Miracle-dz/UniFAR-FTUs huggingface dataset:
Mitochondrial dysfunction and axon degeneration in progressive multiple sclerosis

The neuron is the target of inflammatory demyelinating processes in multiple sclerosis (MS). In progressive MS, however, there is a gathering body of evidence indicating that molecular changes converge on mitochondria within neuronal cell bodies. The most reproducible change relates to mitochondrial respiratory chain complex deficiency, which compromises the capacity of neurons to generate ATP. The resulting energy failure state is coupled with an increase in demand for energy by the demyelinated axon, being particularly relevant to the long tracts such as corticospinal tracts with long projection axons. Recent work in our laboratory and that of our collaborators indicates the limited reflection of the mitochondria changes within neurons in experimental disease models. The mitochondrial changes within neuronal compartments are likely to offer novel targets for the improvement in neuronal function in patients with progressive MS.
Leg muscles that mediate stability: mechanics and control of two distal extensor muscles during obstacle negotiation in the guinea fowl

Here, we used an obstacle treadmill experiment to investigate the neuromuscular control of locomotion in uneven terrain. We measured in vivo function of two distal muscles of the guinea fowl, lateral gastrocnemius (LG) and digital flexor-IV (DF), during level running, and two uneven terrains, with 5 and 7 cm obstacles. Uneven terrain required one step onto an obstacle every four to five strides. We compared both perturbed and unperturbed strides in uneven terrain to level terrain. When the bird stepped onto an obstacle, the leg became crouched, both muscles acted at longer lengths and produced greater work, and body height increased. Muscle activation increased on obstacle strides in the LG, but not the DF, suggesting a greater reflex contribution to LG. In unperturbed strides in uneven terrain, swing pre-activation of DF increased by 5 per cent compared with level terrain, suggesting feed-forward tuning of leg impedance. Across conditions, the neuromechanical factors in work output differed between the two muscles, probably due to differences in muscle–tendon architecture. LG work depended primarily on fascicle length, whereas DF work depended on both length and velocity during loading. These distal muscles appear to play a critical role in stability by rapidly sensing and responding to altered leg–ground interaction.
Defragmentation of Tasks in Many-Core Architecture

Many-cores can execute multiple multithreaded tasks in parallel. A task performs most efficiently when it is executed over a spatially connected and compact subset of cores so that performance loss due to communication overhead imposed by the task’s threads spread across the allocated cores is minimal. Over a span of time, unallocated cores can get scattered all over the many-core, creating fragments in the task mapping. These fragments can prevent efficient contiguous mapping of incoming new tasks leading to loss of performance. This problem can be alleviated by using a task defragmenter, which consolidates smaller fragments into larger fragments wherein the incoming tasks can be efficiently executed. Optimal defragmentation of a many-core is an NP-hard problem in the general case. Therefore, we simplify the original problem to a problem that can be solved optimally in polynomial time. In this work, we introduce a concept of exponentially separable mapping (ESM), which defines a set of task mapping constraints on a many-core. We prove that an ESM enforcing many-core can be defragmented optimally in polynomial time.
Ebola virus vaccines – reality or fiction?

ABSTRACT For 40 years ebolaviruses have been responsible for sporadic outbreaks of severe and often fatal hemorrhagic fever in humans and nonhuman primates. In December 2013 an unprecedented Zaire ebolavirus epidemic began in West Africa. Although “patient zero” has finally been reached after 2 years, the virus is again causing disease in the region. Currently there are no licensed vaccines or therapeutic countermeasures against ebolaviruses; however, the epidemic in West Africa has focused attention on the potential vaccine platforms developed over the past 15 years. There has been remarkable progress using a variety of platforms including DNA, subunit, and several viral vector approaches, replicating and non-replicating, which have shown varying degrees of protective efficacy in the “gold-standard” nonhuman primate models for Ebolavirus infections. A number of these vaccine platforms have moved into clinical trials over the past year with the hope of finding an efficacious vaccine to prevent future outbreaks/epidemics of Ebola hemorrhagic fever on the scale of the West African epidemic.
Quality of Life and African American Women Who are Family Caregivers: A Literature Review with Implications for Psychiatric Mental Health Advanced Practice Registered Nurses

ABSTRACT Purpose: To identify factors affecting the quality of life (QOL) of African American women (AAW) family caregivers of individuals with kidney failure. Methods: Ferrans' Conceptual Model of QOL provided the framework for this literature review. Included studies were (a) peer- reviewed, (b) published within the last ten years, (c) written in English, and (d) examined QOL of AAW family caregivers. Using CINAHL© and PubMed©, we found 14 studies that described factors associated with these caregivers' QOL. Scope: Few studies document the QOL of AAW who are family caregivers, especially in the context of kidney failure. Psychiatric Mental Health Advanced Practice Registered Nurses need to learn about the factors influencing the QOL of these caregivers. Results: No studies were found within the last ten years that explored the QOL of AAW family caregivers of individuals with kidney failure. Findings reflected the QOL of AAW family caregivers in the context of other chronic conditions. Various factors such as stress, insomnia, and employment were linked to an impaired QOL. Implications for practice, research and education for PMH-APRNs are suggested. Conclusion: PMH-APRNs are uniquely trained to address many factors that affect the QOL of these caregivers and may provide holistic care aimed at promoting satisfactory QOL for these caregivers.
Cholinergic interneurons in the rat striatum modulate substitution of habits

Behavioural flexibility is crucial for adaptive behaviour, and recent evidence suggests that cholinergic interneurons of the striatum play a distinct role. Previous studies of cholinergic function have focused on strategy switching by the dorsomedial or ventral striatum. We here investigated whether cholinergic interneurons in the dorsolateral striatum play a similar role at the level of switching of habitual responses. Because the dorsolateral striatum is particularly involved in habitual responding, we developed a habit substitution task that involved switching habitual lever‐press responses to one side to another. We first measured the effect of cholinergic activation in the dorsolateral striatum on this task. Chemogenetic activation of cholinergic interneurons caused an increase in the response rate for the substituted response that was significantly greater than the increase normally seen in control animals. The increase was due to burst‐like responses with shorter inter‐press intervals. However, there was no effect on inhibiting the old habit, or on habitual responding that did not require a switch. There was also no effect on lever‐press performance and its reversal before lever‐press responses became habitual. Conversely, neurochemically specific ablation of cholinergic interneurons did not significantly change habitual responding or response substitution. Thus, activation –but not ablation –of cholinergic interneurons in the dorsolateral striatum modulates expression of a new habit when an old habit is replaced by a new one. Together with previous work, this suggests that striatal cholinergic interneurons facilitate behavioural flexibility in both dorsolateral striatum in addition to dorsomedial and ventral striatum.
CD3 and CD20 Immunohistochemical Staining Patterns of Bone Marrow‐Infiltrating Malignant Lymphoma Cells

Objectives. It is known that CD3 and CD20 are homogenously expressed in T lineage and B lineage lymphoma, respectively; however, there are no standard guidelines to interpret immunohistochemistry findings. In this study, we investigated CD3 and CD20 immunohistochemical staining patterns of bone marrow (BM)‐infiltrating lymphoma cells. Methods. Among 297 patients diagnosed with malignant lymphoma, the BM biopsy slides of all 39 cases found to have BM infiltration (T lineage: 11; B lineage: 28) were reviewed. We specifically investigated the immunohistochemical staining patterns of CD3 and CD20. Results. All 11 T lineage lymphoma cases showed homogenous immunohistochemical staining patterns. In the 28 B lineage lymphoma cases, 15 (53.6%) showed a homogenous pattern while 13 (46.4%) showed a heterogeneous pattern. Ten cases in the latter group showed additional evidence of BM infiltration by lymphoma cells in separate laboratory analyses or imaging studies. There were no differences in overall or progression‐free survival rates in patients exhibiting homogeneous vs. heterogeneous staining patterns (P=0.81 and P=0.59, respectively). Conclusions. A considerable number of B lineage cases showed heterogeneous patterns with evidence of BM infiltration. Thus, heterogeneous immunohistochemical staining patterns (particularly in B lineage lymphomas) may signify malignant lymphoma cell infiltration into the BM.
Measurement of Gender Differences of Gastrocnemius Muscle and Tendon Using Sonomyography during Calf Raises: A Pilot Study

Skeletal muscles are essential to the gender-specific characteristics of human movements. Sonomyography, a new signal for quantifying muscle activation, is of great benefit to understand muscle function through monitoring the real-time muscle architectural changes. The purpose of this pilot study was to investigate gender differences in the architectural changes of gastronomies muscle and tendon by using sonomyography during performing two-legged calf raising exercises. A motion analysis system was developed to extract sonomyography from ultrasound images together with kinematic and kinetic measurements. Tiny fascicle length changes among seven male subjects were observed at the initial part of calf raising, whereas the fascicle of seven female subjects shortened immediately. This result suggested that men would generate higher mechanical power output of plantar flexors to regulate their heavier body mass. In addition, the larger regression coefficient between the fascicle length and muscle force for the male subjects implied that higher muscle stiffness for the men was required in demand of maintaining their heavier body economically. The findings from the current study suggested that the body mass might play a factor in the gender difference in structural changes of muscle and tendon during motion. The sonomyography may provide valuable information in the understanding of the gender difference in human movements.
Contributions of low- and high-level properties to neural processing of visual scenes in the human brain

Visual scene analysis in humans has been characterized by the presence of regions in extrastriate cortex that are selectively responsive to scenes compared with objects or faces. While these regions have often been interpreted as representing high-level properties of scenes (e.g. category), they also exhibit substantial sensitivity to low-level (e.g. spatial frequency) and mid-level (e.g. spatial layout) properties, and it is unclear how these disparate findings can be united in a single framework. In this opinion piece, we suggest that this problem can be resolved by questioning the utility of the classical low- to high-level framework of visual perception for scene processing, and discuss why low- and mid-level properties may be particularly diagnostic for the behavioural goals specific to scene perception as compared to object recognition. In particular, we highlight the contributions of low-level vision to scene representation by reviewing (i) retinotopic biases and receptive field properties of scene-selective regions and (ii) the temporal dynamics of scene perception that demonstrate overlap of low- and mid-level feature representations with those of scene category. We discuss the relevance of these findings for scene perception and suggest a more expansive framework for visual scene analysis. This article is part of the themed issue ‘Auditory and visual scene analysis’.
Varicella Zoster Virus (VZV) in Solid Organ Transplant Recipients

-herpesvirus family. VZV is presentworldwide and is highly infectious. Primary infection leadsto acute varicella or ‘chickenpox,’ usually from exposureeither through direct contact with a skin lesion or throughairborne spread from respiratory droplets (1,2). After initialinfection, VZV establishes lifelong latency in cranial nerveanddorsalrootganglia,andcanreactivateyearstodecadeslater as herpes zoster (HZ) or ‘shingles’ (3). More than90% of adults in the United States acquired the disease inchildhood, while the majority of children and young adultshave been vaccinated with the live virus vaccine (2,4). Primary varicella typically presents with fever, constitu-tional symptoms and a vesicular, pruritic, widely dissem-inated rash that primarily involves the trunk and face (5). Thesymptomsusuallyresolvewithin7–10days,butinrarecases primary varicella leads to more severe disease andvisceral invasion. Complications, such as hepatitis, pancre-atitis, pneumonitis and encephalitis are infrequent but canbelife-threatening;adultsandveryyoungchildrenaremorelikely to develop such complications from primary infection(6,7). Rates of hospitalization and mortality due to varicellahave dropped with the institution of routine childhood vari-cella vaccination (8,9). Nearly all patients with HZ develop an exanthem of vesic-ular lesions in a dermatomal distribution. The annual inci-dence of HZ in the general population is 1.5–3.0 cases per1000 persons (2), and is estimated to occur in up to 20%of individuals during their lifetime (10). Secondary compli-cations such as bacterial superinfection and postherpeticneuralgia (PHN), or chronic neuropathic pain at the site ofHZ, lead to increased morbidity (11). Over 90% of adult solid organ transplant (SOT) recipientswill be seropositive for VZV. Rates are lower in pediatrictransplants(12,13),butimmunitywillincreaseasuptakeofvaricella vaccine improves. Varicella is rare in adult SOT re-cipients,butcanbedevastating,withvisceralinvolvement,severe skin disease, and disseminated intravascular coag-ulation (14–19). HZ is a frequent infectious complication inSOT recipients with an incidence of approximately 8–11%during the ﬁrst 4 years posttransplant (20–22). Invasive dis-ease and dissemination similar to that seen in primary VZVinfection are uncommon but have been reported in SOTand other immunocompromised populations, and level ofimmunosuppression may alter the risk of developing thesecomplications (17,23,24). Rates of PHN in SOT recipi-ents may also be higher than in immunocompetent popu-lations (22).
Role of Fine Needle Aspiration Cytology in the Preoperative Presumptive Diagnosis of Ameloblastoma

OBJECTIVE To determine the role of fine needle aspiration cytology (FNAC) on the preoperative presumptive diagnosis of ameloblastoma. STUDY DESIGN Sixty-three patients, diagnosed preoperatively and postoperatively with ameloblastoma, were evaluated between 1990 and 2003. The patients were classified according to whether they were diagnosed with ameloblastoma preoperatively or postoperatively, on histologic examination. RESULTS The accuracy rate for ameloblastoma was 0.95% for all biopsy methods, while the incisional biopsy rate was 75.00%. Concerning clinical diagnosis, ameloblastoma was mistaken mostly (56.41%) for odontogenic cysts (22 of 39). CONCLUSION FNAC should be utilized more commonly on intraosseous and soft tissue lesions in the oral and maxillofacial regions, to obtain sufficient material. It is convenient, inexpensive and noninvasive as compared with other biopsy methods.
Developing a reflective model of collaborative systems

Recent years have seen a shift in perception of the nature of HCI and interactive systems. As interface work has increasingly become a focus of attention for the social sciences, we have expanded our appreciation of the importance of issues such as work practice, adaptation, and evolution in interactive systems. The reorientation in our view of interactive systems has been accompanied by a call for a new model of design centered around user needs and participation. This article argues that a new process of design is not enough and that the new view necessitates a similar reorientation in the structure of the systems we build. It outlines some requirements for systems that support a deeper conception of interaction and argues that the traditional system design techniques are not suited to creating such systems. Finally, using examples from ongoing work in the design of an open toolkit for collaborative applications, it illustrates how the principles of computational reflection and metaobject protocols can lead us toward a new model based on open abstraction that holds great promise in addressing these issues.
Brain dynamics of post‐task resting state are influenced by expertise: Insights from baseball players

Post‐task resting state dynamics can be viewed as a task‐driven state where behavioral performance is improved through endogenous, non‐explicit learning. Tasks that have intrinsic value for individuals are hypothesized to produce post‐task resting state dynamics that promote learning. We measured simultaneous fMRI/EEG and DTI in Division‐1 collegiate baseball players and compared to a group of controls, examining differences in both functional and structural connectivity. Participants performed a surrogate baseball pitch Go/No‐Go task before a resting state scan, and we compared post‐task resting state connectivity using a seed‐based analysis from the supplementary motor area (SMA), an area whose activity discriminated players and controls in our previous results using this task. Although both groups were equally trained on the task, the experts showed differential activity in their post‐task resting state consistent with motor learning. Specifically, we found (1) differences in bilateral SMA–L Insula functional connectivity between experts and controls that may reflect group differences in motor learning, (2) differences in BOLD‐alpha oscillation correlations between groups suggests variability in modulatory attention in the post‐task state, and (3) group differences between BOLD‐beta oscillations that may indicate cognitive processing of motor inhibition. Structural connectivity analysis identified group differences in portions of the functionally derived network, suggesting that functional differences may also partially arise from variability in the underlying white matter pathways. Generally, we find that brain dynamics in the post‐task resting state differ as a function of subject expertise and potentially result from differences in both functional and structural connectivity. Hum Brain Mapp 37:4454–4471, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.
Spectral Normalization for Generative Adversarial Networks

One of the challenges in the study of generative adversarial networks is the instability of its training. In this paper, we propose a novel weight normalization technique called spectral normalization to stabilize the training of the discriminator. Our new normalization technique is computationally light and easy to incorporate into existing implementations. We tested the efficacy of spectral normalization on CIFAR10, STL-10, and ILSVRC2012 dataset, and we experimentally confirmed that spectrally normalized GANs (SN-GANs) is capable of generating images of better or equal quality relative to the previous training stabilization techniques.
Topical ocular 0.1% cyclosporine A cationic emulsion in dry eye disease patients with severe keratitis: experience through the French early-access program

Purpose The objective of this study was to report the evaluation of efficacy and safety of cyclosporine A cationic emulsion (CsA CE) 0.1% for the treatment of severe keratitis in adults with dry eye disease (DED) in a French early-access program. Methods Patients with DED and severe keratitis (corneal fluorescein staining [CFS] score of 3–5 on the Oxford scale and/or the presence of corneal lesions [filaments or ulcers]) were enrolled in a compassionate use program (Authorization for Temporary Use [ATU]) for once-daily CsA CE, which was approved by French health authorities prior to its registration. Efficacy and safety at 1, 3, 6, and 12-month follow-up visits were evaluated. Results The ATU cohort (n=1,212; mean age =60.5 years; 79.5% female; 98.1% with severe keratitis; 74.5% with corneal lesions) consisted of 601 CsA-naïve patients and 611 patients treated previously with other CsA formulations. The primary DED etiology was Sjögren’s syndrome (48.7%). Clinical benefit could be discerned among 548 evaluable patients from months 1 to 12: keratitis improvement, 44.8% at month 1 and 42.1% at month 12; keratitis stabilization, 47.2% and 45.7%, respectively; symptom improvement, 47.2% and 48.6%; and symptom stabilization, 44.8% and 45.0%. Corneal clearing (CFS score =0) increased from 4.8% (month 1) to 11.4% (month 12). No unexpected safety concerns were identified; instillation site pain (10.2%) and eye irritation (7.8%) were the most common adverse events. Conclusion The French ATU cohort provides supportive data on the clinical benefit of CsA CE in improving/stabilizing symptoms and corneal damage in DED patients with severe keratitis in real-world clinical practice.
Progress and challenges associated with the development of ricin toxin subunit vaccines

ABSTRACT The past several years have seen major advances in the development of a safe and efficacious ricin toxin vaccine, including the completion of two Phase I clinical trials with two different recombinant A subunit (RTA)-based vaccines: RiVax™ and RVEc™ adsorbed to aluminum salt adjuvant, as well as a non-human primate study demonstrating that parenteral immunization with RiVax elicits a serum antibody response that was sufficient to protect against a lethal dose aerosolized ricin exposure. One of the major obstacles moving forward is assessing vaccine efficacy in humans, when neither ricin-specific serum IgG endpoint titers nor toxin-neutralizing antibody levels are accepted as definitive predictors of protective immunity. In this review we summarize ongoing efforts to leverage recent advances in our understanding of RTA-antibody interactions at the structural level to develop novel assays to predict vaccine efficacy in humans.