Miracle-dz/UniFAR-FTUs huggingface dataset:
β‐Adrenergic receptor density and function of peripheral blood mononuclear cells are increased in multiple sclerosis: A regulatory role for cortisol and interleukin‐1

An increased density of β‐adrenergic receptors was demonstrated on peripheral blood mononuclear cells (PMMCs) from patients with progressive or replapsing‐remitting multiple sclerosis (MS). The same observation was made in patients with chronic active rheumatoid arthritis, but not in those with myasthenia gravis. The affinity of the receptors was within the normal range in all tested groups of patients and there was a positive correlation between density and function as determined by intracellular cyclic AMP production after stimulation with isoproterenol. A putative link between inflammatory processes and the functional upregulation of β‐adrenergic receptors on PBMCs was tested by in vitro studies with the soluble mediators interleukin‐1 and hydrocortisone. A functional upregulation of β‐adrenergic receptors was observed when PBMCs from normal control subjects were cultured in the presence of either mediator, whereas the already upregulated receptor density on PBMCs from patients with MS remained unchanged. Whether this represents a recovery mechanism to inflammation in MS or a blunting of homeostatic immunoregulatory mechanisms requires further investigation.
Damage to the Blood-Brain Barrier during Experimental Cerebral Malaria Results from Synergistic Effects of CD8+ T Cells with Different Specificities

ABSTRACT CD8+ T cells play a pathogenic role in the development of murine experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA (PbA) infection in C57BL/6 mice. Only a limited number of CD8+ epitopes have been described. Here, we report the identification of a new epitope from the bergheilysin protein recognized by PbA-specific CD8+ T cells. Induction and functionality of these specific CD8+ T cells were investigated in parallel with previously reported epitopes, using new tools such as tetramers and reporter cell lines that were developed for this study. We demonstrate that CD8+ T cells of diverse specificities induced during PbA infection share many characteristics. They express cytolytic markers (gamma interferon [IFN-γ], granzyme B) and chemokine receptors (CXCR3, CCR5) and damage the blood-brain barrier in vivo. Our earlier finding that brain microvessels in mice infected with PbA, but not with non-ECM-causing strains, cross-presented a shared epitope was generalizable to these additional epitopes. Suppressing the induction of specific CD8+ T cells through tolerization with a high-dose peptide injection was unable to confer protection against ECM, suggesting that CD8+ T cells of other specificities participate in this process. The tools that we developed can be used to further investigate the heterogeneity of CD8+ T cell responses that are involved in ECM.
SDN based traffic engineering without optimization: A centrality based approach

Software defined networks (SDNs) reduce the complexity of implementing multi-commodity flow (MCF) optimization problems and several optimization based SDN Traffic Engineering (TE) schemes have been proposed. This approach has several limitations like the need to know or infer bandwidth demands, the number of forwarding rules needed to implement the solution and the cost of the control-loop communication between controller and switches. This usually results in systems that do not scale and need to adapt the problem formulation to an approximation of the optimal solution. In this work we propose an approach for TE in SDNs without optimization and no need for traffic demand knowledge. We propose a logically hierarchical controller architecture built on the premise of low rule space and sparse controller communication where TE is performed in two actions: the setting of stable paths in the core and the distribution of traffic among them in the access. Different algorithms can be used for these purposes. We start by studying the performance of using a shortest path algorithm for the calculation of the stable core paths and a concept from social networks analysis called betweenness centrality to measure congestion risk and support the traffic distribution decisions in the access.1
Physical layer security enhancement in multi-user multi-full-duplex-relay networks

We propose a novel joint user and full-duplex (FD) relay selection (JUFDRS) scheme to enhance physical layer security in a multi-user multi-relay network. In this scheme, the user and the FD decode-and-forward relay are selected such that the capacity of the end-to-end user-relay-destination channel is maximized to ensure the highest quality of cooperative transmission. To fully examine the benefits of the JUFDRS scheme, we derive a new closed-form expression for the secrecy outage probability. We show that the JUFDRS scheme significantly outperforms the joint user and half-duplex relay selection (JUHDRS) scheme when the self-interference at the FD relay can be reasonably suppressed. This result indicates that adopting the FD technique at relays can effectively enhance the physical layer secrecy performance in the multi-user multi-relay network.
Induction of Cortical Plastic Changes in Wrist Muscles by Paired Associative Stimulation in the Recovery Phase of Stroke Patients

Background. Paired associative stimulation (PAS) combining peripheral nerve and transcranial magnetic stimulation (TMS) have been proposed to induce long-term changes in excitability of the cerebral cortex and potentially optimize motor recovery in stroke patients. Objective. This pilot study examined whether short-lasting changes in cortical excitability could be induced by a single session of PAS within the first months after stroke. Methods. Six hemiparetic patients with a subcortical stroke were included. The single session PAS protocol was applied at 1, 5, and 12 months after stroke. During the follow-up, the clinical recovery of wrist function was assessed in parallel to the PAS study by the Fugl-Meyer motor scale and dynamometry of wrist extension. Results. The PAS protocol induced a significant extensor carpi radialis motor evoked potential facilitation (mean +78.5%) on the paretic side 5 months after stroke. The facilitation was still present 12 months after stroke but on average smaller (+30 %). Conclusions. These electrophysiological findings suggest that patients with subcortical infarcts may respond to PAS in an earlier than later period after stroke. If the clinical efficacy of interventions such as PAS is confirmed, it could be proposed early as add-on therapy to optimize training-induced plasticity processes.
Macrophage-Inducible C-Type Lectin Mincle-Expressing Dendritic Cells Contribute to Control of Splenic Mycobacterium bovis BCG Infection in Mice

ABSTRACT The macrophage-inducible C-type lectin Mincle has recently been identified to be a pattern recognition receptor sensing mycobacterial infection via recognition of the mycobacterial cell wall component trehalose-6′,6-dimycolate (TDM). However, its role in systemic mycobacterial infections has not been examined so far. Mincle-knockout (KO) mice were infected intravenously with Mycobacterium bovis BCG to mimic the systemic spread of mycobacteria under defined experimental conditions. After intravenous infection with M. bovis BCG, Mincle-KO mice responded with significantly higher numbers of mycobacterial CFU in spleen and liver, while reduced granuloma formation was observed only in the spleen. At the same time, reduced Th1 cytokine production and decreased numbers of gamma interferon-producing T cells were observed in the spleens of Mincle-KO mice relative to the numbers in the spleens of wild-type (WT) mice. The effect of adoptive transfer of defined WT leukocyte subsets generated from bone marrow cells of zDC+/DTR mice (which bear the human diphtheria toxin receptor [DTR] under the control of the classical dendritic cell-specific zinc finger transcription factor zDC) to specifically deplete Mincle-expressing classical dendritic cells (cDCs) but not macrophages after diphtheria toxin application on the numbers of splenic and hepatic CFU and T cell subsets was then determined. Adoptive transfer experiments revealed that Mincle-expressing splenic cDCs rather than Mincle-expressing macrophages contributed to the reconstitution of attenuated splenic antimycobacterial immune responses in Mincle-KO mice after intravenous challenge with BCG. Collectively, we show that expression of Mincle, particularly by cDCs, contributes to the control of splenic M. bovis BCG infection in mice.
A Randomized Controlled Trial of Gravity-Supported, Computer-Enhanced Arm Exercise for Individuals With Severe Hemiparesis

Background/Objective. The authors previously developed a passive instrumented arm orthosis (Therapy Wilmington Robotic Exoskeleton [T-WREX]) that enables individuals with hemiparesis to exercise the arm by playing computer games in a gravity-supported environment. The purpose of this study was to compare semiautonomous training with T-WREX and conventional semiautonomous exercises that used a tabletop for gravity support. Methods. Twenty-eight chronic stroke survivors with moderate/severe hemiparesis were randomly assigned to experimental (T-WREX) or control (tabletop exercise) treatment. A blinded rater assessed arm movement before and after twenty-four 1-hour treatment sessions and at 6-month follow-up. Subjects also rated subjective treatment preferences after a single-session crossover treatment. Results. All subjects significantly improved ( P ≤ .05) upper extremity motor control (Fugl-Meyer), active reaching range of motion (ROM), and self-reported quality and amount of arm use (Motor Activity Log). Improvements were sustained at 6 months. The T-WREX group maintained gains on the Fugl-Meyer significantly better than controls at 6 months (improvement of 3.6 ± 3.9 vs 1.5 ± 2.7 points, mean ± SD; P = .04). Subjects also reported a preference for T-WREX training. Conclusion . Gravity-supported arm exercise, using the T-WREX or tabletop support, can improve arm movement ability after chronic severe hemiparesis with brief one-on-one assistance from a therapist (approximately 4 minutes per session). The 3-dimensional weight support, instant visual movement feedback, and simple virtual reality software provided by T-WREX were associated with modest sustained gains at 6-month follow-up when compared with the conventional approach.
The Effects of Bilateral Arm Training on Motor Control and Functional Performance in Chronic Stroke: A Randomized Controlled Study

Background. Most studies of bilateral arm training (BAT) did not employ a randomized controlled trial design and involved very limited functional training tasks. Objective . Compare the effects of BAT with control intervention (CI) on motor control and motor performance of the upper extremity and also functional gains in patients with chronic stroke. Methods. This 2-group randomized controlled trial with pretreatment and posttreatment measures enrolled 33 stroke patients (mean age = 53.85 years) 6 to 67 months after onset of a first stroke. They received either a BAT program concentrating on both upper extremities moving simultaneously in functional tasks by symmetric patterns or CI (control treatment) for 2 hours on weekdays for 3 weeks. Outcome measures included kinematic analyses assessing motor control strategies for unilateral and bimanual reaching and clinical measures involving the Fugl-Meyer Assessment (FMA) of motor-impairment severity and the Functional Independence Measure (FIM) and the Motor Activity Log (MAL) evaluating functional ability. Results. After treatment, the BAT group showed better temporal and spatial efficiency during unilateral and bilateral tasks and less online error correction only during the bilateral task than the control group. The BAT group showed a significantly greater improvement in the FMA than the control group but not in the FIM and MAL. Conclusions. Relative to CI, BAT improved the spatiotemporal control of the affected arm in both bilateral and unilateral tasks, decreased online corrections to perform bilateral tasks, and reduced motor impairment. These findings support the use of BAT to improve motor control and motor function of the affected upper limb in stroke patients.
What Matters in Cellular Transplantation for Spinal Cord Injury: The Cells, the Rehabilitation, or the Best Mix?

Lima and colleagues recently reported the results on 20 patients with chronic sensorimotor or motor complete spinal cord injury (SCI) after they performed partial scar removal and implantation of a mix of neural stem and olfactory ensheathing cells (OECs) derived from mucosal autografts1. In this uncontrolled but well-planned phase 2 study2,3, the subjects also received, immediately prior to the cellular intervention, a median of 400 hours of lower extremity step training either over ground or with a Lokomat electromechanical device. These therapies were restarted and continued for at least a year after surgery. Thus, an intensive, task-related rehabilitation program for walking was built into the trial to try to produce further recovery4. Preoperatively, they sought a stable baseline, reducing the likelihood that latent function might improve from physical therapies alone. Then, they hoped the therapies would maximize contributions from the cells. Remarkably, new signs of motor control were found from 1 to 3 years later. For example, 75% of subjects developed electromyographic activity below their lesions, and the American Spinal Injury Association Impairment Scale of motor strength improved by 4 to 8 points in 5 subjects and by 14 to 20 in another 4. The Walking Index for SCI scores of assisted walking improved in relation to greater motor control5,6. The increase in voluntary movement was found, however, only in the patients at the 2 sites that provided assisted overground stance and step training but not at the site that offered only the robotic stepper. The implication, then, is that the cells had a biological effect that depended on the type of practice. In this case, the 2 rehabilitation strategies differed in that overground training may enable greater incorporation of feedback and more trial and error to successfully approximate components of movements, compared with the rather inflexible kinematics with training on the robotic device. This potential confounder for the utility of electromechanical assists has been noted in randomized clinical trials of upper and lower extremity devices, in which the robotics were no better, or worse than, hands-on therapy of the same intensity and duration7-11.
Knowledge Guided Hierarchical Multi-Label Classification Over Ticket Data

Maximal automation of routine IT maintenance procedures is an ultimate goal of IT service management. System monitoring, an effective and reliable means for IT problem detection, generates monitoring ticket. In light of the ticket description, the underlying categories of the IT problem are determined, and the ticket is assigned to the corresponding processing teams for problem resolving. Automatic IT problem category determination acts as a critical part during the routine IT maintenance procedures. In practice, IT problem categories are naturally organized in a hierarchy by specialization. Utilizing the category hierarchy, this paper comes up with a hierarchical multi-label classification method to classify the monitoring tickets. In order to find the most effective classification, a novel contextual hierarchy (CH) loss is introduced in accordance with the problem hierarchy. Consequently, an arising optimization problem is solved by a new greedy algorithm named GLabel. Furthermore, as well as the ticket instance itself, the knowledge from the domain experts, which partially indicates some categories the given ticket may or may not belong to, can also be leveraged to guide the hierarchical multi-label classification. Accordingly, a multi-label inference with the domain expert knowledge is conducted on the basis of the given label hierarchy. The experiment demonstrates the great performance improvement by incorporating the domain knowledge during the hierarchical multi-label classification over the ticket data.
Motor Cortex Preactivation by Standing Facilitates Word Retrieval in Aphasia

Background and Objectives. A tight link between linguistic functions and activation of motor areas has been consistently reported, indicating that the 2 systems share functional neural resources. Few efforts have been made to explore whether this knowledge could aid the rehabilitation of aphasia. Methods. The authors assessed whether preactivation of the leg motor cortex during standing, compared with sitting, can facilitate language production in patients with chronic aphasia. In a cross-over within-subject design, the authors assessed performance on a picture naming task and controlled for effects on processing speed and simple verbal reaction time. Results. They found that standing compared with sitting had a beneficial effect on the number of semantic self-corrections that resulted in correct naming. In the absence of effects on motor or general processing speed, this points to a specific effect on lexical retrieval and selection. This was further corroborated by an error pattern analysis. Successful semantic self-corrections during standing were only found when there was already partial activation of the target semantic network—that is, when self-corrections were preceded by an incorrect but semantically associated naming response. Discussion. These findings show that preactivation of the motor system, which extends beyond the intrinsic link between manual gestures and language, can facilitate lexical access in chronic aphasia and may open new directions in aphasia rehabilitation.
Mechanical Behavior of the Human Ankle in the Transverse Plane While Turning

In order to better rehabilitate lower limb amputees, prosthetic technology needs to facilitate turning gait by providing torsional control in the transverse plane. This paper characterizes biological ankle function in the transverse plane during turning gait with simple mechanical elements to assist in the design of a biomimetic prosthetic ankle joint. Motion capture data was collected from ten subjects performing left and right turns through a 90 hallway corner. The initiation, apex, and termination steps of the turn were investigated. The data for each step was separated into several states, and passive elements were chosen to model the ankle in each state. During the first state of each turning step, the ankle behaved similarly to straight steps by limiting the kinetic energy of the foot prior to foot flat. During the subsequent states of each turning step, the ankle altered its characteristic properties to accommodate the curved trajectory of the body center of mass. The results suggest controlling transverse plane stiffness with a finite state control system will suffice to mimic biological function during a turn.
Characteristics of Drusen and Bruch's membrane in postmortem eyes with age-related macular degeneration.

We performed a histopathologic study to compare eyes with different stages of age-related macular degeneration (AMD) with age-matched eyes to identify characteristics associated with exudative vs nonexudative AMD. We analyzed 51 eyes, which were obtained from an eye bank, from 40 donors with different stages of AMD and compared them with 40 age-matched control eyes. The eyes were processed for light microscopy, and the degree of calcification of Bruch's membrane, fragmentation of Bruch's membrane, the number of different types of drusen, and the presence of basal laminar (linear) deposit were assessed in the macular and extramacular regions. In the macular area, a statistically significant difference was observed for the degree of calcification (P=.02) and fragmentation (P=.03) of Bruch's membrane in eyes with exudative AMD (1.6 and 5 per eye, respectively) compared with eyes with nonexudative AMD (0.8 and 1 per eye, respectively) and control eyes (0.8 and 0 per eye, respectively). Eyes with AMD displayed notably softer, more confluent, and larger drusen and basal laminar (linear) deposit in the macular area compared with control eyes. Calcification and fragmentation of Bruch's membrane, soft, confluent, and large drusen, and basal laminar (linear) deposit but not hard drusen correlate with the histological presence of AMD. The degree of calcification and fragmentation of Bruch's membrane is greater in eyes with exudative compared with nonexudative AMD.
Enhanced Left-Finger Deftness Following Dominant Upper- and Lower-Limb Amputation

Background. After amputation, the sensorimotor cortex reorganizes, and these alterations might influence motor functions of the remaining extremities. Objective. The authors examined how amputation of the dominant or nondominant upper or lower extremity alters deftness in the intact limbs. Methods. The participants were 32 unilateral upper- or lower-extremity amputees and 6 controls. Upper-extremity deftness was tested by coin rotation (finger deftness) and pegboard (arm, hand, and finger deftness) tasks. Results. Following right-upper- or right-lower-extremity amputation, the left hand’s finger movements were defter than the left-hand fingers of controls. In contrast, with left-upper- or left-lower-extremity amputation, the right hand’s finger performance was the same as that of the controls. Conclusions. Although this improvement might be related to increased use (practice), the finding that right-lower-extremity amputation also improved the left hand’s finger deftness suggests an alternative mechanism. Perhaps in right-handed persons the left motor cortex inhibits the right side of the body more than the right motor cortex inhibits the left side, and the physiological changes induced by right-sided amputation reduced this inhibition.
Activation of the Contact System at the Surface of Fusobacterium necrophorum Represents a Possible Virulence Mechanism in Lemièrre's Syndrome

ABSTRACT Fusobacterium necrophorum causes Lemièrre's syndrome, a serious disease with septic thrombophlebitis of the internal jugular vein, pulmonary involvement, and systemic inflammation. The contact system is a link between inflammation and coagulation, and contact activation by the bacteria could therefore contribute to the abnormal coagulation and inflammation seen in patients with Lemièrre's syndrome. In this study, F. necrophorum was found to bind radiolabeled high-molecular-weight kininogen (HK), a central component of the contact system. Binding was inhibited by the addition of unlabeled HK and domain D5 of HK but not other components of the contact system, indicating a specific interaction mediated through the D5 region. Binding of HK was significantly reduced after pretreatment of the bacteria with trypsin, suggesting that surface proteins are involved in HK binding. Incubation of the bacteria with human plasma resulted in an HK breakdown pattern suggestive of bradykinin release, and bradykinin was also detected in the supernatant. In addition, we show that factor XI (FXI), another component of the contact system, binds to F. necrophorum and that the bound FXI reconstitutes the activated partial thromboplastin time of FXI-deficient plasma. Thrombin activity was detected at the surface of the bacteria following incubation with plasma, indicating that the intrinsic pathway of coagulation is activated at the surface. This activity was completely blocked by inhibitors of the contact system. The combined results show that the contact system is activated at the surface of F. necrophorum, suggesting a pathogenic role for this system in Lemièrre's syndrome.