Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanoskin® Subcutaneous Implant in Guinea Pigs.

PURPOSE To evaluate the suitability of Nanoskin, a biomaterial derived from bacterial cellulose, as an alternate material for repairing the posterior lamellae of the eyelids. METHODS Forty guinea pigs received a fragment of Nanoskin subcutaneously in the dorsal region. The animals received Nanoskin (group 1) or Nanoskin coated with a gelatin layer (group 2). The animals were observed daily for over 7, 30, 90, or 180 days with the subcutaneous implants in place. The animals were euthanized at a designated time and the Nanoskin was removed for histologic, morphometric, and transmission electron microscopy evaluation. RESULTS The results were similar for both groups. The subcutaneously implanted Nanoskin resulted in good tissue integration, induced mild inflammation, and was surrounded by a delicate pseudocapsule. CONCLUSION The good tissue integration of Nanoskin in study indicates that it may be a potential material for application as a substitute of posterior eyelid lamellar tissue. Further clinical studies are required to confirm the preliminary outcomes of this experimental study.
In vitro and in vivo efficacies of novel carbazole aminoalcohols in the treatment of cystic echinococcosis

Objectives Cystic echinococcosis (CE), caused by the cestode Echinococcus granulosus, is a worldwide chronic zoonosis. Current chemotherapeutic options are limited to albendazole and mebendazole, which only exert parasitostatic effects and have to be administered at high dosages for long periods. In an effort to find alternative treatment options, the in vitro and in vivo efficacies of novel carbazole aminoalcohols were evaluated. Methods Carbazole aminoalcohols were tested against E. granulosus protoscoleces in vitro and metacestodes ex vivo. The in vivo chemotherapeutic effect of representative compounds was assessed in experimentally infected mice. Oral and intravenous pharmacokinetic profiles were determined in mice. Results The carbazole aminoalcohols exhibited potent protoscolicidal activity with LC50 values ranging from 18.2 to 34.3 μM. Among them, compounds 2 and 24 killed all ex vivo cultured metacestodes at concentrations of 34.3 and 30.6 μM. In vivo studies showed that oral administration of compounds 2 and 24 (25 mg/kg/day) for 30 days led to reductions of 68.4% and 54.3% in parasite weight compared with the untreated group (both groups: P < 0.001). Compound 2 (25 mg/kg/day) and compound 24 (50 mg/kg/day) induced significantly higher cyst mortality rates in comparison with that of the albendazole group (both groups: P < 0.01). Analysis of cysts collected from compound 2- or 24-treated mice by transmission electron microscopy revealed a drug-induced structural destruction. The structural integrity of the germinal layer was lost, and the majority of the microtriches disappeared. Pharmacokinetic profiling of compounds 2 and 24 revealed low clearance and decent oral bioavailability (>70%). Conclusions Our study identifies carbazole aminoalcohols as a class of novel anti-CE agents. Compounds 2 and 24 represent promising drug candidates in anti-CE chemotherapy.
Reversible switching of ultrastrong light-molecule coupling

Strong coupling of light and matter can give rise to a multitude of exciting physical effects [1]. Following the first observation of strong coupling between a cavity and dye molecules [2], organic molecules have been increasingly used for the study of strong coupling, since their large transition dipole moment permits the observation of Rabi splitting in the range of a few hundreds of meV at room temperature. However, organic molecules, as we show here, can also be used for combining light-matter interaction with molecular functionality [3], and for the study of strong coupling at the interface between physics and chemistry [4]. Remarkable, the light-molecule interaction in our system enters the regime of ultrastrong coupling [5], where the energy splitting is substantial fraction of the coupled transition energies, and new phenomena such squeezed vacuum state and generation of entangled photon pairs are predicted.
Toward online profit-driven scheduling of inter-DC data-transfers for cloud applications

For an inter-datacenter (inter-DC) network that carries multiple cloud applications, tasks may arise in the DCs and need to transfer data to others with different latency requirements. Therefore, it is desired that a highly efficient online scheduling algorithm could be developed to consider the request admission, routing selection and bandwidth allocation for the data-transfers jointly. In this work, we investigate this problem, and propose an online scheduling algorithm, namely, GlobeAny, to maximize the time-average profit from provisioning the requests. The proposed algorithm leverages Lyapunov optimization techniques and can achieve arbitrarily approaching to the optimal value within O(1/V) gap. We also show that by adjusting the application weights, it can provide differentiated services to requests with different latency requirements.
Quantifying the kinetics and morphological changes of the fusion of spheroid building blocks

Tissue fusion, whereby two or more spheroids coalesce, is a process that is fundamental to biofabrication. We have designed a quantitative, high-throughput platform to investigate the fusion of multicellular spheroids using agarose micro-molds. Spheroids of primary human chondrocytes (HCH) or human breast cancer cells (MCF-7) were self-assembled for 24 h and then brought together to form an array comprised of two spheroids (one doublet) per well. To quantify spheroid fusogenicity, we developed two assays: (1) an initial tack assay, defined as the minimum amount of time for two spheroids to form a mechanically stable tissue complex or doublet, and (2) a fusion assay, in which we defined and tracked key morphological parameters of the doublets as a function of time using wide-field fluorescence microscopy over a 24 h time-lapse. The initial tack of spheroid fusion was measured by inverting the micro-molds and centrifuging doublets at various time points to assess their connectedness. We found that the initial tack between two spheroids forms rapidly, with the majority of doublets remaining intact after centrifugation following just 30 min of fusion. Over the course of 24 h of fusion, several morphological changes occurred, which were quantified using a custom image analysis pipeline. End-to-end doublet lengths decreased over time, doublet widths decreased for chondrocytes and increased for MCF-7, contact lengths increased over time, and chondrocyte doublets exhibited higher intersphere angles at the end of fusion. We also assessed fusion by measuring the fluorescence intensity at the plane of fusion, which increased over time for both cell types. Interestingly, we observed that doublets moved and rotated in the micro-wells during fusion and this rotation was inhibited by ROCK inhibitor Y-27632 and myosin II inhibitor blebbistatin. Understanding and optimizing tissue fusion is essential for creating larger tissues, organs, or other structures using individual microtissues as building parts.
Neuroimaging of Priming: New Perspectives on Implicit and Explicit Memory

Priming refers to a change in the ability to identify or produce an item as a consequence of a specific prior encounter. Priming has been studied extensively in cognitive studies of healthy volunteers, neuropsychological investigations of brain-damaged patients, and, more recently, studies using modern functional neuroimaging techniques such as positron emission tomography and functional magnetic resonance imaging. We review recent neuroimaging studies that have converged upon the conclusion that priming is reliably accompanied by decreased activity in a variety of brain regions. The establishment of this cortical signature of priming is beginning to generate new hypotheses concerning the relation between priming and explicit retrieval, which we illustrate by considering recent experiments on within- and cross-modality priming.
Is Lung Ultrasound Useful for Diagnosing Pneumonia in Children?: A Meta-Analysis and Systematic Review

Background Childhood mortality due to pneumonia is high. Chest radiography is the primary imaging modality used for the evaluation of pneumonia in children. Lung ultrasonography (LUS) is a newer, alternative diagnostic method that has been gaining popularity in recent years. We conducted a meta-analysis to summarize the diagnostic usefulness of LUS for childhood pneumonia. Methods All studies included in this meta-analysis were retrieved from PubMed, Elsevier's Science Direct, and Springer, and by manual searches including the use of reference lists, through March 31, 2017. Two researchers independently screened the literature, extracted the data, and evaluated risks of bias in accordance with the inclusion and exclusion criteria. For the meta-analysis, we calculated the pooled sensitivity and specificity, pooled positive likelihood ratio, negative likelihood ratio, and the diagnostic odds ratio. Summary receiver operating characteristic curve was used to assess the overall performance of LUS. Results Our search identified 1038 articles, and we selected 51 of these for detailed review. Eight studies containing 1013 patients met all the inclusion criteria and were included in the final meta-analysis. The pooled sensitivity and specificity for the diagnosis of pneumonia using LUS were 93.0% (95% confidence interval, 88.0%–96.0%) and 96.0% (95% confidence interval, 92.0%–98.0%), respectively. The pooled positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 25.8 (11.0, 60.4), 0.07 (0.05, 0.12), and 344 (104, 1140), respectively. In addition, the summary receiver operating characteristic area under the curve was calculated to be 0.98 (0.97, 0.99). A Fagan plot analysis demonstrated that when pretest probabilities were 25%, 50%, and 75%, the positive posttest probabilities were 90%, 96%, and 99%, respectively, and the negative posttest probabilities were 2%, 7%, and 18%, respectively. Four clinical signs were most frequently observed using LUS in the screening of children with pneumonia: pulmonary consolidation, positive air bronchogram, abnormal pleural line, and pleural effusion. Conclusions Current evidence supports LUS as a useful imaging alternative for the diagnosis of childhood pneumonia. That it is easily carried out, readily available, relatively inexpensive, and free from the hazards of radiation make it an attractive alternative to chest radiography and physical examination for the diagnosis and the follow-up of pneumonia in children.
Genetic association between PSA-158G/A polymorphism and the susceptibility of benign prostatic hyperplasia: a meta-analysis

Inconsistency between reported findings on the association of prostate specific antigen (PSA) gene -158G/A polymorphism with benign prostatic hyperplasia (BPH) susceptibility need a meta-analysis to obtain a more accurate conclusion. A systematic search was conducted in electronic databases for the collection of eligible studies on PSA -158G/A polymorphism and BPH susceptibility. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were then calculated. 7 case-control studies with 758 cases and 752 controls were included into the present meta-analysis. The analysis results showed no significant relationship between PSA -158G/A polymorphism and BPH susceptibility in total analysis. Interestingly, after subgroup analyses based on ethnicity and source of control, the polymorphism reduced the susceptibility of BPH in Caucasian group (AA vs. GG: OR=0.47, 95% CI=0.25-0.89; allele A vs. allele G: OR=0.68, 95% CI=0.49-0.93), but it increased the disease susceptibility in Asian (AA vs. GG: OR=1.63, 95% CI=1.02-2.60; allele A vs. allele G: OR=1.37, 95% CI=1.03-1.83) and population-based (AA vs. GG: OR=2.39, 95% CI=1.07-5.38; allele A vs. allele G: OR=1.83, 95% CI=1.26-2.65) groups. PSA-158G/A polymorphism may be an inhibitor to the incidence of BPH in Caucasians, but it is likely to be a susceptible factor in Asians.
Esx Systems and the Mycobacterial Cell Envelope: What's the Connection?

ABSTRACT Mycobacterial 6-kDa early secreted antigenic target (ESAT-6) system (ESX) exporters transport proteins across the cytoplasmic membrane. Many proteins transported by ESX systems are then translocated across the mycobacterial cell envelope and secreted from the cell. Although the mechanism underlying protein transport across the mycolate outer membrane remains elusive, the ESX systems are closely connected with and localize to the cell envelope. Links between ESX-associated proteins, cell wall synthesis, and the maintenance of cell envelope integrity have been reported. Genes encoding the ESX systems and those required for biosynthesis of the mycobacterial envelope are coregulated. Here, we review the interplay between ESX systems and the mycobacterial cell envelope.
Sleep deprivation affects fear memory consolidation: bi-stable amygdala connectivity with insula and ventromedial prefrontal cortex

Abstract Sleep plays an important role for successful fear memory consolidation. Growing evidence suggests that sleep disturbances might contribute to the development and the maintenance of posttraumatic stress disorder (PTSD), a disorders characterized by dysregulations in fear learning mechanisms, as well as exaggerated arousal and salience processing. Against this background, the present study examined the effects of sleep deprivation (SD) on the acquisition of fear and the subsequent neural consolidation. To this end, the present study assessed fear acquisition and associated changes in fMRI-based amygdala-functional connectivity following 24 h of SD. Relative to non-sleep deprived controls, SD subjects demonstrated increased fear ratings and skin conductance responses (SCR) during fear acquisition. During fear consolidation SD inhibited increased amygdala-ventromendial prefrontal cortex (vmPFC) connectivity and concomitantly increased changes in amygdala-insula connectivity. Importantly, whereas in controls fear indices during acquisition were negatively associated with amygdala-vmPFC connectivity during consolidation, fear indices were positively associated with amygdala-insula coupling following SD. Together the findings suggest that SD may interfere with vmPFC control of the amygdala and increase bottom-up arousal signaling in the amygdala-insula pathway during fear consolidation, which might mediate the negative impact of sleep disturbances on PSTD symptomatology.
Phase II Proof-of-Concept Trial of the Orexin Receptor Antagonist Filorexant (MK-6096) in Patients with Major Depressive Disorder

Abstract Background We evaluated the orexin receptor antagonist filorexant (MK-6096) for treatment augmentation in patients with major depressive disorder. Methods We conducted a 6-week, double-blind, placebo-controlled, parallel-group, Phase II, proof-of-concept study. Patients with major depressive disorder (partial responders to ongoing antidepressant therapy) were randomized 1:1 to once-daily oral filorexant 10 mg or matching placebo. Results Due to enrollment challenges, the study was terminated early, resulting in insufficient statistical power to detect a prespecified treatment difference; of 326 patients planned, 129 (40%) were randomized and 128 took treatment. There was no statistically significant difference in the primary endpoint of change from baseline to week 6 in Montgomery Asberg Depression Rating Scale total score; the estimated treatment difference for filorexant-placebo was -0.7 (with negative values favoring filorexant) (P=.679). The most common adverse events were somnolence and suicidal ideation. Conclusions The interpretation of the results is limited by the enrollment, which was less than originally planned, but the available data do not suggest efficacy of orexin receptor antagonism with filorexant for the treatment of depression. (Clinical Trial Registry: clinicaltrials.gov: NCT01554176)
Single-centre study of therapeutic drug monitoring of posaconazole in lung transplant recipients: factors affecting trough plasma concentrations

Objectives This study describes therapeutic drug monitoring (TDM) of posaconazole suspension and modified release (MR) tablets in lung transplant (LTx) recipients and evaluates factors that may affect posaconazole trough plasma concentration (Cmin). Methods A single-centre, retrospective study evaluating posaconazole Cmin in LTx recipients receiving posaconazole suspension or MR tablets between January 2014 and December 2016. Results Forty-seven LTx patients received posaconazole suspension, and 78 received the MR tablet formulation; a total of 421 and 617 Cmin measurements were made, respectively. Posaconazole was concurrently administered with proton pump inhibitor in ≥ 90% of patients. The median (IQR) of initial posaconazole Cmin following 300 mg daily of posaconazole tablet was significantly higher than that of 800 mg daily of posaconazole suspension [1.65 (0.97-2.13) mg/L versus 0.81 (0.48-1.15) mg/L, P < 0.01]. Variability in posaconazole Cmin was apparent regardless of the formulations prescribed and dose adjustments were routinely undertaken to maintain therapeutic Cmin. A clear dose-response relationship was observed in patients receiving posaconazole MR tablets. Non-specific adverse events (fatigue, tremor, lethargy, sweating, nausea/vomiting and weight loss) were reported in 3/78 (4%) patients receiving posaconazole MR tablets. Posaconazole Cmin in these three patients was determined to be 9.6, 6.2 and 2.3 mg/L. Conclusions The current study has provided clinically important insights into the TDM of posaconazole in LTx recipients. Routine TDM should be undertaken in LTx recipients receiving posaconazole suspension and/or MR tablets.
Automating the sizing of transistors in CMOS gates for low‐power and high‐noise margin operation

This paper presents an automatic method for sizing the transistors in CMOS gates. The method utilizes a feedback control system to efficiently optimize the transistor sizes in small and large fan‐in gates, with the primary goal of enhancing noise robustness (as characterized by the static noise margin). The gates retain their robustness under threshold‐voltage variations over a range of supply voltages. The optimized gates not only expend reduced power and energy, but also take up less area than the conventional ones. These multi‐faceted gains, however, do incur some performance loss. Copyright © 2014 John Wiley & Sons, Ltd.
Proliferation in the Alzheimer Hippocampus Is due to Microglia, Not Astroglia, and Occurs at Sites of Amyloid Deposition

Microglia and astrocytes contribute to Alzheimer's disease (AD) etiology and may mediate early neuroinflammatory responses. Despite their possible role in disease progression and despite the fact that they can respond to amyloid deposition in model systems, little is known about whether astro- or microglia can undergo proliferation in AD and whether this is related to the clinical symptoms or to local neuropathological changes. Previously, proliferation was found to be increased in glia-rich regions of the presenile hippocampus. Since their phenotype was unknown, we here used two novel triple-immunohistochemical protocols to study proliferation in astro- or microglia in relation to amyloid pathology. We selected different age-matched cohorts to study whether proliferative changes relate to clinical severity or to neuropathological changes. Proliferating cells were found across the hippocampus but never in mature neurons or astrocytes. Almost all proliferating cells were colabeled with Iba1+, indicating that particularly microglia contribute to proliferation in AD. Proliferating Iba1+ cells was specifically seen within the borders of amyloid plaques, indicative of an active involvement in, or response to, plaque accumulation. Thus, consistent with animal studies, proliferation in the AD hippocampus is due to microglia, occurs in close proximity of plaque pathology, and may contribute to the neuroinflammation common in AD.
Close-range laser scanning in forests: towards physically based semantics across scales

Laser scanning with its unique measurement concept holds the potential to revolutionize the way we assess and quantify three-dimensional vegetation structure. Modern laser systems used at close range, be it on terrestrial, mobile or unmanned aerial platforms, provide dense and accurate three-dimensional data whose information just waits to be harvested. However, the transformation of such data to information is not as straightforward as for airborne and space-borne approaches, where typically empirical models are built using ground truth of target variables. Simpler variables, such as diameter at breast height, can be readily derived and validated. More complex variables, e.g. leaf area index, need a thorough understanding and consideration of the physical particularities of the measurement process and semantic labelling of the point cloud. Quantified structural models provide a framework for such labelling by deriving stem and branch architecture, a basis for many of the more complex structural variables. The physical information of the laser scanning process is still underused and we show how it could play a vital role in conjunction with three-dimensional radiative transfer models to shape the information retrieval methods of the future. Using such a combined forward and physically based approach will make methods robust and transferable. In addition, it avoids replacing observer bias from field inventories with instrument bias from different laser instruments. Still, an intensive dialogue with the users of the derived information is mandatory to potentially re-design structural concepts and variables so that they profit most of the rich data that close-range laser scanning provides.
Alterations in CA1 hippocampal synapses in a mouse model of fragile X syndrome

Fragile X Syndrome (FXS) is the major cause of inherited mental retardation and the leading genetic cause of Autism spectrum disorders. FXS is caused by mutations in the Fragile X Mental Retardation 1 (Fmr1) gene, which results in transcriptional silencing of Fragile X Mental Retardation Protein (FMRP). To elucidate cellular mechanisms involved in the pathogenesis of FXS, we compared dendritic spines in the hippocampal CA1 region of adult wild‐type (WT) and Fmr1 knockout (Fmr1‐KO) mice. Using diolistic labeling, confocal microscopy, and three‐dimensional electron microscopy, we show a significant increase in the diameter of secondary dendrites, an increase in dendritic spine density, and a decrease in mature dendritic spines in adult Fmr1‐KO mice. While WT and Fmr1‐KO mice had the same mean density of spines, the variance in spine density was three times greater in Fmr1‐KO mice. Reduced astrocyte participation in the tripartite synapse and less mature post‐synaptic densities were also found in Fmr1‐KO mice. We investigated whether the increase in synaptic spine density was associated with altered synaptic pruning during development. Our data are consistent with reduced microglia‐mediated synaptic pruning in the CA1 region of Fmr1‐KO hippocampi when compared with WT littermates at postnatal day 21, which is the peak period of synaptic pruning in the mouse hippocampus. Collectively, these results support abnormal synaptogenesis and synaptic remodeling in mice deficient in FMRP. Deficits in the maturation and distribution of synaptic spines on dendrites of CA1 hippocampal neurons may play a role in the intellectual disabilities associated with FXS.