Miracle-dz/UniFAR-FTUs huggingface dataset:
Cerebrospinal Fluid Biomarkers of Myeloid and Glial Cell Activation Are Correlated With Multiple Sclerosis Lesional Inflammatory Activity

Multiple sclerosis (MS)-related inflammation can be divided into lesional activity, mediated by immune cells migrating from the periphery to the central nervous system (CNS) and non-lesional activity, mediated by inflammation compartmentalized to CNS tissue. Lesional inflammatory activity, reflected by contrast-enhancing lesions (CELs) on the magnetic resonance imaging (MRI), is effectively inhibited by current disease modifying therapies (DMTs). While, the effect of DMTs on non-lesional inflammatory activity is currently unknown. Reliable and simultaneous measurements of both lesional and non-lesional MS activity is necessary to understand their contribution to CNS tissue destruction in individual patients. We previously demonstrated that CNS compartmentalized inflammation can be measured by combined quantification of cerebrospinal fluid (CSF) immune cells and cell-specific soluble markers. The goal of this study is to develop and validate a CSF-biomarker-based molecular surrogate of MS lesional activity. The training cohort was dichotomized into active (CELs > 1 or clinical relapse) and inactive lesional activity (no CELs or relapse) groups. Matched CSF and serum samples were analyzed for 20 inflammatory and axonal damage biomarkers in a blinded fashion. Only the findings from the training cohort with less than 0.1% probability of false positive (i.e., p < 0.001) were validated in an independent validation cohort. MS patients with lesional activity have elevated IL-12p40, CHI3L1, TNFα, TNFβ, and IL-10, with the first two having the strongest effects and validated statistically-significant association with lesional activity in an independent validation cohort. Marker of axonal damage, neurofilament light (NfL), measured in CSF (cNfL) was also significantly elevated in MS patients with active lesions. NfL measured in serum (sNfL) did not differentiate the two MS subgroups with pre-determined significance, (p = 0.0690) even though cCSF and sNfL correlated (Rho = 0.66, p < 0.0001). Finally, the additive model of IL12p40 and CHI3L1 outperforms any biomarker discretely. IL12p40 and CHI3L1, released predominantly by immune cells of myeloid lineage are reproducibly the best CSF biomarkers of MS lesional activity. The residuals from the IL12p40/CHI3L1-cNfL correlations may identify MS patients with more destructive inflammation or contributing neurodegeneration.
Biofeedback for Post-stroke Gait Retraining: A Review of Current Evidence and Future Research Directions in the Context of Emerging Technologies

Real-time gait biofeedback is a promising rehabilitation strategy for improving biomechanical deficits in walking patterns of post-stroke individuals. Because wearable sensor technologies are creating avenues for novel applications of gait biofeedback, including use in tele-health, there is a need to evaluate the state of the current evidence regarding the effectiveness of biofeedback for post-stroke gait training. The objectives of this review are to: (1) evaluate the current state of biofeedback literature pertaining to post-stroke gait training; and (2) determine future research directions related to gait biofeedback in context of evolving technologies. Our overall goal was to determine whether gait biofeedback is effective at improving stroke gait deficits while also probing why and for whom gait biofeedback may be an efficacious treatment modality. Our literature review showed that the effects of gait biofeedback on post-stroke walking dysfunction are promising but are inconsistent in methodology and therefore results. We summarize sources of methodological heterogeneity in previous literature, such as inconsistencies in feedback target, feedback mode, dosage, practice structure, feedback structure, and patient characteristics. There is a need for larger-sample studies that directly compare different feedback parameters, employ more uniform experimental designs, and evaluate characteristics of potential responders. However, as these uncertainties in existing literature are resolved, the application of gait biofeedback has potential to extend neurorehabilitation clinicians' cues to individuals with post-stroke gait deficits during ambulation in clinical, home, and community settings, thereby increasing the quantity and quality of skilled repetitions during task-oriented stepping training. In addition to identifying gaps in previous research, we posit that future research directions should comprise an amalgam of mechanism-focused and clinical research studies, to develop evidence-informed decision-making guidelines for gait biofeedback strategies that are tailored to individual-specific gait and sensorimotor impairments. Wearable sensor technologies have the potential to transform gait biofeedback and provide greater access and wider array of options for clinicians while lowering rehabilitation costs. Novel sensing technologies will be particularly valuable for telehealth and home-based stepping exercise programs. In summary, gait biofeedback is a promising intervention strategy that can enhance efficacy of post-stroke gait rehabilitation in both clinical and tele-rehabilitation settings and warrants more in-depth research.
An Adaptable, Open-Access Test Battery to Study the Fractionation of Executive-Functions in Diverse Populations

The umbrella-term ‘executive functions’ (EF) includes various domain-general, goal-directed cognitive abilities responsible for behavioral self-regulation. The influential unity and diversity model of EF posits the existence of three correlated yet separable executive domains: inhibition, shifting and updating. These domains may be influenced by factors such as socioeconomic status (SES) and culture, possibly due to the way EF tasks are devised and to biased choice of stimuli, focusing on first-world testees. Here, we propose a FREE (Free Research Executive Function Evaluation) test battery that includes two open-access tasks for each of the three abovementioned executive domains to allow latent variables to be obtained. The tasks were selected from those that have been shown to be representative of each domain, that are not copyrighted and do not require special hardware/software to be administered. These tasks were adapted for use in populations with varying SES/schooling levels by simplifying tasks/instructions and using easily recognized stimuli such as pictures. Items are answered verbally and tasks are self-paced to minimize interference from individual differences in psychomotor and perceptual speed, to better isolate executive from other cognitive abilities. We tested these tasks on 146 early adolescents (aged 9–15 years) of both sexes and varying SES, because this is the age group in which the executive domains of interest become distinguishable and in order to confirm that SES effects were minimized. Performance was determined by Rate Correct Scores (correct answers divided by total time taken to complete blocks/trial), which consider speed-accuracy trade-offs. Scores were sensitive to the expected improvement in performance with age and rarely/inconsistently affected by sex and SES, as expected, with no floor or ceiling effects, or skewed distribution, thus suggesting their adequacy for diverse populations in these respects. Using structural equation modeling, evidence based on internal structure was obtained by replicating the three correlated-factor solution proposed by the authors of the model. We conclude that the FREE test battery, which is open access and described in detail, holds promise as a tool for research that can be adapted for a wide range of populations, as well as altered and/or complemented in coming studies.
Survival Rates and Capture Heterogeneity of Bottlenose Dolphins (Tursiops truncatus) in the Shannon Estuary, Ireland

Adult survival is arguably the most important demographic parameter for long-lived species as it has a large impact on population growth, and it can be estimated for cetacean populations using natural markings and mark-recapture (MR) modelling. Here we describe a 26-year study of a genetically discrete, resident population of bottlenose dolphins in the Shannon Estuary, Ireland, conducted by an NGO using multiple platforms. We estimated survival rates (SRs) using Cormack-Jolly-Seber models and explored the effects of variable survey effort, multiple researchers, and changes in camera equipment as well as capture heterogeneity induced by changes in marks and site fidelity variation, all common issues affecting longitudinal dolphin studies. The mean adult SR was 0.94 (±0.001 SD) and thus comparable to the estimates reported for other bottlenose dolphin populations. Capture heterogeneity through variation in mark severity was confirmed, with higher capture probabilities for well-marked individuals than for poorly marked individuals and a “transience” effect being detected for less well-marked individuals with 43% only recorded once. Likewise, both SR and capture probabilities were comparatively low for individuals with low site fidelity to the Shannon Estuary, and SR of these individuals additionally decreased even further toward the end of the study, reflecting a terminal bias. This bias was attributed to non-random temporal migration, and, together with high encounter rates in Brandon Bay, supported the hypothesis of range expansion. Our results highlight the importance of consistent and geographically homogenous survey effort and support the differentiation of individuals according to their distinctiveness to avoid biased survival estimates.
Epigenetic Modifiers: Anti-Neoplastic Drugs With Immunomodulating Potential

Cancer cells are under the surveillance of the host immune system. Nevertheless, a number of immunosuppressive mechanisms allow tumors to escape protective responses and impose immune tolerance. Epigenetic alterations are central to cancer cell biology and cancer immune evasion. Accordingly, epigenetic modulating agents (EMAs) are being exploited as anti-neoplastic and immunomodulatory agents to restore immunological fitness. By simultaneously acting on cancer cells, e.g. by changing expression of tumor antigens, immune checkpoints, chemokines or innate defense pathways, and on immune cells, e.g. by remodeling the tumor stroma or enhancing effector cell functionality, EMAs can indeed overcome peripheral tolerance to transformed cells. Therefore, combinations of EMAs with chemo- or immunotherapy have become interesting strategies to fight cancer. Here we review several examples of epigenetic changes critical for immune cell functions and tumor-immune evasion and of the use of EMAs in promoting anti-tumor immunity. Finally, we provide our perspective on how EMAs could represent a game changer for combinatorial therapies and the clinical management of cancer.
Estimating the Magnetic Structure of an Erupting CME Flux Rope From AR12158 Using Data-Driven Modeling

We investigate here the magnetic properties of a large-scale magnetic flux rope related to a coronal mass ejection (CME) that erupted from the Sun on September 12, 2014 and produced a well-defined flux rope in interplanetary space on September 14–15, 2014. We apply a fully data-driven and time-dependent magnetofrictional method (TMFM) using Solar Dynamics Observatory (SDO) magnetograms as the lower boundary condition. The simulation self-consistently produces a coherent flux rope and its ejection from the simulation domain. This paper describes the identification of the flux rope from the simulation data and defining its key parameters (e.g., twist and magnetic flux). We define the axial magnetic flux of the flux rope and the magnetic field time series from at the apex and at different distances from the apex of the flux rope. Our analysis shows that TMFM yields axial magnetic flux values that are in agreement with several observational proxies. The extracted magnetic field time series do not match well with in-situ components in direct comparison presumably due to interplanetary evolution and northward propagation of the CME. The study emphasizes also that magnetic field time-series are strongly dependent on how the flux rope is intercepted which presents a challenge for space weather forecasting.
Comparison of the effect of acetic acid with axially and radially viewed inductively coupled plasma atomic emission spectrometry: influence of the operating conditions

Acetic acid was selected as a highly perturbing matrix for the comparison of matrix effects between axial and radial viewing modes in ICP-AES. The effect of acetic acid (5 and 10% v/v) on the intensities of various ionic lines in ICP-AES was studied under extreme operating conditions,i.e., robust and non-robust conditions. A cross-flow nebulizer associated with a double-pass spray chamber was chosen as a sample introduction system. The influence of the operating conditions on the Mg II 280 nm/Mg I 285 nm line intensity ratio was also studied. This work confirmed that, under so-called robust conditions, i.e., high rf power and low carrier gas flow rate, the acetic acid caused an enhancement of the signal intensity, regardless of the energy line and the viewing mode, which could be assigned to a change in the aerosol formation and transport. An increase in the solvent transport rate and a significant modification of the primary, and especially the tertiary, aerosol drop size distributions were observed in the presence of acetic acid. Hence, finer aerosols were obtained when acetic acid was present.
The Association of Family-Related Adversity With Fighting in Adolescents: Does Hopelessness Mediate This Association?

Objectives: To explore the association of family-related adversities with physical fighting, and whether this association is mediated by hopelessness. Methods: The sample consisted of 3712 Slovak adolescents (mean age: 13.9, 50.7% girls). Participants answered questions regarding experienced family-related adversities, involvement in physical fighting in the last 12 months and the Hopelessness Questionnaire. First, the association of family adversities in general with fighting and of each of family-related adversity separately was assessed using linear regression models and second, mediation was assessed using the a*b product method with bootstrapped 95% confidence intervals Results: Adolescents who had experienced at least one family adversity reported more frequent fighting. Similarly, each of reported family adversities (death of a parent, substance abuse problems of a parent, conflicts/physical fights, divorce) was associated with more frequent fighting among adolescents. The mediation effect of hopelessness was found in each association of family-related adversity with fighting. Conclusion: These findings suggest that interventions to support adolescents who had experienced family adversities could among other things be directed at better coping with hopelessness.
Complex RNA Secondary Structures Mediate Mutually Exclusive Splicing of Coleoptera Dscam1

Mutually exclusive splicing is an important mechanism for expanding protein diversity. An extreme example is the Down syndrome cell adhesion molecular (Dscam1) gene of insects, containing four clusters of variable exons (exons 4, 6, 9, and 17), which potentially generates tens of thousands of protein isoforms through mutually exclusive splicing, of which regulatory mechanisms are still elusive. Here, we systematically analyzed the variable exon 4, 6, and 9 clusters of Dscam1 in Coleoptera species. Through comparative genomics and RNA secondary structure prediction, we found apparent evidence that the evolutionarily conserved RNA base pairing mediates mutually exclusive splicing in the Dscam1 exon 4 cluster. In contrast to the fly exon 6, most exon 6 selector sequences in Coleoptera species are partially located in the variable exon region. Besides, bidirectional RNA–RNA interactions are predicted to regulate the mutually exclusive splicing of variable exon 9 of Dscam1. Although the docking sites in exon 4 and 9 clusters are clade specific, the docking sites-selector base pairing is conserved in secondary structure level. In short, our result provided a mechanistic framework for the application of long-range RNA base pairings in regulating the mutually exclusive splicing of Coleoptera Dscam1.
Disturbances in Brain Physiology Due to Season Play: A Multi-Sport Study of Male and Female University Athletes

High-performance university athletes experience frequent exertion, resulting in disrupted biological homeostasis, but it is unclear to what extent brain physiology is affected. We examined whether athletes without overtraining symptoms show signs of increased neurophysiological stress over the course of a single athletic season, and whether the effects are modified by demographic factors of age, sex and concussion history, and sport-related factors of contact exposure and season length. Fifty-three university-level athletes were recruited from multiple sports at a single institution and followed longitudinally from beginning of season (BOS) to end of season (EOS) and 1 month afterwards, with a subset followed up at the subsequent beginning of season. MRI was used to comprehensively assess white matter (WM) diffusivity, cerebral blood flow (CBF), and brain activity, while overtraining symptoms were assessed with Hooper’s Index (HI). Although athletes did not report increased HI scores, they showed significantly increased white matter diffusivity and decreased CBF at EOS and 1 month afterwards, with recovery at follow-up. Global brain activity was not significantly altered though, highlighting the ability of the brain to adapt to exercise-related stressors. Male athletes had greater white matter diffusivity at EOS, but female athletes had greater declines in CBF at 1 month afterwards. Post-season changes in MRI measures were not related to change in HI score, age, concussion history, contact exposure, or length of athletic season. Hence, the brain shows substantial but reversible neurophysiological changes due to season play in the absence of overtraining symptoms, with effects that are sex-dependent but otherwise insensitive to demographic variations. These findings provide new insights into the effects of training and competitive play on brain health.
Electrode and Electrolyte Materials From Atomistic Simulations: Properties of LixFEPO4 Electrode and Zircon-Based Ionic Conductors

LixFePO4 orthophosphates and fluorite- and pyrochlore-type zirconate materials are widely considered as functional compounds in energy storage devices, either as electrode or solid state electrolyte. These ceramic materials show enhanced cation exchange and anion conductivity properties that makes them attractive for various energy applications. In this contribution we discuss thermodynamic properties of LixFePO4 and yttria-stabilized zirconia compounds, including formation enthalpies, stability, and solubility limits. We found that at ambient conditions LixFePO4 has a large miscibility gap, which is consistent with existing experimental evidence. We show that cubic zirconia becomes stabilized with Y content of ~8%, which is in line with experimental observations. The computed activation energy of 0.92eV and ionic conductivity for oxygen diffusion in yttria-stabilized zirconia are also in line with the measured data, which shows that atomistic modeling can be applied for accurate prediction of key materials properties. We discuss these results with the existing simulation-based data on these materials produced by our group over the last decade. Last, but not least, we discuss similarities of the considered compounds in considering them as materials for energy storage and radiation damage resistant matrices for immobilization of radionuclides.
Characterization and Mechanism of Linearized-Microcystinase Involved in Bacterial Degradation of Microcystins

Microcystins (MCs) are extremely hazardous to the ecological environment and public health. How to control and remove MCs is an unsolved problem all over the world. Some microbes and their enzymes are thought to be effective in degrading MCs. Microcystinase can linearize microcystin-leucine-arginine (MC-LR) via a specific locus. However, linearized MC-LR is also very toxic and needs to be removed. How linearized MC-LR was metabolized by linearized-microcystinase, especially how linearized-microcystinase binds to linearized MC-LR, has not been defined. A combination of in vitro experiments and computer simulation was applied to explore the characterization and molecular mechanisms for linearized MC-LR degraded by linearized-microcystinase. The purified linearized-microcystinase was obtained by recombinant Escherichia coli overexpressing. The concentration of linearized MC-LR was detected by high-performance liquid chromatography, and linearized MC-LR degradation products were analyzed by the mass spectrometer. Homology modeling was used to predict the structure of the linearized-microcystinase. Molecular docking techniques on the computer were used to simulate the binding sites of linearized-microcystinase and linearized MC-LR. The purified linearized-microcystinase was obtained successfully. The linearized-microcystinase degraded linearized MC-LR to tetrapeptide efficiently. The second structure of linearized-microcystinase consisted of many alpha-helices, beta-strands, and colis. Linearized-microcystinase interacted the linearized MC-LR with hydrogen bond, hydrophobic interaction, electrostatic forces, and the Van der Waals force. This study firstly reveals the characterization and specific enzymatic mechanism of linearized-microcystinase for catalyzing linearized MC-LR. These findings encourage the application of MC-degrading engineering bacteria and build a great technique for MC-LR biodegradation in environmental engineering.
The Onset of Falls Reduces Subjective Well-Being. Findings of a Nationally Representative Longitudinal Study

Introduction: The prevalence of older individuals experiencing a fall is high. Moreover, falls can have deleterious effects on health status. Additionally, falls can affect the subjective well-being of individuals. However, there is a lack of studies examining the link between falls and subjective well-being. Therefore, the objective of this study was to investigate whether the onset of falling is associated with (intraindividual) decreases in subjective well-being in men and women. Materials and Methods: Longitudinal data (from wave 5 to wave 6) were taken from a population-based sample of individuals residing in private households in Germany [in our analytical sample: 3,906 observations (men), and 3,718 observations (women)]. Positive and negative affect were quantified using the Positive and Negative Affect Schedule (PANAS). Life satisfaction was assessed using the Satisfaction with Life Scale (SWLS). Results: Adjusting for various potential confounders, fixed effects regressions showed that the onset of falls was associated with a decrease in positive affect (β = 0.08, p < 0.01), and an increase in negative affect (β = 0.07, p < 0.01) among men. While the onset of falls was not associated with changes in positive affect in women, it was associated with a decrease in negative affect in women (β = 0.06, p < 0.05). Sex differences were significant. The onset of falls was not associated with decreases in life satisfaction in men, nor in women. Discussion: The present study particularly highlights the link between the onset of falls and reduced affective well-being among men. Avoiding falls may contribute to maintaining affective well-being among middle-aged and older men.