Miracle-dz/UniFAR-FTUs huggingface dataset:
Emergence of Hybrid Resistance and Virulence Plasmids Harboring New Delhi Metallo-β-Lactamase in Klebsiella pneumoniae in Russia

The emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) is a new threat to healthcare. In this study, we analyzed nine CR-hvKp isolates of different sequence-types (ST) recovered from patients with nosocomial infections in two hospitals in Saint Petersburg. Whole-genome sequencing showed that eight of them harbored large mosaic plasmids carrying resistance to carbapenems and hypervirulence simultaneously, and four different types of hybrid plasmids were identified. BLAST analysis showed a high identity with two hybrid plasmids originating in the UK and Czech Republic. We demonstrated that hybrid plasmids emerged due to the acquisition of resistance genes by virulent plasmids. Moreover, one of the hybrid plasmids carried a novel New Delhi metallo-beta-lactamase (NDM) variant, differing from NDM-1 by one amino acid substitution (D130N), which did not provide significant evolutionary advantages compared to NDM-1. The discovery of structurally similar plasmids in geographically distant regions suggests that the actual distribution of hybrid plasmids carrying virulence and resistance genes is much wider than expected.
Detecting Impending Malnutrition of (Pre-) Frail Older Adults in Domestic Smart Home Environments

Malnutrition is a well-known risk factor for deteriorated physical function, disability and loss in independence in older adults. An unintended loss in body weight of more than 5% in 3 months is one indicator for malnutrition. In this study we examined the relationship between meal preparation time, hand grip strength, and body weight in order to map impending nutritional problems using ambient sensors. Data were collected in the domestic environments of 20 (pre-) frail older adults aged 85.75 y (Standard Deviation: 5.19 y) over 10-months of observation. Collecting included physical function and nutritional status of the participants and meal preparation time by a combination of motion and power sensor events. Analysis was done by rank correlation of hand grip strength, body weight, and meal preparation time. Ten participants aged 85.1 years (Standard Deviation: 4.6 y) were included. The results show a significant correlation (≥0.99) of the meal preparation time with the hand grip strength. This result validated the meal preparation time as a suitable measure for analysing the correlation between meal preparation time and body weight, and a significant correlation (≥0.99) found. Hence the meal preparation time could be used as an indicator for malnutrition. However, causalities have to be conducted by further clinical studies.
Oligometastatic Breast Cancer: How to Manage It?

Breast cancer (BC) is the most frequent cancer among women and represents the second leading cause of cancer-specific death. A subset of patients with metastatic breast cancer (MBC) presents limited disease, termed ‘oligometastatic’ breast cancer (OMBC). The oligometastatic disease can be managed with different treatment strategies to achieve long-term remission and eventually cure. Several approaches are possible to cure the oligometastatic disease: locoregional treatments of the primary tumor and of all the metastatic sites, such as surgery and radiotherapy; systemic treatment, including target-therapy or immunotherapy, according to the biological status of the primary tumor and/or of the metastases; or the combination of these approaches. Encouraging results involve local ablative options, but these trials are limited by being retrospective and affected by selection bias. Systemic therapy, e.g., the use of CDK4/6 inhibitors for hormone receptor-positive (HR+)/HER-2 negative BC, leads to an increase of progression-free survival (PFS) and overall survival (OS) in all the subgroups, with favorable toxicity. Regardless of the lack of substantial data, this subset of patients could be treated with curative intent; the appropriate candidates could be mostly young women, for whom a multidisciplinary aggressive approach appears suitable. We provide a global perspective on the current treatment paradigms of OMBC.
Parvaxanthines D–F and Asponguanosines C and D, Racemic Natural Hybrids from the Insect Cyclopelta parva

Five new compounds including three pairs of enantiomeric xanthine analogues, parvaxanthines D–F (1–3), two new guanosine derivatives, asponguanosines C and D (6 and 7), along with two known adenine derivatives were isolated from the insect Cyclopelta parva. Racemic 1–3 were further separated by chiral HPLC. Their absolute configurations were assigned by spectroscopic and computational methods. It is interesting that all of these isolates are natural product hybrids. Antiviral, immunosuppressive, antitumor and anti-inflammatory properties of all the isolates were evaluated.
A Sparse and Low-Rank Regression Model for Identifying the Relationships Between DNA Methylation and Gene Expression Levels in Gastric Cancer and the Prediction of Prognosis

DNA methylation is an important regulator of gene expression that can influence tumor heterogeneity and shows weak and varying expression levels among different genes. Gastric cancer (GC) is a highly heterogeneous cancer of the digestive system with a high mortality rate worldwide. The heterogeneous subtypes of GC lead to different prognoses. In this study, we explored the relationships between DNA methylation and gene expression levels by introducing a sparse low-rank regression model based on a GC dataset with 375 tumor samples and 32 normal samples from The Cancer Genome Atlas database. Differences in the DNA methylation levels and sites were found to be associated with differences in the expressed genes related to GC development. Overall, 29 methylation-driven genes were found to be related to the GC subtypes, and in the prognostic model, we explored five prognoses related to the methylation sites. Finally, based on a low-rank matrix, seven subgroups were identified with different methylation statuses. These specific classifications based on DNA methylation levels may help to account for heterogeneity and aid in personalized treatments.
Morphological Features and Cold-Response Gene Expression in Mesophilic Bacillus cereus Group and Psychrotolerant Bacillus cereus Group under Low Temperature

At low temperatures, psychrotolerant B. cereus group strains exhibit a higher growth rate than mesophilic strains do. However, the different survival responses of the psychrotolerant strain (BCG34) and the mesophilic strain (BCGT) at low temperatures are unclear. We investigated the morphological and genomic features of BCGT and BCG34 to characterize their growth strategies at low temperatures. At low temperatures, morphological changes were observed only in BCGT. These morphological changes included the elongation of rod-shaped cells, whereas the cell shape in BCG34 was unchanged at the low temperature. A transcriptomic analysis revealed that both species exhibited different growth-related traits during low-temperature growth. The BCGT strain induces fatty acid biosynthesis, sulfur assimilation, and methionine and cysteine biosynthesis as a survival mechanism in cold systems. Increases in energy metabolism and fatty acid biosynthesis in the mesophilic B. cereus group strain might explain its ability to grow at low temperatures. Several pathways involved in carbohydrate mechanisms were downregulated to conserve the energy required for growth. Peptidoglycan biosynthesis was upregulated, implying that a change of gene expression in both RNA-Seq and RT-qPCR contributed to sustaining its growth and rod shape at low temperatures. These results improve our understanding of the growth response of the B. cereus group, including psychrotolerant B. cereus group strains, at low temperatures and provide information for improving bacterial inhibition strategies in the food industry.
Machine Learning Algorithms, Applied to Intact Islets of Langerhans, Demonstrate Significantly Enhanced Insulin Staining at the Capillary Interface of Human Pancreatic β Cells

Pancreatic β cells secrete the hormone insulin into the bloodstream and are critical in the control of blood glucose concentrations. β cells are clustered in the micro-organs of the islets of Langerhans, which have a rich capillary network. Recent work has highlighted the intimate spatial connections between β cells and these capillaries, which lead to the targeting of insulin secretion to the region where the β cells contact the capillary basement membrane. In addition, β cells orientate with respect to the capillary contact point and many proteins are differentially distributed at the capillary interface compared with the rest of the cell. Here, we set out to develop an automated image analysis approach to identify individual β cells within intact islets and to determine if the distribution of insulin across the cells was polarised. Our results show that a U-Net machine learning algorithm correctly identified β cells and their orientation with respect to the capillaries. Using this information, we then quantified insulin distribution across the β cells to show enrichment at the capillary interface. We conclude that machine learning is a useful analytical tool to interrogate large image datasets and analyse sub-cellular organisation.
UAV-Based and WebRTC-Based Open Universal Framework to Monitor Urban and Industrial Areas

Nowadays, we are observing a rapid development of UAV-based monitoring systems, which are faced with more and more new tasks, such as high temporal resolution and high spatial resolution of measurements, or Artificial Intelligence on board. This paper presents the open universal framework intended for fast prototyping or building a short series of specialized flying monitoring systems able to work in urban and industrial areas. The proposed framework combines mobility of UAV with IoT measurements and full-stack WebRTC communications. WebRTC offers simultaneous transmission of both a real-time video stream and the flow of data coming from sensors, and ensures a kind of protection of data flow, which leads to preserving its near-real-time character and enables contextual communication. Addition of the AI accelerator hardware makes this system AI-ready, i.e., the IoT communication hub, which is the air component of our system, is able to perform tasks of AI-supported computing. The exemplary prototype of this system was evaluated in terms of the ability to work with fast-response sensors, the ability to work with high temporal and high spatial resolutions, video information in poor visibility conditions and AI-readiness. Results show that prototypes based on the proposed framework are able to meet the challenges of monitoring systems in smart cities and industrial areas.
What Can We Change in Diet and Behaviour in Order to Decrease Carotid Intima-Media Thickness in Patients with Obesity?

Atherosclerosis—considered the major cause of cardiovascular diseases (CVDs)—is strongly associated with obesity, to which it strongly contributes. Moreover, atherosclerosis is characterised by a long asymptomatic phase, and its progression can lead to serious cardiovascular (CV) events. The carotid intima-media thickness (cIMT) has been determined as a predictor of CV events, as well as a marker of subclinical atherosclerosis, and has been used in clinical trials as an alternative assessment method or a surrogate endpoint. It should be noted that several behavioural approaches can directly influence the cIMT values, and decrease or increase the CV risk. In our paper, we aimed to summarize the current knowledge regarding IMT measurement among patients with obesity as a risk group—also in terms of the obesity paradox where the diagnosis of subclinical atherosclerosis is especially essential and implements the early therapeutic approach. We also summarized behavioural, modifiable factors, such as the Mediterranean diet, the Dietary Approach to Stop Hypertension Diets, body weight reduction or the intake of micro- and macronutrients, with a particular focus on the studies where the cIMT values were one of the outcomes. In order to collect the literature data related to the presented topic, the PubMed database was explored.
High Performance Mixed-Matrix Electrospun Membranes for Ammonium Removal from Wastewaters

Mixed-matrix electrospun membranes were developed to investigate ammonium removal from low ammonium concentration wastewaters for the first time. Particles derived from the inexpensive zeolite 13X were successfully incorporated into polyethersulfone (PES) matrices. The fabricated mixed-matrix electrospun membranes demonstrate high ammonium removal capacity reaching over 55 mg/gzeolite, more than 2.5 times higher than the previously fabricated mixed-matrix membranes via non-solvent induced phase inversion. Moreover, the membranes fabricated exhibit high permeability and ease of regeneration. Over 90% of total ammonium nitrogen (TAN) can be removed from low TAN wastewaters such as aquaculture wastewaters. In addition to zeolite 13X, other zeolite particles including zeolite Y, zeolite 3A and 4A were also incorporated into the membrane matrix. The inexpensive zeolite 13X show the highest ammonium exchange capacity. Particle type, loading and the level of its dispersion all affect TAN removal capacity.
Potential Contribution of Climate Change to the Protein Haze of White Wines from the French Southwest Region

The aim of this study was to evaluate the role played by climatic conditions during grape ripening in the protein instability of white wines produced in the French southwest region. For this purpose, basic wine analyses were carried out on 268 musts and the corresponding wines, all produced during the 2016, 2017, 2018, and 2019 vintages, with distinctive climatic conditions. Qualitative and quantitative variables were correlated with levels of protein haze determined by heat test (80 °C/2 h) in the wines using analysis of covariance (ANCOVA), principal component analysis (PCA), and classification and regression trees (CART). Our results show that the climatic change, with the increase in temperatures, and the decrease in precipitation during the grape ripening phase, tends to enhance the risk of protein instability in wines. Indeed, the values of pH, titratable acidity, and malic acid concentrations of the musts, which are good indicators of the conditions in which the grapes ripened and of the level of ripeness of the grapes, were also the variables that correlated best with the protein haze. By measuring these parameters at harvest before alcoholic fermentation, it may be possible to predict the risk of protein haze, and thus early and precisely adapt the stabilization treatment to be applied.
Promising Activities of Marine Natural Products against Hematopoietic Malignancies

According to the WHO classification of tumors, more than 150 typologies of hematopoietic and lymphoid tumors exist, and most of them remain incurable diseases that require innovative approaches to improve therapeutic outcome and avoid side effects. Marine organisms represent a reservoir of novel bioactive metabolites, but they are still less studied compared to their terrestrial counterparts. This review is focused on marine natural products with anticancer activity against hematological tumors, highlighting recent advances and possible perspectives. Until now, there are five commercially available marine-derived compounds for the treatment of various hematopoietic cancers (e.g., leukemia and lymphoma), two molecules in clinical trials, and series of compounds and/or extracts from marine micro- and macroorganisms which have shown promising properties. In addition, the mechanisms of action of several active compounds and extracts are still unknown and require further study. The continuous upgrading of omics technologies has also allowed identifying enzymes with possible bioactivity (e.g., l-asparaginase is currently used for the treatment of leukemia) or the enzymes involved in the synthesis of bioactive secondary metabolites which can be the target of heterologous expression and genetic engineering.
Higher Dietary Inflammation in Patients with Schizophrenia: A Case-Control Study in Korea

Inflammation is a risk factor for the onset and progression of schizophrenia, and dietary factors are related to chronic inflammation. We investigated whether the dietary inflammatory index (DII) is associated with schizophrenia in the Korean population. Of the 256 subjects who responded to the questionnaire, 184 subjects (117 controls; 67 individuals with schizophrenia) were included in this case-control study. A semi-quantitative food frequency questionnaire was used to evaluate the dietary intakes of the study participants. The energy-adjusted DII (E-DII) was used to assess the inflammatory potential of the participants’ diets. Dietary intakes of vitamin C, niacin, and folate were significantly reduced in the patients with schizophrenia. The patients with schizophrenia had higher E-DII scores than the controls (p = 0.011). E-DII was positively associated with schizophrenia (odds ratio = 1.254, p = 0.010). The additional analysis confirmed that E-DII was significantly associated with schizophrenia, especially in the third tertile group of E-DII scores (odds ratio = 2.731, p = 0.016). Our findings suggest that patients with schizophrenia have more pro-inflammatory diets.
Live Cell Assays for the Assessment of Antioxidant Activities of Plant Extracts

Plant extracts and pharmacopoeias represent an exceptional breeding ground for the discovery of new antioxidants. Until recently, the antioxidant activity was only measured by chemical hydrogen atom transfer (HAT) and single-electron transfer (SET) cell-free assays that do not inform about the actual effect of antioxidants in living systems. By providing information about the mode of action of antioxidants at the subcellular level, recently developed live cell assays are now changing the game. The idea of this review is to present the different cell-based approaches allowing a quantitative measurement of antioxidant effects of plant extracts. Up to date, only four different approaches have reached a certain degree of standardization: (1) the catalase-like assay using H2O2 as a stressor, (2) the cell antioxidant assay (CAA) using AAPH as a stressor and DCFH-DA as a readout, (3) the AOP1 assay which uses photoinduction to monitor and control cell ROS production, and (4) the Nrf2/ARE gene reporter system. The molecular aspects of these assays are presented in detail along with their features, drawbacks, and benefits. The Nrf2/ARE gene reporter system dedicated to indirect antioxidant effect measurement currently represents the most standardized approach with high-throughput applications. AOP1, the first technology linking a fine-tuning of cell ROS production with a quantitative signal, appears to be the most promising tool for the assessment of direct cellular ROS-scavenging effects at an industrial scale.
Pathophysiological Responses and Roles of Astrocytes in Traumatic Brain Injury

Traumatic brain injury (TBI) is immediate damage caused by a blow to the head resulting from traffic accidents, falls, and sporting activity, which causes death or serious disabilities in survivors. TBI induces multiple secondary injuries, including neuroinflammation, disruption of the blood–brain barrier (BBB), and brain edema. Despite these emergent conditions, current therapies for TBI are limited or insufficient in some cases. Although several candidate drugs exerted beneficial effects in TBI animal models, most of them failed to show significant effects in clinical trials. Multiple studies have suggested that astrocytes play a key role in the pathogenesis of TBI. Increased reactive astrocytes and astrocyte-derived factors are commonly observed in both TBI patients and experimental animal models. Astrocytes have beneficial and detrimental effects on TBI, including promotion and restriction of neurogenesis and synaptogenesis, acceleration and suppression of neuroinflammation, and disruption and repair of the BBB via multiple bioactive factors. Additionally, astrocytic aquaporin-4 is involved in the formation of cytotoxic edema. Thus, astrocytes are attractive targets for novel therapeutic drugs for TBI, although astrocyte-targeting drugs have not yet been developed. This article reviews recent observations of the roles of astrocytes and expected astrocyte-targeting drugs in TBI.
Meta-Assessment of Metformin Absorption and Disposition Pharmacokinetics in Nine Species

The objective of this study was to systematically assess literature datasets and quantitatively analyze metformin PK in plasma and some tissues of nine species. The pharmacokinetic (PK) parameters and profiles of metformin in nine species were collected from the literature. Based on a simple allometric scaling, the systemic clearances (CL) of metformin in these species highly correlate with body weight (BW) (R2 = 0.85) and are comparable to renal plasma flow in most species except for rabbit and cat. Reported volumes of distribution (VSS) varied appreciably (0.32 to 10.1 L/kg) among species. Using the physiological and anatomical variables for each species, a minimal physiologically based pharmacokinetic (mPBPK) model consisting of blood and two tissue compartments (Tissues 1 and 2) was used for modeling metformin PK in the nine species. Permeability-limited distribution (low fd1 and fd2) and a single tissue-to-plasma partition coefficient (Kp) value for Tissues 1 and 2 were applied in the joint mPBPK fitting. Nonlinear regression analysis for common tissue distribution parameters along with species-specific CL values reasonably captured the plasma PK profiles of metformin across most species, except for rat and horse with later time deviations. In separate fittings of the mPBPK model to each species, Tissue 2 was considered as slowly-equilibrating compartment consisting of muscle and skin based on in silico calculations of the mean transit times through tissues. The well-fitted mPBPK model parameters for absorption and disposition PK of metformin for each species were compared with in vitro/in vivo results found in the literature with regard to the physiological details and physicochemical properties of metformin. Bioavailability and absorption rates decreased with the increased BW among the species. Tissues such as muscle dominate metformin distribution with low permeability and partitioning while actual tissue concentrations found in rats and mice show likely transporter-mediated uptake in liver, kidney, and gastrointestinal tissues. Metformin has diverse pharmacologic actions, and this assessment revealed allometric relationships in its absorption and renal clearance but considerable variability in actual and modeled tissue distribution probably caused by transporter differences.