Miracle-dz/UniFAR-FTUs huggingface dataset:
A novel bioreactor for combined magnetic resonance spectroscopy and optical imaging of metabolism in 3D cell cultures

Fluorescence lifetime imaging microscopy (FLIM) of endogenous fluorescent metabolites permits the measurement of cellular metabolism in cell, tissue and animal models. In parallel, magnetic resonance spectroscopy (MRS) of dynamic nuclear (hyper)polarized (DNP) 13C‐pyruvate enables measurement of metabolism at larger in vivo scales. Presented here are the design and initial application of a bioreactor that connects these 2 metabolic imaging modalities in vitro, using 3D cell cultures.
Long-Term, Targeted Delivery of GDNF from Encapsulated Cells Is Neuroprotective and Reduces Seizures in the Pilocarpine Model of Epilepsy

Neurotrophic factors are candidates for treating epilepsy, but their development has been hampered by difficulties in achieving stable and targeted delivery of efficacious concentrations within the desired brain region. We have developed an encapsulated cell technology that overcomes these obstacles by providing a targeted, continuous, de novo synthesized source of high levels of neurotrophic molecules from human clonal ARPE-19 cells encapsulated into hollow fiber membranes. Here we illustrate the potential of this approach for delivering glial cell line-derived neurotrophic factor (GDNF) directly to the hippocampus of epileptic rats. In vivo studies demonstrated that bilateral intrahippocampal implants continued to secrete GDNF that produced high hippocampal GDNF tissue levels in a long-term manner. Identical implants robustly reduced seizure frequency in the pilocarpine model. Seizures were reduced rapidly, and this effect increased in magnitude over 3 months, ultimately leading to a reduction of seizures by 93%. This effect persisted even after device removal, suggesting potential disease-modifying benefits. Importantly, seizure reduction was associated with normalized changes in anxiety and improved cognitive performance. Immunohistochemical analyses revealed that the neurological benefits of GDNF were associated with the normalization of anatomical alterations accompanying chronic epilepsy, including hippocampal atrophy, cell degeneration, loss of parvalbumin-positive interneurons, and abnormal neurogenesis. These effects were associated with the activation of GDNF receptors. All in all, these results support the concept that the implantation of encapsulated GDNF-secreting cells can deliver GDNF in a sustained, targeted, and efficacious manner, paving the way for continuing preclinical evaluation and eventual clinical translation of this approach for epilepsy. SIGNIFICANCE STATEMENT Epilepsy is one of the most common neurological conditions, affecting millions of individuals of all ages. These patients experience debilitating seizures that frequently increase over time and can associate with significant cognitive decline and psychiatric disorders that are generally poorly controlled by pharmacotherapy. We have developed a clinically validated, implantable cell encapsulation system that delivers high and consistent levels of GDNF directly to the brain. In epileptic animals, this system produced a progressive and permanent reduction (>90%) in seizure frequency. These benefits were accompanied by improvements in cognitive and anxiolytic behavior and the normalization of changes in CNS anatomy that underlie chronic epilepsy. Together, these data suggest a novel means of tackling the frequently intractable neurological consequences of this devastating disorder.
Seasonal Activity of Influenza in Iran: Application of Influenza-like Illness Data from Sentinel Sites of Healthcare Centers during 2010 to 2015

This study aimed to predict seasonal influenza activity and detection of influenza outbreaks. Data of all registered cases (n = 53,526) of influenza-like illnesses (ILIs) from sentinel sites of healthcare centers in Iran were obtained from the FluNet web-based tool, World Health Organization (WHO), from 2010 to 2015. The status of the ILI activity was obtained from the FluNet and considered as the gold standard of the seasonal activity of influenza during the study period. The cumulative sum (CUSUM) as an outbreak detection method was used to predict the seasonal activity of influenza. Also, time series similarity between the ILI trend and CUSUM was assessed using the cross-correlogram. Of 7684 (14%) positive cases of influenza, about 71% were type A virus and 28% were type B virus. The majority of the outbreaks occurred in winter and autumn. Results of the cross-correlogram showed that there was a considerable similarity between time series graphs of the ILI cases and CUSUM values. However, the CUSUM algorithm did not have a good performance in the timely detection of influenza activity. Despite a considerable similarity between time series of the ILI cases and CUSUM algorithm in weekly lag, the seasonal activity of influenza in Iran could not be predicted by the CUSUM algorithm. HIGHLIGHTS• Activity of influenza in Iran could not be predicted by CUSUM algorithm. • The majority of the outbreaks occurred in winter and autumn. • CUSUM algorithm did not have a good performance in detection of influenza outbreaks.
Radiomics-Based Intracranial Thrombus Features on CT and CTA Predict Recanalization with Intravenous Alteplase in Patients with Acute Ischemic Stroke

Sixty-seven patients with ICA/M1 MCA segment thrombus treated with IV alteplase were included in this analysis. Three hundred twenty-six radiomics features were extracted from each thrombus on both NCCT and CTA images. Linear discriminative analysis was applied to select features most strongly associated with early recanalization with IV alteplase. These features were then used to train a linear support vector machine classifier. Thrombus radiomics features derived from NCCT and CTA are more predictive of recanalization with IV alteplase in patients with acute ischemic stroke with proximal occlusion than previously known thrombus imaging features such as length, volume, and permeability. BACKGROUND AND PURPOSE: Thrombus characteristics identified on non-contrast CT (NCCT) are potentially associated with recanalization with intravenous (IV) alteplase in patients with acute ischemic stroke (AIS). Our aim was to determine the best radiomics-based features of thrombus on NCCT and CT angiography associated with recanalization with IV alteplase in AIS patients and proximal intracranial thrombi. MATERIALS AND METHODS: With a nested case-control design, 67 patients with ICA/M1 MCA segment thrombus treated with IV alteplase were included in this analysis. Three hundred twenty-six radiomics features were extracted from each thrombus on both NCCT and CTA images. Linear discriminative analysis was applied to select features most strongly associated with early recanalization with IV alteplase. These features were then used to train a linear support vector machine classifier. Ten times 5-fold cross-validation was used to evaluate the accuracy of the trained classifier and the stability of the selected features. RESULTS: Receiver operating characteristic curves showed that thrombus radiomics features are predictive of early recanalization with IV alteplase. The combination of radiomics features from NCCT, CTA, and radiomics changes is best associated with early recanalization with IV alteplase (area under the curve = 0.85) and was significantly better than any single feature such as thrombus length (P < .001), volume (P < .001), and permeability as measured by mean attenuation increase (P < .001), maximum attenuation in CTA (P < .001), maximum attenuation increase (P < .001), and assessment of residual flow grade (P < .001). CONCLUSIONS: Thrombus radiomics features derived from NCCT and CTA are more predictive of recanalization with IV alteplase in patients with acute ischemic stroke with proximal occlusion than previously known thrombus imaging features such as length, volume, and permeability.
The Effects of Three Types of Sexual Orientation Victimization on HIV Sexual Risk Behavior Among Black South African Men Who Have Sex With Men (MSM)

ABSTRACT The goal of this study is to examine the relations between histories of three types of sexual orientation victimization (childhood, personal, and institutional) and HIV sexual risk behavior among Black South African men who have sex with men (MSM). Secondarily, this study examines whether marijuana use and problem drinking mediate the relations. Participants were 125 Black MSM recruited from neighborhoods in Eastern Cape Province, South Africa. Questionnaires administered through audio computerized self-interviewing assessed sexual orientation victimizations, problem drinking and marijuana use, and unprotected anal sex with casual partners. Data were analyzed using multiple regression and multiple mediation modeling. Personal and institutional sexual victimizations were associated with condomless anal sex. Childhood sexual orientation victimization was positively associated with problem drinking. Neither problem drinking nor marijuana use mediated the relations between sexual orientation victimizations and having condomless anal sex with casual partners.
Preadmission Statin Therapy Is Associated with a Lower Incidence of Acute Kidney Injury in Critically Ill Patients: A Retrospective Observational Study

This study aimed to investigate the association between preadmission statin use and acute kidney injury (AKI) incidence among critically ill patients who needed admission to the intensive care unit (ICU) for medical care. Medical records of patients admitted to the ICU were reviewed. Patients who continuously took statin for >1 month prior to ICU admission were defined as statin users. We investigated whether preadmission statin use was associated with AKI incidence within 72 h after ICU admission and whether the association differs according to preadmission estimated glomerular filtration rate (eGFR; in mL min-1 1.73 m-2). Among 21,236 patients examined, 5756 (27.1%) were preadmission statin users and 15,480 (72.9%) were non-statin users. Total AKI incidence within 72 h after ICU admission was 31% lower in preadmission statin users than in non-statin users [odds ratio (OR), 0.69; 95% confidence interval (CI), 0.61⁻0.79; p < 0.001]. This association was insignificant among individuals with eGFR <30 mL min-1 1.73 m-2 (p > 0.05). Our results suggested that preadmission statin therapy is associated with a lower incidence of AKI among critically ill patients; however, this effect might not be applicable for patients with eGFR <30 mL min-1 1.73 m-2.
The fission yeast Greatwall–Endosulfine pathway is required for proper quiescence/G0 phase entry and maintenance

Cell proliferation and cellular quiescence/G0 phase must be regulated in response to intra‐/extracellular environments, and such regulation is achieved by the orchestration of protein kinases and protein phosphatases. Here, we investigated fission yeast potential orthologs (Cek1, Ppk18 and Ppk31) of the metazoan Greatwall kinase (Gwl), which inhibits type‐2A protein phosphatase with B55 subunit (PP2AB55) by phosphorylating and activating the PP2AB55 inhibitors, α‐endosulfine/ARPP‐19 (Ensa/ARPP‐19). Gwl and Ensa/ARPP‐19 regulate mitosis; however, we found Ppk18, Cek1 and Mug134/Igo1, the counterpart of Ensa/ARPP‐19, are not essential for normal mitosis but regulate nitrogen starvation (−N)‐induced proper G0 entry and maintenance. Genetic and biochemical analyses indicated that the conserved Gwl site (serine 64) was phosphorylated in the G0 phase in a Ppk18‐dependent manner, and the phosphorylated Mug134/Igo1 inhibited PP2AB55 in vitro. The alanine substitution of the serine 64 caused defects in G0 entry and maintenance as well as the mug134/igo1+ deletion. These results indicate that PP2AB55 activity must be regulated properly to establish the G0 phase. Consistently, simultaneous deletion of the B55 gene with mug134/igo1+ partially rescued the Mug134/Igo1 mutant phenotype. We suggest that in fission yeast, PP2AB55 regulation by the Ppk18‐Mug134/Igo1 pathway is required for G0 entry and establishment of robust viability during the G0 phase.
LINE-1 and EPAS1 DNA methylation associations with high-altitude exposure

ABSTRACT Recent discoveries indicate a genetic basis for high-altitude adaptation among human groups who have resided at high altitude for millennia, including Andeans, Tibetans, and Ethiopians. Yet, genetics alone does not explain the extent of variation in altitude-adaptive phenotypes. Current and past environments may also play a role, and one way to determine the effect of the environment is through the epigenome. To characterize if Andean adaptive responses to high altitude have an epigenetic component, we analyzed DNA methylation of the promoter region of EPAS1 and LINE-1 repetitive element among 572 Quechua individuals from high- (4,388 m) and low-altitude (0 m) in Peru. Participants recruited at high altitude had lower EPAS1 DNA methylation and higher LINE-1 methylation. Altitude of birth was associated with higher LINE-1 methylation, not with EPAS1 methylation. The number of years lived at high altitude was negatively associated with EPAS1 methylation and positively associated with LINE-1 methylation. We found four one-carbon metabolism SNPs (MTHFD1 rs2236225, TYMS rs502396, FOLH1 rs202676, GLDC rs10975681) that cumulatively explained 11.29% of the variation in average LINE-1 methylation. And identified an association between LINE-1 methylation and genome-wide SNP principal component 1 that distinguishes European from Indigenous American ancestry suggesting that European admixture decreases LINE-1 methylation. Our results indicate that both current and lifetime exposure to high-altitude hypoxia have an effect on EPAS1 and LINE-1 methylation among Andean Quechua, suggesting that epigenetic modifications may play a role in high-altitude adaptation.
The Role of Innate Immune Cells in Nonalcoholic Steatohepatitis

Inflammation and metabolic dysfunction are hallmarks of nonalcoholic steatohepatitis (NASH), which is one of the fastest‐growing liver diseases worldwide. Emerging evidence indicates that innate immune mechanisms are pivotal drivers of inflammation and other pathological manifestations observed in NASH, such as hepatosteatosis, insulin resistance (IR), and fibrosis. This robust innate immune reaction is intrinsic to the liver, which is an important immunological organ that contains a coordinated network of innate immune cells, including Kupffer cells (KCs), dendritic cells (DCs), and lymphocytes. Hepatocytes and liver sinusoidal endothelial cells (LSECs) are not formally innate immune cells, but they take on immune cell function when stressed. These cells can sense excess metabolites and bacterial products and translate those signals into immune responses and pathological hepatic changes during the development of NASH. In this review, we take a historical perspective in describing decades of research that aimed to identify the key molecular and cellular players in the innate immune system in the setting of NASH. Furthermore, we summarize the innate immune cells that are involved in the progression of NASH and illustrate how they sense disturbances in circulating metabolic factors by innate immune receptors and subsequently initiate the intercellular signaling cascades that lead to persistent inflammation and progression of hepatic complications.
A historical reflection on our understanding of radiation-induced DNA double strand break repair in somatic mammalian cells; interfacing the past with the present

Abstract Purpose: The International Journal of Radiation Biology (IJRB) is celebrating 60 years of publishing in 2019. IJRB has made an enormous contribution to publishing papers that have enhanced our understanding of the DNA damage response (DDR) activated following exposure to ionizing radiation (IR). The IR-induced DDR field has a rich history but many outstanding papers pass unread by young scientists overwhelmed by the current literature. We provide a historical reflection on key advances in the DDR field and interface them with current knowledge. Conclusions: DNA double strand breaks (DSBs) were identified as the major biological lesion induced by IR. But early studies on cells from IR-sensitive ataxia telangiectasia patients showed that DSB repair was not sufficient to prevent IR hypersensitivity. Subsequently, the ATM-dependent signal transduction process was revealed, with the breadth of the response being slowly unearthed. Early studies demonstrated at least two processes of DSB repair and revealed that mis-repair causes translocation formation. Recent studies, however, are unraveling more complexity in the repair process, including the specific processing of DSBs within transcriptionally active regions, and the significance of the chromatin environment. Despite the quality of these early and current studies, many questions remain to be addressed.
Efficacy of Biophysical Energies on Healing of Diabetic Skin Wounds in Cell Studies and Animal Experimental Models: A Systematic Review

We have systematically assessed published cell studies and animal experimental reports on the efficacy of selected biophysical energies (BPEs) in the treatment of diabetic foot ulcers. These BPEs include electrical stimulation (ES), pulsed electromagnetic field (PEMF), extracorporeal shockwave (ECSW), photo energies and ultrasound (US). Databases searched included CINAHL, MEDLINE and PubMed from 1966 to 2018. Studies reviewed include animal and cell studies on treatment with BPEs compared with sham, control or other BPEs. Information regarding the objective measures of tissue healing and data was extracted. Eighty-two studies were eventually selected for the critical appraisal: five on PEMF, four each on ES and ECSW, sixty-six for photo energies, and three about US. Based on the percentage of original wound size affected by the BPEs, both PEMF and low-level laser therapy (LLL) demonstrated a significant clinical benefit compared to the control or sham treatment, whereas the effect of US did not reveal a significance. Our results indicate potential benefits of selected BPEs in diabetic wound management. However, due to the heterogeneity of the current clinical trials, comprehensive studies using well-designed trials are warranted to confirm the results.
Optimal Resource Management and Binary Power Control in Network-Assisted D2D Communications for Higher Frequency Reuse Factor

Device-to-device (D2D) communications can be adopted as a promising solution to attain high quality of service (QoS) for a network. However, D2D communications generates harmful interference when available resources are shared with traditional cellular users (CUs). In this paper, network architecture for the uplink resource management issue for D2D communications underlaying uplink cellular networks is proposed. We develop a fractional frequency reuse (FFR) technique to mitigate interference induced by D2D pairs (DPs) to CUs and mutual interference among DPs in a cell. Then, we formulate a sum throughput optimization problem to achieve the QoS requirements of the system. However, the computational complexity of the optimization problem is very high due to the exhaustive search for a global optimal solution. In order to reduce the complexity, we propose a greedy heuristic search algorithm for D2D communications so as to find a sub-optimal solution. Moreover, a binary power control scheme is proposed to enhance the system throughput by reducing overall interference. The performance of our proposed scheme is analyzed through extensive numerical analysis using Monte Carlo simulation. The results demonstrate that our proposed scheme provides significant improvement in system throughput with the lowest computational complexity.
Accelerated Guided Sampling for Multistructure Model Fitting

The performance of many robust model fitting techniques is largely dependent on the quality of the generated hypotheses. In this paper, we propose a novel guided sampling method, called accelerated guided sampling (AGS), to efficiently generate the accurate hypotheses for multistructure model fitting. Based on the observations that residual sorting can effectively reveal the data relationship (i.e., determine whether two data points belong to the same structure), and keypoint matching scores can be used to distinguish inliers from gross outliers, AGS effectively combines the benefits of residual sorting and keypoint matching scores to efficiently generate accurate hypotheses via information theoretic principles. Moreover, we reduce the computational cost of residual sorting in AGS by designing a new residual sorting strategy, which only sorts the top-ranked residuals of input data, rather than all input data. Experimental results demonstrate the effectiveness of the proposed method in computer vision tasks, such as homography matrix and fundamental matrix estimation.
Natural alleles of GLA for grain length and awn development were differently domesticated in rice subspecies japonica and indica

Summary Rice (Oryza sativa L.) cultivars harbour morphological and physiological traits different from those of wild rice (O. rufipogon Griff.), but the molecular mechanisms underlying domestication remain controversial. Here, we show that awn and long grain traits in the near‐isogenic NIL‐GLA are separately controlled by variations within the GLA (Grain Length and Awn Development) gene, a new allele of GAD1/RAE2, which encodes one member of the EFPL (epidermal patterning factor‐like protein) family. Haplotype analyses and transgenic studies revealed that InDel1 (variation for grain length, VGL) in the promoter region of GLA (GLAVGL) increases grain length by promoting transcription of GLA. Absence of InDel3 (variation for awn formation, VA) in the coding region (CDS) of GLA (GLA va) results in short awn or no awn phenotypes. Analyses of minimum spanning trees and introgression regions demonstrated that An‐1, an important gene for awn formation, was preferentially domesticated and its mutation to an‐1 was followed by GLA and An‐2. Gene flow then occurred between the evolved japonica and indica populations. Quality analysis showed that GLA causes poor grain quality. During genetic improvement, awnlessness was selected in ssp. indica, whereas short–grained and awnless phenotypes with good quality were selected in japonica. Our findings facilitate an understanding of rice domestication and provide a favourable allele for rice breeding.
Self-localization of a mobile robot using a single vision sensor

The most important factor of autonomous mobile robot is to build a map for surrounding environment and estimate its localization. This paper proposes a real-time localization and map building method through 3-D reconstruction using scale invariant feature from single camera. Mobile robot attached monocular camera looking wall extracts scale invariant features in each image using SIFT(Scale Invariant Feature Transform) as it follows wall. Matching is carried out by the extracted features and matching feature map that is transformed into absolute coordinates using 3-D reconstruction of point and geometrical analysis of surrounding environment build, and store it map database. After finished feature map building, the robot finds some points matched with previous feature map and find its pose by affine parameter in real time. Position error of the proposed method was max. 6.2cm and angle error was within 5°.