Miracle-dz/UniFAR-FTUs huggingface dataset:
Real-Time Impedance Monitoring of Epithelial Cultures with Inkjet-Printed Interdigitated-Electrode Sensors

From electronic devices to large-area electronics, from individual cells to skin substitutes, printing techniques are providing compelling applications in wide-ranging fields. Research has thus fueled the vision of a hybrid, printing platform to fabricate sensors/electronics and living engineered tissues simultaneously. Following this interest, we have fabricated interdigitated-electrode sensors (IDEs) by inkjet printing to monitor epithelial cell cultures. We have fabricated IDEs using flexible substrates with silver nanoparticles as a conductive element and SU-8 as the passivation layer. Our sensors are cytocompatible, have a topography that simulates microgrooves of 300 µm width and ~4 µm depth, and can be reused for cellular studies without detrimental in the electrical performance. To test the inkjet-printed sensors and demonstrate their potential use for monitoring laboratory-growth skin tissues, we have developed a real-time system and monitored label-free proliferation, migration, and detachment of keratinocytes by impedance spectroscopy. We have found that variations in the impedance correlate linearly to cell densities initially seeded and that the main component influencing the total impedance is the isolated effect of the cell membranes. Results obtained show that impedance can track cellular migration over the surface of the sensors, exhibiting a linear relationship with the standard method of image processing. Our results provide a useful approach for non-destructive in-situ monitoring of processes related to both in vitro epidermal models and wound healing with low-cost ink-jetted sensors. This type of flexible sensor as well as the impedance method are promising for the envisioned hybrid technology of 3D-bioprinted smart skin substitutes with built-in electronics.
A Semantic-Based Belief Network Construction Approach in IoT

Uncertainty is intrinsic in most of the complex systems, especially when the systems have to interact with the physical environment; therefore, handling uncertainty is critical in the Internet of Things (IoT). In this paper, we propose a semantic-based approach to build the belief network in IoT systems to handle the uncertainties. Semantics is the functionality description of any system component. Semantic Match mechanisms can construct the appropriate structures to compare the consistency between different sources of data based on the same functionality. In the approach, we define the belief property of every system component and develop the related algorithms to update the belief value. Furthermore, the related mechanisms and algorithms for data fusion and fault detection based on the belief property are described to explain how the approach works in the IoT systems. Several simulation experiments are used to evaluate the proposed approach, and the results indicate that the approach can work as expected. More accurate data are fused from the inaccurate devices and the fault in one node is automatically detected.
Mixed Forests of Red Fir and White Fir in Yosemite National Park, California

Thirty mixed stands of white fir (Abies concolor) and red fir (Abies magnifica) were sampled in the ecotone between montane and subalpine forests (1950-2500 m) in Yosemite National Park, California. Detrended correspondence analysis and direct gradient analysis revealed that red fir predominates above 2260 m on steep slopes characterized by acidic substrates and open canopied forests. Below 2260 m, white fir predominates on xeric aspects characterized by higher soil fertility and greater canopy closure. Closed forests on mesic sites between 1956 and 2300 m include stands dominated by either (or both) species. Patterns of habitat segregation between these two dominant congeners are believed to be related to growing season length, nutrient availability and increased importance of windthrow at higher elevations. The sparse ground layer has maximum cover and species richness on mesic sites at lower elevations, where ferns and herbs are most conspicuous. Shrubs and saprophytes/low ericads show less elevational/topographic restriction, favoring canopy gaps and shaded areas, respectively.
Exploring the Potential of Therapeutic Agents Targeted towards Mitigating the Events Associated with Amyloid-β Cascade in Alzheimer’s Disease

One of the most commonly occurring neurodegenerative disorders, Alzheimer’s disease (AD), encompasses the loss of cognitive and memory potential, impaired learning, dementia and behavioral defects, and has been prevalent since the 1900s. The accelerating occurrence of AD is expected to reach 65.7 million by 2030. The disease results in neural atrophy and disrupted inter-neuronal connections. Amongst multiple AD pathogenesis hypotheses, the amyloid beta (Aβ) cascade is the most relevant and accepted form of the hypothesis, which suggests that Aβ monomers are formed as a result of the cleavage of amyloid precursor protein (APP), followed by the conversion of these monomers to toxic oligomers, which in turn develop β-sheets, fibrils and plaques. The review targets the events in the amyloid hypothesis and elaborates suitable therapeutic agents that function by hindering the steps of plaque formation and lowering Aβ levels in the brain. The authors discuss treatment possibilities, including the inhibition of β- and γ-secretase-mediated enzymatic cleavage of APP, the immune response generating active immunotherapy and passive immunotherapeutic approaches targeting monoclonal antibodies towards Aβ aggregates, the removal of amyloid aggregates by the activation of enzymatic pathways or the regulation of Aβ circulation, glucagon-like peptide-1 (GLP-1)-mediated curbed accumulation and the neurotoxic potential of Aβ aggregates, bapineuzumab-mediated vascular permeability alterations, statin-mediated Aβ peptide degradation, the potential role of ibuprofen and the significance of natural drugs and dyes in hindering the amyloid cascade events. Thus, the authors aim to highlight the treatment perspective, targeting the amyloid hypothesis, while simultaneously emphasizing the need to conduct further investigations, in order to provide an opportunity to neurologists to develop novel and reliable treatment therapies for the retardation of AD progression.
Joint analysis of recurrence and termination: A Bayesian latent class approach

Like many other clinical and economic studies, each subject of our motivating transplant study is at risk of recurrent events of non-fatal tissue rejections as well as the terminating event of death due to total graft rejection. For such studies, our model and associated Bayesian analysis aim for some practical advantages over competing methods. Our semiparametric latent-class-based joint model has coherent interpretation of the covariate (including race and gender) effects on all functions and model quantities that are relevant for understanding the effects of covariates on future event trajectories. Our fully Bayesian method for estimation and prediction uses a complete specification of the prior process of the baseline functions. We also derive a practical and theoretically justifiable partial likelihood-based semiparametric Bayesian approach to deal with the analysis when there is a lack of prior information about baseline functions. Our model and method can accommodate fixed as well as time-varying covariates. Our Markov Chain Monte Carlo tools for both Bayesian methods are implementable via publicly available software. Our Bayesian analysis of transplant study and simulation study demonstrate practical advantages and improved performance of our approach.
Genome-wide DNA methylation profiling in human breast tissue by Illumina TruSeq methyl capture EPIC sequencing and infinium methylationEPIC beadchip microarray

ABSTRACT A newly-developed platform, the Illumina TruSeq Methyl Capture EPIC library prep (TruSeq EPIC), builds on the content of the Infinium MethylationEPIC Beadchip Microarray (EPIC-array) and leverages the power of next-generation sequencing for targeted bisulphite sequencing. We empirically examined the performance of TruSeq EPIC and EPIC-array in assessing genome-wide DNA methylation in breast tissue samples. TruSeq EPIC provided data with a much higher density in the regions when compared to EPIC-array (~2.74 million CpGs with at least 10X coverage vs ~752 K CpGs, respectively). Approximately 398 K CpGs were common and measured across the two platforms in every sample. Overall, there was high concordance in methylation levels between the two platforms (Pearson correlation r = 0.98, P < 0.0001). However, we observed that TruSeq EPIC measurements provided a wider dynamic range and likely a higher quantitative sensitivity for CpGs that were either hypo- or hyper-methylated (β close to 0 or 1, respectively). In addition, when comparing different breast tissue types TruSeq EPIC identified more differentially methylated CpGs than EPIC-array, not only out of additional sites interrogated by TruSeq EPIC alone, but also out of common sites interrogated by both platforms. Our results suggest that both platforms show high reproducibility and reliability in genome-wide DNA methylation profiling, while TruSeq EPIC had a significant improvement over EPIC-array regarding genomic resolution and coverage. The wider dynamic range and likely higher precision of the estimates by the TruSeq EPIC may lead to the identification of novel differentially methylated markers that are associated with disease risk.
Effects of Self-efficacy and Self-control on Internet Addiction in Middle School Students: A Social Cognitive Theory-Driven Focus on the Mediating Influence of Social Support

Purpose The aim of this study was to investigate internet addiction among middle school students and to examine the mediating effects of social support in the relationships of self-efficacy and self-control with internet addiction. Methods The participants in the study were 119 middle school students in J city. The measurements included a self-efficacy scale, a self-control scale, a social support scale, and the Internet Addiction Scale for Youth. Data were analyzed using the independent t-test or Mann-Whitney U test, one-way analysis of variance, the Scheffé test, Pearson correlation coefficients, and multiple-regression using SPSS version 22.0. Mediation effects were analyzed by the Sobel test and Baron and Kenny's hierarchical analysis technique. Results Significant correlations were found among self-efficacy, self-control, and internet addiction. Social support had partial mediating effects in the relationship between self-efficacy and internet addiction, as well as in the relationship between self-control and internet addition. Conclusion In order to prevent internet addiction, the promotion of interactions among peers, which is a component of social support, is particularly important. It is also necessary to promote face-to-face activities that can strengthen relationships. The findings suggest that intensifying social support may help reduce the level of internet addiction in middle school students.
Autoreactivity of Broadly Neutralizing Influenza Human Antibodies to Human Tissues and Human Proteins

Broadly neutralizing monoclonal antibodies (bNAbs) against conserved domains in the influenza hemagglutinin are in clinical trials. Several next generation influenza vaccines designed to elicit such bNAbs are also in clinical development. One of the common features of the isolated bNAbs is the use of restricted IgVH repertoire. More than 80% of stem-targeting bNAbs express IgVH1-69, which may indicate genetic constraints on the evolution of such antibodies. In the current study, we evaluated a panel of influenza virus bNAbs in comparison with HIV-1 MAb 4E10 and anti-RSV MAb Palivizumab (approved for human use) for autoreactivity using 30 normal human tissues microarray and human protein (>9000) arrays. We found that several human bNAbs (CR6261, CR9114, and F2603) reacted with human tissues, especially with pituitary gland tissue. Importantly, protein array analysis identified high-affinity interaction of CR6261 with the autoantigen “Enhancer of mRNA decapping 3 homolog” (EDC3), which was not previously described. Moreover, EDC3 competed with hemagglutinin for binding to bNAb CR6261. These autoreactivity findings underscores the need for careful evaluation of such bNAbs for therapeutics and stem-based vaccines against influenza virus.
Prevalence of Alpha(α)-Thalassemia in Southeast Asia (2010–2020): A Meta-Analysis Involving 83,674 Subjects

Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart’s hydrops fetalis that leads to early foetal death. Therefore, the aim of this meta-analysis was to provide an update from year 2010 to 2020 on the prevalence of α-thalassemia in Southeast Asia. A systematic literature search was performed using PubMed and SCOPUS databases for related studies published from 2010 to 2020, based on specified inclusion and exclusion criteria. Heterogeneity of included studies was examined with the I2 index and Q-test. Funnel plots and Egger’s tests were performed in order to determine publication bias in this meta-analysis. Twenty-nine studies with 83,674 subjects were included and pooled prevalence rates in this meta-analysis were calculated using random effect models based on high observed heterogeneity (I2 > 99.5, p-value < 0.1). Overall, the prevalence of α-thalassemia is 22.6%. The highest α-thalassemia prevalence was observed in Vietnam (51.5%) followed by Cambodia (39.5%), Laos (26.8%), Thailand (20.1%), and Malaysia (17.3%). No publication bias was detected. Conclusions: This meta-analysis suggested that a high prevalence of α-thalassemia occurred in selected Southeast Asia countries. This meta-analysis data are useful for designing thalassemia screening programs and improve the disease management.
Mesoporous Silica Nanoparticles as Theranostic Antitumoral Nanomedicines

Nanoparticles have become a powerful tool in oncology not only as carrier of the highly toxic chemotherapeutic drugs but also as imaging contrast agents that provide valuable information about the state of the disease and its progression. The enhanced permeation and retention effect for loaded nanocarriers in tumors allow substantial improvement of selectivity and safety of anticancer nanomedicines. Additionally, the possibility to design stimuli-responsive nanocarriers able to release their payload in response to specific stimuli provide an excellent control on the administered dosage. The aim of this review is not to present a comprehensive revision of the different theranostic mesoporous silica nanoparticles (MSN) which have been published in the recent years but just to describe a few selected examples to offer a panoramic view to the reader about the suitability and effectiveness of these nanocarriers in the oncology field.
High Expression of MUC15 Is Correlated with Poor Prognosis of Pancreatic Cancer and Promotes Migration, Invasion, and Chemo-Resistance In Vitro

Background MUC15, one of the hydrophilic glycoproteins that protect wet-surfaced epithelia, has been shown to be involved in tumorigenesis of various tumors. However, the mechanism of MUC15 in pancreatic cancer have not been revealed yet. Our study focused on investigating its clinical significance and function in pancreatic cancer. Material/Methods Using tissue microarrays and immunohistochemical staining, we evaluated MUC15 expression in 92 patients diagnosed with pancreatic ductal adenocarcinoma (PDAC). The correlations between MUC15 expression and clinicopathological variables and prognosis were analyzed. To validate our findings, we analyzed the data from an online database. We then demonstrated its function or mechanism in pancreatic cancer cell lines using transwell assay, cytotoxicity assay, cell apoptotic detection, and western blot. Results The expression level of MUC15 was remarkably increased in PDAC tissues in comparison with para-cancerous tissues, and was associated with poor prognosis. Cytoplasmic MUC15 expression was identified as an independent prognostic indicator for overall survival by multivariate Cox regression analysis. Functionally, overexpressed MUC15 enhanced the migration and invasion ability in cancer cells. In vitro studies revealed that MUC15 enhanced the gemcitabine resistance of pancreatic cancer. Additionally, the regulatory mechanism of MUC15 in PDAC were correlated with ERK and AKT signaling pathways. Conclusions We performed integrated analysis and revealed that MUC15 is a good prognostic predictor for patients with PDAC. The functional experiments showed that MUC15 contributed to the malignant behaviors of pancreatic cancer in vitro.
Transcriptome-Based Analysis of Phosphite-Induced Resistance against Pathogens in Rice

Phosphite (PHI) has been used in the management of Phytophthora diseases since the 1970s.We assessed the effect of PHI on controlling the incidence of Xanthomonas oryzae pv.oryzae and Pyricularia grisea. As a result, PHI application significantly inhibited the incidence of the diseases. To clarify the molecular mechanism underlying this, a transcriptome study was employed. In total, 2064 differentially expressed genes (DEGs) were identified between control and PHI treatment. The key DEGs could be classified into phenylpropanoid biosynthesis (ko00940), starch and sucrose metabolism (ko00500), and plant hormone signal transduction (ko04075). The expressions of defense-related genes had a higher expression lever upon PHI treatment. This study provides new insights into the mechanism of protection effect of PHI against pathogens.
Sound perception and its effects in plants and algae

ABSTRACT Life evolved in an acoustic world. Sound is perceived in different ways by the species that inhabit the Planet. Among organisms, also some algal species seem to respond to sound stimuli with increased cell growth and productivity. The purpose of this Short Communication is to provide an overview of the current literature about various organisms and sound, with particular attention to algal organisms, which, when subjected to sound applications, can change their metabolism accordingly.
Safety and feasibility of the PEPPER adaptive bolus advisor and safety system; a randomized control study.

Background: The Patient Empowerment through Predictive Personalised Decision Support (PEPPER) system provides personalised bolus advice for people with Type 1 diabetes. The system incorporates an adaptive insulin recommender system (based on case-based reasoning, an artificial intelligence methodology), coupled with a safety system which includes predictive glucose alerts and alarms, predictive low-glucose suspend, personalised carbohydrate recommendations and dynamic bolus insulin constraint. We evaluated the safety and feasibility of the PEPPER system compared to a standard bolus calculator. Methods: This was an open-labelled multicentre randomized controlled cross-over study. Following 4-week run-in, participants were randomized to PEPPER/Control or Control/PEPPER in a 1:1 ratio for 12-weeks. Participants then crossed over after a wash-out period. The primary end-point was percentage time in range (TIR, 3.9mmol/L-10.0mmol/L (70-180mg/dL)). Secondary outcomes included glycaemic variability, quality of life, and outcomes on the safety system and insulin recommender. Results: 54 participants on multiple daily injections (MDI) or insulin pump completed the run-in period, making up the intention-to-treat analysis. Median (interquartile range) age was 41.5 (32.3-49.8) years, diabetes duration 21.0 (11.5-26.0) years and HbA1c 61.0 (58.0-66.1) mmol/mol. No significant difference was observed for percentage TIR between the PEPPER and Control groups (62.5 (52.1-67.8) % vs 58.4 (49.6-64.3) % respectively, p=0.27). For quality of life, participants reported higher perceived hypoglycaemia with the PEPPER system despite no objective difference in time spent in hypoglycaemia. Conclusions: The PEPPER system was safe but did not change glycaemic outcomes, compared to control. There is wide scope for integrating PEPPER into routine diabetes management for pump and MDI users. Further studies are required to confirm overall effectiveness.
Increased Expression of NPM1 Suppresses p27Kip1 Function in Cancer Cells

Simple Summary Cancer malignancy frequently correlates with a low expression of p27Kip1, a major cyclin-dependent kinase inhibitor, and the p27 protein level has been reportedly responsible for its antiproliferative function. However, we found the function of overexpressed p27 is suppressed in some cancer cells, suggesting that p27 function is also regulated independently of its protein level. The aim of this study was to clarify this unknown p27 regulatory mechanism and its impact on cancer proliferation. We isolated nucleophosmin isoform 1 (NPM1), which is highly expressed in variety of cancers, as a novel p27-interacting protein. Overexpressing NPM1 in normal cells suppressed and silencing NPM1 in cancer cells rescued the p27 function, respectively, in vitro. Moreover, NPM1 silencing and p27 induction in cancer cells significantly suppressed their proliferation in mouse xenografts. Our findings reveal that NPM1 is a novel p27 functional suppressor and a potential anti-cancer target, especially in cancers with normal p27 expression. Abstract p27Kip1, a major cyclin-dependent kinase inhibitor, is frequently expressed at low levels in cancers, which correlates with their malignancy. However, in this study, we found a qualitative suppression of p27 overexpressed in some cancer cells. By proteomic screening for factors interacting with p27, we identified nucleophosmin isoform 1 (NPM1) as a novel p27-interacting factor and observed that NPM1 protein was expressed at high levels in some cancer cells. NPM1 overexpression in normal cells suppressed p27 function, and conversely, NPM1 knockdown in cancer cells restored the function in vitro. Furthermore, the tumors derived from cancer cells carrying the combination of p27 overexpression and NPM1 knockdown constructs showed significant suppression of growth as compared with those carrying other combinations in mouse xenograft models. These results strongly suggest that increased expression of NPM1 qualitatively suppresses p27 function in cancer cells.
Relationships between Prenatal Distress and Infant Body Mass Index in the First Year of Life in a Lower-Middle Income Country

Prenatal stress affects body composition in childhood and later in life. However, few studies assess body composition in infancy. Furthermore, most are in high-income countries and do not consider interactive or curvilinear relationships. We assessed distress and diet during pregnancy via questionnaires among 310 women in Vanuatu, a lower-middle income country. We measured body mass index (BMI) among 54 infants at 4–12 months of age. We analyzed interactive relationships between prenatal distress and diet with BMI Z-scores, and curvilinear relationships between distress and BMI Z-scores. There were no direct linear or interactive relationships between prenatal distress or diet with BMI Z-scores. We observed curvilinear relationships between prenatal distress and BMI Z-scores (p = 0.008), explaining 13.3 percent of unique variance. Results highlight that relationships between prenatal stress and body composition are evident in infancy but might not be detected if only linear relationships are assessed. Analyses in more diverse samples might help to explain inconsistencies in past studies.