Miracle-dz/UniFAR-FTUs huggingface dataset:
How different priming stimulations affect the corticospinal excitability induced by noninvasive brain stimulation techniques: a systematic review and meta-analysis

Abstract Noninvasive brain stimulation (NIBS) techniques could induce changes in corticospinal excitability (CSE) and neuroplasticity. These changes could be affected by different factors, including having a session of stimulation called the ‘priming’ protocol before the main stimulation session called the ‘test’ protocol. Literature indicates that a priming protocol could affect the activity of postsynaptic neurons, form a neuronal history, and then modify the expected effects of the test protocol on CSE indicated by the amplitude of transcranial magnetic stimulation-induced motor-evoked potentials. This prior history affects a threshold to activate the necessary mechanism stabilizing the neuronal activity within a useful dynamic range. For studying the effects of this history and related metaplasticity mechanisms in the human primary motor cortex (M1), priming-test protocols are successfully employed. Thirty-two studies were included in this review to investigate how different priming protocols could affect the induced effects of a test protocol on CSE in healthy individuals. The results showed that if the history of synaptic activity were high or low enough to displace the threshold, the expected effects of the test protocol would be the reverse. This effect reversal is regulated by homeostatic mechanisms. On the contrary, the effects of the test protocol would not be the reverse, and at most we experience a prolongation of the lasting effects if the aforementioned history is not enough to displace the threshold. This effect prolongation is mediated by nonhomeostatic mechanisms. Therefore, based on the characteristics of priming-test protocols and the interval between them, the expected results of priming-test protocols would be different. Moreover, these findings could shed light on the different mechanisms of metaplasticity involved in NIBS. It helps us understand how we can improve the expected outcomes of these techniques in clinical approaches.
Safety, tolerability, pharmacokinetics, and pharmacodynamics of novel glucokinase activator HMS5552: results from a first-in-human single ascending dose study

Background HMS5552, a novel fourth-generation glucokinase (GK) activator, has demonstrated promising effects on glycemic control in preclinical models of type 2 diabetes. This single ascending dose study was conducted to investigate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of HMS5552 during its first-in-human exposure. Methods Sixty healthy subjects were enrolled. In each of six dose-cohorts (5, 10, 15, 25, 35, and 50 mg), ten subjects were randomized with eight subjects receiving the same cohort-dose of HMS5552 and two receiving placebo. Plasma HMS5552 exposure, glucose, and insulin were measured repeatedly during fasting and after a standardized meal. Assessment included safety, PK, and PD endpoints. Results HMS5552 showed dose-proportional increases in area under the curve 0 to the last quantifiable concentration (AUC0–t) and maximum plasma concentration (Cmax). Slopes estimated by linear regression for AUC0–t and Cmax were ~1.0 (0.932 and 0.933, respectively). Geometric mean elimination half-life ranged from 4.48 to 7.51 hours and apparent clearance ranged from 11.5 to 13.1 L/h across all doses. No significant sex effect was observed in PK parameters. HMS5552 also demonstrated dose-related PD responses in terms of maximum glucose change from baseline (%) and mean glucose area under effect curve 0–4 hours change from baseline (%) (P<0.001). Fifteen adverse events were reported by nine subjects (ten with HMS5552 and five with the placebo). All adverse events were mild in intensity and resolved without any treatment. Conclusion This first-in-human single ascending dose study provided predicted PK of HMS5552 with dose-proportional increases in AUC0–t and Cmax, as well as dose-related glucose-lowering effects over the range of 5–50 mg in healthy subjects. HMS5552 at doses up to 50 mg in healthy subjects was safe and well-tolerated.
Vitamin C and the risk of acute myocardial infarction 1–3

Background: Low-fat soluble-antioxidant status is associated with an increased risk of heart disease. Objective: The aim of this study was to examine whether low plasma concentrations of vitamin C confer an independent risk of acute myocardial infarction (AMI). Design: Male patients ( n = 180) aged <65 y with a first AMI and without an existing diagnosis of angina (>6 mo) who were admitted within 12 h after onset of symptoms were compared with apparently healthy volunteers ( n = 177). Plasma concentrations and dietary intakes of vitamin C were determined during hospitalization and 3 mo later. Results: Compared with the control subjects, the patients had higher total cholesterol and lower HDL-cholesterol concentrations and more of them smoked. The relative risk of AMI for the lowest compared with the highest quintile of plasma vitamin C during hospitalization (14.5 and >60.5 m mol/L, respectively) was 8.37 (95% CI: 3.28, 21.4) after adjustment for classic risk factors. At 3 mo, mean ( – SEM) plasma vitamin C concentrations in patients had increased signiﬁcantly, from 19.6 – 1.2 to 35.1 – 1.9 m mol/L ( P < 0.001) and no longer conferred a risk of AMI [relative risk: 1.02 (95% CI: 0.51, 2.03)]. Habitual dietary vitamin C intake of patients (before AMI) did not differ signiﬁcantly from that of control subjects. The increase in plasma vitamin C after recovery from the infarction could not be explained by a similarly large increase in dietary vitamin C. Conclusions: A low plasma concentration of vitamin C was not associated with an increased risk of AMI, irrespective of smoking status. The apparent risk of AMI due to a low plasma vitamin C concentration was distorted by the acute phase response. Am J
Negotiation and Reconciliation of Preferences in a Group Recommender System

This article presents an approach to group recommender systems that focuses its attention on the group’s social interaction during the formulation, discussion and negotiation of the features the item to be jointly selected should possess. Current group recommender techniques are mainly based on aggregating existing user profiles or on a profile of the group as a whole. Our method supports collaborative preference elicitation and negotiation process where desired features have to be chosen individually, but group consensus is needed for them to become active in the item filtering process. Users provide feedback on the selected preferences and change their significance, bringing up new recommendations each time individual settings are modified. The last stage in the decision process is also supported, when users collectively select the final item from the recommendation set. We explored the possible benefits of our approach through the development of three prototypes, each based on a different variant of the approach with a different emphasis on private and group-wide preference spaces. They were evaluated with user groups of different size, addressing questions regarding the effectiveness of different information sharing methods and the repercussion of group size in the recommendation process. We compare the different methods and consolidate the findings in an initial model of recommending for group.
The unassembled flavoprotein subunits of human and bacterial complex II have impaired catalytic activity and generate only minor amounts of ROS

Complex II (SdhABCD) is a membrane-bound component of mitochondrial and bacterial electron transport chains, as well as of the TCA cycle. In this capacity, it catalyzes the reversible oxidation of succinate. SdhABCD contains the SDHA protein harboring a covalently bound FAD redox center and the iron–sulfur protein SDHB, containing three distinct iron–sulfur centers. When assembly of this complex is compromised, the flavoprotein SDHA may accumulate in the mitochondrial matrix or bacterial cytoplasm. Whether the unassembled SDHA has any catalytic activity, for example in succinate oxidation, fumarate reduction, reactive oxygen species (ROS) generation, or other off-pathway reactions, is not known. Therefore, here we investigated whether unassembled Escherichia coli SdhA flavoprotein, its homolog fumarate reductase (FrdA), and the human SDHA protein have succinate oxidase or fumarate reductase activity and can produce ROS. Using recombinant expression in E. coli, we found that the free flavoproteins from these divergent biological sources have inherently low catalytic activity and generate little ROS. These results suggest that the iron–sulfur protein SDHB in complex II is necessary for robust catalytic activity. Our findings are consistent with those reported for single-subunit flavoprotein homologs that are not associated with iron–sulfur or heme partner proteins.
Nasal Packing after Functional Endoscopic Sinus Surgery

This chapter was to have a systematic review and meta‐analysis on the available lit‐ erature in order to compare the efficacy and postoperative outcomes of nasal packing (absorbable vs. nonabsorbable) after treatment of chronic rhinosinusitis with functional endoscopic sinus surgery (FESS). The systematic review included five studies with 241 nasal cavities in each treatment group. The prevalence of synechia in the absorbable groups ranged from 4.6 to 8.0% while nonabsorbable groups ranged from 8.0 to 35.7%. The absorbable group had a lower postoperative bleeding; however, there were no clear findings on postoperative pain. Postoperative edema was in general similar among groups, and no consistent findings were found on bleeding and pain while removing packing. The meta‐analysis included two studies using the same type of packing mate ‐ rial. The combined OR (0.33, 95% CI = 0.04–2.78) for postoperative synechia did not significantly favor (P = 0.016308) absorbable packing over nonabsorbable packing. The available literature showed that there is some evidence that absorbable nasal packing may provide superior outcomes to nonabsorbable packing after FESS. However, lack of homogeneity between these studies makes it impossible to have a definitive conclusion.
Generalized Lagrangian Path Approach to Manifestly-Covariant Quantum Gravity Theory

A trajectory-based representation for the quantum theory of the gravitational field is formulated. This is achieved in terms of a covariant Generalized Lagrangian-Path (GLP) approach which relies on a suitable statistical representation of Bohmian Lagrangian trajectories, referred to here as GLP-representation. The result is established in the framework of the manifestly-covariant quantum gravity theory (CQG-theory) proposed recently and the related CQG-wave equation advancing in proper-time the quantum state associated with massive gravitons. Generally non-stationary analytical solutions for the CQG-wave equation with non-vanishing cosmological constant are determined in such a framework, which exhibit Gaussian-like probability densities that are non-dispersive in proper-time. As a remarkable outcome of the theory achieved by implementing these analytical solutions, the existence of an emergent gravity phenomenon is proven to hold. Accordingly, it is shown that a mean-field background space-time metric tensor can be expressed in terms of a suitable statistical average of stochastic fluctuations of the quantum gravitational field whose quantum-wave dynamics is described by GLP trajectories.
Comparing planning time, delivery time and plan quality for IMRT, RapidArc and tomotherapy

The purpose of this study is to examine plan quality, treatment planning time, and estimated treatment delivery time for 5‐ and 9‐field sliding window IMRT, single and dual arc RapidArc, and tomotherapy. For four phantoms, 5‐ and 9‐field IMRT, single and dual arc RapidArc and tomotherapy plans were created. Plans were evaluated based on the ability to meet dose‐volume constraints, dose homogeneity index, radiation conformity index, planning time, estimated delivery time, integral dose, and volume receiving more than 2 and 5 Gy. For all of the phantoms, tomotherapy was able to meet the most optimization criteria during planning (50% for P1, 67% for P2, 0% for P3, and 50% for P4). RapidArc met less of the optimization criteria (25% for P1, 17% for P2, 0% for P3, and 0% for P4), while IMRT was never able to meet any of the constraints. In addition, tomotherapy plans were able to produce the most homogeneous dose. Tomotherapy plans had longer planning time, longer estimated treatment times, lower conformity index, and higher integral dose. Tomotherapy plans can produce plans of higher quality and have the capability to conform dose distributions better than IMRT or RapidArc in the axial plane, but exhibit increased dose superior and inferior to the target volume. RapidArc, however, is capable of producing better plans than IMRT for the test cases examined in this study. PACS number: 87.55. x, 87.55. D, 87.55. de, 87.55. dk
RCoal: Mitigating GPU Timing Attack via Subwarp-Based Randomized Coalescing Techniques

Graphics processing units (GPUs) are becoming default accelerators in many domains such as high-performance computing (HPC), deep learning, and virtual/augmented reality. Recently, GPUs have also shown significant speedups for a variety of security-sensitive applications such as encryptions. These speedups have largely benefited from the high memory bandwidth and compute throughput of GPUs. One of the key features to optimize the memory bandwidth consumption in GPUs is intra-warp memory access coalescing, which merges memory requests originating from different threads of a single warp into as few cache lines as possible. However, this coalescing feature is also shown to make the GPUs prone to the correlation timing attacks as it exposes the relationship between the execution time and the number of coalesced accesses. Consequently, an attacker is able to correctly reveal an AES private key via repeatedly gathering encrypted data and execution time on a GPU. In this work, we propose a series of defense mechanisms to alleviate such timing attacks by carefully trading off performance for improved security. Specifically, we propose to randomize the coalescing logic such that the attacker finds it hard to guess the correct number of coalesced accesses generated. To this end, we propose to randomize: a) the granularity (called as subwarp) at which warp threads are grouped together for coalescing, and b) the threads selected by each subwarp for coalescing. Such randomization techniques result in three mechanisms: fixed-sized subwarp (FSS), random-sized subwarp (RSS), and random-threaded subwarp (RTS). We find that the combination of these security mechanisms offers 24- to 961-times improvement in the security against the correlation timing attacks with 5 to 28% performance degradation.
Responses of an Agricultural Soil Microbiome to Flooding with Seawater after Managed Coastal Realignment

Coastal areas have become more prone to flooding with seawater due to climate-change-induced sea-level rise and intensified storm surges. One way to cope with this issue is by “managed coastal realignment”, where low-lying coastal areas are no longer protected and instead flooded with seawater. How flooding with seawater impacts soil microbiomes and the biogeochemical cycling of elements is poorly understood. To address this, we conducted a microcosm experiment using soil cores collected at the nature restoration project site Gyldensteen Strand (Denmark), which were flooded with seawater and monitored over six months. Throughout the experiment, biogeochemical analyses, microbial community fingerprinting and the quantification of marker genes documented clear shifts in microbiome composition and activity. The flooding with seawater initially resulted in accelerated heterotrophic activity that entailed high ammonium production and net removal of nitrogen from the system, also demonstrated by a concurrent increase in the abundances of marker genes for ammonium oxidation and denitrification. Due to the depletion of labile soil organic matter, microbial activity decreased after approximately four months. The event of flooding caused the largest shifts in microbiome composition with the availability of labile organic matter subsequently being the most important driver for the succession in microbiome composition in soils flooded with seawater.
Distinct In Vitro T-Helper 17 Differentiation Capacity of Peripheral Naive T Cells in Rheumatoid and Psoriatic Arthritis

Background The T-helper 17 (Th17) cells have a prominent role in inflammation as well as in bone and join destruction in both rheumatoid and psoriatic arthritis (RA and PsA). Here, we studied Th17 cell differentiation in RA and PsA. Methods Blood samples from healthy donors, RA and PsA patients were collected. CD45RO− (naive) and CD45RO+ (memory) T cells were isolated from peripherial blood mononuclear cell by magnetic separation. Naive T cells were stimulated with anti-CD3, anti-CD28, and goat anti-mouse IgG antibodies and treated with transforming grow factor beta, interleukin (IL)-6, IL-1β, and IL-23 cytokines and also with anti-IL-4 antibody. IL-17A and IL-22 production were measured by enzyme linked immunosorbent assay, RORC, and T-box 21 (TBX21) expression were analyzed by quantitative polymerase chain reaction and flow cytometry. C-C chemokine receptor 6 (CCR6), CCR4, and C-X-C motif chemokine receptor 3 expression were determined by flow cytometry. Cell viability was monitored by impedance-based cell analyzer (CASY-TT). Results RORC, TBX21, CCR6, and CCR4 expression of memory T cells of healthy individuals (but not RA or PsA patients) were increased (p < 0.01; p < 0.001; p < 0.05; p < 0.05, respectively) compared to the naive cells. Cytokine-induced IL-17A production was different in both RA and PsA patients when compared to healthy donors (p = 0.0000026 and p = 0.0001047, respectively). By contrast, significant differences in IL-22 production were observed only between RA versus healthy or RA versus PsA patients (p = 0.000006; p = 0.0013454, respectively), but not between healthy donors versus PsA patients. Conclusion The naive CD4 T-lymphocytes are predisposed to differentiate into Th17 cells and the in vitro Th17 cell differentiation is profoundly altered in both RA and PsA.
Relationships between total lightning, deep convection, and tropical cyclone intensity change

This study investigates the characteristics of total lightning in the inner core (INCO, 0–100 km) and outer rainband (OB, 200–400 km) of tropical cyclones (TC). Relationships between flash density (FLD), convective intensity, and TC intensity change are further examined. FLD shows a bimodal structure with a strong maximum in the eyewall (INCO, 0–50 km) and a secondary maximum in the OB. FLD maximizes under conditions of warmest sea surface temperature (SST) and large values of vertical wind shear. Compared to OB FLD, INCO FLD is less sensitive to SST increase but shows greater variability in relation to shear. Intensifying TCs have substantially lower INCO (but higher OB) FLD compared to weakening and neutral TCs. Similar trends are shown in radar quantities (volume of 30 dBZ echoes in the mixed phase). rapidly intensifying (RI) TCs also show significantly smaller FLD and VOL30 than slowly intensifying TCs, indicating the potential of these parameters in forecasting RI. INCO (OB) FLD decreases (increases) 12–18 h preceding the onset of RI, while INCO (OB) FLD increases (decreases) 6–12 h prior to TC weakening. These relationships between lightning and TC intensity change (+24 h) are generally maintained regardless of prior (−24 h) TC intensity change status. However, convective depth and vertically integrated ice content in the INCO increased preceding TC intensification, suggesting the lack of supercooled liquid content and establishment of glaciated conditions (evident by an increase in the 20 dBZ and decrease in the 30 dBZ echo volume) in the INCO of intensifying TCs, especially RI.
A Dog in the Cancer Fight: Comparative Oncology in Osteosarcoma

Since the great Rudolf Virchow advised, “Between animal and human medicine there is no dividing line, nor should there be,” limited attention has been paid to cancer in ani -mals. This is finally changing thanks to a renewed focus on studying pet dogs with can - cer. Unlike the laboratory mice who have been the mainstay of animal models of disease, pet dogs share an environment with their human owners, have an intact immune system, and often develop diseases spontaneously in ways that mimic their human counterparts. Osteosarcoma (OSA) – while uncommon in humans - is a common malignancy in dogs. This comparatively high incidence alone renders pet dogs an ideal “model” to conduct translational and clinical research into OSA. Indeed, there are many similarities between the two species with respect to this disease. However, owing to the shorter life span and accelerated disease progression, treatment effects can be assessed much more rapidly in canines than in humans. Overall, dogs represent a unique model to study OSA; this chap ter aims to discuss the ways that comparative oncology between dogs and humans are being used from basic science research, to genetics and mechanisms of disease, to tumor biology and finally to developing novel treatments.
The Impact of Solar Irradiance on Visible Light Communications

This paper aims to address the perception that visible light communication (VLC) systems cannot work under the presence of sunlight. A complete framework is presented to evaluate the performance of VLC systems in the presence of solar irradiance at any given location and time. The effect of solar irradiance is investigated in terms of degradations in signal to noise ratio, data rate, and bit error rate. Direct current (DC) optical orthogonal frequency division multiplexing is used with adaptive bit and energy loading to mitigate DC wander interference and low-frequency ambient light noise. It was found that reliable communication can be achieved under the effect of solar irradiance at high-speed data rates. An optical bandpass blue filter is shown to compensate for half of the reduced data rate in the presence of sunlight. This work demonstrates data rates above 1 Gb/s of a VLC link under strong solar illuminance measured at 50350 lux in clear weather conditions.
Sox2 Level Is a Determinant of Cellular Reprogramming Potential

Epiblast stem cells (EpiSCs) and embryonic stem cells (ESCs) differ in their in vivo differentiation potential. While ESCs form teratomas and efficiently contribute to the development of chimeras, EpiSCs form teratomas but very rarely chimeras. In contrast to their differentiation potential, the reprogramming potential of EpiSCs has not yet been investigated. Here we demonstrate that the epiblast-derived pluripotent stem cells EpiSCs and P19 embryonal carcinoma cells (ECCs) exhibit a lower reprogramming potential than ESCs and F9 ECCs. In addition, we show that the low reprogramming ability is due to the lower levels of Sox2 in epiblast-derived stem cells. Consistent with this observation, overexpression of Sox2 enhances reprogramming efficiency. In summary, these findings suggest that a low reprogramming potential is a general feature of epiblast-derived stem cells and that the Sox2 level is a determinant of the cellular reprogramming potential.