Miracle-dz/UniFAR-FTUs huggingface dataset:
Can Virtual Contrast Enhancement in Brain MRI Replace Gadolinium?: A Feasibility Study.

OBJECTIVES Gadolinium-based contrast agents (GBCAs) have become an integral part in daily clinical decision making in the last 3 decades. However, there is a broad consensus that GBCAs should be exclusively used if no contrast-free magnetic resonance imaging (MRI) technique is available to reduce the amount of applied GBCAs in patients. In the current study, we investigate the possibility of predicting contrast enhancement from noncontrast multiparametric brain MRI scans using a deep-learning (DL) architecture. MATERIALS AND METHODS A Bayesian DL architecture for the prediction of virtual contrast enhancement was developed using 10-channel multiparametric MRI data acquired before GBCA application. The model was quantitatively and qualitatively evaluated on 116 data sets from glioma patients and healthy subjects by comparing the virtual contrast enhancement maps to the ground truth contrast-enhanced T1-weighted imaging. Subjects were split in 3 different groups: enhancing tumors (n = 47), nonenhancing tumors (n = 39), and patients without pathologic changes (n = 30). The tumor regions were segmented for a detailed analysis of subregions. The influence of the different MRI sequences was determined. RESULTS Quantitative results of the virtual contrast enhancement yielded a sensitivity of 91.8% and a specificity of 91.2%. T2-weighted imaging, followed by diffusion-weighted imaging, was the most influential sequence for the prediction of virtual contrast enhancement. Analysis of the whole brain showed a mean area under the curve of 0.969 ± 0.019, a peak signal-to-noise ratio of 22.967 ± 1.162 dB, and a structural similarity index of 0.872 ± 0.031. Enhancing and nonenhancing tumor subregions performed worse (except for the peak signal-to-noise ratio of the nonenhancing tumors). The qualitative evaluation by 2 raters using a 4-point Likert scale showed good to excellent (3-4) results for 91.5% of the enhancing and 92.3% of the nonenhancing gliomas. However, despite the good scores and ratings, there were visual deviations between the virtual contrast maps and the ground truth, including a more blurry, less nodular-like ring enhancement, few low-contrast false-positive enhancements of nonenhancing gliomas, and a tendency to omit smaller vessels. These "features" were also exploited by 2 trained radiologists when performing a Turing test, allowing them to discriminate between real and virtual contrast-enhanced images in 80% and 90% of the cases, respectively. CONCLUSIONS The introduced model for virtual gadolinium enhancement demonstrates a very good quantitative and qualitative performance. Future systematic studies in larger patient collectives with varying neurological disorders need to evaluate if the introduced virtual contrast enhancement might reduce GBCA exposure in clinical practice.
Uncoupling Traditional Functionalities of Metastasis: The Parting of Ways with Real-Time Assays

The experimental evaluation of metastasis overly focuses on the gain of migratory and invasive properties, while disregarding the contributions of cellular plasticity, extra-cellular matrix heterogeneity, niche interactions, and tissue architecture. Traditional cell-based assays often restrict the inclusion of these processes and warrant the implementation of approaches that provide an enhanced spatiotemporal resolution of the metastatic cascade. Time lapse imaging represents such an underutilized approach in cancer biology, especially in the context of disease progression. The inclusion of time lapse microscopy and microfluidic devices in routine assays has recently discerned several nuances of the metastatic cascade. Our review emphasizes that a complete comprehension of metastasis in view of evolving ideologies necessitates (i) the use of appropriate, context-specific assays and understanding their inherent limitations; (ii) cautious derivation of inferences to avoid erroneous/overestimated clinical extrapolations; (iii) corroboration between multiple assay outputs to gauge metastatic potential; and (iv) the development of protocols with improved in situ implications. We further believe that the adoption of improved quantitative approaches in these assays can generate predictive algorithms that may expedite therapeutic strategies targeting metastasis via the development of disease relevant model systems. Such approaches could potentiate the restructuring of the cancer metastasis paradigm through an emphasis on the development of next-generation real-time assays.
Seasonality of Rotavirus Hospitalizations at Costa Rica’s National Children’s Hospital in 2010–2015

Rotavirus is a leading cause of acute diarrhea in children worldwide. Costa Rica recently started universal rotavirus vaccinations for infants with a two-dose schedule in February 2019. We aimed to study the seasonality of rotavirus during the pre-vaccination era. We retrospectively studied a six-year period of hospital admissions due to rotavirus gastroenteritis. We estimated seasonal peak timing and relative intensities using trend-adjusted negative binomial regression models with the δ-method. We assessed the relationship between rotavirus cases and weather characteristics and estimated their effects for the current month, one-month prior and two months prior, by using Pearson correlation coefficients. A total of 798 cases were analyzed. Rotavirus cases predominated in the first five months of the year. On average, the peak of admissions occurred between late-February and early-March. During the seasonal peaks, the monthly count tended to increase 2.5–2.75 times above the seasonal nadir. We found the strongest negative association of monthly hospitalizations and joint percentiles of precipitation and minimal temperature at a lag of two months (R = −0.265, p = 0.027) and we detected correlations of −0.218, −0.223, and −0.226 (p < 0.05 for all three estimates) between monthly cases and the percentile of precipitation at lags 0, 1, and 2 months. In the warm tropical climate of Costa Rica, the increase in rotavirus hospitalizations coincided with dry and cold weather conditions with a two-month lag. The findings serve as the base for predictive modeling and estimation of the impact of a nation-wide vaccination campaign on pediatric rotaviral infection morbidity.
The relation of basic self‐disturbance to self‐harm, eating disorder symptomatology and other clinical features: Exploration in an early psychosis sample

The notion of basic self‐disturbance has been proposed as a core feature of schizophrenia‐spectrum disorders and as an indicator of future transition to psychosis in high‐risk populations. However, the relation of this notion to many clinical characteristics has not been explored. The aim of this study was: (a) to investigate the distribution of self‐disturbance and other symptoms dimensions in ultra‐high risk (UHR), first‐episode psychosis (FEP) and healthy control groups; and (b) to explore the association of self‐disturbance with a history of self‐harm, suicidal attempt, eating disorder symptomatology, school bullying victimization and sexual or physical abuse.
Identification of Subterranean Termite Genus, Reticulitermes (Blattodea: Rhinotermitidae) in Taiwan

Abstract Species identification in the genus Reticulitermes is often difficult because of ambiguous morphological characters. Challenges in Reticulitermes spp. recognition have also been encountered in East Asia, includingTaiwan. Because of unknown Reticulitermes taxa in Taiwan and the possible origin of alien Reticulitermes kanmonensisTakematsu in Japan and Korea, reexamining Reticulitermes fauna in Taiwan is imperative. To clarify the Reticulitermes fauna in Taiwan, this study applied two mitochondrial genes (cytochrome oxidase subunit II [COII] and 16S rDNA) and morphological characters for species delimitation. Reticulitermes specimens collected from 63 localities across the main and adjacent islands ofTaiwan were analyzed. Phylogenetic analyses, morphological comparisons, and ecological traits suggested the existence of three species inTaiwan: Reticulitermes flaviceps (Oshima), R. kanmonensis, and Reticulitermes leptomandibularis Hsia and Fan. Altitudinal distributions among the three Reticulitermes termites tended to differ: R. flaviceps adapted to low hills, but R. kanmonensis and R. leptomandibularis occurred in medium mountainous areas. The combined data, including haplotype diversities and distribution range, suggest that 1) R. flaviceps is an endemic species and only found in Taiwan; 2) R. kanmonensis and R. leptomandibularis are both native species in Taiwan and China; 3) Japanese R. kanmonensis populations originated from southern China and/or Taiwan and that Korean populations were possibly introduced from Japan.
Simultaneous determination of eight bioactive components of Cirsium setosum flavonoids in rat plasma using Triple Quadrupole LC/MS and its application to a pharmacokinetic study.

Cirsium setosum (Willd.) MB. has been reported to exert significant anti-hemorrhagic, anti-inflammation, antimicrobial, sedative and detoxicating efficacy. At present, it has been widely used to treat gastrointestinal bleeding, uterine bleeding, infectious hepatitis and cardiovascular disease in China. Recent studies have shown that flavonoids are the main active components in C. setosum. Nevertheless, to the best of our knowledge, there is no report concerning the simultaneous determinations and pharmacokinetics of constituents in C.setosum flavonoids in rat plasma. In this study, a rapid, sensitive and selective Triple Quadrupole Liquid Chromatography-Mass Spectrometry method was developed to determine eight analytes from the flavonoids of C. setosum in rat plasma. In addition, the pharmacokinetic study of the eight analytes in rats after oral administration of C. setosum flavonoids was successfully completed through this method. According to the pharmacokinetic parameters of the eight analytes, Rutin, Naringin, Quercetin, Acacetin, Wogonin were the long-acting components in C. setosum flavonoids, which have long elimination time and high bioavailability. Of note, the method developed in this study would definitely fill a blank in pharmacokinetic studies of C. setosum flavonoids. And our findings provide valuable views to the understanding of the absorption mechanism of C. setosum flavonoids and their clinical efficacy.
Spectral analysis of molecular dynamics simulations on PDZ: MD sectors

Abstract The idea of protein “sectors” posits that sparse subsets of amino acid residues form cooperative networks that are key elements of protein stability, ligand binding, and allosterism. To date, protein sectors have been calculated by the statistical coupling analysis (SCA) method of Ranganathan and co-workers via the spectral analysis of conservation-weighted evolutionary covariance matrices obtained from a multiple sequence alignments of homologous families of proteins. SCA sectors, a knowledge-based protocol, have been indentified with functional properties and allosterism for a number of systems. In this study, we investigate the utility of the sector idea for the analysis of physics-based molecular dynamics (MD) trajectories of proteins. Our test case for this procedure is PSD95- PDZ3, one of the smallest proteins for which allosterism has been observed. It has served previously as a model system for a number of prediction algorithms, and is well characterized by X-ray crystallography, NMR spectroscopy and site specific mutagenisis. All-atom MD simulations were performed for a total of 500 nanoseconds using AMBER, and MD-calculated covariance matrices for the fluctuations of residue displacements and non-bonded interaction energies were subjected to spectral analysis in a manner analogous to that of SCA. The composition of MD sectors was compared with results from SCA, site specific mutagenesis, and allosterism. The concordance indicates that MD sectors are a viable protocol for analyzing MD trajectories and provide insight into the physical origin of the phenomenon. Communicated by Ramaswamy H. Sarma
Pharmacokinetics and Pharmacodynamics of the Nitroimidazole DNDI-0690 in Mouse Models of Cutaneous Leishmaniasis

The nitroimidazole DNDI-0690 is a clinical drug candidate for visceral leishmaniasis (VL) that also shows potent in vitro and in vivo activity against cutaneous leishmaniasis (CL). To support further development of this compound into a patient-friendly oral or topical formulation for the treatment of CL, we investigated the free drug exposure at the dermal site of infection and subsequent elimination of the causative Leishmania pathogen. ABSTRACT The nitroimidazole DNDI-0690 is a clinical drug candidate for visceral leishmaniasis (VL) that also shows potent in vitro and in vivo activity against cutaneous leishmaniasis (CL). To support further development of this compound into a patient-friendly oral or topical formulation for the treatment of CL, we investigated the free drug exposure at the dermal site of infection and subsequent elimination of the causative Leishmania pathogen. This study evaluates the pharmacokinetics (PK) and pharmacodynamics (PD) of DNDI-0690 in mouse models of CL. Skin microdialysis and Franz diffusion cell permeation studies revealed that DNDI-0690 permeated poorly (<1%) into the skin lesion upon topical drug application (0.063% [wt/vol], 30 μl). In contrast, a single oral dose of 50 mg/kg of body weight resulted in the rapid and nearly complete distribution of protein-unbound DNDI-0690 from the plasma into the infected dermis (ratio of the area under the curve [0 to 6 h] of the free DNDI-0690 concentration in skin tissue to blood [fAUC0-6 h, skin tissue/fAUC0-6 h, blood] is greater than 80%). Based on in vivo bioluminescence imaging, two doses of 50 mg/kg DNDI-0690 were sufficient to reduce the Leishmania mexicana parasite load by 100-fold, while 6 such doses were needed to achieve similar killing of L. major; this was confirmed by quantitative PCR. The combination of rapid accumulation and potent activity in the Leishmania-infected dermis indicates the potential of DNDI-0690 as a novel oral treatment for CL.
Toxin–antitoxin operon kacAT of Klebsiella pneumoniae is regulated by conditional cooperativity via a W-shaped KacA–KacT complex

Abstract Bacterial toxin–antitoxin pairs play important roles in bacterial multidrug tolerance. Gcn5-related N-acetyltransferase (GNAT) toxins inhibit translation by acetylation of aminoacyl-tRNAs and are counteracted by direct contacts with cognate ribbon–helix–helix (RHH) antitoxins. Our previous analysis showed that the GNAT toxin KacT and RHH antitoxin KacA of Klebsiella pneumoniae form a heterohexamer in solution and that the complex interacts with the cognate promoter DNA, resulting in negative autoregulation of kacAT transcription. Here, we present the crystal structure of DNA-bound KacAT complex at 2.2 Å resolution. The crystal structure revealed the formation of a unique heterohexamer, KacT–KacA2–KacA2–KacT. The direct interaction of KacA and KacT involves a unique W-shaped structure with the two KacT molecules at opposite ends. Inhibition of KacT is achieved by the binding of four KacA proteins that preclude the formation of an active KacT dimer. The kacAT operon is auto-regulated and we present an experimentally supported molecular model proposing that the KacT:KacA ratio controls kacAT transcription by conditional cooperativity. These results yield a profound understanding of how transcription GNAT–RHH pairs are regulated.
Enhancing Photocurrent Performance Based on Photoanode Thickness and Surface Plasmon Resonance Using Ag-TiO2 Nanocomposites in Dye-Sensitized Solar Cells

This study investigated the different thicknesses of TiO2 photoanode films and the effect of surface plasmon resonance (SPR) of Ag-TiO2 nanocomposites on the current-voltage (I–V) performance of dye-sensitized solar cells (DSSC). The TiO2 layer was deposited using the doctor blade technique and the thickness of the TiO2 films was controlled by using a different number of Scotch tape layers. The silver nanoparticles (AgNP) were synthesised using a chemical reduction method and the concentration of sodium citrate as a reducing agent was varied from 4 to 12 mM to study the effect of citrate ion on the size of the nanoparticles. Ag-TiO2 nanopowder was prepared by adding pure anatase TiO2 powder into AgNP colloidal solution. The mixture was left to dry for 24 h to obtain Ag-TiO2 powder for paste preparation. The three-layer Scotch tape, with thickness of 14.38 µm, achieved a high efficiency of 4.14%. This results showed that three layers was the optimal thickness to improve dye loading and to reduce the charge recombination rate. As for the Ag-TiO2 nanocomposites, 10 mM of AgNP, with a mean diameter of 65.23 nm and high efficiency of 6.92%, proved that SPR can enhance the absorption capability of dye and improve the photon-to-electron generation.
Prevalence and associated factors of mortality after percutaneous coronary intervention for adult patients with ST elevation myocardial infarction

Abstract Background: The percutaneous coronary intervention (PCI) has been one of the fastest growing therapeutic interventions for patients with ST elevation myocardial infarction (STEMI). However, the mortality of patients with STEMI after PCI is uncertain currently. There is a paucity of systematic review on the associated factors of mortality among patients with STEMI after PCI. Therefore, this meta-analysis was designed to synthesize available evidence on the prevalence and associated factors of mortality after PCI for adult patients with STEMI. Methods: Both case–control and cohort studies reporting on mortality after PCI for patients with STEMI, published in Chinese and English will be eligible for inclusion. Studies from 12 databases covering the period from 2008 to present will be considered for systematic searches. Two reviewers will independently screen and select studies, extract data, and assess methodologic quality. When available, meta-analysis will be performed. Pooled proportions of mortality, and proportions in the exposed and unexposed groups, and population attributable fraction of each factor will be calculated by a suitable transformation of proportions. If necessary, meta-regression models, subgroup analysis, sensitivity analysis, funnel plot, and Egger test will be performed. Narrative synthesis will be done where meta-analysis cannot be performed. Reporting of this protocol will comply with the preferred reporting items for systematic review and meta-analyses (PRISMA-P) guidelines. Results: This systematic review will be developed according to the meta-analysis of observational studies in epidemiology (MOOSE) guidelines. Conclusion: This study will provide a comprehensive review on the available evidence regarding the prevalence and associated factors of mortality for patients with STEMI following PCI. This review will be constrained by the divergence of definition and assessment of specific factors between studies. However, the development of a qualitative description of definition and assessment tools will also provide an overview of the current practice. Formal ethical approval is not required since the secondary data will be collected for systematic review. The findings will be disseminated in a relevant peer-reviewed journal and academic presentations. Systematic review registration: PROSPERO CRD42017070969
Optochemogenetic Stimulation of Transplanted iPS-NPCs Enhances Neuronal Repair and Functional Recovery after Ischemic Stroke

Cell transplantation therapy provides a regenerative strategy for neural repair. We tested the hypothesis that selective excitation of transplanted induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) could recapitulate an activity-enriched microenvironment that confers regenerative benefits for the treatment of stroke. Mouse iPS-NPCs were transduced with a novel optochemogenetics fusion protein, luminopsin 3 (LMO3), which consisted of a bioluminescent luciferase, Gaussia luciferase, and an opsin, Volvox Channelrhodopsin 1. These LMO3-iPS-NPCs can be activated by either photostimulation using light or by the luciferase substrate coelenterazine (CTZ). In vitro stimulations of LMO3-iPS-NPCs increased expression of synapsin-1, postsynaptic density 95, brain derived neurotrophic factor (BDNF), and stromal cell-derived factor 1 and promoted neurite outgrowth. After transplantation into the ischemic cortex of mice, LMO3-iPS-NPCs differentiated into mature neurons. Synapse formation between implanted and host neurons was identified using immunogold electron microscopy and patch-clamp recordings. Stimulation of transplanted cells with daily intranasal administration of CTZ enhanced axonal myelination, synaptic transmission, improved thalamocortical connectivity, and functional recovery. Patch-clamp and multielectrode array recordings in brain slices showed that CTZ or light stimulation facilitated synaptic transmission and induced neuroplasticity mimicking the LTP of EPSPs. Stroke mice received the combined LMO3-iPS-NPC/CTZ treatment, but not cell or CTZ alone, showed enhanced neural network connections in the peri-infarct region, promoted optimal functional recoveries after stroke in male and female, young and aged mice. Thus, excitation of transplanted cells via the noninvasive optochemogenetics treatment provides a novel integrative cell therapy with comprehensive regenerative benefits after stroke. SIGNIFICANCE STATEMENT Neural network reconnection is critical for repairing damaged brain. Strategies that promote this repair are expected to improve functional outcomes. This study pioneers the generation and application of an optochemogenetics approach in stem cell transplantation therapy after stroke for optimal neural repair and functional recovery. Using induced pluripotent stem cell-derived neural progenitor cells (iPS-NPCs) expressing the novel optochemogenetic probe luminopsin (LMO3), and intranasally delivered luciferase substrate coelenterazine, we show enhanced regenerative properties of LMO3-iPS-NPCs in vitro and after transplantation into the ischemic brain of different genders and ages. The noninvasive repeated coelenterazine stimulation of transplanted cells is feasible for clinical applications. The synergetic effects of the combinatorial cell therapy may have significant impacts on regenerative approach for treatments of CNS injuries.
A Deep Learning Approach for Fusing Sensor Data from Screw Compressors

Chillers are commonly used for thermal regulation to maintain indoor comfort in medium and large buildings. However, inefficiencies in this process produce significant losses, and optimization tasks are limited because of accessibility to the system. Data analysis techniques transform measurements coming from several sensors into useful information. Recent deep learning approaches have achieved excellent results in many applications. These techniques can be used for computing new data representations that provide comprehensive information from the device. This allows real-time monitoring, where information can be checked with current working operation to detect any type of anomaly in the process. In this work, a model based on a 1D convolutional neural network is proposed for fusing data in order to predict four different control stages of a screw compressor in a chiller. The evaluation of the method was performed using real data from a chiller in a hospital building. Results show a satisfactory performance and acceptable training time in comparison with other recent methods. In addition, the model is capable of predicting control states of other screw compressors different than the one used in the training. Furthermore, two failure cases are simulated, providing an early alarm detection when a continuous wrong classification is performed by the model.