Miracle-dz/UniFAR-FTUs huggingface dataset:
Local Drug Delivery for Prevention of Hearing Loss

Systemic delivery of therapeutics for targeting the cochlea to prevent or treat hearing loss is challenging. Systemic drugs have to cross the blood-labyrinth barrier (BLB). BLB can significantly prevent effective penetration of drugs in appropriate concentrations to protect against hearing loss caused by inflammation, ototoxic drugs, or acoustic trauma. This obstacle may be obviated by local administration of protective agents. This route can deliver higher concentration of drug compared to systemic application and preclude systemic side effects. Protective agents have been administered by intra-tympanic injection in numerous preclinical studies. Drugs such as steroids, etanercept, D and L-methionine, pifithrin-alpha, adenosine agonists, melatonin, kenpaullone (a cyclin-dependent kinase 2 (CDK2) inhibitor) have been reported to show efficacy against cisplatin ototoxicity in animal models. Several siRNAs have been shown to ameliorate cisplatin ototoxicity when administered by intra-tympanic injection. The application of corticosteroids and a number of other drugs with adjuvants appears to enhance efficacy. Administration of siRNAs to knock down AMPK kinase, liver kinase B1 (LKB1) or G9a in the cochlea have been found to ameliorate noise-induced hearing loss. The local administration of these compounds appears to be effective in protecting the cochlea against damage from cisplatin or noise trauma. Furthermore the intra-tympanic route yields maximum protection in the basal turn of the cochlea which is most vulnerable to cisplatin ototoxicity and noise trauma. There appears to be very little transfer of these agents to the systemic circulation. This would avoid potential side effects including interference with anti-tumor efficacy of cisplatin. Nanotechnology offers strategies to effectively deliver protective agents to the cochlea. This review summarizes the pharmacology of local drug delivery by intra-tympanic injection to prevent hearing loss caused by cisplatin and noise exposure in animals. Future refinements in local protective agents provide exciting prospects for amelioration of hearing loss resulting from cisplatin or noise exposure.
Interaction-Specific Changes in the Transcriptome of Polynucleobacter asymbioticus Caused by Varying Protistan Communities

We studied the impact of protist grazing and exudation on the growth and transcriptomic response of the prokaryotic prey species Polynucleobacter asymbioticus. Different single- and multi-species communities of chrysophytes were used to determine a species-specific response to the predators and the effect of chrysophyte diversity. We sequenced the mRNA of Pn. asymbioticus in communities with three single chrysophyte species (Chlorochromonas danica, Poterioochromonas malhamensis and Poteriospumella lacustris) and all combinations. The molecular responses of Pn. asymbioticus significantly changed in the presence of predators with different trophic modes and combinations of species. In the single-species samples we observed significant differences related to the relative importance of grazing and exudation in the protist-bacteria interaction, i.e., to the presence of either the heterotrophic Ps. lacustris or the mixotrophic C. danica. When grazing dominates the interaction, as in the presence of Ps. lacustris, genes acting in stress response are up-regulated. Further genes associated with transcription and translation are down-regulated indicating a reduced growth of Pn. asymbioticus. In contrast, when the potential use of algal exudates dominates the interaction, genes affiliated with iron transport are up-regulated. Rapid phototrophic growth of chrysophytes, with a high demand on soluble iron, could thus lead to iron-limitation and cause changes in the iron metabolism of Pn. asymbioticus. Additionally, we observe a benefit for Pn. asymbioticus from a more diverse protistan community, which could be due to shifts in the relative importance of phototrophy in the mixotrophic chrysophytes when competing for food with other species. Our study highlights the importance of biotic interactions and the specificity of such interactions, in particular the differential effect of grazing and algal exudation in the interaction of bacteria with mixotrophic protists.
Host Genetics, Innate Immune Responses, and Cellular Death Pathways in Poliomyelitis Patients

Purpose Poliovirus (PV) is one of the most studied viruses. Despite efforts to understand PV infection within the host, fundamental questions remain unanswered. These include the mechanisms determining the progression to viremia, the pathogenesis of neuronal infection and paralysis in only a minority of patients. Because of the rare disease phenotype of paralytic poliomyelitis (PPM), we hypothesize that a genetic etiology may contribute to the disease course and outcome. Methods We used whole-exome sequencing (WES) to investigate the genetic profile of 18 patients with PPM. Functional analyses were performed on peripheral blood mononuclear cells (PBMCs) and monocyte-derived macrophages (MdMs). Results We identified rare variants in host genes involved in interferon signaling, viral replication, apoptosis, and autophagy. Upon PV infection of MdMs, we observed a tendency toward increased viral burden in patients compared to controls, suggesting reduced control of PV infection. In MdMs from patients, the IFNβ response correlated with the viral burden. Conclusion We suggest that genetic variants in innate immune defenses and cell death pathways contribute to the clinical presentation of PV infection. Importantly, this study is the first to uncover the genetic profile in patients with PPM combined with investigations of immune responses and viral burden in primary cells.
An MRI Study of Neurovascular Restorative After Combination Treatment With Xiaoshuan Enteric-Coated Capsule and Enriched Environment in Rats After Stroke

Xiaoshuan enteric-coated capsule (XSEC) is a Chinese medicinal compound widely used for treatment of ischemic cerebrovascular diseases. Enriched environment (EE) is an effective rehabilitative protocol designed to enhance sensorimotor, cognitive and social stimulation. This study aimed to apply magnetic resonance imaging (MRI) to non-invasively assess whether EE could augment the therapeutic benefits of XSEC on post-ischemic neurovascular remodeling. Male Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO) and treated with XSEC and EE alone or combination for 30 consecutive days. Beam walking test and Morris water maze (MWM) test were performed to evaluate motor and cognitive function, respectively. Multimodal MRI was applied to examine alterations to brain structures, intracranial vessels, and cerebral perfusion on the 31st day after MCAO. Double-immunofluorescent staining was used to evaluate neurogenesis and angiogenesis. Western blot and RT-PCR were used to detect the expressions of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and the axon guidance molecules. Combination therapy with XSEC and EE significantly reduced cystic volume compared with XSEC and EE monotherapies. In line with this, combination treated rats performed better in the beam walking test and exhibited improved spatial memory in the probe trial of the MWM. Moreover, XSEC and EE combination treatment improved cerebral blood flow (CBF), amplified angiogenesis and upregulated VEGF protein levels. This proangiogenic effect was consistent with the increased progenitor cell proliferation and neuronal differentiation in the peri-infarct cortex and striatum. Specifically, the combined therapy of XSEC and EE markedly increased the Netrin-1 and Robo-1 protein expression levels compared with vehicle group, while no difference was observed between XSEC or EE monotherapy and vehicle group. Together, these findings indicate that the combination of XSEC and EE benefits neurovascular reorganization. This correlates with restoration of CBF, promotion of neurogenesis and angiogenesis, and activation of the intrinsic axonal guidance molecules, thereby facilitating greater physical rehabilitation after ischemic stroke.
A neural network approach to distributed adaptive routing of LEO intersatellite link traffic

A neural network (NN) approach to distributed traffic adaptive routing in intersatellite link (ISL) trunk networks of emerging low Earth orbit (LEO) satellite systems is proposed. This approach is basically motivated by the idea that due to the high complexity of the problem it may show a superior performance compared to deterministic algorithm approaches. A good performance is shown for an implementation using classical multilayer perceptrons (MLP) with backpropagation learning (BPA) in a distributed fashion-one MLP being placed in each satellite. A deterministic adaptive routing scheme is used as reference in the learning phase of the MLP. With the learnt "knowledge", the distributed MLPs can perform a source routing in such a manner that the global traffic flows are efficiently shaped to reduce worst case link loads and to increase average link utilization, at the expense of an only slight increase of average transfer delay.
The Prevalence of Overweight and Obesity in an Adult Kuwaiti Population in 2014

Background: According to World Health Organization (WHO) estimates, Kuwait is ranked amongst the top countries in the world in obesity prevalence. This study aims to describe the prevalence of overweight, obesity, and various types of adiposity in Kuwaiti adults. Methods: This cross-sectional study of 3,915 Kuwaiti adults aged 18–69 years used the STEP-wise approach to surveillance of non-communicable diseases, a WHO Instrument for Chronic Disease Risk Factor Surveillance. We assessed demographic information, lifestyle, personal and family history of diseases and physical measurements (height, weight, waist, and hip circumferences). All participants with valid height and weight measurements (n = 3,589) were included in the present analysis. Overweight was defined as BMI 25–29.9 kg/m2 and obesity as BMI ≥30 kg/m2. Results: Obesity prevalence was 40.3% [95% confidence interval, 38.6–42.0%] (men, 36.5%; women, 44.0%); and overweight prevalence was 37% [35.4–38.7%] (men, 42%; women, 32.1%). The median BMI was 28.4 kg/m2 among men and 29.1 kg/m2 among women. Obesity prevalence was directly associated with female sex, age, history of diabetes, and being married in both men and women; and was inversely associated with education level in women. The prevalence of elevated waist-to-hip ratio was 46.9% among men and 37.9% among women. Waist circumference, waist-hip and waist-height ratios were directly associated with diabetes in both men and women, and inversely associated with education level in women. Conclusion: Almost eight in ten Kuwaiti adults were overweight or obese. Urgent public health action is warranted to tackle the obesity epidemic in Kuwait.
Tracking the Main States of Dynamic Functional Connectivity in Resting State

Dynamical changes have recently been tracked in functional connectivity (FC) calculated from resting-state functional magnetic resonance imaging (R-fMRI), when a person is conscious but not carrying out a directed task during scanning. Diverse dynamical FC states (dFC) are believed to represent different internal states of the brain, in terms of brain-regional interactions. In this paper, we propose a novel protocol, the signed community clustering with the optimized modularity by two-step procedures, to track dynamical whole brain functional connectivity (dWFC) states. This protocol is assumption free without a priori threshold for the number of clusters. By applying our method on sliding window based dWFC’s with automated anatomical labeling 2 (AAL2), three main dWFC states were extracted from R-fMRI datasets in Human Connectome Project, that are independent on window size. Through extracting the FC features of these states, we found the functional links in state 1 (WFC-C1) mainly involved visual, somatomotor, attention and cerebellar (posterior lobe) modules. State 2 (WFC-C2) was similar to WFC-C1, but more FC’s linking limbic, default mode, and frontoparietal modules and less linking the cerebellum, sensory and attention modules. State 3 had more FC’s linking default mode, limbic, and cerebellum, compared to WFC-C1 and WFC-C2. With tests of robustness and stability, our work provides a solid, hypothesis-free tool to detect dWFC states for the possibility of tracking rapid dynamical change in FCs among large data sets.
Interleukin-1β Promotes Schwann Cells De-Differentiation in Wallerian Degeneration via the c-JUN/AP-1 Pathway

Schwann cells (SCs) de-differentiate in Wallerian degeneration (WD) following nerve injury and, by doing so, can actively promote nerve repair and functional recovery. An innate-immune response is an important component of the complex of events referred to as WD. Damaged peripheral nervous system SCs produce IL-1β and other inflammatory cytokines. We hypothesized that, in addition to a role in immune responses, IL-1β participates in de-differentiation and proliferation of SCs. qPCR and ELISA demonstrated that expression of IL-1β mRNAs and protein increased after nerve injury. Immunofluorescent staining and western blotting demonstrated that expression of the p75 neurotrophin receptor (p75NTR) was significantly increased and levels of myelin protein zero (MPZ) were significantly decreased after IL-1β exposure compared with control groups in vitro WD. Additionally, qPCR demonstrated that IL-1β elevated expression of the de-differentiation gene p75NTR and decreased expression of myelination locus MPZ and promoted SCs de-differentiation. Furthermore, immunofluorescent staining, western blotting, qPCR and ELISA revealed that IL-1β promoted c-JUN expression and activation of AP-1 activity of SCs in an in vitro WD model. Finally, Immunofluorescent staining illustrated that IL-1β elevated expression of Ki67 in SCs nuclei, the apoptosis of SCs were detected by TUNEL. SCs of WD produce IL-1β which promotes SCs de-differentiation and proliferation.
Response-Time Analysis of Limited-Preemptive Parallel DAG Tasks Under Global Scheduling

Most recurrent real-time applications can be modeled as a set of sequential code segments (or blocks) that must be (repeatedly) executed in a specific order. This paper provides a schedulability analysis for such systems modeled as a set of parallel DAG tasks executed under any limited-preemptive global job-level fixed priority scheduling policy. More precisely, we derive response-time bounds for a set of jobs subject to precedence constraints, release jitter, and execution-time uncertainty, which enables support for a wide variety of parallel, limited-preemptive execution models (e.g., periodic DAG tasks, transactional tasks, generalized multi-frame tasks, etc.). Our analysis explores the space of all possible schedules using a powerful new state abstraction and state-pruning technique. An empirical evaluation shows the analysis to identify between 10 to 90 percentage points more schedulable task sets than the state-of-the-art schedulability test for limited-preemptive sporadic DAG tasks. It scales to systems of up to 64 cores with 20 DAG tasks. Moreover, while our analysis is almost as accurate as the state-of-the-art exact schedulability test based on model checking (for sequential non-preemptive tasks), it is three orders of magnitude faster and hence capable of analyzing task sets with more than 60 tasks on 8 cores in a few seconds.
High-performance routing at the nanometer scale

In this work we describe significant improvements to core routing technologies and outperform the best results from the ISPD '07 global routing contest, as well as previous literature, in terms of route completion, runtime and total wirelength. In particular, our router, FGR, improves upon wirelengths produced by BoxRouter and MaizeRouter in March 2007 by 9.9% and 8.4%. respectively. Additionally, we reveal the mathematical basis of negotiated-congestion routing. offer comprehensive analysis of existing routing techniques and discuss several applications at the nanometer scale.
Introduction: syntactic influences on phonological rules

Phonological theory asks how phonological shapes are assigned to linguistic units. In this issue of the Phonology Yearbook we bring together examinations of the role that syntactic structure plays in this assignment. The focus is therefore on phenomena that have been labelled, in one framework or another, as external sandhi (as opposed to internal sandhi), phrase phonology (as opposed to word phonology), or postlexical phonology (as opposed to lexical phonology).
Notes on Support Vector Machines

This report describes an empirical study of Support Vector Machines (SVM) which aims to review the foundations and properties of SVM based on the graphical analysis of simple binary classification tasks. SVM theory is briefly reviewed by discussing possible learning rules for linear separable problems and the role of the classification margin in generalization. This leads to the formulation of the SVM learning procedure for linear separable problems. It is then shown how it is possible to extend the SVM approach to non-separable problem by relaxing the strict separability constraint of the original formulation. The application of SVM to nonlinear problems by feature expansion techniques is then briefly reviewd. The effect of the dimension of the feature space on the SVM solution is briefly considered based on a simple bi-dimensional problem. Finally, it is discussed how explicit feature expansion can be avoided by the use of kernels. A qualitative analysis of the generalization behavior of support vector machines is performed by the analysis of the classification regions found by SVM in simple, synthetic examples. These classification regions are compared with those found by conventional multi-layer and radial basis functions networks. In the last part of this document, practical problems regarding SVM optimization are briefly discussed and some pointers and references regarding this issue are supplied.
Toward a Unique Representation for AVL and Red-Black Trees

We propose a unique representation of both AVL and Red-Black trees with the same time and space complexity. We describe all the maintenance operation and the algorithms for the insertion and deletion. We give the implementation of the proposed tree and the results. We then give a comparison of the three structures. The simulation results confirm the performance of the new representation relatively to the AVL and Red-Black tree.
Performance evaluation of CDMA ALOHA systems with modified channel load sensing protocol

One of the problems that arises in the satellite packet communication system is the existence of a long access timing delay. In this paper, we clarify the effect of this access timing delay on the performance of CDMA ALOHA systems and then propose a new access control protocol, called modified channel load sensing protocol (MCLSP). As a result, we found that by employing MCLSP, a significant improvement in the throughput performance was obtained even in the presence of a long access timing delay.
Preserved repetition in thalamic afasia. A pathophysiological hypothesis

ABSTRACT. The ability to repeat words is almost always preserved in thalamic aphasia. The pathophysiology of both thalamic aphasia and preservation of repetition are not fully understood. In a case of severe aphasia with preserved repetition after a left thalamic hemorrhage, MRI disclosed left thalamic lesion and loss of fractional anisotropy in the left centrum semiovale. FDG-PET showed severe hypometabolism in the left cerebral hemisphere, except for superior and transverse temporal gyri, calcarine fissure and frontopolar regions. Primary sensory function may be less functionally dependent on thalamic connections than heteromodal and paralimbic areas, which have connections with several thalamic nuclei. The extensive cortical hypometabolism due to diaschisis may have been responsible for the severity of the aphasia, whereas the less severe reduction of metabolism in the superior and transverse temporal gyri, and also, albeit less evident, in Broca’s area, might explain the preservation of repetition.
Molecular docking analysis of netropsin and novobiocin with the viral protein targets HABD, MTD and RCD

Dengue, West Nile and Zika virus belongs to the family flaviviridae and genus flavivirus. It is of interest to design and develop inhibitors with improved activity against these diseases. We used the helicases target to screen for potential inhibitors against these viruses using molecular docking analysis. NS3 helicases of flavivirus family of viruses such as Dengue, West Nile and Zika are prime targets for drug development. The computer aided molecular docking analysis of netropsin and novobiocin with the viral protein targets HABD, MTD and RCD is reported for further consideration.
Third-line systemic treatment in advanced/metastatic gastric cancer: a comprehensive review

The management of advanced gastric cancer has improved over the past decade. There is more evidence to support the efficacy of systemic treatment in refractory gastric cancer beyond second-line treatment. Important randomized controlled trials of chemotherapies, targeted agents and immunotherapies have been reported. With the development of these novel therapies, clinicians can better individualize treatment for patients beyond progression on second-line therapy. However, there is no guideline on third-line therapy available for clinicians. This review discussed the efficacy and safety data from the pivotal trials of the agents proven to be effective in third-line settings, including the quality of study design, level of evidence and subgroup analysis, and how the data can help to guide clinicians on selecting the most appropriate third-line therapy for their patients.
Olfactory impairment in frontotemporal dementia: A systematic review and meta-analysis

ABSTRACT. Frontotemporal dementia (FTD) presents clinically in three variants: one behavioral and two with progressive primary aphasia - non-fluent/agrammatic and semantic. Defined by the degenerative process and cerebral atrophy, olfactory dysfunction occurs in up to 96% of previous FTD case series. Objective: the present study aims to critically synthesize data about the relationship between FTD and olfactory impairment to analyze the usefulness of olfactory evaluation tests as a complementary element in early diagnosis. Methods: a database search was performed using the keywords “olfactory OR smell OR olfaction AND frontotemporal dementia”. We included studies that evaluated olfactory function in patients diagnosed with frontotemporal dementia, all subtypes, compared with age-matched healthy controls. For comparative purposes, the effect size was calculated using Cohen’s D. The studies selected were categorized according to dementia variant and olfactory test type. A meta-analysis was performed using forest plots - homogeneity was evaluated by statistical tests (i2 and Cochran Q). Results: ten articles met the inclusion criteria. Heterogeneity was classified as low for semantic dementia olfactory identification and behavioral variant olfactory discrimination groups (i2 = 0 and 3.4%, respectively) and as moderate for the behavioral variant olfactory identification group (i2 = 32.6%). Conclusion: patients with the frontotemporal dementia behavioral variant seem to present with alterations in odor identification, but with preserved discrimination. Scent identification also seems to be impaired in semantic dementia. Therefore, we conclude that olfactory evaluation in these patients is possibly impacted by cognitive alterations and not by sensory deficits. Application of olfactory tests may prove important in differentiating prodromal states from other types of dementia with more pronounced olfactory impairment.