorter than saccades summoned to ipsilesional targets. Reflexive saccades toward the ipsilesional field had abnormally prolonged latencies; they were comparable to the latencies observed for voluntary Saccades. The effect of FEF lesions on saccacles contrasted with those observed in a second experiment requiring a key press response: FEF lesion patients were slower in making key press responses to signals detected in the contralesional field. To assess covert attention and preparatory set the effects of precues providing advance information were measured in both saccade and key press experiments. Neither patient group showed any deficiency in using precues to shift attention or to prepare saccades. The FEF facilitates the generation of voluntary saccatles and also inhibits reflexive saccades to exogenous signals. FEF lesions may disinhibit the ipsilesional midbrain which in turn may inhibit the opposite colliculus to slow reflexive saccades toward the ipsilesional field.
Hippocampal Sclerosis, Argyrophilic Grain Disease, and Primary Age-Related Tauopathy

PURPOSE OF REVIEW Hippocampal sclerosis, argyrophilic grain disease, and primary age-related tauopathy are common Alzheimer disease mimics that currently lack clinical diagnostic criteria. Increased understanding of these pathologic entities is important for the neurologist who may encounter patients with an unusually slowly progressive degenerative dementia that may appear to meet criteria for Alzheimer disease but who progress to develop symptoms that are unusual for classic Alzheimer disease RECENT FINDINGS Hippocampal sclerosis has traditionally been associated with hypoxic/ischemic injury and poorly controlled epilepsy, but it is now recognized that hippocampal sclerosis may also be associated with a unique degenerative disease of aging or may be an associated pathologic finding in many cases of frontotemporal lobar degeneration. Argyrophilic grain disease has been recognized as an enigma in the field of pathology for over 30 years, but recent discoveries suggest that it may overlap with other tau-related disorders within the spectrum of frontotemporal lobar degeneration. Primary age-related tauopathy has long been recognized as a distinct clinical entity that lies on the Alzheimer pathologic spectrum, with the presence of neurofibrillary tangles that lack the coexistent Alzheimer plaque development; thus, it is thought to represent a distinct pathologic entity. SUMMARY Despite advances in dementia diagnosis that suggest that we have identified and unlocked the mysteries of the major degenerative disease states responsible for cognitive decline and dementia in the elderly, diseases such as hippocampal sclerosis, argyrophilic grain disease, and primary age-related tauopathy demonstrate that we remain on the frontier of discovery and that our diagnostic repertoire of diseases responsible for such clinical symptoms remains in its infancy. Understanding such diagnostic confounds is important for the neurologist in assigning appropriate diagnoses and selecting appropriate therapeutic management strategies for patients with mild cognitive impairment and dementia.
Impact of shift duration on alertness among air‐medical emergency care clinician shift workers

BACKGROUND Greater than half of Emergency Medical Services (EMS) shift workers report fatigue at work and most work long duration shifts. We sought to compare the alertness level of EMS shift workers by shift duration. METHODS We used a multi-site, 14-day prospective observational cohort study design of EMS clinician shift workers at four air-medical EMS organizations. The primary outcome was behavioral alertness as measured by psychomotor vigilance tests (PVT) at the start and end of shifts. We stratified shifts by duration (< 24 h and 24 h), night versus day, and examined the impact of intra-shift napping on PVT performance. RESULTS One hundred and twelve individuals participated. The distribution of shifts <24 h and 24 h with complete data were 54% and 46%, respectively. We detected no differences in PVT performance measures stratified by shift duration (P > 0.05). Performance for selected PVT measures (lapses and false starts) was worse on night shifts compared to day shifts (P < 0.05). Performance also worsened with decreasing time between waking from a nap and the end of shift PVT assessment. CONCLUSIONS Deficits in performance in the air-medical setting may be greatest during night shifts and proximal to waking from an intra-shift nap. Future research should examine alertness and performance throughout air-medical shifts, as well as investigate the timing and duration of intra-shift naps on outcomes.
Induction of squamous cell carcinoma after MAP3K8 overexpression in murine salivry gland epithelial cells

Salivary gland neoplasms are relatively rare and comprise only 1%‐4% of all human neoplasms. Salivary gland neoplasms also show an extremely wide range of morphological diversity. Currently, the genetic alterations and corresponding molecular mechanisms underlying salivary gland neoplasms development remain largely unknown.
Cortical stimulation for the rehabilitation of patients with hemiparetic stroke: a multicenter feasibility study of safety and efficacy.

OBJECT In this prospective multicenter study the authors hypothesized that investigational epidural cortical stimulation (CS) delivered concurrently with rehabilitation therapy may enhance motor recovery following stroke. METHODS Patients who had suffered their index stroke >or= 4 months previously were randomized into 6 weeks of rehabilitation therapy with or without CS. Cortical stimulation, targeted by functional imaging, was delivered at approximately 50% of motor movement threshold. Primary outcome measures were Upper Extremity Fugl-Meyer (UEFM [a measure of neurological and motor function]) and Arm Motor Ability Test (AMAT [a measure of activities of daily living]) scores. The primary study end point was 4 weeks following rehabilitation therapy. RESULTS A total of 24 patients, 12 per group, completed the treatment protocol. The mean interval since the patients' index stroke was 33 months (range 4-100 months). There were no deaths or cases of neurological deterioration; 1 acute postoperative seizure occurred unrelated to the device or treatment. Patients who underwent CS experienced improved hand/arm function more than control patients. The UEFM score improved 5.5 +/- 4.4 points in patients in the CS group compared with 1.9 +/- 4.4 points for controls (p = 0.03). A 3.5-point UEFM improvement is considered clinically meaningful. The AMAT scores for the CS group improved by 0.4 +/- 0.6 points, whereas the scores in the control group improved by 0.2 +/- 0.4 points (p = 0.2). A 0.21-point improvement in AMAT score is considered clinically meaningful. In the CS group, 67% of patients had clinically meaningful improvement in UEFM scores, compared with 25% of the control group (p = 0.05). Of patients in the CS group 50% had clinically meaningful improvement in UEFM as well as AMAT scores, compared with only 8% of those in the control group (p = 0.03). CONCLUSIONS These results suggest that subthreshold epidural CS is safe and effective during rehabilitation for recovery of arm and hand function following hemiparetic stroke. Further research in a larger cohort is needed to validate the therapeutic effect.