Miracle-dz/UniFAR-FTUs huggingface dataset:
A Comparison of Magnetic Resonance Imaging Methods to Assess Multiple Sclerosis Lesions: Implications for Patient Characterization and Clinical Trial Design

Magnetic resonance imaging (MRI) is a sensitive imaging modality for identifying inflammatory and/or demyelinating lesions, which is critical for a clinical diagnosis of MS and evaluating drug responses. There are many unique means of probing brain tissue status, including conventional T1 and T2 weighted imaging (T1WI, T2WI), T2 fluid attenuated inversion recovery (FLAIR), magnetization transfer, myelin water fraction, diffusion tensor imaging (DTI), phase-sensitive inversion recovery and susceptibility weighted imaging (SWI), but no study has combined all of these modalities into a single well-controlled investigation. The goals of this study were to: compare different MRI measures for lesion visualization and quantification; evaluate the repeatability of various imaging methods in healthy controls; compare quantitative susceptibility mapping (QSM) with myelin water fraction; measure short-term longitudinal changes in the white matter of MS patients and map out the tissue properties of the white matter hyperintensities using STAGE (strategically acquired gradient echo imaging). Additionally, the outcomes of this study were anticipated to aid in the choice of an efficient imaging protocol reducing redundancy of information and alleviating patient burden. Of all the sequences used, T2 FLAIR and T2WI showed the most lesions. To differentiate the putative demyelinating lesions from inflammatory lesions, the fusion of SWI and T2 FLAIR was used. Our study suggests that a practical and efficient imaging protocol combining T2 FLAIR, T1WI and STAGE (with SWI and QSM) can be used to rapidly image MS patients to both find lesions and study the demyelinating and inflammatory characteristics of the lesions.
Activity, Participation, and Goal Awareness After Acquired Brain Injury: A Prospective Observational Study of Inpatient Rehabilitation

Objective To examine the frequency and timing of inpatient engagement in meaningful activities within rehabilitation (within and outside of structured therapy times) and determine the associations between activity type, goal awareness, and patient affect. Methods This prospective observational study performed behavioral mapping in a 42-bed inpatient brain injury rehabilitation unit by recording patient activity every 15 minutes (total 42 hours). The participants were randomly selected rehabilitation inpatients with acquired brain injury; all completed the study. The main outcome measures included patient demographics, observation of activity, participation, goal awareness, and affect. Results The inpatients spent 61% of the therapeutic day (8:30 to 16:30) in their single room and were alone 49% of the time. They were physically socially inactive for 76% and 74% of their awake time, respectively, with neutral affect observed for about half of this time. Goal-related activities were recorded for only 25% of the inpatients’ awake time. The odds of physical activity were 10.3-fold higher among in patients receiving support to address their goals within their rehabilitation program (odds ratio=10.3; 95% confidence interval, 5.02–21.16). Conclusion Inpatients in a mixed brain injury rehabilitation unit spent a large amount of their awake hours inactive and only participated in goal-related activities for a quarter of their awake time. Rehabilitation models that increase opportunities for physical, cognitive, and social activities outside of allied health sessions are recommended to increase overall activity levels during inpatient rehabilitation.
Car Jack Based on 6R Overconstrained Mechanism

The paper presents a possible practical application based on two 6R overconstrained mechanism, more precisely 6R Wohlhart overconstrained mechanism. Two of these mechanisms are put in a mirror position, in order to obtain a car jack. The mechanisms are disposed in other position than the original one, three non-adjacent joints being constrained to remain in a fixed plane.
Intrahost evolution of the HIV-2 capsid correlates with progression to AIDS

Abstract HIV-2 infection will progress to AIDS in most patients without treatment, albeit at approximately half the rate of HIV-1 infection. HIV-2 capsid (p26) amino acid polymorphisms are associated with lower viral loads and enhanced processing of T cell epitopes, which may lead to protective Gag-specific T cell responses common in slower progressors. Lower virus evolutionary rates, and positive selection on conserved residues in HIV-2 env have been associated with slower progression to AIDS. In this study we analysed 369 heterochronous HIV-2 p26 sequences from 12 participants with a median age of 30 years at enrolment. CD4% change over time was used to stratify participants into relative faster and slower progressor groups. We analysed p26 sequence diversity evolution, measured site-specific selection pressures and evolutionary rates, and determined if these evolutionary parameters were associated with progression status. Faster progressors had lower CD4% and faster CD4% decline rates. Median pairwise sequence diversity was higher in faster progressors (5.7x10-3 versus 1.4x10-3 base substitutions per site, P<0.001). p26 evolved under negative selection in both groups (dN/dS=0.12). Median virus evolutionary rates were higher in faster than slower progressors – synonymous rates: 4.6x10-3 vs. 2.3x10-3; and nonsynonymous rates: 6.9x10-4 vs. 2.7x10-4 substitutions/site/year, respectively. Virus evolutionary rates correlated negatively with CD4% change rates (ρ = -0.8, P=0.02), but not CD4% level. The signature amino acid at p26 positions 6, 12 and 119 differed between faster (6A, 12I, 119A) and slower (6G, 12V, 119P) progressors. These amino acid positions clustered near to the TRIM5α/p26 hexamer interface surface. p26 evolutionary rates were associated with progression to AIDS and were mostly driven by synonymous substitutions. Nonsynonymous evolutionary rates were an order of magnitude lower than synonymous rates, with limited amino acid sequence evolution over time within hosts. These results indicate HIV-2 p26 may be an attractive therapeutic target.
Kinetics Of Interferon-λ And Receptor Expression In Response To In Vitro Respiratory Viral Infection

The major protective immune response against viruses is production of type I and III interferons (IFNs). IFNs induce the expression of hundreds of IFN-stimulated genes (ISGs) that block viral replication and further viral spread. The ability of respiratory viruses to suppress induction of IFN-mediated antiviral defenses in infected epithelial cells may be a factor contributing to the particular pathogenicity of several strains. In this report, we analyzed expression of IFNs and some ISGs in an alveolar epithelial cell subtype (A549) in response to infection with: influenza A viruses (A/California/07/09pdm (H1N1), A/Texas/50/12 (H3N2)); influenza B virus (B/Phuket/3073/13); adenovirus type 5 and 6; or respiratory syncytial virus (strain A2). IFNL and ISGs expression significantly increased in response to infection with all RNA viruses 24 hpi. Nevertheless, only IBV led to early increase in IFNL and ISGs mRNA level. IBV and H1N1 infection led to elevated proinflammatory cytokine production. We speculate that augmented IFN-α, IFN-β, IL-6 levels negatively correlate to SOCS1 expression. Importantly, we showed a decrease in IFNLR1 mRNA in case of IBV infection that implies the existence of negative ISGs expression regulation at IFNλR level. It could be either a specific feature of IBV or a consequence of early IFNL expression.
WIDEBAND HIGH-REFLECTION CHIRAL DIELECTRIC METASURFACE

Compared to natural materials, artificial subwavelength structures can enhance chiroptical effects in a stronger way, and the requirement of low material loss and wideband operation is desired in many situations. Here, we propose an all-dielectric chiral metasurface as a periodic array of centrosymmetric staggered silicon cuboid pairs to achieve strong circular dichroism in a wide band. As a demonstration, the designed chiral metasurface may strongly reflect the chosen circularly polarized light with the spin preserved in the operating wavelength range of 1.51 ∼ 1. 60μm while highly transmit (with an efficiency greater than 95%) the opposite circularly polarized light with the spin flipped. Then, two application cases are given for the designed chiral metasurface. A flat chiral meta-lens is constructed to produce wideband focusing in the transmission/reflection side while the disturbing from the opposite circular polarization is well blocked by high reflection/transmission. A chiral Fabry-Perot cavity is also constructed, which has an extremely high quality factor (2.1E4). The proposed method provides an efficient way to produce strong chiroptical effects and has a promising potential for various applications such as signal processing, sensing, radiation and detection.
Phytoclimatic spectrum of Weeds flora of Toormang Valley, Dir Lower, Koh-E-Hindukush Range, Pakistan

Four season’s data of floristic structure and biological spectrum of Toormang Valley, Dir lower was explored during 2018-2019. The flora comprised 238 species, 164 genera associated with 60 families. The most prevailing family was Asteraceae with 42 species (17.64%), trailed by Rosaceae 16 (6.72%), Brassicaceae 13(5.46%), Solanaceae 11 (4.62%), Papilionaceae 10 (4.20%), Apiaceae, and Poaceae each with 9(3.78%), Lamiaceae 8 (3.36%), Boraginaceae, Euphorbiaceae and Moraceae each contributed by 7 species (2.94%), Amaranthaceae and Cucurbitaceae each consisted of 6 species (2.52%), Caryophyllaceae and Chenopodiaceae each with 5(2.10%) while rest of 23 families contributed by 01 species each (0.42%). The largest genera were Euphorbia (6 species), followed by Sonchus and Medicago (4 species) each. Therophytes were the dominant with 102 species (42.85%), followed by nanophanerophytes with 27 (11.34%), hemicryptophytes with 25 (10.50%), chamaephytes with 20(8.40%), microphanerophytes with 18(7.56%), megaphanerophytes with 16(6.72%), geophytes with 15 (6.30%), mesophanerophytes with 14 (5.88%) and parasite with 1 species (0.42%). The observations on leaf size revealed that microphyll was the prevailing class with 73 species (30.67%), followed by mesophyll 69(28.99%), nanophyll 60 (25.21%), leptophyll 23(9.66%), macrophyll 8(3.36%), megaphylly 4(1.1.68%) and aphyllous with 1 species (0.42%). Simple lamina species 154 while 5 species have spiny lamina shape.
What Is the Cause of Toxicity of Silicone Oil?

Purpose: To investigate the toxicity of the low-molecular-weight components (LMWCs) in ophthalmic silicone oils (SilOils) on retinal cell lines. Methods: The toxicity of six types of LMWCs were studied and compared with conventional SilOil 1000 cSt. In vitro cytotoxic tests of LMWCs, in both liquid and emulsified forms, on three retinal cell lines (Müller cells (rMC-1), photoreceptor cells (661W) and retinal pigment epithelial cells (ARPE-19)) were conducted using a transwell cell culturing system. The morphology and viability of cells were assessed by light microscopy and Cell Counting Kit-8 (CCK-8) assay at different time points (6, 24 and 72 h). The ARPE-19 apoptotic pathway was investigated by Mitochondrial Membrane Potential/Annexin V Apoptosis Kit at different time points (6, 24 and 72 h). Results: Apart from dodecamethylpentasiloxane (L5), all liquid LMWCs showed varying degrees of acute cytotoxicity on retinal cell lines within 72 h. Emulsified LMWCs showed comparable cytotoxicity with liquid LMWCs on retinal cell lines. Cyclic LMWCs, octamethylcyclotetrasiloxane (D4) and decamethylcyclopentasiloxane (D5) had significantly higher cytotoxicity when compared with their linear counterparts decamethyltetrasiloxane (L4) and L5 with similar molecular formula. Using ARPE-19 cells as an example, we showed that LMWCs induce the apoptosis of retinal cells. Conclusions: Most LMWCs, in both liquid and emulsified forms, can induce acute cytotoxicity. In addition, cyclic LMWCs are suspected to have higher cytotoxicity than their linear counterparts. Therefore, LMWCs are suspected to be the main cause of the long-term toxicity of ophthalmic SilOil, due to their toxicity and propensity to cause ophthalmic SilOil to emulsify. The amount of LMWCs should be considered as the paramount parameter when referring to the quality of SilOil.
Design of joints of thin sheet parts with mechanical connections (according to EN 1993-1-3)

The main direction of development of steel building structures is to reduce the cost of implementation of buildings without changing their load-bearing capacity and value in use. Therefore, an essential factor in the development is the introduction of modern technologies. Solutions from other industries such as automotive or aerospace, have been adapted to perform building structures. As a result, today in the construction industry we use lightweight steel profiles from cold-bent elements. Modern technology and advanced calculation theory make it possible to build these structures much more economically than previous conventional systems. Elements and products made of thin sheets allow to reduce costs of construction, but at the same time is associated with the possibility of defects resulting in the appearance of a state of failure of structural elements or the entire facility. Connection zones of thin-walled elements are always the critical points, hence the need for a particularly thorough assessment at the design stage, and then at the implementation of the investment. Correct application of the presented calculation procedure in article will allow the design and realization of modern structures, which will be durable and safe in operation for the expected period of time.
Cooperative Continuum Robots: Enhancing Individual Continuum Arms by Reconfiguring Into a Parallel Manipulator

Continuum robots are able of in-situ inspection tasks in cluttered environments and narrow passages, where conventional robots and human operators cannot intervene. However, such intervention often requires the robot to interact with the environment, and the low stiffness and payload of continuum robots limits their intervention capabilities. In this letter, we propose a paradigm shift from individual to multiple continuum robots, which can reach the target environment from different paths and then physically connect, reconfiguring into a parallel architecture to enhance precision, stiffness, and payload. The main challenges in modelling and controlling cooperative continuum robots are outlined, and an experimental comparison between individual and cooperating continuum robots that connect through a novel shape-memory-alloy-based clutch highlights the advantages of the proposed technology.
Adaptive Deep Learning based Cryptocurrency Price Fluctuation Classification

—This paper proposes a deep learning based predictive model for forecasting and classifying the price of cryptocurrency and the direction of its movement. These two tasks are challenging to address since cryptocurrencies prices fluctuate with extremely high volatile behavior. However, it has been proven that cryptocurrency trading market doesn’t show a perfect market property, i.e., price is not totally a random walk phenomenon. Based upon this, this study proves that the price value forecast and price movement direction classification is both predictable. A recurrent neural networks based predictive model is built to regress and classify prices. With adaptive dynamic features selection and the use of external dependable factors with a potential degree of predictability, the proposed model achieves unprecedented performance in terms of movement classification. A naïve simulation of a trading scenario is developed and it shows a 69% profitability score a cross a six months trading period for bitcoin.
Migraine Headaches after Major Surgery with General or Neuraxial Anesthesia: A Nationwide Propensity-Score Matched Study

Migraine headaches can be provoked by surgical stress and vasoactive effects of anesthetics of general anesthesia in the perioperative period. However, it is unclear whether general anesthesia increases the migraine risk after major surgery. Incidence and risk factors of postoperative migraine are also largely unknown. We utilized reimbursement claims data of Taiwan’s National Health Insurance and performed propensity score matching analyses to compare the risk of postoperative migraine in patients without migraine initially who underwent general or neuraxial anesthesia. Multivariable logistic regressions were applied to calculate the adjusted odds ratio (aOR) and 95% confidence interval (CI) for migraine risk. A total of 68,131 matched pairs were analyzed. The overall incidence of migraine was 9.82 per 1000 person-years. General anesthesia was not associated with a greater risk of migraine compared with neuraxial anesthesia (aORs: 0.93, 95% CI: 0.80–1.09). This finding was consistent across subgroups of different migraine subtypes, uses of migraine medications, and varying postoperative periods. Influential factors for postoperative migraine were age (aOR: 0.99), sex (male vs. female, aOR: 0.50), pre-existing anxiety disorder (aOR: 2.43) or depressive disorder (aOR: 2.29), concurrent uses of systemic corticosteroids (aOR: 1.45), ephedrine (aOR: 1.45), and theophylline (aOR: 1.40), and number of emergency room visits before surgery. There was no difference in the risk of postoperative migraine between surgical patients undergoing general and neuraxial anesthesia. This study identified the risk factors for postoperative migraine headaches, which may provide an implication in facilitating early diagnoses and treatment.
Spider Toxin SNX-482 Gating Modifier Spontaneously Partitions in the Membrane Guided by Electrostatic Interactions

Spider toxin SNX-482 is a cysteine-rich peptide that interferes with calcium channel activity by binding to voltage-sensing domains of the CaV2.3 subtype. Two mechanisms dominate the binding process of cysteine-rich peptides: direct binding from the aqueous phase or through lateral diffusion from the membrane, the so-called reduction in dimensionality mechanism. In this work, via coarse-grained and atomistic molecular dynamics simulations, we have systematically studied the spontaneous partitioning of SNX-482 with membranes of different anionic compositions and explored via diffusional analysis both binding mechanisms. Our simulations revealed a conserved protein patch that inserts in the membrane, a preference for binding towards partially negatively charged membranes, and that electrostatics guides membrane binding by incrementing and aligning the molecular dipole. Finally, diffusivity calculations showed that the toxin diffusion along the membrane plane is an order of magnitude slower than the aqueous phase suggesting that the critical factor in determining the SNX-482-CaV2.3 binding mechanism is the affinity between the membrane and SNX-482.
Connexons Coupling to Gap Junction Channel: Potential Role for Extracellular Protein Stabilization Centers

Connexin (Cx) proteins establish intercellular gap junction channels (Cx GJCs) through coupling of two apposed hexameric Cx hemichannels (Cx HCs, connexons). Pre- and post-GJ interfaces consist of extracellular EL1 and EL2 loops, each with three conserved cysteines. Previously, we reported that known peptide inhibitors, mimicking a variety of Cx43 sequences, appear non-selective when binding to homomeric Cx43 vs. Cx36 GJC homology model subtypes. In pursuit of finding potentially Cx subtype-specific inhibitors of connexon-connexon coupling, we aimed at to understand better how the GJ interface is formed. Here we report on the discovery of Cx GJC subtype-specific protein stabilization centers (SCs) featuring GJ interface architecture. First, the Cx43 GJC homology model, embedded in two opposed membrane bilayers, has been devised. Next, we endorsed the fluctuation dynamics of SCs of the interface domain of Cx43 GJC by applying standard molecular dynamics under open and closed cystine disulfide bond (CS-SC) preconditions. The simulations confirmed the major role of the unique trans-GJ SC pattern comprising conserved (55N, 56T) and non-conserved (57Q) residues of the apposed EL1 loops in the stabilization of the GJC complex. Importantly, clusters of SC patterns residing close to the GJ interface domain appear to orient the interface formation via the numerous SCs between EL1 and EL2. These include central 54CS-S198C or 61CS-S192C contacts with residues 53R, 54C, 55N, 197D, 199F or 64V, 191P, respectively. In addition, we revealed that GJC interface formation is favoured when the psi dihedral angle of the nearby 193P residue is stable around 180° and the interface SCs disappear when this angle moves to the 0° to −45° range. The potential of the association of non-conserved residues with SC motifs in connexon-connexon coupling makes the development of Cx subtype-specific inhibitors viable.
Empagliflozin—A New Chance for Patients with Chronic Heart Failure

The heart failure (HF) epidemic is one of the challenges that has been faced by the healthcare system worldwide for almost 25 years. With an ageing world population and a fast-paced lifestyle that promotes the development of cardiovascular disease, the number of people suffering from heart failure will continue to rise. To improve the treatment regimen and consequently the prognosis and quality of life of heart failure patients, new therapeutic solutions have been introduced, such as an inclusion of Sodium-glucose co-transporter 2 (SGLT-2) inhibitors in a new treatment regimen as announced by the European Society of Cardiology in August 2021. This article focuses on the SGLT2 inhibitor empagliflozin and its use in patients with heart failure. Empagliflozin is a drug originally intended for the treatment of diabetes due to its glycosuric properties, yet its beneficial effects extend beyond lowering glycemia. The pleiotropic effects of the drug include nephroprotection, improving endothelial function, lowering blood pressure and reducing body weight. In this review we discuss the cardioprotective mechanism of the drug in the context of the benefits of empagliflozin use in patients with chronic cardiac insufficiency. Numerous findings confirm that despite its potential limitations, the use of empagliflozin in HF treatment is advantageous and effective.
Determinants of Foreign Direct Investment in Developed and Developing Countries: Impact of Political Stability

Stable political environment and prominent development of political institutions increase foreign direct investment flows by providing lower risks for investors. However, this impact can vary according to the development of the country. This study aims to investigate the impact of various indicators of political stability on foreign direct investment attraction for different economies distinguished by their development level. Our database includes 66 FDI-recipient countries and 98 FDI-investing countries for the period from 2001 to 2018. By applying the gravity approach and Poisson Pseudo Maximum Likelihood method with instrumental variables (IV PPML), we model bilateral FDI flows, incorporating variables reflecting various aspects of political stability formed by the principal components analysis. Interestingly, we found mixed results regarding the impact of political stability on FDI flows. In particular, political stability indicators were found to be insignificant, when analysing the bilateral FDI flows for the group of developed economies. We obtained similar result for the group of developing economies. However, political stability variables significantly influence FDI flows for countries with different development level, confirming the hypothesis that countries’ development affects bilateral FDI flows. Besides, we discover the significant difference between developed and developing countries referring to FDI-investors. Based on the obtained results, we highlight a few policy implications for developing and developed economies.