PET-Derived Radiomics and Artificial Intelligence in Breast Cancer: A Systematic Review

Breast cancer (BC) is a heterogeneous malignancy that still represents the second cause of cancer-related death among women worldwide. Due to the heterogeneity of BC, the correct identification of valuable biomarkers able to predict tumor biology and the best treatment approaches are still far from clear. Although molecular imaging with positron emission tomography/computed tomography (PET/CT) has improved the characterization of BC, these methods are not free from drawbacks. In recent years, radiomics and artificial intelligence (AI) have been playing an important role in the detection of several features normally unseen by the human eye in medical images. The present review provides a summary of the current status of radiomics and AI in different clinical settings of BC. A systematic search of PubMed, Web of Science and Scopus was conducted, including all articles published in English that explored radiomics and AI analyses of PET/CT images in BC. Several studies have demonstrated the potential role of such new features for the staging and prognosis as well as the assessment of biological characteristics. Radiomics and AI features appear to be promising in different clinical settings of BC, although larger prospective trials are needed to confirm and to standardize this evidence.     

Whole Body Vibration Improves Brain and Musculoskeletal Health by Modulating the Expression of Tissue-Specific Markers: FNDC5 as a Key Regulator of Vibration Adaptations

Whole body vibration (WBV) is well known to exert beneficial effects on multiple tissues, improving synaptic transmission, muscle mass, bone quality, and reducing anxiety and depressive behavior. However, the underlying molecular mechanisms are not yet fully understood, and organs and tissues may respond differently to the vibratory stimulus depending on multiple factors. Therefore, we investigated the WBV effects on the brain and musculoskeletal tissue of 4-month-old young mice, evaluating synaptic plasticity by electrophysiological recordings and tissue organization by histology and histomorphometric analysis. Specifically, WBV protocols were characterized by the same vibration frequency (45 Hz), but different in vibration exposure time (five series of 3 min for the B protocol and three series of 2 min and 30 s for the C protocol) and recovery time between two vibration sessions (1 min for the B protocol and 2 min and 30 s for the C protocol). In addition, immunohistochemistry was conducted to evaluate the expression of fibronectin type III domain-containing protein 5 (FNDC5), as well as that of tissue-specific markers, such as brain-derived neurotrophic factor (BDNF) in brain, myostatin in muscle and collagen I (COL-1) in bone. Our results suggest that the WBV effects depend closely on the type of protocol used and support the hypothesis that different organs or tissues have different susceptibility to vibration. Further studies will be needed to deepen our knowledge of physiological adaptations to vibration and develop customized WBV protocols to improve and preserve cognitive and motor functions.     

CD73-Adenosinergic Axis Mediates the Protective Effect of Extracellular Vesicles Derived from Mesenchymal Stromal Cells on Ischemic Renal Damage in a Rat Model of Donation after Circulatory Death

We propose a new organ-conditioning strategy based on mesenchymal stromal cell (MSCs)/extracellular vesicle (EVs) delivery during hypothermic perfusion. MSCs/EVs marker CD73 is present on renal proximal tubular cells, and it protects against renal ischemia-reperfusion injury by converting adenosine monophosphate into adenosine (ADO). In this study, after checking if CD73-silenced EVs (EVsi) would impact in vitro tubular-cell proliferation, we perfused kidneys of a rat model of donation after circulatory death, with Belzer solution (BS) alone, BS supplemented with MSCs, EVs, or EVsi. The ADO and ATP levels were measured in the effluents and tissues. Global renal ischemic damage score (GRS), and tubular cell proliferation index (IPT) were evaluated in the tissue. EVsi did not induce cell proliferation in vitro. Ex vivo kidneys perfused with BS or BS + EVsi showed the worst GRS and higher effluent ADO levels than the MSC- and EV-perfused kidneys. In the EV-perfused kidneys, the tissue and effluent ATP levels and IPT were the highest, but not if CD73 was silenced. Tissue ATP content was positively correlated with tissue ADO content and negatively correlated with effluent ADO level in all groups. In conclusion, kidney conditioning with EVs protects against ischemic damage by activating the CD73/ADO system.     

A theory of ultimately periodic languages and automata with an application to time granularity

In this paper, we develop a theory of regular ω-languages that consist of ultimately periodic words only and we provide it with an automaton-based characterization. The resulting class of automata, called ultimately periodic automata (UPA), is a subclass of the class of Büchi automata and inherits some properties of automata over finite words (NFA). Taking advantage of the similarities among UPA, Büchi automata, and NFA, we devise efficient solutions to a number of basic problems for UPA, such as the inclusion, the equivalence, and the size optimization problems. The original motivation for developing a theory of ultimately periodic languages and automata was to represent and to reason about sets of time granularities in knowledge-based and database systems. In the last part of the paper, we show that UPA actually allow one to represent (possibly infinite) sets of granularities, instead of single ones, in a compact and suitable to algorithmic manipulation way. In particular, we describe an application of UPA to a concrete time granularity scenario taken from clinical medicine.     

Symposium review: The importance of the ruminal epithelial barrier for a healthy and productive cow

The stratified squamous ruminal epithelium is the main site for absorption of key nutrients (e.g., short-chain fatty acids; SCFA) and electrolytes (e.g., sodium and magnesium). The absorptive function has to be highly selective to prevent simultaneous entry of microbes and toxins from the rumen into the blood. As such, epithelial absorption is primarily transcellular, whereas the paracellular pathway appears rather tightly sealed. A network of tight junction (claudin-1, claudin-4, and occludin) and tight junction-associated proteins (e.g., zonula occludens) accomplishes the latter. When microbial fermentation activity is high such as with highly fermentable diets, rumen epithelial functions are often challenged by acidity, high osmolarity, toxins (e.g., endotoxin and histamine), and immune mediators (inflammatory mediators and cytokines) released during local and systemic inflammation. Epithelial damage by low pH in combination with high luminal SCFA concentrations is not immediately reversible and may initially aggravate upon return to physiological pH. In contrast, barrier opening upon hyperosmolarity is acutely transient. The initial insults set by luminal acidity and SCFA and the increasing concentrations of microbial-associated molecular patterns such as lipopolysaccharides are key factors that trigger inflammation not only in the rumen but also in the hindgut (cecum and colon), which reach out to the liver and other organs, causing systemic inflammation. Low feed intake during parturition, transportation, heat stress, or disease is the second most relevant challenge for the ruminal epithelial barrier. The barrier opening is usually only transient and quickly restored upon refeeding. Due to a rapid, dose-dependent, and prolonged decrease in absorption capacity for SCFA, however, any feed restriction increases the odds for postrestriction subacute ruminal acidosis. Inflammation due to acidosis can be alleviated by supplemental thiamine, yeasts, and plant bioactive (phytogenic) compounds. Butyrate is used in weaning calves to support ruminal barrier development; however, excess butyrate may promote hyperkeratosis, parakeratosis, and epithelial injury in the fully developed rumen of adult cows. Further research is needed to enhance the understanding of the various factors that counteract barrier impairment and help barrier restoration during acidogenic feeding, especially when concurring with unavoidable periods of feed restriction.     

Sensorische Analyse, Malat- und Saccharosegehalt und Fruchtfleischfestigkeit verschiedener Apfelsorten

Zusammenfassung Neben einer ausführlichen sensorischen Beurteilung der Frühsorte Jamba, der mittelspäten Sorten Holsteiner Cox und Roter Holsteiner Cox sowie der späten Sorte Gloster wurden parallel dazu der Malat- und Saccharosegehalt und die Fruchtfleischfestigkeit bestimmt. Die Korrelation dieser chemisch-physikalischen Parameter mit der Bewertung des Geschmacks und der Fruchtfleischstruktur sollte die Frage klären, ob eine Qualitätsaussage unter Umgehung der sensorischen Beurteilung möglich ist. Durch Vergleich ergab sich, daß für alle untersuchten Sorten der Malat- und/oder Saccharosegehalt wenig über die geschmacklichen Qualität der Früchte aussagt. Engere Beziehungen traten zwischen den Parametern sensorische Fruchtfleischbewertung und Festigkeit auf, wo bei einem Festigkeitswert von 5–5,3 kp/cm² und mehr das entsprechende senorische Urteil nicht schlechter als mittelmäßig ausfiel.

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Sensory evaluation, content of malate and sucrose, and fruit firmness of different apple varieties

Summary Parallel to a detailed sensory evaluation of the apple varieties Jamba, Holsteiner Cox, Red Holsteiner Cox and Gloster the content of malate and sucrose and fruit flesh firmness were measured. Comparisons between chemical and physical parameters and the sensory evaluation of taste and fruit flesh structure were performed to see, if apple quality can be determined without sensory assessment. The results for all samples show that content of malate and sucrose means little in relation to fruit taste. Recommendations for an optimum storage period could not be made. There was a closer relationship between sensory fruit flesh assessment and flesh firmness with a firmness of 5–5,3 kp/cm² or higher sensory evaluation was not worse than fair.

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Teil der Dissertation Mast, Kiel 1982     

The State of the Art of Piezo1 Channels in Skeletal Muscle Regeneration

Piezo1 channels are highly mechanically-activated cation channels that can sense and transduce the mechanical stimuli into physiological signals in different tissues including skeletal muscle. In this focused review, we summarize the emerging evidence of Piezo1 channel-mediated effects in the physiology of skeletal muscle, with a particular focus on the role of Piezo1 in controlling myogenic precursor activity and skeletal muscle regeneration and vascularization. The disclosed effects reported by pharmacological activation of Piezo1 channels with the selective agonist Yoda1 indicate a potential impact of Piezo1 channel activity in skeletal muscle regeneration, which is disrupted in various muscular pathological states. All findings reported so far agree with the idea that Piezo1 channels represent a novel, powerful molecular target to develop new therapeutic strategies for preventing or ameliorating skeletal muscle disorders characterized by an impairment of tissue regenerative potential.     

Lipidomic Approaches to Study HDL Metabolism in Patients with Central Obesity Diagnosed with Metabolic Syndrome

The metabolic syndrome (MetS) is a cluster of cardiovascular risk factors characterised by central obesity, atherogenic dyslipidaemia, and changes in the circulating lipidome; the underlying mechanisms that lead to this lipid remodelling have only been partially elucidated. This study used an integrated “omics” approach (untargeted whole serum lipidomics, targeted proteomics, and lipoprotein lipidomics) to study lipoprotein remodelling and HDL composition in subjects with central obesity diagnosed with MetS (vs. controls). Compared with healthy subjects, MetS patients showed higher free fatty acids, diglycerides, phosphatidylcholines, and triglycerides, particularly those enriched in products of de novo lipogenesis. On the other hand, the “lysophosphatidylcholines to phosphatidylcholines” and “cholesteryl ester to free cholesterol” ratios were reduced, pointing to a lower activity of lecithin cholesterol acyltransferase (LCAT) in MetS; LCAT activity (directly measured and predicted by lipidomic ratios) was positively correlated with high-density lipoprotein cholesterol (HDL-C) and negatively correlated with body mass index (BMI) and insulin resistance. Moreover, many phosphatidylcholines and sphingomyelins were significantly lower in the HDL of MetS patients and strongly correlated with BMI and clinical metabolic parameters. These results suggest that MetS is associated with an impairment of phospholipid metabolism in HDL, partially led by LCAT, and associated with obesity and underlying insulin resistance. This study proposes a candidate strategy to use integrated “omics” approaches to gain mechanistic insights into lipoprotein remodelling, thus deepening the knowledge regarding the molecular basis of the association between MetS and atherosclerosis.     

Integrated membrane operations in the ethylene oxide production

Petrochemical industry, highly energy and capital intensive, might significantly benefit from the implementation of membrane operations for meeting stringent environmental standards, controlling production cost and final product's quality. Membrane units have been proved effective for improving the efficiency of different industrial productions. Ethylene oxide (EO), an important petrochemical intermediate, is produced by selective catalytic oxidation of ethylene, a valuable hydrocarbon feedstock. In this study, the EO manufacturing cycle is redesigned by integrating different membrane operations. Both the conversion and separation sections of the plant are investigated, considering the use of membrane reactors (MRs) for the separate feeding of the oxidant, membrane contactors (MCs) for the absorption of EO and carbon dioxide, and gas separation (GS) membrane units for the hydrocarbon recovery before their being recycled to the reactor. Design considerations are provided, and the benefits coming from each membrane operation, as well as from their synergic integration, are outlined with particular attention to environmental impact, raw materials and energy consumption.