Miracle-dz/UniFAR-FTUs huggingface dataset:
Brain-derived neurotrophic factor mediates macrophage migration inhibitory factor to protect neurons against oxygen-glucose deprivation

Macrophage migration inhibitory factor (MIF) is a chemokine that plays an essential role in immune system function. Previous studies suggested that MIF protects neurons in ischemic conditions. However, few studies are reported on the role of MIF in neurological recovery after ischemic stroke. The purpose of this study is to identify the molecular mechanism of neuroprotection mediated by MIF. Human neuroblastoma cells were incubated in Dulbecco’s modified Eagle’s medium under oxygen-glucose deprivation (OGD) for 4 hours and then returned to normal aerobic environment for reperfusion (OGD/R). 30 ng/mL MIF recombinant (30 ng/mL) or ISO-1 (MIF antagonist; 50 μM) was administered to human neuroblastoma cells. Then cell cultures were assigned to one of four groups: control, OGD/R, OGD/R with MIF, OGD/R with ISO-1. Cell viability was analyzed using WST-1 assay. Expression levels of brain-derived neurotrophic factor (BDNF), microtubule-associated protein 2 (MAP2), Caspase-3, Bcl2, and Bax were detected by western blot assay and immunocytochemistry in each group to measure apoptotic activity. WST-1 assay results revealed that compared to the OGD/R group, cell survival rate was significantly higher in the OGD/R with MIF group and lower in the OGD/R with ISO-1 group. Western blot assay and immunocytochemistry results revealed that expression levels of BDNF, Bcl2, and MAP2 were significantly higher, and expression levels of Caspase-3 and Bax were significantly lower in the MIF group than in the OGD/R group. Expression levels of BDNF, Bcl2, and MAP2 were significantly lower, and expression levels of Caspase-3 and Bax were significantly higher in the ISO-1 group than in the OGD/R group. MIF administration promoted neuronal cell survival and induced high expression levels of BDNF, MAP2, and Bcl2 (anti-apoptosis) and low expression levels of Caspase-3 and Bax (pro-apoptosis) in an OGD/R model. These results suggest that MIF administration is effective for inducing expression of BDNF and leads to neuroprotection of neuronal cells against hypoxic injury.
Bicoherence Interpretation in EEG Requires Signal to Noise Ratio Quantification: An Application to Sensorimotor Rhythms

Objective: In the electroencephalogram (EEG) the quadratic phase coupling (QPC) phenomenon indicates the presence of non-linear interactions among brain rhythms that could affect the interpretation of their physiological meaning. We propose the use of the bicoherence as a QPC quantification method to understand the nature of brain rhythm interplay. Methods: We firstly provide a simulation study to show under which condition of signal to noise ratio (SNR) the bicoherence is a reliable QPC quantifier and how to interpret the results. Secondly, in the light of the simulation results, we applied the bicoherence analysis to real EEG data acquired on thirteen volunteers during a cue-paced reaching motor task to quantify coupling and decoupling between mu and beta rhythms. An inter-trial averaging procedure was adopted in order to allow the correct calculation of the bicoherence during a motor task. Results: Simulations demonstrated that SNR has a strong impact on the correct quantification of bicoherence and that a reliable detection of QPC is possible when the SNR is favorable (>−5 dB). Results from EEG data demonstrated a QPC between mu and beta rhythms during the resting state and its fading during movement planning and execution, providing valuable information for the interpretation of their dynamics. Conclusion: The bicoherence was proven to be an effective tool for the investigation of coupling between the sensorimotor rhythms during all the phases of a motor task. This was assessed in relation to the physiological changing of the SNR characterizing the frequency components of interest.
Protamine stimulates platelet aggregation in vitro with activation of the fibrinogen receptor and alpha-granule release, but impairs secondary activation via ADP and thrombin receptors

Abstract Heparin and protamine are fundamental in the management of anticoagulation during cardiac surgery. Excess protamine has been associated with increased bleeding. Interaction between protamine and platelet function has been demonstrated but the mechanism remains unclear. We examined the effect of protamine on platelet function in vitro using impedance aggregometry, flow cytometry, and thrombin generation. Platelets were exposed to protamine at final concentrations of 0, 20, 40, and 80 µg/mL, alone or together with adenosine diphosphate (ADP) or thrombin PAR1 receptor-activating peptide (TRAP). We found that in the absence of other activators, protamine (80 µg/mL) increased the proportion of platelets with active fibrinogen receptor (binding of PAC-1) from 3.6% to 97.0% (p < .001) measured with flow cytometry. Impedance aggregometry also increased slightly after exposure to protamine alone. When activated with ADP or TRAP protamine at 80 µg/mL reduced aggregation, from 73.8 ± 29.4 U to 46.9 ± 21.1 U (p < .001) with ADP and from 126.4 ± 16.1 U to 94.9 ± 23.7 U (p < .01) with TRAP. P-selectin exposure (a marker of alpha-granule release) measured by median fluorescence intensity (MFI) increased dose dependently with protamine alone, from 0.76 ± 0.20 (0 µg/mL) to 10.2 ± 3.1 (80 µg/mL), p < . 001. Protamine 80 µg/mL by itself resulted in higher MFI (10.16 ± 3.09) than activation with ADP (2.2 ± 0.7, p < .001) or TRAP (5.7 ± 2.6, p < .01) without protamine. When protamine was combined with ADP or TRAP, there was a concentration-dependent increase in the alpha-granule release. In conclusion, protamine interacts with platelets in vitro having both a direct activating effect and impairment of secondary activation of aggregation by other agonists.
Regulation of TRPC5 currents by intracellular ATP: Single channel studies

TRPC5 channels are nonselective cation channels activated by G‐protein‐coupled receptors. It was previously found that recombinant TRPC5 currents are inhibited by intracellular ATP, when studied by whole‐cell patch‐clamp recording. In the present study, we investigated the mechanism of ATP inhibition at the single‐channel level using patches from HEK‐293 cells transiently transfected with TRPC5 and the M1 muscarinic receptor. In inside‐out patches, application of ATP to the intracellular face of the membrane reduced TRPC5 channel activity at both positive and negative potentials without affecting the unitary current amplitude or open dwell time of the channel. The effect of ATP was rapidly reversible. These results suggest that ATP may bind to the channel protein and affect the ability of the channel to open or to remain in an open, nondesensitized state. The activity of TRPC5 channels may be influenced by cellular metabolism via changes in ATP levels.
Goal-Framing and Temporal-Framing: Effects on the Acceptance of Childhood Simple Obesity Prevention Messages among Preschool Children’s Caregivers in China

A range of intervention models are available for childhood obesity prevention; however, few studies have examined the effectiveness of intervention messages. This study developed childhood simple obesity prevention messages on the basis of goal-framing and temporal-framing effects to improve message acceptance among the caregivers of preschool children and explored associated factors. A cross-sectional study was conducted among 592 caregivers of preschool children in urban kindergartens in China during March to April 2019. The framing messages were developed based on prospect theory and construal level theory. The majority (48.4%) of caregivers found the gain-framed, present-oriented message most salient for acceptance. We found that gender, education background, theme, and the use of negative words have impacts on goal-framing effects; and previous participation in a health related intervention, career category, and the theme have impacts on temporal-framing effects (p < 0.001). Goal-framing effects and temporal-framing effects can influence each other (p < 0.001). The findings suggest that the gain-framed, present-oriented message could be considered a strategy to improve the acceptance of information by caregivers. When framing a message, subtle differences like using negative words might affect the exertion of framing effects.
Length of Stay for Patients With Limited English Proficiency in Pediatric Urgent Care

This retrospective chart review compared the length of stay (LOS) of families with limited English proficiency (LEP) versus English-speaking families seen in 3 pediatric urgent care centers (PUCCs). Visits were included for patients aged 2 months to 17 years seen between January 1, 2016, and December 31, 2016, with 1 of 5 primary diagnoses. For each LEP encounter, we randomly selected 3 English-speaking encounters within the same PUCC and diagnosis class. We compared overall LOS between LEP and English-speaking encounters. Of our entire sample, 184 (1.03%) were LEP encounters, of which 145 (78.8%) preferred Spanish. Comparing the LEP visits to 552 matched English-speaking visits, we found a significant difference in average LOS (LEP 85.5 minutes; English-speaking 76.4 minutes) and in prescriptions provided (P = .005) but not in triaged acuity nor number of medications administered, laboratory or radiological studies, or suction treatments. This study serves as a starting point to better care for patients/families with LEP in PUCCs.
No place like home: initiation of non-invasive ventilation for stable severe COPD

For nearly 60 years, clinicians and investigators have explored the possibility that non-invasive ventilatory assistance might improve the function of patients with stable severe chronic obstructive pulmonary disease (COPD). 1 Early studies used negative pressure ventilators with the idea that the rest of the respiratory muscles would make them stronger, but these were poorly tolerated.2 For the past 30 years, studies using non-invasive positive pressure ventilation (NIV) have been performed to see if gas exchange and sleep quantity and quality would improve but results have been conflicting. As recently as 2013, a Cochrane analysis concluded that NIV for stable severe hypercapnic COPD ‘had no clinically or statistically significant effect on gas exchange, exercise tolerance, quality of life, lung function, respiratory muscle strength or sleep efficiency’ and should only be used in the context of a clinical trial’. 3 Over the past 5 years, though, several important studies have been published that have altered thinking about the role of NIV for stable severe COPD. Kohnlein et al 4 randomised almost 200 severe stable patients (PaCO2 >6.67 kPa) to receive ‘high-intensity’ NIV (inspiratory pressure to lower PaCO2 by at least 20% and backup rate 2 breaths/min below spontaneous), or standard home oxygen. Twelve-month mortality (12% vs 33%) and St George’s Respiratory Questionnaire score were significantly better in the NIV group. More recently, Murphy et al 5 using ‘high-pressure NIV’ (with a lower set respiratory rate to allow spontaneous triggering) showed significant prolongation of the time to rehospitalisation or death in the NIV group compared with the standard oxygen group (4.3 vs 1.4 months) in patients with hypercapnic COPD recovering from acute exacerbations. However, another randomised controlled trial examining the role of …
Neurologically Motivated Coupling Functions in Models of Motor Coordination

We present an analysis of two Haken-Kelso-Bunz (HKB) oscillators coupled by a neurologically motivated function. We study the effect of time delay and weighted self-feedback and mutual feedback on the synchronization behavior of the model. We focus on identifying parameter regimes supporting experimentally observed decrease in oscillation amplitude and loss of anti-phase stability that has inspired the development of the HKB model. We show that a combination of cross-talk and nonlinearity in the coupling, along with physiologically relevant time delay, is able to quantitatively account for both drop in oscillation amplitude and loss of anti-phase stability in a frequency dependent manner. Furthermore, we demonstrate that the transition between discrete and rhythmic movements could be captured by this model. To this end, we carry out theoretical and numerical analysis of the emergence of in-phase and anti-phase oscillations.
Mapping proteome-wide targets of protein kinases in plant stress responses

Significance Despite the importance of phosphorylation-dependent signaling for cellular physiology, identification of kinase substrates remains very challenging. In this study, we developed an approach that uses natural phosphopeptides as the substrate pool to identify peptides that can be phosphorylated in vitro, which correspond to putative direct targets of the tested protein kinases. Our results demonstrate the simplicity, sensitivity, and reproducibility of this approach. By identifying more than 5,000 putative kinase–substrate pairs, our study reveals an unprecedented proteome-wide map of the targets of protein kinases during plant stress responses, which provides comprehensive information on the role of these kinases in controlling cellular activities and constitutes a valuable resource for the community. Protein kinases are major regulatory components in almost all cellular processes in eukaryotic cells. By adding phosphate groups, protein kinases regulate the activity, localization, protein–protein interactions, and other features of their target proteins. It is known that protein kinases are central components in plant responses to environmental stresses such as drought, high salinity, cold, and pathogen attack. However, only a few targets of these protein kinases have been identified. Moreover, how these protein kinases regulate downstream biological processes and mediate stress responses is still largely unknown. In this study, we introduce a strategy based on isotope-labeled in vitro phosphorylation reactions using in vivo phosphorylated peptides as substrate pools and apply this strategy to identify putative substrates of nine protein kinases that function in plant abiotic and biotic stress responses. As a result, we identified more than 5,000 putative target sites of osmotic stress-activated SnRK2.4 and SnRK2.6, abscisic acid-activated protein kinases SnRK2.6 and casein kinase 1-like 2 (CKL2), elicitor-activated protein kinase CDPK11 and MPK6, cold-activated protein kinase MPK6, H2O2-activated protein kinase OXI1 and MPK6, and salt-induced protein kinase SOS1 and MPK6, as well as the low-potassium-activated protein kinase CIPK23. These results provide comprehensive information on the role of these protein kinases in the control of cellular activities and could be a valuable resource for further studies on the mechanisms underlying plant responses to environmental stresses.
Thematic content of video narratives in patients and survivors of adolescent cancer

Modern day adolescents and young adults (AYAs) connect with their peers via a number of increasingly novel ways, many of which involve social media. These online relationships are often translated offline to increase one's social standing and quality of in‐person relationships. However, when an AYA is diagnosed with a chronic medical condition, like cancer, in‐person relationships with peers become difficult and the online component of socialization is all that is left. Video testimonials are a way that some AYAs have chosen to reach out to their peers; however, little is known about what AYAs are saying in these videos and how they are using them to connect with peers on a more intimate level.
Identifying delirium in Parkinson disease: A pilot study

People with Parkinson disease (PD) may be at increased risk of delirium and associated adverse outcomes. Delirium is an acute neuropsychiatric syndrome defined by confusion and inattention and is common in older adults. Previous studies may have underestimated the prevalence of delirium in PD because of overlapping symptoms, lack of awareness, and poorly defined criteria. We aimed to identify the prevalence and incidence of delirium in inpatients with PD.
Influence of the ACTN3 R577X genotype on the injury epidemiology of marathon runners

A common single nucleotide polymorphism in the ACTN3 gene might result in the complete deficiency of α-actinin-3 (i.e., XX genotype). It has been found that ACTN3 XX individuals have several traits related to lessened muscle performance. This study aimed to determine the influence, if any, of ACTN3 genotypes on injury incidence of marathoners during the year preceding to participating in a competitive marathon race. Using a cross-sectional experimental design, the type and conditions of sports injuries were documented for one year in a group of 139 marathoners. Injuries were recorded following a consensus statement on injuries in Athletics. Afterward, ACTN3 genotyping was performed, and injury epidemiology was compared among RR, RX, and XX genotypes. The distribution of the RR/RX/XX genotypes was 28.8/42.8/23.5%, respectively. A total of 67 injuries were recorded. The frequency of marathoners that reported any injury during the previous year was not different across the genotypes (55.0/38.8/40.6%, P = 0.241). Although the overall injury incidence was not different among genotypes (2.78/1.65/1.94 injuries/1000 h of running, P = 0.084), the likelihood of suffering an injury was higher in RR than in RX (OR = 1.93: 95%CI = 0.87–4.30), and higher than in XX (OR = 1.79: 0.70–4.58). There was no difference in the conditions, severity, body location, time of year, or leading cause of injury among genotypes. However, XX presented a higher frequency of sudden-onset injuries (P = 0.024), and the OR for muscle-type injuries was 2.0 (0.51–7.79) times higher compared to RR runners. Although XX marathoners did not have a higher overall incidence of injury, the OR in these runners for muscle-type injuries was superior to RR and RX runners. The likelihood of suffering a muscle injury, especially with a sudden-onset, was twice in XX than in RR endurance runners.
Immune correlates of tuberculosis disease and risk translate across species

Comparison of human TB gene signature to mouse and macaque models reveals common immune correlates of TB disease and risk. Translating TB Mycobacterium tuberculosis can cause tuberculosis (TB) disease in humans, although the majority of infected individuals naturally control infection and never show symptoms. To better understand immune control of M. tuberculosis, Ahmed et al. compared gene expression data from infected humans and different animal models. Gene expression differing between disease progression and control identified potentially beneficial shared pathways. Some pathways were followed up by examining M. tuberculosis infection in gene-deficient inbred mice. These results highlight how focusing on commonalities in TB infection can lead to new insights for treating TB. One quarter of the world’s population is infected with Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB). Although most infected individuals successfully control or clear the infection, some individuals will progress to TB disease. Immune correlates identified using animal models are not always effectively translated to human TB, thus resulting in a slow pace of translational discoveries from animal models to human TB for many platforms including vaccines, therapeutics, biomarkers, and diagnostic discovery. Therefore, it is critical to improve our poor understanding of immune correlates of disease and protection that are shared across animal TB models and human TB. In this study, we have provided an in-depth identification of the conserved and diversified gene/immune pathways in TB models of nonhuman primate and diversity outbred mouse and human TB. Our results show that prominent differentially expressed genes/pathways induced during TB disease progression are conserved in genetically diverse mice, macaques, and humans. In addition, using gene-deficient inbred mouse models, we have addressed the functional role of individual genes comprising the gene signature of disease progression seen in humans with Mtb infection. We show that genes representing specific immune pathways can be protective, detrimental, or redundant in controlling Mtb infection and translate into identifying immune pathways that mediate TB immunopathology in humans. Together, our cross-species findings provide insights into modeling TB disease and the immunological basis of TB disease progression.
The In Vivo Effect of Transcellular Permeation Enhancers on the Intestinal Permeability of Two Peptide Drugs Enalaprilat and Hexarelin

Permeation enhancers like sodium dodecyl sulfate (SDS) and caprate increase the intestinal permeability of small model peptide compounds, such as enalaprilat (349 Da). However, their effects remain to be investigated for larger low-permeability peptide drugs, such as hexarelin (887 Da). The objective of this single-pass perfusion study in rat was to investigate the effect of SDS at 5 mg/mL and of caprate administered at different luminal concentrations (5, 10, and 20 mg/mL) and pH (6.5 and 7.4). The small intestinal permeability of enalaprilat increased by 8- and 9-fold with SDS at 5 mg/mL and with caprate at 10 and 20 mg/mL but only at pH 7.4, where the free dissolved caprate concentration is higher than at pH 6.5 (5 vs. 2 mg/mL). Neither SDS nor caprate at any of the investigated luminal concentrations enhanced absorption of the larger peptide hexarelin. These results show that caprate requires doses above its saturation concentration (a reservoir suspension) to enhance absorption, most likely because dissolved caprate itself is rapidly absorbed. The absent effect on hexarelin may partly explain why the use of permeation enhancers for enabling oral peptide delivery has largely failed to evolve from in vitro evaluations into approved oral products. It is obvious that more innovative and effective drug delivery strategies are needed for this class of drugs.
Understanding the Solution Behavior of Epinephrine in the Presence of Toxic Cations: A Thermodynamic Investigation in Different Experimental Conditions

The interactions of epinephrine ((R)-(−)-3,4-dihydroxy-α-(methylaminomethyl)benzyl alcohol; Eph−) with different toxic cations (methylmercury(II): CH3Hg+; dimethyltin(IV): (CH3)2Sn2+; dioxouranium(VI): UO22+) were studied in NaClaq at different ionic strengths and at T = 298.15 K (T = 310.15 K for (CH3)2Sn2+). The enthalpy changes for the protonation of epinephrine and its complex formation with UO22+ were also determined using isoperibolic titration calorimetry: ΔHHL = −39 ± 1 kJ mol−1, ΔHH2L = −67 ± 1 kJ mol−1 (overall reaction), ΔHML = −26 ± 4 kJ mol−1, and ΔHM2L2(OH)2 = 39 ± 2 kJ mol−1. The results were that UO22+ complexation by Eph− was an entropy-driven process. The dependence on the ionic strength of protonation and the complex formation constants was modeled using the extended Debye–Hückel, specific ion interaction theory (SIT), and Pitzer approaches. The sequestering ability of adrenaline toward the investigated cations was evaluated using the calculation of pL0.5 parameters. The sequestering ability trend resulted in the following: UO22+ >> (CH3)2Sn2+ > CH3Hg+. For example, at I = 0.15 mol dm−3 and pH = 7.4 (pH = 9.5 for CH3Hg+), pL0.5 = 7.68, 5.64, and 2.40 for UO22+, (CH3)2Sn2+, and CH3Hg+, respectively. Here, the pH is with respect to ionic strength in terms of sequestration.