Miracle-dz/UniFAR-FTUs huggingface dataset:
Personalised Medicine for Colorectal Cancer Using Mechanism-Based Machine Learning Models

Gaining insight into the mechanisms of signal transduction networks (STNs) by using critical features from patient-specific mathematical models can improve patient stratification and help to identify potential drug targets. To achieve this, these models should focus on the critical STNs for each cancer, include prognostic genes and proteins, and correctly predict patient-specific differences in STN activity. Focussing on colorectal cancer and the WNT STN, we used mechanism-based machine learning models to identify genes and proteins with significant associations to event-free patient survival and predictive power for explaining patient-specific differences of STN activity. First, we identified the WNT pathway as the most significant pathway associated with event-free survival. Second, we built linear-regression models that incorporated both genes and proteins from established mechanistic models in the literature and novel genes with significant associations to event-free patient survival. Data from The Cancer Genome Atlas and Clinical Proteomic Tumour Analysis Consortium were used, and patient-specific STN activity scores were computed using PROGENy. Three linear regression models were built, based on; (1) the gene-set of a state-of-the-art mechanistic model in the literature, (2) novel genes identified, and (3) novel proteins identified. The novel genes and proteins were genes and proteins of the extant WNT pathway whose expression was significantly associated with event-free survival. The results show that the predictive power of a model that incorporated novel event-free associated genes is better compared to a model focussing on the genes of a current state-of-the-art mechanistic model. Several significant genes that should be integrated into future mechanistic models of the WNT pathway are DVL3, FZD5, RAC1, ROCK2, GSK3B, CTB2, CBT1, and PRKCA. Thus, the study demonstrates that using mechanistic information in combination with machine learning can identify novel features (genes and proteins) that are important for explaining the STN heterogeneity between patients and their association to clinical outcomes.
Nursing-Sensitive Outcomes among Patients Cared for in Paediatric Intensive Care Units: A Scoping Review

Measuring the effectiveness of nursing interventions in intensive care units has been established as a priority. However, little is reported about the paediatric population. The aims of this study were (a) to map the state of the art of the science in the field of nursing-sensitive outcomes (NSOs) in paediatric intensive care units (PICUs) and (b) to identify all reported NSOs documented to date in PICUs by also describing their metrics. A scoping review was conducted by following the framework proposed by Arksey and O’Malley. Fifty-eight articles were included. Publications were mainly authored in the United States and Canada (n = 28, 48.3%), and the majority (n = 30, 51.7%) had an observational design. A total of 46 NSOs were documented. The most reported were related to the clinical (n = 83), followed by safety (n = 41) and functional (n = 18) domains. Regarding their metrics, the majority of NSOs were measured in their occurrence using quantitative single measures, and a few validated tools were used to a lesser extent. No NSOs were reported in the perceptual domain. Nursing care of critically ill children encompasses three levels: improvement in clinical performance, as measured by clinical outcomes; assurance of patient care safety, as measured by safety outcomes; and promotion of fundamental care needs, as measured by functional outcomes. Perceptual outcomes deserve to be explored.
Metabolome Characteristics of Liver Autophagy Deficiency under Starvation Conditions in Infancy

The liver function is essential for metabolism, detoxification, and bile synthesis, even in the neonatal period. Autophagy plays significance roles in THE adult liver, whereas the role of liver autophagy in the early neonatal period largely remains unclear. To clarify the importance of liver autophagy in the neonatal starvation period, we generated liver-specific autophagy-deficient (Atg5flox/flox; Albumin-Cre) mice and investigated under starvation conditions comparing with control (Atg5flox/+; Albumin-Cre) mice, focusing on serum metabolites and liver histopathology. As a result, autophagy in the liver was found to unessential for the survival under postnatal starvation. A metabolomics analysis of serum metabolites by gas chromatography-tandem mass spectrometry showed a significant difference between the groups, especially after 12-h starvation, suggesting the synergistical adaption of metabolic pathways, such as the “malate-aspartate shuttle”, “aspartate metabolism”, “urea cycle”, and “glycine and serine metabolism”. Liver-specific autophagy-deficiency under postnatal starvation conditions can cause a characteristic metabolic alteration suggesting a change of the mitochondrial function. Neonates seemed to maintain ketone production under starvation conditions, even in the autophagy-deficient liver, through a change in the mitochondrial function, which may be an adaptive mechanism for avoiding fatal starvation.
A Machine Learning Approach for Gearbox System Fault Diagnosis

This study proposes a fully automated gearbox fault diagnosis approach that does not require knowledge about the specific gearbox construction and its load. The proposed approach is based on evaluating an adaptive filter’s prediction error. The obtained prediction error’s standard deviation is further processed with a support-vector machine to classify the gearbox’s condition. The proposed method was cross-validated on a public dataset, segmented into 1760 test samples, against two other reference methods. The accuracy achieved by the proposed method was better than the accuracies of the reference methods. The accuracy of the proposed method was on average 9% higher compared to both reference methods for different support vector settings.
Impact of Nutritional Assessment on the Clinical Outcomes of Patients with Non-albicans Candidemia: A Multicenter Study

Several studies have demonstrated that malnutrition is a negative prognostic factor for clinical outcomes. However, there is limited evidence for the effect of malnutrition on clinical outcomes in patients with candidemia. We investigated the relationship between malnutrition and all-cause 28-day mortality among patients with non-albicans candidemia. Between July 2011 and June 2014, all adult patients with non-albicans candidemia, including C. tropicalis, C. glabrata, C. parapsilosis and so on, were enrolled. The Malnutrition Universal Screening Tool (MUST) scores were used to determine the patients’ nutritional status before the onset of candidemia. A total of 378 patients were enrolled; 43.4% developed septic shock and 57.1% had a high risk of malnutrition (MUST ≥ 2). The all-cause 28-day mortality rate was 40.7%. The Cox proportional hazards model revealed that C. tropicalis (HR, 2.01; 95% CI, 1.24–3.26; p = 0.005), Charlson comorbidity index (HR, 1.10; 95% CI, 1.03–1.18; p = 0.007), Foley catheter use (HR, 1.68; 95% CI, 1.21–1.35; p = 0.002), concomitant bacterial infections (HR, 1.55; 95% CI, 1.11–2.17; p = 0.010), low platelet count (HR, 3.81; 95% CI, 2.45–5.91; p < 0.001), not receiving antifungals initially (HR, 4.73; 95% CI, 3.07–7.29; p < 0.001), and MUST ≥ 2 (HR, 1.54; 95% CI, 1.09–2.17; p = 0.014) were independently associated with all-cause 28-day mortality. A simple screening tool for nutritional assessment should be used for patients with non-albicans candidemia to detect early clinical deterioration, and a tailored nutritional care plan should be established for malnourished individuals, to improve their clinical outcomes.
Antibiotic-Resistant Genes and Bacteria as Evolving Contaminants of Emerging Concerns (e-CEC): Is It Time to Include Evolution in Risk Assessment?

The pressing issue of the abundance of antibiotic resistance genes and resistant bacteria in the environment (ARGs and ARB, respectively) requires procedures for assessing the risk to health. The chemo-centric environmental risk assessment models identify hazard(s) in a dose–response manner, obtaining exposure, toxicity, risk, impact and policy. However, this risk assessment approach based on ARGs/ARB evaluation from a quantitative viewpoint shows high unpredictability because ARGs/ARB cannot be considered as standard hazardous molecules: ARB duplicate and ARGs evolve within a biological host. ARGs/ARB are currently listed as Contaminants of Emerging Concern (CEC). In light of such characteristics, we propose to define ARGs/ARB within a new category of evolving CEC (or e-CEC). ARGs/ARB, like any other evolving determinants (e.g., viruses, bacteria, genes), escape environmental controls. When they do so, just one molecule left remaining at a control point can form the origin of a new dangerous and selection-responsive population. As a consequence, perhaps it is time to acknowledge this trait and to include evolutionary concepts within modern risk assessment of e-CEC. In this perspective we analyze the evolutionary responses most likely to influence risk assessment, and we speculate on the means by which current methods could measure evolution. Further work is required to implement and exploit such experimental procedures in future risk assessment protocols.
Polymerase θ Coordinates Multiple Intrinsic Enzymatic Activities during DNA Repair

The POLQ gene encodes DNA polymerase θ, a 2590 amino acid protein product harboring DNA-dependent ATPase, template-dependent DNA polymerase, dNTP-dependent endonuclease, and 5′–dRP lyase functions. Polymerase θ participates at an essential step of a DNA double-strand break repair pathway able to join 5′-resected substrates by locating and pairing microhomologies present in 3′-overhanging single-stranded tails, cleaving the extraneous 3′-DNA by dNTP-dependent end-processing, before extending the nascent 3′ end from the microhomology annealing site. Metazoans require polymerase θ for full resistance to DNA double-strand break inducing agents but can survive knockout of the POLQ gene. Cancer cells with compromised homologous recombination, or other DNA repair defects, over-utilize end-joining by polymerase θ and often over-express the POLQ gene. This dependency points to polymerase θ as an ideal drug target candidate and multiple drug-development programs are now preparing to enter clinical trials with small-molecule inhibitors. Specific inhibitors of polymerase θ would not only be predicted to treat BRCA-mutant cancers, but could thwart accumulated resistance to current standard-of-care cancer therapies and overcome PARP-inhibitor resistance in patients. This article will discuss synthetic lethal strategies targeting polymerase θ in DNA damage-response-deficient cancers and summarize data, describing molecular structures and enzymatic functions.
Ladostigil Attenuates Induced Oxidative Stress in Human Neuroblast-like SH-SY5Y Cells

A hallmark of the aging brain is the robust inflammation mediated by microglial activation. Pathophysiology of common neurodegenerative diseases involves oxidative stress and neuroinflammation. Chronic treatment of aging rats by ladostigil, a compound with antioxidant and anti-inflammatory function, prevented microglial activation and learning deficits. In this study, we further investigate the effect of ladostigil on undifferentiated SH-SY5Y cells. We show that SH-SY5Y cells exposed to acute (by H2O2) or chronic oxidative stress (by Sin1, 3-morpholinosydnonimine) induced apoptotic cell death. However, in the presence of ladostigil, the decline in cell viability and the increase of oxidative levels were partially reversed. RNA-seq analysis showed that prolonged oxidation by Sin1 resulted in a simultaneous reduction of the expression level of endoplasmic reticulum (ER) genes that participate in proteostasis. By comparing the differential gene expression profile of Sin1 treated cells to cells incubated with ladostigil before being exposed to Sin1, we observed an over-expression of Clk1 (Cdc2-like kinase 1) which was implicated in psychophysiological stress in mice and Alzheimer’s disease. Ladostigil also suppressed the expression of Ccpg1 (Cell cycle progression 1) and Synj1 (Synaptojanin 1) that are involved in ER-autophagy and endocytic pathways. We postulate that ladostigil alleviated cell damage induced by oxidation. Therefore, under conditions of chronic stress that are observed in the aging brain, ladostigil may block oxidative stress processes and consequently reduce neurotoxicity.
Porin 1 Modulates Autophagy in Yeast

Autophagy is a cellular recycling program which efficiently reduces the cellular burden of ageing. Autophagy is characterised by nucleation of isolation membranes, which grow in size and further expand to form autophagosomes, engulfing cellular material to be degraded by fusion with lysosomes (vacuole in yeast). Autophagosomal membranes do not bud from a single cell organelle, but are generated de novo. Several lipid sources for autophagosomal membranes have been identified, but the whole process of their generation is complex and not entirely understood. In this study, we investigated how the mitochondrial outer membrane protein porin 1 (Por1), the yeast orthologue of mammalian voltage-dependent anion channel (VDAC), affects autophagy in yeast. We show that POR1 deficiency reduces the autophagic capacity and leads to changes in vacuole and lipid homeostasis. We further investigated whether limited phosphatidylethanolamine (PE) availability in por1∆ was causative for reduced autophagy by overexpression of the PE-generating phosphatidylserine decarboxylase 1 (Psd1). Altogether, our results show that POR1 deficiency is associated with reduced autophagy, which can be circumvented by additional PSD1 overexpression. This suggests a role for Por1 in Psd1-mediated autophagy regulation.
Preliminary Study on Light-Activated Antimicrobial Agents as Photocatalytic Method for Protection of Surfaces with Increased Risk of Infections

Preventing and controlling the spread of multidrug-resistant (MDR) bacteria implicated in healthcare-associated infections is the greatest challenge of the health systems. In recent decades, research has shown the need for passive antibacterial protection of surfaces in order to reduce the microbial load and microbial biofilm development, frequently associated with transmission of infections. The aim of the present study is to analyze the efficiency of photocatalytic antimicrobial protection methods of surfaces using the new photocatalytic paint activated by light in the visible spectrum. The new composition is characterized by a wide range of analytical methods, such as UV-VIS spectroscopy, electron microscopy (SEM), X-ray powder diffraction (PXRD) or X-ray photoelectron spectroscopy (XPS). The photocatalytic activity in the UV-A was compared with the one in the visible light spectrum using an internal method developed on the basis of DIN 52980: 2008-10 standard and ISO 10678—2010 standard. Migration of metal ions in the composition was tested based on SR EN1186-3: 2003 standard. The new photocatalytic antimicrobial method uses a type of photocatalytic paint that is active in the visible spectral range and generates reactive oxygen species with inhibitory effect against all tested microbial strains.
Image Acquisition Device for Smart-City Access Control Applications Based on Iris Recognition

In this work, we present an eye-image acquisition device that can be used as an image acquisition front-end application in compact, low-cost, and easy-to-integrate products for smart-city access control applications, based on iris recognition. We present the advantages and disadvantages of iris recognition compared to fingerprint- or face recognition. We also present the main drawbacks of the existing commercial solutions and propose a concept device design for door-mounted access control systems based on iris recognition technology. Our eye-image acquisition device was built around a low-cost camera module. An integrated infrared distance measurement was used for active image focusing. FPGA image processing was used for raw-RGB to grayscale demosaicing and passive image focusing. The integrated visible light illumination meets the IEC62471 photobiological safety standard. According to our results, we present the operation of the distance-measurement subsystem, the operation of the image-focusing subsystem, examples of acquired images of an artificial toy eye under different illumination conditions, and the calculation of illumination exposure hazards. We managed to acquire a sharp image of an artificial toy eye sized 22 mm in diameter from an approximate distance of 10 cm, with 400 pixels over the iris diameter, an average acquisition time of 1 s, and illumination below hazardous exposure levels.
Relative Importance of Deterministic and Stochastic Processes on Soil Microbial Community Assembly in Temperate Grasslands

Changes in species composition across communities, i.e., β-diversity, is a central focus of ecology. Compared to macroorganisms, the β-diversity of soil microbes and its drivers are less studied. Whether the determinants of soil microbial β-diversity are consistent between soil depths and between abundant and rare microorganisms remains controversial. Here, using the 16S-rRNA of soil bacteria and archaea sampled at different soil depths (0–10 and 30–50 cm) from 32 sites along an aridity gradient of 1500 km in the temperate grasslands in northern China, we compared the effects of deterministic and stochastic processes on the taxonomic and phylogenetic β-diversity of soil microbes. Using variation partitioning and null models, we found that the taxonomic β-diversity of the overall bacterial communities was more strongly determined by deterministic processes in both soil layers (the explanatory power of environmental distance in topsoil: 25.4%; subsoil: 47.4%), while their phylogenetic counterpart was more strongly determined by stochastic processes (the explanatory power of spatial distance in topsoil: 42.1; subsoil 24.7%). However, in terms of abundance, both the taxonomic and phylogenetic β-diversity of the abundant bacteria in both soil layers was more strongly determined by deterministic processes, while those of rare bacteria were more strongly determined by stochastic processes. In comparison with bacteria, both the taxonomic and phylogenetic β-diversity of the overall abundant and rare archaea were strongly determined by deterministic processes. Among the variables representing deterministic processes, contemporary and historical climate and aboveground vegetation dominated the microbial β-diversity of the overall and abundant microbes of both domains in topsoils, but soil geochemistry dominated in subsoils. This study presents a comprehensive understanding on the β-diversity of soil microbial communities in the temperate grasslands in northern China. Our findings highlight the importance of soil depth, phylogenetic turnover, and species abundance in the assembly processes of soil microbial communities.
Valorisation Potential of Using Organic Side Streams as Feed for Tenebrio molitor, Acheta domesticus and Locusta migratoria

Simple Summary The demand for more sustainable protein sources is growing. Insects are believed to have potential as a sustainable protein source since they can be produced with lower environmental impact than current livestock. Furthermore, they have proven to be able to convert low-nutrient biomass into own nutrient-rich body mass, making them nutritionally interesting for applications such as food, feed and technical applications. The aim of this review was to provide more insight on the valorisation potential of agricultural side streams in feed for the rearing of yellow mealworm (Tenebrio molitor), house cricket (Acheta domesticus) and migratory locust (Locusta migratoria). Several key aspects need to be considered when aiming to valorise side streams in insect feed. The following aspects are discussed in detail: European legislation, the insects’ dietary requirements, the nutritional composition of insects and the availability of agricultural side streams in the EU. Additionally, research focusing on the production of insects on side streams is reviewed. Through this review, it is concluded that there is a huge potential to valorise residues in feed for the insects of interest. However, it is not a self-evident process. Abstract Due to increasing welfare and population, the demand for alternative protein sources, obtained with minimal use of natural resources, is rising in today’s society. Insects have the potential to be used as an alternative protein source since they are considered to be able to convert low-value biomass into high-value components, resulting in opportunities for valorisation of organic side streams. Moreover, insects are suggested to be a sustainable protein source, referring to the efficient “feed to body” mass conversion potential. The aim of this review was to explore the potential to rear the yellow mealworm (Tenebrio molitor), the house cricket (Acheta domesticus) and the migratory locust (Locusta migratoria) on low or not yet valorised organic side streams within the food supply chain. This was performed by collecting research information focusing on the rearing of the insects in scope on organic biomass. In addition, the nutritional composition of the produced insects as well as their dietary requirements will be reviewed. Finally, the availability of side streams in the EU will be discussed as well as their potential to be used as insects feed.
Nanocellulose Based Filtration Membrane in Industrial Waste Water Treatment: A Review

In the field of industrial wastewater treatment, membrane separation technology, as an emerging separation technology, compared with traditional separation technology such as precipitation, adsorption, and ion exchange, has advantages in separation efficiency, low energy consumption, low cost, simple operation, and no secondary pollution. The application has been expanding in recent years, but membrane fouling and other problems have seriously restricted the development of membrane technology. Natural cellulose is one of the most abundant resources in nature. In addition, nanocellulose has characteristics of high strength and specific surface area, surface activity groups, as well as being pollution-free and renewable, giving it a very wide development prospect in many fields, including membrane separation technology. This paper reviews the current status of nanocellulose filtration membrane, combs the widespread types of nanocellulose and its derivatives, and summarizes the current application of cellulose in membrane separation. In addition, for the purpose of nanocellulose filtration membrane in wastewater treatment, nanocellulose membranes are divided into two categories according to the role in filtration membrane: the application of nanocellulose as membrane matrix material and as a modified additive in composite membrane in wastewater treatment. Finally, the advantages and disadvantages of inorganic ceramic filtrations and nanocellulose filtrations are compared, and the application trend of nanocellulose in the filtration membrane direction is summarized and discussed.