Influence of augmentation on the performance of the double ResNet-based model for chest X-ray classification

Purpose: A pandemic disease elicited by the SARS-CoV-2 virus has become a serious health issue due to infecting millions of people all over the world. Recent publications prove that artificial intelligence (AI) can be used for medical diagnosis purposes, including interpretation of X-ray images. X-ray scanning is relatively cheap, and scan processing is not computationally demanding. Material and methods: In our experiment a baseline transfer learning schema of processing of lung X-ray images, including augmentation, in order to detect COVID-19 symptoms was implemented. Seven different scenarios of augmentation were proposed. The model was trained on a dataset consisting of more than 30,000 X-ray images. Results: The obtained model was evaluated using real images from a Polish hospital, with the use of standard metrics, and it achieved accuracy = 0.9839, precision = 0.9697, recall = 1.0000, and F1-score = 0.9846. Conclusions: Our experiment proved that augmentations and masking could be important steps of data pre-processing and could contribute to improvement of the evaluation metrics. Because medical professionals often tend to lack confidence in AI-based tools, we have designed the proposed model so that its results would be explainable and could play a supporting role for radiology specialists in their work

Female Fabry disease patients and X-chromosome inactivation

Fabry disease is an X-linked inherited lysosomal storage disorder caused by mutations in the gene encoding α- galactosidase A (GLA). Once it was thought to affect only hemizygous males. Over the last fifteen years, research has shown that most females carrying mutated allele also develop symptoms, demonstrating a wide range of disease severity, from a virtually asymptomatic to more classical profile, with cardiac, renal, and cerebrovascular manifestations. This variable expression in females is thought to be influenced by the process of X-chromosome inactivation (XCI). The aim of this study was to assess severity of the clinical phenotype, to analyze XCI patterns, and to estimate their effect on disease manifestation in twelve female Fabry disease patients from five unrelated Polish families. Our analyses revealed that patients presented with the broad range of disease expression - from mild to severe, and their clinical involvement did not correlate with XCI profiles. Female carriers of the mutation in the GLA gene with the random XCI may present with the wide range of disease signs and symptoms. Thus, XCI is not a main factor in the phenotype variability of Fabry disease manifestation in heterozygous females

Synthetic genistein derivatives as modulators of glycosaminoglycan synthesis

Background: Mucopolysaccharidoses (MPS) are severe metabolic disorders caused by 26 accumulation of undegraded glycosaminoglycans (GAGs) in lysosomes due to defects in certain 27 lysosomal hydrolases. Substrate reduction therapy (SRT) has been proposed as one of potential 28 treatment procedures of MPS. Importantly, small molecules used in such a therapy might 29 potentially cross the blood-brain barrier (BBB) and improve neurological status of patients, as 30 reported for a natural isoflavone, 5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one, 31 also known as genistein. Although genistein is able to cross BBB to some extent, its delivery to 32 the central nervous system is still relatively poor (below 10% efficiency). Thus, we aimed to 33 develop a set of synthetically modified genistein molecules and characterize physicochemical as 34 well as biological properties of these compounds. Methods: Following parameters were 35 determined for the tested synthetic derivatives of genistein: cytotoxicity, effects on cell 36 proliferation, kinetics of GAG synthesis, effects on epidermal growth factor (EGF) receptor’s 37 tyrosine kinase activity, effects on lysosomal storage, potential ability to cross BBB. Results: We 38 observed that some synthetic derivatives inhibited GAG synthesis similarly to, or more 39 efficiently than, genistein and were able to reduce lysosomal storage in MPS III fibroblasts. The 40 tested compounds were generally of low cytotoxicity and had minor effects on cell proliferation. 41 Moreover, synthetic derivatives of genistein revealed higher lipophilicity (assessed in silico) than 42 the natural isoflavone. Conclusion: Some compounds tested in this study might be promising 43 candidates for further studies on therapeutic agents in MPS types with neurological symptoms

Lipophagy and lipolysis status in lipid storage and lipid metabolism diseases

This review discusses how lipophagy and cytosolic lipolysis degrade cellular lipids, as well as how these pathway ys communicate, how they affect lipid metabolism and energy homeostasis in cells and how their dysfunction affects the pathogenesis of lipid storage and lipid metabolism diseases. Answers to these questions will likely uncover novel strategies for the treatment of aforementioned human diseases, but, above all, will avoid destructive effects of high concentrations of lipids—referred to as lipotoxicity—resulting in cellular dysfunction and cell death

Modulation of expression of genes involved in glycosaminoglycan metabolism and lysosome biogenesis by flavonoids

Flavonoids were found previously to modulate efficiency of synthesis of glycosaminoglycans (GAGs), compounds which are accumulated in cells of patients suffering from mucopolysaccharidoses (MPSs). The aim of this work was to determine effects of different flavonoids (genistein, kaempferol, daidzein) used alone or in combinations, on expression of genes coding for proteins involved in GAG metabolism. Analyses with DNA microarray, followed by real-time qRT-PCR revealed that genistein, kaempferol and combination of these two compounds induced dose- and time-dependent remarkable alterations in transcript profiles of GAG metabolism genes in cultures of wild-type human dermal fibroblasts (HDFa). Interestingly, effects of the mixture of genistein and kaempferol were stronger than those revealed by any of these compounds used alone. Similarly, the most effective reduction in levels of GAG production, in both HDFa and MPS II cells, was observed in the presence of genistein, keampferol and combination of these compounds. Forty five genes were chosen for further verification not only in HDFa, but also inMPS II fibroblasts by using real-time qRT-PCR. Despite effects on GAG metabolism-related genes, we found that genistein, kaempferol and mixture of these compounds significantly stimulated expression of TFEB. Additionally, a decrease inMTOR transcript level was observed at these conditions

Glycosaminoglycans and mucopolysaccharidosis type III

Mucopolysaccharidosis type III (MPS III), or Sanfilippo syndrome, is a lysosomal storage disease in which heparan sulfate is accumulated in lysosomes, as well as outside of cells, as the primary storage material. This disease is a complex of four conditions caused by dysfunctions of one of genes coding for lysosomal enzymes involved in degradation of heparan sulfate: SGSH (coding for heparan N-sulfatase) – causing MPS IIIA, NAGLU (coding for -N-acetylglucosaminidase) - causing MPS IIIB, HGSNAT (coding for acetyl CoA -glucosaminide acetyltransferase) - causing MPS IIIC), and GNS (coding for N-acetylglucosamine-6-sulfatase) – causing MPS IIID. The primary storage is responsible for some disease symptoms, but other arise as a result of secondary storage, including glycosphingolipids, and subsequent processes, like oxidative stress and neuroinflammation. Central nervous system is predominantly affected in all subtypes of MPS III. Heparan sulfate and its derivatives are the most commonly used biomarkers for diagnosis and prediction procedures. Currently, there is no therapy for Sanfilippo syndrome, however, clinical trials are ongoing for enzyme replacement therapy, gene therapy and substrate reduction therapy (particularly gene expression-targeted isoflavone therapy)

A Machine-Learning-Based Approach to Prediction of Biogeographic Ancestry within Europe

Data obtained with the use of massive parallel sequencing (MPS) can be valuable in population genetics studies. In particular, such data harbor the potential for distinguishing samples from different populations, especially from those coming from adjacent populations of common origin. Machine learning (ML) techniques seem to be especially well suited for analyzing large datasets obtained using MPS. The Slavic populations constitute about a third of the population of Europe and inhabit a large area of the continent, while being relatively closely related in population genetics terms. In this proof-of-concept study, various ML techniques were used to classify DNA samples from Slavic and non-Slavic individuals. The primary objective of this study was to empirically evaluate the feasibility of discerning the genetic provenance of individuals of Slavic descent who exhibit genetic similarity, with the overarching goal of categorizing DNA specimens derived from diverse Slavic population representatives. Raw sequencing data were pre-processed, to obtain a 1200 character-long binary vector. A total of three classifiers were used—Random Forest, Support Vector Machine (SVM), and XGBoost. The most-promising results were obtained using SVM with a linear kernel, with 99.9% accuracy and F1-scores of 0.9846–1.000 for all classes

Experimental Plant Biology: Why Not?! Genistein: a natural isoflavone with a potential for treatment of genetic diseases

Abstract Genistein [4 ,5,7-trihydroxyisoflavone or 5,7-dihydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one] is a natural isoflavone occurring in many plants known to possess various biological activities, ranging from phyto-oestrogenic to antioxidative actions. Recent studies indicated that this isoflavone can also be considered as a drug for as yet untreatable genetic diseases. In the present review, we discuss a plausible use of genistein in treatment of two genetic disorders: CF (cystic fibrosis) and MPS (mucopolysaccharidosis). Although various biological actions of genistein are employed in these two cases, in vitro studies, tests on animal models and pilot clinical trials suggest that this plant-derived compound might be a real hope for patients suffering from severe inherited disorders with relatively complicated pathomechanisms, including those affecting the central nervous system