Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative Evaluation of Prosopis cineraria (L.) Druce and Its ZnO Nanoparticles on Scopolamine Induced Amnesia

Over recent years, utilization of green synthesized nanomaterials has been widely growing on human body because of its special properties. With the increasing acceptance of nanoparticle approach for various clinical treatments, the biosafety and toxicological effects on the vital organs such as central nervous system, have received more concern. Main focus of this study was to evaluate acute exposure of n-butanol fraction of Prosopis cineraria (L.) Druce hydroethanolic extract (BuPC) and green synthesized zinc oxide nanoparticles of BuPC (ZnOPC) on spatial cognition behavior, and to assess underlying mechanism by estimation of enzymatic antioxidative status along with acetylcholinesterase (AChE) activity in mice brain. Strongest in vitro antioxidant and AChE inhibitory activity exhibiting fraction, BuPC, was examined for inhibition kinetic study by Lineweaver–Burk and Dixon plots. BuPC was further used for fabrication ZnOPC and characterized by UV-visible spectroscopy, Fourier Transform Infrared (FTIR), Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X ray (EDX), and Dynamic Light Scattering (DLS) analysis. Old male swiss albino mice were randomly divided into seven groups and treated for 21 days. Subsequently spatial memory was determined by two behavioral models [Elevated plus maze (EPM) and Hebbs William maze (HWM)] and supernatant of brain homogenate was analyzed for enzymatic antioxidant level and AChE inhibitory activity. Zinc content of blood plasma and brain was estimated. Results showed prolonged transfer latency (TL) and time taken to reach reward chamber (TRC) by scopolamine was not ameliorated by the ZnOPC group, whereas BuPC group showed significant reduction in scopolamine induced increase in TL and TRC compared to control and scopolamine treated groups. ZnOPC alleviated enzymatic antioxidant activity and AChE as compared to donepezil and BuPC treated groups. Study concludes that ZnOPC attenuated spatial learning and memory by increase in oxidative stress and decrease in AChE activity at both dose levels. Our results suggest that BuPC exhibited a strong neuroprotective effect on cognitive deficit mice and it may be employed as a strong substance for the treatment of dementia whereas the green synthesized ZnOPC was not proficient to reverse the memory impairment induced by scopolamine.
Personalized medicine: a perspective on the patient, disease and causal diagnostics.

In this commentary, I intend to use my ‘invitation to be provocative’ to provide my thoughts on the difference between the concept and the practice of several themes that have become both investment and strategy buzzwords, such as translational research, systems biology and personalized medicine, and the gap between where they are today and their ability to truly address patient and physician needs. My goal is to provoke thought and discussion about bridging the gaps between research and clinical utility for improving patient care and quality of life (QoL). This, to me, means understanding the differences between the disease, the patient and how they separately develop and interact. A simple Google™ search indicates incredible activity in each of these areas, with over 1,000,000 hits for ‘personalized medicine’ (compared with >52,000,000 for ‘medicine’), over 250,000 for ‘translational medicine or research’ and over 900,000 for ‘systems biology’. This probably reflects the diversity in interpretation and application of these terms rather than deep, focused efforts along specific research tracks. More importantly, I believe that these concepts have generally evolved from a focus on technology rather than a focus on clinical need, although their stated goals are to improve patient care. A fundamental problem that exists within the scientific community is the perception that ‘more data’ implies ‘more knowledge’. This reflects an incomplete appreciation of the significant chasm between data and knowledge and the even greater gap that exists when we evaluate knowledge in terms of clinical utility. For the purposes of this article, I provide my definitions of these terms and recognize that they may not be universal in their acceptance or use. While it is critical to understand these concepts individually, it is their synergies that will provide the basis for improving patient care and QoL. Translational research Translational research targets the conversion of laboratory results into clinical utility; however, translational research must start in the clinic and not at the laboratory bench, with the identification and communication of clinically significant problems into the laboratory for research and resolution. The only true measure of success of this targeted research is in terms of what translates into the clinic. Unfortunately, this is currently somewhat limited because the driving force still appears to be academically focused research rather than clinically established needs [1–3,101,102].
Bisphenol S modulates concentrations of bisphenol A and oestradiol in female and male mice

Abstract Concern over endocrine-disrupting actions of bisphenol A (BPA) has prompted some manufacturers to remove it from consumer products. Among the chemical replacements in “BPA-free” products are other bisphenol analogues, such as bisphenol S (BPS). Given evidence that BPA and BPS possess similar oestrogenic activity, their capacity to interact and disrupt oestrogen homeostasis should be examined. We investigated whether BPS can modulate concentrations of 14C-BPA, exogenous 3H-oestradiol (E2), or natural E2. CF-1 mice were each given a single subcutaneous injection of oil containing 0 (vehicle), 1, 3, or 9 mg BPS, then given a dietary supplement containing either 50 μg/kg 14C-BPA or 5 μCi (14.5 ng) 3H-E2. BPS treatment elevated 14C-BPA concentrations in blood serum and certain reproductive organs of both sexes, but reduced 3H-E2 concentrations in blood serum of females. In another experiment, natural E2 was measured in urine 2–12 h after injection of 0 (vehicle), 1, or 3 mg BPS. BPS reduced E2 concentrations at 10 h after injection in both sexes. These results are consistent with evidence that BPS and BPA compete for access to metabolic enzymes, and that BPS can disrupt oestrogen homeostasis. These findings demonstrate the importance of considering multiple toxicants when determining regulatory exposure limits.
Stamp-it: A more Thread-efficient, Concurrent Memory Reclamation Scheme in the C++ Memory Model

We present Stamp-it, a new, concurrent, lock-less memory reclamation scheme with amortized, constant-time (thread-count independent) reclamation overhead. Stamp-it has been implemented and proved correct in the C++ memory model using as weak memoryconsistency assumptions as possible. We have likewise (re)implemented six other comparable reclamation schemes. We give a detailed performance comparison, showing that Stamp-it performs favorably (sometimes better, at least as good as) than most of these other schemes while being able to reclaim free memory nodes earlier.
Effects of Immunonutrition in Advanced Human Immunodeficiency Virus Disease: A Randomized Placebo-controlled Clinical Trial (Promaltia Study)

Background While nutritional interventions with prebiotics and probiotics seem to exert immunological effects, their clinical implications in human immunodeficiency virus (HIV)-infected subjects initiating antiretroviral therapy (ART) at advanced HIV disease remain unclear. Methods This was a pilot multicenter randomized, placebo-controlled, double-blind study in which 78 HIV-infected, ART-naive subjects with <350 CD4 T cells/μL or AIDS were randomized to either daily PMT25341 (a mixture of synbiotics, omega-3/6 fatty acids and amino acids) or placebo for 48 weeks, each in combination with first-line ART. Primary endpoints were changes in CD4 T-cell counts and CD4/CD8 ratio from baseline to week 48 and safety. Secondary endpoints were changes in markers of T-cell activation, bacterial translocation, inflammation, and α and β microbiota diversity. Results Fifty-nine participants completed the follow-up with a mean CD4+ T-cell count of 221 ± 108 cells/μL and mean CD4/CD8 ratio of 0.26 ± 0.19. PMT25341 was well tolerated, without grade 3-4 adverse effects attributable to the intervention. While most of the assessed biomarkers improved during the follow-up in both arms, PMT25341-treated subjects did not experience any significant change, compared to placebo-treated subjects, in mean CD4+ T-cell count change (278 vs 250 cells/μL, P = .474) or CD4/CD8 ratio change (0.30 vs 0.32, P = .854). Similarly, we did not detect differences between treatment arms in secondary endpoints. Conclusions In HIV-infected patients initiating ART at advanced disease, the clear immunological benefits of ART were not enhanced by this nutritional intervention targeting the gut-associated lymphoid tissue and microbiota. Clinical Trials Registration NCT00870363.
Tetraspanins as Organizers of Antigen-Presenting Cell Function

Professional antigen-presenting cells (APCs) include dendritic cells, monocytes, and B cells. APCs internalize and process antigens, producing immunogenic peptides that enable antigen presentation to T lymphocytes, which provide the signals that trigger T-cell activation, proliferation, and differentiation, and lead to adaptive immune responses. After detection of microbial antigens through pattern recognition receptors (PRRs), APCs migrate to secondary lymphoid organs where antigen presentation to T lymphocytes takes place. Tetraspanins are membrane proteins that organize specialized membrane platforms, called tetraspanin-enriched microdomains, which integrate membrane receptors, like PRR and major histocompatibility complex class II (MHC-II), adhesion proteins, and signaling molecules. Importantly, through the modulation of the function of their associated membrane partners, tetraspanins regulate different steps of the immune response. Several tetraspanins can positively or negatively regulate the activation threshold of immune receptors. They also play a role during migration of APCs by controlling the surface levels and spatial arrangement of adhesion molecules and their subsequent intracellular signaling. Finally, tetraspanins participate in antigen processing and are important for priming of naïve T cells through the control of T-cell co-stimulation and MHC-II-dependent antigen presentation. In this review, we discuss the role of tetraspanins in APC biology and their involvement in effective immune responses.
The patient safety culture: a systematic review by characteristics of Hospital Survey on Patient Safety Culture dimensions

Purpose To learn the weaknesses and strengths of safety culture as expressed by the dimensions measured by the Hospital Survey on Patient Safety Culture (HSOPSC) at hospitals in the various cultural contexts. The aim of this study was to identify studies that have used the HSOPSC to collect data on safety culture at hospitals; to survey their findings in the safety culture dimensions and possible contributions to improving the quality and safety of hospital care. Data sources Medline (via PubMed), Web of Science and Scopus were searched from 2005 to July 2016 in English, Portuguese and Spanish. Study selection Studies were identified using specific search terms and inclusion criteria. A total of 33 articles, reporting on 21 countries, was included. Data extraction Scores were extracted by patient safety culture dimensions assessed by the HSOPSC. The quality of the studies was evaluated by the STROBE Statement. Results The dimensions that proved strongest were 'Teamwork within units' and 'Organisational learning-continuous improvement'. Particularly weak dimensions were 'Non-punitive response to error', 'Staffing', 'Handoffs and transitions' and 'Teamwork across units'. Conclusion The studies revealed a predominance of hospital organisational cultures that were underdeveloped or weak as regards patient safety. For them to be effective, safety culture evaluation should be tied to strategies designed to develop safety culture hospital-wide.
Distributed Partitioned Big-Data Optimization via Asynchronous Dual Decomposition

In this paper, we consider a novel partitioned framework for distributed optimization in peer-to-peer networks. In several important applications, the agents of a network have to solve an optimization problem with two key features: i) the dimension of the decision variable depends on the network size, and ii) cost function and constraints have a sparsity structure related to the communication graph. For this class of problems, a straightforward application of existing consensus methods would show two inefficiencies: poor scalability and redundancy of shared information. We propose an asynchronous distributed algorithm, based on dual decomposition and coordinate methods, to solve partitioned optimization problems. We show that by exploiting the problem structure, the solution can be partitioned among the nodes, so that each node just stores a local copy of a portion of the decision variable (rather than a copy of the entire decision vector) and solves a small-scale local problem.
Observing Without Acting: A Balance of Excitation and Suppression in the Human Corticospinal Pathway?

Transcranial magnetic stimulation (TMS) studies of human primary motor cortex (M1) indicate an increase corticospinal excitability during the observation of another's action. This appears to be somewhat at odds with recordings of pyramidal tract neurons in primate M1 showing that there is a balance of increased and decreased activity across the population. TMS is known to recruit a mixed population of cortical neurons, and so one explanation for previous results is that TMS tends to recruit those excitatory output neurons whose activity is increased during action observation. Here we took advantage of the directional sensitivity of TMS to recruit different subsets of M1 neurons and probed whether they responded differentially to action observation in a manner consistent with the balanced change in activity in primates. At the group level we did not observe the expected increase in corticospinal excitability for either TMS current direction during the observation of a precision grip movement. Instead, we observed substantial inter-individual variability ranging from strong facilitation to strong suppression of corticospinal excitability that was similar across both current directions. Thus, we found no evidence of any differential changes in the excitability of distinct M1 neuronal populations during action observation. The most notable change in corticospinal excitability at the group level was a general increase, across muscles and current directions, when participants went from a baseline state outside the task to a baseline state within the actual observation task. We attribute this to arousal- or attention-related processes, which appear to have a similar effect on the different corticospinal pathways targeted by different TMS current directions. Finally, this rather non-specific increase in corticospinal excitability suggests care should be taken when selecting a “baseline” state against which to compare changes during action observation.
Integrative Analysis of Hippocampus Gene Expression Profiles Identifies Network Alterations in Aging and Alzheimer’s Disease

Alzheimer’s disease (AD) is a neurodegenerative disorder contributing to rapid decline in cognitive function and ultimately dementia. Most cases of AD occur in elderly and later years. There is a growing need for understanding the relationship between aging and AD to identify shared and unique hallmarks associated with the disease in a region and cell-type specific manner. Although genomic studies on AD have been performed extensively, the molecular mechanism of disease progression is still not clear. The major objective of our study is to obtain a higher-order network-level understanding of aging and AD, and their relationship using the hippocampal gene expression profiles of young (20–50 years), aging (70–99 years), and AD (70–99 years). The hippocampus is vulnerable to damage at early stages of AD and altered neurogenesis in the hippocampus is linked to the onset of AD. We combined the weighted gene co-expression network and weighted protein–protein interaction network-level approaches to study the transition from young to aging to AD. The network analysis revealed the organization of co-expression network into functional modules that are cell-type specific in aging and AD. We found that modules associated with astrocytes, endothelial cells and microglial cells are upregulated and significantly correlate with both aging and AD. The modules associated with neurons, mitochondria and endoplasmic reticulum are downregulated and significantly correlate with AD than aging. The oligodendrocytes module does not show significant correlation with neither aging nor disease. Further, we identified aging- and AD-specific interactions/subnetworks by integrating the gene expression with a human protein–protein interaction network. We found dysregulation of genes encoding protein kinases (FYN, SYK, SRC, PKC, MAPK1, ephrin receptors) and transcription factors (FOS, STAT3, CEBPB, MYC, NFKβ, and EGR1) in AD. Further, we found genes that encode proteins with neuroprotective function (14-3-3 proteins, PIN1, ATXN1, BDNF, VEGFA) to be part of the downregulated AD subnetwork. Our study highlights that simultaneously analyzing aging and AD will help to understand the pre-clinical and clinical phase of AD and aid in developing the treatment strategies.
Exome Sequencing Discloses Ionizing-radiation-induced DNA Variants in the Genome of Human Gingiva Fibroblasts

Abstract Ionizing radiation can induce genomic lesions such as DNA double-strand breaks whose incomplete or faulty repair can result in mutations, which in turn can influence cellular functions and alter the fate of affected cells and organ systems. Ionizing-radiation-induced sequence alterations/mutations occur in a stochastic manner, which contributes to an increased cancer risk in irradiated individuals. Ionizing radiation exposure, and particularly acute doses at high dose rates (as often observed in radiation accidents), induce alterations in the genome that in part will reflect specific characteristics of the DNA damage response and the repair mechanisms involved. Here, the exome of primary human gingival fibroblasts not exposed or exposed to 0.2, 2, 5, or 10 Gy of x rays was investigated after 16 h of DNA repair for ionizing-radiation-induced mutations. The irradiation effect with varying dose was investigated using three different bioinformatic filters for the analysis of accumulated variants per Mb of genomic DNA and per cytogenetic bands. A highly stringent cutoff of 20‐fold coverage was used for all analyses. Comparing exome DNA from irradiated and nonirradiated cells disclosed a characteristic variation of the frequency of ionizing-radiation-induced single-nucleotide variants as well as small insertions and deletions among chromosomes and their subregions. Increases in ionizing-radiation-induced variants with increasing dose were highly significant (p = 2.2 × 10−16, Kruskal-Wallis test). These results indicate that certain chromosomal regions may be more prone to accumulating particular ionizing-radiation-induced alterations than others, which points to a characteristic metasignature in the irradiated exome.
Plume Origins and Plumbing ( Ocean to Surface ) ( resubmitted version )

The plume of Enceladus provides a unique window into subsurface processes in the ice shell and ocean of an icy world. Thanks to a decade of observations and modeling, a coherent picture is emerging of a thin ice shell extending across the south polar region, cut through by fractures directly connected to the underlying ocean, and at least partially filled with water. The plume jets emerging from the fractures directly sample this water reservoir. The shell undergoes daily tidal flexing, which modulates plume activity by opening and closing the fractures. Dissipation in the ice and conduit water components due to this flexing is likely to generate the several Gigawatts of observed power, which is lost from the south pole as infrared radiation and plume latent heat.
N-Acetyl and Glutamatergic Neurometabolites in Perisylvian Brain Regions of Methamphetamine Users

Abstract Background Methamphetamine induces neuronal N-acetyl-aspartate synthesis in preclinical studies. In a preliminary human proton magnetic resonance spectroscopic imaging investigation, we also observed that N-acetyl-aspartate+N-acetyl-aspartyl-glutamate in right inferior frontal cortex correlated with years of heavy methamphetamine abuse. In the same brain region, glutamate+glutamine is lower in methamphetamine users than in controls and is negatively correlated with depression. N-acetyl and glutamatergic neurochemistries therefore merit further investigation in methamphetamine abuse and the associated mood symptoms. Methods Magnetic resonance spectroscopic imaging was used to measure N-acetyl-aspartate+N-acetyl-aspartyl-glutamate and glutamate+glutamine in bilateral inferior frontal cortex and insula, a neighboring perisylvian region affected by methamphetamine, of 45 abstinent methamphetamine-dependent and 45 healthy control participants. Regional neurometabolite levels were tested for group differences and associations with duration of heavy methamphetamine use, depressive symptoms, and state anxiety. Results In right inferior frontal cortex, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate correlated with years of heavy methamphetamine use (r = +0.45); glutamate+glutamine was lower in methamphetamine users than in controls (9.3%) and correlated negatively with depressive symptoms (r = -0.44). In left insula, N-acetyl-aspartate+N-acetyl-aspartyl-glutamate was 9.1% higher in methamphetamine users than controls. In right insula, glutamate+glutamine was 12.3% lower in methamphetamine users than controls and correlated negatively with depressive symptoms (r = -0.51) and state anxiety (r = -0.47). Conclusions The inferior frontal cortex and insula show methamphetamine-related abnormalities, consistent with prior observations of increased cortical N-acetyl-aspartate in methamphetamine-exposed animal models and associations between cortical glutamate and mood in human methamphetamine users.
The limit shape of convex hull peeling

We prove that the convex peeling of a random point set in dimension d approximates motion by the 1/(d + 1) power of Gaussian curvature. We use viscosity solution theory to interpret the limiting partial differential equation. We use the Martingale method to solve the cell problem associated to convex peeling. Our proof follows the program of Armstrong-Cardaliaguet for homogenization of geometric motions, but with completely different ingredients.
On Incorporating Affective Support to an Intelligent Tutoring System: an Empirical Study

Previous research studies have reported strong evidence that the emotional state of students may have a considerable impact on their learning. In this paper, we present an empirical study that evidences that it is possible to influence the user’s affective state in a controlled way, by adapting the system’s response. As part of this paper, we have analyzed the affective impact of varying the level of help provided in an existing Intelligent Tutoring System. Results show that it is possible to use classification approaches to predict positive and negative variations in dominance, valence, arousal, and performance to a reasonable level of accuracy.