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Prediction of methane hydrate equilibrium in saline water solutions based on support vector machine and decision tree techniques
Optimization of low-temperature nitrogen plasma in reducing fungi and aflatoxin human exposure through maize
Abstract Globally, aflatoxin contamination in maize remains a huge burden despite many interventions put in place. The use of low-temperature plasma to decontaminate the maize is a potential solution for ensuring the safety and extended shelf life of the grain. This study optimized the parameters and investigated the efficacy of low-temperature nitrogen plasma (LTNP) in destroying fungi and reducing exposure to aflatoxins in naturally contaminated maize from an endemic region. The study generated 17 experimental runs using the Response Surface Methodology (RSM) of the Box Behnken Design (BBD) with exposure time, pressure, and ionization density as independent variables. Quantitative exposure assessment was conducted using Monte Carlo simulations followed by sensitivity and scenario analysis to study factors influencing exposure and best aflatoxin-reducing plasma parameters. The best-fitting RSM model, the linear model, indicated that increased exposure time but not pressure and power led to a corresponding statistically significant decrease in the fungal load and aflatoxin content. LTNP reduced aflatoxin contamination to levels below all the main global regulatory limits. Numerical optimization of the percent reduction in aflatoxin and fungal load indicated that an exposure time of 1793.4 s, pressure of 0.98 pascal and ionization power of 189.8 W are required to achieve an optimal reduction of aflatoxin content of 82.6% and fungal load of 96.9%. Exposure assessment indicated high exposure especially for populations with lower body weight with ρ = -0.46 between body weight and exposure. The best LTNP combinations achieved aflatoxin exposure reduction results comparable to but with markedly less variation than existing practically used decontamination methods. Further optimization studies during upscaling are recommended, incorporating independent factors such as temperature and processing volume and outcomes such as organoleptic, physical, and chemical changes in the food matrices after treatment.
Implications of intrinsic capacity subtypes for post-PCI patients older than 45
Uncertainty quantification with graph neural networks for efficient molecular design
Cytogenetic signatures favoring metastatic organotropism in colorectal cancer
Abstract Colorectal carcinoma (CRC) exhibits metastatic organotropism, primarily targeting liver, lung, and rarely the brain. Here, we study chromosomal imbalances (CIs) in cohorts of primary CRCs and metastases. Brain metastases show the highest burden of CIs, including aneuploidies and focal CIs, with enrichment of +12p encoding KRAS. Compared to liver and lung metastases, brain metastases present with increased co-occurrence of KRAS mutation and amplification. CRCs with concurrent KRAS mutation and amplification display significant metabolic reprogramming with upregulation of glycolysis, alongside upregulation of cell cycle pathways, including copy number gains of MDM2 and CDK4. Evolutionary modeling suggests early acquisition of many organotropic CIs enriched in both liver and brain metastases, while brain-enriched CIs preferentially emerge later. Collectively, this study supports a model where cytogenetic events in CRCs favor site-specific metastatic colonization. These site-enriched CI patterns may serve as biomarkers for metastatic potential in precision oncology.
Redox disruption using electroactive liposome coated gold nanoparticles for cancer therapy
Universal law of hierarchical dynamics in gels arising from confluence of local physically dynamic bonds
Bright upconversion over extended temperatures enabled by an organic surface layer
Cooperative role of PACT and ADAR1 in preventing aberrant PKR activation by self-derived double-stranded RNA
Abstract Double-stranded RNAs (dsRNAs) produced during viral infections are recognized by the innate immune sensor protein kinase R (PKR), triggering a host translation shutoff that inhibits viral replication and propagation. Given the harmful effects of uncontrolled PKR activation, cells must tightly regulate PKR to ensure that its activation occurs only in response to viral infections, not endogenous dsRNAs. Here, we use CRISPR-Translate, a FACS-based genome-wide CRISPR-Cas9 knockout screening method that exploits translation levels as a readout and identifies PACT as a key inhibitor of PKR during viral infection. We find that PACT-deficient cells hyperactivate PKR in response to different RNA viruses, raising the question of why cells need to limit PKR activity. Our results demonstrate that PACT cooperates with ADAR1 to suppress PKR activation from self-dsRNAs in uninfected cells. The simultaneous deletion of PACT and ADAR1 results in synthetic lethality, which can be fully rescued in PKR-deficient cells. We propose that both PACT and ADAR1 act as essential barriers against PKR, creating a threshold of tolerable levels to endogenous dsRNA in cells without activating PKR-mediated translation shutdown and cell death.
Preclinical concept studies showing advantage of an inhaled anti-CTGF/CCN2 protein for pulmonary fibrosis treatment
The Estonian Biobank’s journey from biobanking to personalized medicine
Abstract Large biobanks have set a new standard for research and innovation in human genomics and implementation of personalized medicine. The Estonian Biobank was founded a quarter of a century ago, and its biological specimens, clinical, health, omics, and lifestyle data have been included in over 800 publications to date. What makes the biobank unique internationally is its translational focus, with active efforts to conduct clinical studies based on genetic findings, and to explore the effects of return of results on participants. In this review, we provide an overview of the Estonian Biobank, highlight its strengths for studying the effects of genetic variation and quantitative phenotypes on health-related traits, development of methods and frameworks for bringing genomics into the clinic, and its role as a driving force for implementing personalized medicine on a national level and beyond.
Integration of high strength, flexibility, and room-temperature plasticity in ceramic nanofibers
A comparative study of deterministic and stochastic computational modeling approaches for analyzing and optimizing COVID-19 control
A bifunctional snoRNA with separable activities in guiding rRNA 2’-O-methylation and scaffolding gametogenesis effectors
Abstract Small nucleolar RNAs are non-coding transcripts that guide chemical modifications of RNA substrates and modulate gene expression at the epigenetic and post-transcriptional levels. However, the extent of their regulatory potential and the underlying molecular mechanisms remain poorly understood. Here, we identify a conserved, previously unannotated intronic C/D-box snoRNA, termed snR107 , hosted in the fission yeast long non-coding RNA mamRNA and carrying two independent cellular functions. On the one hand, snR107 guides site-specific 25S rRNA 2’-O-methylation and promotes pre-rRNA processing and 60S subunit biogenesis. On the other hand, snR107 associates with the gametogenic RNA-binding proteins Mmi1 and Mei2, mediating their reciprocal inhibition and restricting meiotic gene expression during sexual differentiation. Both functions require distinct cis -motifs within snR107 , including a conserved 2’-O-methylation guiding sequence. Together, our results position snR107 as a dual regulator of rRNA modification and gametogenesis effectors, expanding our vision on the non-canonical functions exerted by snoRNAs in cell fate decisions.
A cross-sectional study of public knowledge and stigma towards autism spectrum disorder in Lebanon
scRNA-seq uncovers the transcriptional dynamics of Encephalitozoon intestinalis parasites in human macrophages
Sex-specific aspects in a population of patients undergoing evaluation for interstitial lung disease with transbronchial cryobiopsy
Abstract There are well-documented differences in idiopathic pulmonary fibrosis (IPF) between sexes. The sex-specific prevalence of interstitial lung disease (ILD) subtypes in patients who require a full diagnostic work-up, including transbronchial cryobiopsy (TCB), after initial multidisciplinary discussion (MDD) is still unknown. Retrospective analysis of sex dispareties in patients with ILD who received an interdisciplinary indication for lung biopsy and underwent bronchoalveolar lavage, TCB and, if necessary, surgical lung biopsy at our ILD centre in Heidelberg between 11/17 and 12/21. The analysis included clinical parameters, visual assessment of computed tomography (CT), automated histogram analyses of lung density by validated software and final MDD-ILD classifications. A total of 402 patients (248 men, 154 women; mean age 68 ± 12 years) were analysed. Smoking behaviour was similar between the sexes, but women were more exposed to environmental factors, whereas men were more exposed to occupational factors. Women had higher rates of thyroid disease (29.9% vs. 12.5%; p < 0.001) and extrathoracic malignancies (16.2% vs. 9.3%; p = 0.041), but lower rates of coronary heart disease (7.1% vs. 19.8%; p < 0.001), stroke (1.3% vs. 6.5%; p = 0.014) and sleep apnoea (5.8% vs. 17.7%; p < 0.001). There were no sex differences regarding CT lung density. On visual inspection, women were less likely to have reticular opacities (65% vs. 76%; p = 0.017) and features of usual interstitial pneumonia (17% vs. 34%; p < 0.001). Among final diagnoses, hypersensitivity pneumonitis was more common in women (34.4%) compared to men (21.8%; p = 0.007). In contrast, IPF was more common in men (22.6%) than in women (7.1%; p < 0.001), and unclassifiable interstitial lung disease was also more frequent in men (21.8%) compared to women (6.5%; p < 0.001). This study highlights significant sex-based differences in the prevalence and characteristics of ILD requiring comprehensive diagnostic work-up. These findings underscore the importance of considering sex-specific factors in the diagnosis and management of ILD.