Miracle-dz/UniFAR-FTUs huggingface dataset:
Introducing the GEV Activation Function for Highly Unbalanced Data to Develop COVID-19 Diagnostic Models

Fast and accurate diagnosis is essential for the efficient and effective control of the COVID-19 pandemic that is currently disrupting the whole world. Despite the prevalence of the COVID-19 outbreak, relatively few diagnostic images are openly available to develop automatic diagnosis algorithms. Traditional deep learning methods often struggle when data is highly unbalanced with many cases in one class and only a few cases in another; new methods must be developed to overcome this challenge. We propose a novel activation function based on the generalized extreme value (GEV) distribution from extreme value theory, which improves performance over the traditional sigmoid activation function when one class significantly outweighs the other. We demonstrate the proposed activation function on a publicly available dataset and externally validate on a dataset consisting of 1,909 healthy chest X-rays and 84 COVID-19 X-rays. The proposed method achieves an improved area under the receiver operating characteristic (DeLong's p-value < 0.05) compared to the sigmoid activation. Our method is also demonstrated on a dataset of healthy and pneumonia vs. COVID-19 X-rays and a set of computerized tomography images, achieving improved sensitivity. The proposed GEV activation function significantly improves upon the previously used sigmoid activation for binary classification. This new paradigm is expected to play a significant role in the fight against COVID-19 and other diseases, with relatively few training cases available.
Autoantibody-Based Diagnostic Biomarkers: Technological Approaches to Discovery and Validation

Autoantibodies produced against self-antigens, or ‘autoantigens’, result from a loss of selftolerance triggered by genetic and/or environmental factors which induce the immune system to attack the host’s own cells, resulting in a condition referred to as autoimmunity. In classic autoimmune diseases, it is well established that the pathology relates directly to the autoantibodies. However, it is increasingly recognised that autoantibodies are also found in many other disease areas, including cancers, cardiovascular and neurodegenerative diseases, as well infectious diseases such as malaria, albeit in such diseases it is unclear whether the autoantibodies play a direct role in the pathology or whether they are merely symptomatic of disease. Irrespective of whether they are causative or symptomatic of specific diseases though, there is increasing interest globally in exploring the clinical potential of circulating autoantibodies as diagnostic biomarkers. This chapter provides an overview of the diagnostic utility of autoantibody biomarkers in a range of disease areas and discusses their potential utility in disease staging, treatment monitoring and in prediction of immune-related adverse events. It also provides an overview of traditional and contemporary technological approaches to autoantibody biomarker discovery and validation, focusing on protein microarrays that are ideally suited to this important area of research.
ANTIOXIDANT, FREE RADICAL SCAVENGING ACTIVITY AND GC-MS STUDIES ON PEDILANTHUS TITHYMALOIDES (L.) POIT

Objective: To evaluate the methanolic extract of the leaves of Pedilanthus tithymaloides for total phenol, total flavonoid, total antioxidant and free radical scavenging ability and detect the phytoconstituents using GC-MS. Methods: The total phenols were quantified using Folin-Ciocalteu method. Aluminium chloride method and Phosphomolybdenum method were used to quantify total flavonoid and total antioxidant contentrespectively. In addition to the above, Ferric thiocyanate assay, the thiobarbituric acid assay,Ferric Reducing Antioxidant Power assay and ABTS assay were performed to know the antioxidant potency of the methanolic extract of leaves of Pedilanthus tithymaloides . The phytoconstituents was detected using GC-MS. Results: The leaves of Pedilanthus tithymaloides recorded a phenolic content of 10.98±0.08 mg TAE/g DW, flavonoid content of 11.49±0.15 µg QE/g DW and total antioxidant content of 6.64±0.05 mg TAE/g DW. The study also revealed significant free radical scavenging ability of the plant leaves as assessed by FTC, TBA, FRAP and ABTS assays. The structural elucidation by GC-MS analysis revealed five different compounds, includingthree esters, an amine and an alkaloid. Conclusion: The study proves the anticipative potential ability of Pedilanthus tithymaloides, suggesting its exploitation in pharmaceutical applications.
IsoSearch: An Untargeted and Unbiased Metabolite and Lipid Isotopomer Tracing Strategy from HR-LC-MS/MS Datasets

Stable isotopic tracer analysis is a technique used to determine carbon or nitrogen atom incorporation into biological systems. A number of mass spectrometry based approaches have been developed for this purpose, including high-resolution tandem mass spectrometry (HR-LC-MS/MS), selected reaction monitoring (SRM) and parallel reaction monitoring (PRM). We have developed an approach for analyzing untargeted metabolomic and lipidomic datasets using high-resolution mass spectrometry with polarity switching and implemented our approach in the open-source R script IsoSearch and in Scaffold Elements software. Using our strategy, which requires an unlabeled reference dataset and isotope labeled datasets across various biological conditions, we traced metabolic isotopomer alterations in breast cancer cells (MCF-7) treated with the metabolic drugs 2-deoxy-glucose, 6-aminonicotinamide, compound 968, and rapamycin. Metabolites and lipids were first identified by the commercial software Scaffold Elements and LipidSearch, then IsoSearch successfully profiled the 13C-isotopomers extracted metabolites and lipids from 13C-glucose labeled MCF-7 cells. The results interpreted known models, such as glycolysis and pentose phosphate pathway inhibition, but also helped to discover new metabolic/lipid flux patterns, including a reactive oxygen species (ROS) defense mechanism induced by 6AN and triglyceride accumulation in rapamycin treated cells. The results suggest the IsoSearch/Scaffold Elements platform is effective for studying metabolic tracer analysis in diseases, drug metabolism, and metabolic engineering for both polar metabolites and non-polar lipids.
Explaining Racial Inequality in Food Security in Columbus, Ohio: A Blinder–Oaxaca Decomposition Analysis

Food insecurity is a leading public health challenge in the United States. In Columbus, Ohio, as in many American cities, there exists a great disparity between Black and White households in relation to food insecurity. This study investigates the degree to which this gap can be attributed to differences in food shopping behavior, neighborhood perception, and socioeconomic characteristics. A Blinder–Oaxaca decomposition method is used to analyze a household survey dataset collected in 2014. We find a 34.2 percent point difference in food security between White and Black households. Variables related to food shopping behavior, neighborhood perception, and socioeconomic characteristics explain 13.8 percent, 11.6 percent, and 63.1 percent of the difference, respectively. These independent variables combined can explain 68.2 percent of the food security gap between White and Black households. Most of this is attributable to socioeconomic variables. Sense of friendship in neighborhood, use of private vehicles, and satisfaction of neighborhood food environment also partially contribute to the food security gap.
The Acceptance of Key Public Health Interventions by the Polish Population Is Related to Health Literacy, But Not eHealth Literacy

Background: Public health and health promotion rely on many different interventions, which range from health education and communication, through community mobilisation and changes to environmental conditions, to legal and fiscal actions. The introduction of the increased tax on sugar-sweetened beverages (SSB), popularly called sugar tax (ST), and a mandatory programme of vaccinations are the strategies inciting the most vivid discussions in Polish society. The study was intended to assess the determinants of the attitudes of Polish society regarding the ST and to vaccinations. Methods: For the analysis, the data originating from the survey of a representative adult sample of Polish society (n = 1000) was used. The survey was based on computer-assisted telephone interviewing (CATI). The assessment of the relationships between the selected variables and the opinions about the introduction of the ST and the safety and effectiveness of vaccinations were carried out using the chi2 test and univariate logistic regression models. Results: The acceptance of the ST and vaccination showed a significant relationship to the level of health literacy (HL) but not to eHealth literacy (eHL). Respondents having a higher rather than lower HL; older rather than younger; married rather than singles; retired, or on a disability pension, rather than vocationally active and nonusers of the Internet rather than users were more likely to show an acceptance for both interventions. Those more frequently using health care services and those with chronic diseases showed a greater belief in the safety and effectiveness of vaccinations. Conclusions: The relationship between the opinions of the two public health interventions analysed and the sociodemographic variables demonstrated similar patterns. Interestingly, the opinions were associated only with HL and not with eHL and users of the Internet were more sceptical about the interventions.
Influence of Cathodic Water Invigoration on the Emergence and Subsequent Growth of Controlled Deteriorated Pea and Pumpkin Seeds

The quality of seeds in gene banks gradually deteriorates during long-term storage, which is probably, at least in part, a result of the progressive development of oxidative stress. Here, we report a greenhouse study that was carried out to test whether a novel approach of seed invigoration using priming with cathodic water (cathodic portion of an electrolysed calcium magnesium solution) could improve seedling emergence and growth in two deteriorated crop seeds. Fresh seeds of Pisum sativum and Cucurbita pepo were subjected to controlled deterioration to 50% viability at 14% seed moisture content (fresh weight basis), 40 °C and 100% relative humidity. The deteriorated seeds were thereafter primed with cathodic water, calcium magnesium solution and deionized water. In addition, to study the mechanism of the impacts of invigoration, the effects of such priming on the lipid peroxidation products malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) and on the reactive oxygen species (ROS) scavenging enzymes superoxide dismutase and catalase were also determined in the fresh and deteriorated seeds. All priming treatments improved seed emergence parameters, subsequent seedling photosynthesis and growth relative to the unprimed seeds. In general, cathodic water was most effective at invigorating deteriorated seeds. Analysis of the lipid peroxidation products and antioxidant enzyme activities in invigorated seeds provided support for the hypothesis that the effectiveness of cathodic water in invigoration of debilitated orthodox seeds in general and of pea and pumpkin seeds in particular derive from its ability to act as an antioxidant.
Validation of the Turkey Semen Cryopreservation by Evaluating the Effect of Two Diluents and the Inseminating Doses

Simple Summary Achieving an effective freezing protocol, that is able to preserve the fertilizing ability of turkey semen, is a key aim for the establishment of the first national semen cryobank of autochthonous chicken and turkey breeds within our national project (Tutela della biodiversità nelle razze avicole italiane—TuBAvI). In this regard, we have performed different studies in order to define the best conditions for cryopreservation of turkey semen; namely, we identified an effective freezing protocol which is based on the use of dimethylsulfoxide as a permeant cryoprotectant (CPA) combined with Ficoll as a non-permeant CPA. Here, our purpose was to test this protocol in vivo, by evaluating the effect of two extenders and three inseminating doses. The good fertility and hatching rates achieved here are promising for future studies, in which our cryopreservation protocol will be tested on Italian autochthonous turkey breeds and also to the advantages offered by the extensive use of frozen semen in the turkey breeding industry. Abstract This study was designed to test the fertilizing ability of cryopreserved turkey semen, and here, two experiments were performed: an in vitro analysis to assess the effects of Tselutin and Lake diluents and an in vivo test to determine the fertility and hatching rates by also studying the feat of three insemination doses (250, 400 and 600 × 106 sperm/hen). Pooled semen samples were diluted with Tselutin or Lake extender which contained 20% of dimethylsulfoxide and 1 mM of Ficoll at final sperm concentration of 3 × 109 sperm/mL. Thereafter, semen was packaged into straws and frozen on liquid nitrogen. The post-thaw sperm quality was evaluated considering motility (computer-aided sperm analysis—CASA system) and membrane integrity (flow cytometry). Significantly higher values of progressive motility and some kinetic parameters in semen frozen with Lake were found. When we compared the extenders in vivo, no significant effects were detected, whilst sperm concentration significantly affected both fertility and hatching rates, with the best results obtained with the sperm concentration of 400 × 106 sperm/hen. From the results obtained, it emerged that the extender type only affected sperm motility characteristics, not the fertilizing ability of frozen-thawed semen, while inseminating dose markedly affected fertility and hatching rates.
Extracts of Phellinus linteus, Bamboo (Sasa senanensis) Leaf and Chaga Mushroom (Inonotus obliquus) Exhibit Antitumor Activity through Activating Innate Immunity

Natural products have attracted great interest for some time as alternative methods against cancers by fulfilling immunomodulating properties. In this study, we investigated the activity of hot water extracts (120 °C, >30 min) of Phellinus linteus, fresh leaves of Kumaizasa bamboo and Chaga mushroom which we called MeshimaMax, for cancer prevention and treatment by using different solid tumor models. In the implanted mouse sarcoma S180 tumor, MeshimaMax treatment significantly inhibited tumor growth when it was applied at the early stage of tumor inoculation. The effect was further confirmed by using carcinogen induced tumors, i.e., azoxymethane (AOM)/dextran sulfate sodium (DSS) induced mouse colon cancer and 7,12-dimethylbenz anthracene (DMBA) induced rat breast cancer. In both cases the occurrences of tumors were remarkably suppressed by administration of MeshimaMax which consists of three components above. More importantly, when MeshimaMax was combined with an anticancer chemotherapeutic drug, the therapeutic effect was remarkably improved. In vitro studies showed that when MeshimaMax was applied to mouse macrophage RAW264.7 cells the phagocytosis of macrophages was significantly activated, which was evaluated by using living yeast cells as well as synthetic nanoparticles. A cytotoxicity assay showed the 50% inhibitory concentration (IC50) was higher than 1 mg/mL and normal cells were 2–3 times more tolerant to MeshimaMax than cancer cells. These findings suggest the potential application of MeshimaMax for cancer prevention and as supplement regimen for anticancer chemotherapy, probably functioning through activation of innate immunity, which may benefit cancer patients as an alternative supplement.
Effect of Mutations on mRNA and Globin Stability: The Cases of Hb Bernalda/Groene Hart and Hb Southern Italy

We identified two unstable variants in the third exon of α-globin genes: Hb Bernalda/Groene Hart (HBA1:c.358C>T), and Hb Caserta (HBA2:c.79G>A) in cis to Hb Sun Prairie (HBA2:c.391G>C), also named Hb Southern Italy. These mutations occurred in the H helix of the α-globin that is involved in heme contacting, specific recognition of α-hemoglobin-stabilizing protein (AHSP), and α1β1 interactions. The carriers showed α-thalassemia phenotype, but one also jaundice and cholelithiasis. Molecular identification of clusters of families in Southern Italy encouraged molecular characterization of mRNA, globin chain analyses, molecular modeling studies, and comparison with globin variants to understand the mechanisms causing the α-thalassemia phenotype. A normal amount of Hb Bernalda/Groene Hart mRNA were found, and molecular modeling highlighted additional H bonds with AHSP. For Hb Southern Italy, showing an unexpected α/β biosynthetic ratio typical of the β-thalassemia type, two different molecular mechanisms were shown: Reduction of the variant mRNA, likely due to the No-Go Decay for the presence of unused triplet ACG at cod 26, and protein instability due to the impairment of AHSP interaction. The UDP glucuronosyltransferase 1A (UGT1A1) genotyping was conclusive in the case of jaundice and cholelithiasis. Multiple approaches are needed to properly identify the mechanisms leading to unstable variants and the effect of a mutation.
Objective Olfactory Findings in Hospitalized Severe COVID-19 Patients

Objective: We investigate the prevalence of the self-reported and objective sudden loss of smell (SLS) in patients with severe coronavirus disease 2019 (COVID-19). Methods: Severe COVID-19 patients with self-reported SLS were recruited at hospitalization discharge. Epidemiological and clinical data were collected. The Sino-nasal Outcome Test-22 (SNOT-22) was used to evaluate rhinological complaints. Subjective olfactory and gustatory functions were assessed with the National Health and Nutrition Examination Survey (NHNES). Objective SLS was evaluated using psychophysical tests. Potential associations between olfactory evaluation and the clinical outcomes (duration of hospitalization; admission biology; one month serology (IgG), and chest computed tomography findings) were studied. Results: Forty-seven patients completed the study (25 females). Subjectively, eighteen (38.3%) individuals self-reported subjective partial or total SLS. Among them, only three and four were anosmic and hyposmic, respectively (38.9%). Considering the objective evaluation in the entire cohort, the prevalence of SLS was 21.3%. Elderly patients and those with diabetes had lower objective olfactory evaluation results than young and non-diabetic individuals. Conclusions: The prevalence of SLS in severe COVID-19 patients appears to be lower than previously estimated in mild-to-moderate COVID-19 forms. Future comparative studies are needed to explore the predictive value of SLS for COVID-19 severity.
Cell Cycle Regulation in Macrophages and Susceptibility to HIV-1

Macrophages are the first line of defence against invading pathogens. They play a crucial role in immunity but also in regeneration and homeostasis. Their remarkable plasticity in their phenotypes and function provides them with the ability to quickly respond to environmental changes and infection. Recent work shows that macrophages undergo cell cycle transition from a G0/terminally differentiated state to a G1 state. This G0-to-G1 transition presents a window of opportunity for HIV-1 infection. Macrophages are an important target for HIV-1 but express high levels of the deoxynucleotide-triphosphate hydrolase SAMHD1, which restricts viral DNA synthesis by decreasing levels of dNTPs. While the G0 state is non-permissive to HIV-1 infection, a G1 state is very permissive to HIV-1 infection. This is because macrophages in a G1 state switch off the antiviral restriction factor SAMHD1 by phosphorylation, thereby allowing productive HIV-1 infection. Here, we explore the macrophage cell cycle and the interplay between its regulation and permissivity to HIV-1 infection.
The Relationship between Neighborhood Environment and Child Mental Health in Japanese Elementary School Students

Limited research has examined the relationship between neighborhood environment and mental health outcomes in elementary school students (middle childhood). In countries with high relative poverty, little is known about how neighborhood conditions are related to children’s health after controlling for family socioeconomic status; thus, it is necessary to distinguish the particular neighborhood characteristics relevant to behavioral risk in children, independent of socioeconomic position. Using a self-report survey completed by parents, we assessed neighborhood environment characteristics, children’s behavioral outcomes, and family socioeconomic status in fourth grade students from Nagoya, in Aichi prefecture, Japan (n = 695). A multiple linear regression was conducted to evaluate to what extent neighborhood characteristics predict child behaviors, after adjusting for socioeconomic variables. Greater aesthetic quality, walkability, accessibility of healthy foods, safety, and social cohesion were inversely linked to children’s behavioral problems and positively linked to social competence, suggesting that quality of living environment may affect behavioral outcomes in children, even after controlling for socioeconomic factors. Developing a quality environment that matches these characteristics may minimize the negative impact of a family’s socioeconomic distress and is likely to aid socioeconomically disadvantaged parents and their children. Thus, policies and programs that enhance the neighborhood environment for socioeconomically disadvantaged families should be promoted.
Conduct problems and depressive symptoms in association with problem gambling and gaming: A systematic review

Abstract Background and aims Behavioral addictions such as gambling and gaming disorder are significant public health issues that are of increasing importance to policy makers and health care providers. Problem gambling and gaming behaviors have been identified as being associated with externalizing and internalizing problems, with theoretical models suggesting that both conduct problems and depressive symptoms may be significant risk factors in the development of problem gambling and gaming. As such, the purpose of this systematic review is to provide an overview of research identifying the relationship between conduct problems, depressive symptoms and problem gambling and gaming among adolescents and young adults. Methods Systematic literature searches in accordance with PRISMA guidelines found 71 eligible studies that met the inclusion criteria, 47 for problem gambling, 23 for problem gaming and one for both problem behaviors. Results Based on cross-sectional evidence, both problem gambling and gaming are consistently concurrently associated with conduct problems and depressive symptoms. Longitudinal evidence appears to be clearer for conduct problems as a risk factor for problem gambling, and depressive symptoms as a risk factor for problem gaming. However, both risk factors appear to increase the risk for these problem behaviors. Discussion and Conclusions Results from the literature review suggest that problem gambling and gaming are associated with the presence of conduct problems and depressive symptoms, with the potential of sharing common etiological factors. Additional research is necessary to confirm these longitudinal relationships with an emphasis on investigating the interaction of both early conduct problems and depressive symptoms.