Miracle-dz/UniFAR-FTUs huggingface dataset:
Ensemble Method of Convolutional Neural Networks with Directed Acyclic Graph Using Dermoscopic Images: Melanoma Detection Application

The early detection of melanoma is the most efficient way to reduce its mortality rate. Dermatologists achieve this task with the help of dermoscopy, a non-invasive tool allowing the visualization of patterns of skin lesions. Computer-aided diagnosis (CAD) systems developed on dermoscopic images are needed to assist dermatologists. These systems rely mainly on multiclass classification approaches. However, the multiclass classification of skin lesions by an automated system remains a challenging task. Decomposing a multiclass problem into a binary problem can reduce the complexity of the initial problem and increase the overall performance. This paper proposes a CAD system to classify dermoscopic images into three diagnosis classes: melanoma, nevi, and seborrheic keratosis. We introduce a novel ensemble scheme of convolutional neural networks (CNNs), inspired by decomposition and ensemble methods, to improve the performance of the CAD system. Unlike conventional ensemble methods, we use a directed acyclic graph to aggregate binary CNNs for the melanoma detection task. On the ISIC 2018 public dataset, our method achieves the best balanced accuracy (76.6%) among multiclass CNNs, an ensemble of multiclass CNNs with classical aggregation methods, and other related works. Our results reveal that the directed acyclic graph is a meaningful approach to develop a reliable and robust automated diagnosis system for the multiclass classification of dermoscopic images.
Selenium and Vitamin E Concentrations in Miranda Jennies and Foals (Equus asinus) in Northeast Portugal

Simple Summary Despite the importance of donkeys through history and their productive resuscitation during the last decades, reference values for common elements are not yet readily available. Such a challenge becomes even more noticeable when practitioners aim at evaluating the physiological and pathological concentrations of certain elements across the different stages that a donkey can go through along its life. The aims of this study are to determine baseline selenium and vitamin E concentrations for Miranda donkeys both jennies and foals. Miranda donkeys are considered to be endangered and it is possible that selenium and vitamin E may be associated with foal survival. Critical points may be identified related to overdosing or deficient levels of selenium and vitamin E, at different stages of development of gestation in utero during fetal development, parturition, and post foaling. Our study suggests that vitamin E and Se levels can have a major impact and effect on foal health and mortality levels. Multiple factors including location, diet, management practices, parity and time of breeding, and age of jenny may affect blood profiles in jennies, which ultimately may affect the profiles of her foals. Abstract The increase in donkeys treated by practitioners in recent years has led to an increased interest in finding more information on basic biochemical preliminary reference values. The aims of this study were to measure Se and Vit E levels in plasma from Miranda jennies peripartum and postpartum and in their foals to compare blood profiles of the jenny and foal related to the overall foal’s health. Twenty-two healthy peripartum and postpartum Miranda donkeys were sampled (12 jennies and 10 foals) in the northeast of Portugal (Atenor and Paradela) from May to November, 2018. Amounts of selenium in soil were significantly correlated (0.97) to concentrations of selenium in jennies (42.412 μg/L in Atenor and 9.612 μg/L in Paradela) and foals (19.378 μg/L in Atenor and 6.430 μg/L in Paradela). Selenium levels were lower in foals than adults and in males than females. Vitamin E was associated with overall foal health. Foals with a mean vitamin E of 3.585–5.307 mg/L showed signs of weakness, but carpal flexural deformities were observed when the average vitamin E was 11.520 mg/L. Low vitamin E levels (5.307 mg/L) in jennies were related to foal mortality. Diets, location, parity, and age affect blood profiles of jennies and, ultimately, foal health.
Factors Related to Breastfeeding Support in Lebanese Daycare Centers: A Qualitative Study among Daycare Directors and Employees

Breastfeeding has an important impact on maternal and child health, and is affected by several factors influencing its initiation and continuation. This qualitative study aimed to assess the main promoting and hindering factors for breastfeeding support in Lebanese daycare centers (DCCs), through the perspective of their directors and employees. The study was based on semi-structured interviews with 13 directors and 9 employees. It explored the influence of various cognitive factors as well as different environment types (physical, economic, political, and sociocultural) on their breastfeeding support. Findings suggested the directors and employees valued improving breastfeeding support in DCCs and the physical set-up of the DCCs allowed for this. However, various other factors restricted their abilities to support breastfeeding in the DCC, including limited knowledge and training on the topic, absence of written internal policies on breastfeeding, lack of enforcement in the application of national policies, and the current mothers’ work policies that negatively influenced the decision to breastfeed. Improvements could be achieved through integrated interventions, targeting the interaction of internal DCCs factors and national and DCCs breastfeeding policies, as well as several social factors, to create a multilevel approach targeting breastfeeding continuation support in breastfeeding-friendly DCCs in Lebanon and the region.
Effects of Lactobacillus rhamnosus and Enterococcus faecalis Supplementation as Direct-Fed Microbials on Rumen Microbiota of Boer and Speckled Goat Breeds

The effects on rumen microbial communities of direct-fed probiotics, Lactobacillus rhamnosus and Enterococcus faecalis, singly and in combination as feed supplements to both the Boer and Speckled goats were studied using the Illumina Miseq platform targeting the V3-V4 region of the 16S rRNA microbial genes from sampled rumen fluid. Thirty-six goats of both the Boer and Speckled were divided into five experimental groups: (T1) = diet + Lactobacillus rhamnosus; (T2) = diet + Enterococcus faecalis; (T3) = diet + Lactobacillus rhamnosus + Enterococcus faecalis; (T4, positive control) = diet + antibiotic and (T5, negative control) = diet without antibiotics and without probiotics. Our results revealed that Bacteroidetes, Firmicutes, TM7, Proteobacteria, and Euryarchaeota dominate the bacterial communities. In our observations, Lactobacillus rhamnosus and Enterococcus faecalis supplements reduced the archaeal population of Methanomassiliicocca in the T1, T2 and T3 groups, and caused an increase in the T4 group. Chlamydiae were present only in the T5 group, suggesting that probiotic and antibiotic inhibit the growth of pathogens in the rumen. We inferred, based on our results, that Lactobacillus rhamnosus and Enterococcus faecalis favour the survival of beneficial microbial communities in the goats’ rumen. This may lead to an overall improved feed efficacy and growth rate.
Chimeric Stimuli-Responsive Liposomes as Nanocarriers for the Delivery of the Anti-Glioma Agent TRAM-34

Nanocarriers are delivery platforms of drugs, peptides, nucleic acids and other therapeutic molecules that are indicated for severe human diseases. Gliomas are the most frequent type of brain tumor, with glioblastoma being the most common and malignant type. The current state of glioma treatment requires innovative approaches that will lead to efficient and safe therapies. Advanced nanosystems and stimuli-responsive materials are available and well-studied technologies that may contribute to this effort. The present study deals with the development of functional chimeric nanocarriers composed of a phospholipid and a diblock copolymer, for the incorporation, delivery and pH-responsive release of the antiglioma agent TRAM-34 inside glioblastoma cells. Nanocarrier analysis included light scattering, protein incubation and electron microscopy, and fluorescence anisotropy and thermal analysis techniques were also applied. Biological assays were carried out in order to evaluate the nanocarrier nanotoxicity in vitro and in vivo, as well as to evaluate antiglioma activity. The nanosystems were able to successfully manifest functional properties under pH conditions, and their biocompatibility and cellular internalization were also evident. The chimeric nanoplatforms presented herein have shown promise for biomedical applications so far and should be further studied in terms of their ability to deliver TRAM-34 and other therapeutic molecules to glioblastoma cells.
Do Hot Executive Functions Relate to BMI and Body Composition in School Age Children?

Deficits of ‘hot’ executive functions (EFs) involving emotional and motivational processes are considered as a risk factor for excessive weight, but few studies have tested the relationship between hot EFs and body composition in children. The aim of the study was to assess the association of the ability to delay gratification and affective decision-making with the body mass index (BMI) and body composition in children with typical neurocognitive development. The sample consisted of 553 Polish children aged between 6–12 y. The delay of gratification task (DGT) was applied to assess the ability to delay gratification. The Hungry Donkey test (HDT) was applied to assess affective decision-making. The indicators of decision-making in the HDT were net score and learning rate. The relationships between hot EFs and BMI, fat mass index (FMI), lean body mass index (LBMI) were tested. The association of the z scores of BMI and FMI, overweight/obesity, and the ability to delay gratification was found insignificant after controlling cofounding factors. Most of the results on affective decision-making and z scores for BMI, FMI and LBMI were insignificant as well. The relationship between the ability to delay gratification, affective decision-making, and adiposity is not pronounced in typically developed children.
Changes in Lifestyle and Dietary Habits during COVID-19 Lockdown in Italy: Results of an Online Survey

COVID-19 is an unprecedented global pandemic. On 12 March 2020, a lockdown order was issued in Italy in attempt to contain the health crisis. The study aimed to assess the impact of the COVID-19 lockdown on diet, physical activity, sleep quality, and distress in an Italian cohort. An online anonymous interview, which included validated questionnaires was created to compare lifestyle habits pre- and during the lockdown. Data analysis from 604 subjects with a mean age of 29.8 years was carried out using multivariate analysis. Compared to pre-COVID-19 times, 67% of people changed their eating habits and increased consumption of foods containing added sugars. Women and men with low adherence to the Mediterranean Diet (MedDiet) were more likely to be physically inactive (p < 0.0001 and p < 0.01, respectively). Results from logistic regression showed a three times higher risk of being inactive if adherence to the MedDiet was low (p < 0.0001), especially in men between 26 and 35 years. Lower levels of distress were reported in males who were physically active (89%) (p < 0.001). Our findings may help to identify effective lifestyle interventions during restrictive conditions.
Brief Mindfulness Intervention vs. Health Enhancement Program for Patients Undergoing Dialysis: A Randomized Controlled Trial

Background: Between 20–50% of patients undergoing maintenance dialysis for end-stage kidney disease experience symptoms of depression and/or anxiety, associated with increased mortality, greater health care utilization, and decreased quality of life. It is unknown whether mindfulness-based interventions can improve depression and anxiety symptoms in patients receiving this treatment. Methods: We conducted an 8-week multicenter randomized controlled trial comparing a brief mindfulness intervention (BMI) vs. an active control (Health Enhancement Program [HEP]) in 55 patients receiving dialysis with symptoms of depression and/or anxiety. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) depression scores, with a primary analysis in participants with baseline PHQ-9 ≥ 10, and a secondary analysis including all participants. The secondary outcome was change in Generalized Anxiety Disorder-7 (GAD-7) anxiety scores with corresponding primary and secondary analyses. Results: Both BMI and HEP reduced depressive symptoms, with no difference between trial arms (PHQ-9 change = −7.0 vs. −6.1, p = 0.62). BMI was more effective than HEP in reducing anxiety (GAD-7 change = −8.7 vs. −1.4, p = 0.01). Secondary analyses revealed no differences between arms. Conclusions: For patients undergoing dialysis, both BMI and HEP may be helpful interventions for depression symptoms, and BMI may be superior to HEP for anxiety symptoms. Mindfulness-based and other psychosocial interventions may be further evaluated in those undergoing dialysis as treatment options for symptoms of depression and anxiety.
Human Papilloma Virus Vaccination

Human papilloma virus (HPV) is the most common sexually transmitted infection worldwide causing a variety of benign and malignant conditions. A significant portion of the global population is infected with HPV, with the virus attributed to causing up to 5% of cancers worldwide. Bivalent, quadrivalent, and nine-valent vaccinations exist to aid in the prevention of these diseases and have been proven to be effective at preventing both benign and malignant disease. While vaccination is readily accessible in more developed countries, barriers exist to worldwide distribution and acceptance of vaccination. Vaccination and screening of HPV infection when used in combination are proven and predicted to decrease HPV related pathology. Improvements in vaccination formulations, for treatment as well as prevention, are actively being sought from a variety of mechanisms. Despite these advancements, and the data supporting their efficacy, there has been substantial delay in obtaining adequate vaccination coverage. In reviewing these challenges and looking forward to new vaccine development—especially within the current pandemic—it is clear from the challenges of HPV we require methods to more effectively encourage vaccination, ways to dispel vaccination myths as they occur, and implement better processes for vaccine distribution globally.
Model-Informed Optimization of a Pediatric Clinical Pharmacokinetic Trial of a New Spironolactone Liquid Formulation

Quantitative pharmacology brings important advantages in the design and conduct of pediatric clinical trials. Herein, we demonstrate the application of a model-based approach to select doses and pharmacokinetic sampling scenarios for the clinical evaluation of a novel oral suspension of spironolactone in pediatric patients with edema. A population pharmacokinetic model was developed and qualified for spironolactone and its metabolite, canrenone, using data from adults and bridged to pediatrics (2 to <17 years old) using allometric scaling. The model was then used via simulation to explore different dosing and sampling scenarios. Doses of 0.5 and 1.5 mg/kg led to target exposures (i.e., similar to 25 and 100 mg of the reference product in adults) in all the reference pediatric ages (i.e., 2, 6, 12 and 17 years). Additionally, two different sampling scenarios were delineated to accommodate patients into sparse sampling schemes informative to characterize drug pharmacokinetics while minimizing phlebotomy and burden to participating children.
Anemia Is a Risk Factor for the Development of Ischemic Stroke and Post-Stroke Mortality

Background: anemia is known to be a risk factor for developing ischemic stroke in long-term follow-up studies, and it is also known to increase the risk of death in ischemic stroke patients. We aimed to determine the association of anemia with the risk of ischemic stroke and the risk of death after ischemic stroke. Methods: The study included patients from National Health Insurance Service cohort, from January 2005 to December 2015. Anemia patients were defined as those with confirmed diagnostic codes and related medications in the sample cohort, and patients under the age of 18 were excluded. To perform a comparative analysis with the control group, twice as many patients were extracted by propensity score matching. The effects of anemia on the development of ischemic stroke were analyzed. Results: A total of 58,699 patients were newly diagnosed with anemia during the study period. In anemia group, the rate of ischemic stroke occurring within 1 year was 0.550%, and the rate was 0.272% in the control group. The odds ratio of anemia related to ischemic stroke was 1.602 (95% confidence intervals (CI) 1.363–1.883). During the follow-up period, 175 out of 309 (56.6%) died in anemia group, and 130 out of 314 (41.4%) died in control group. The anemia group showed a higher risk of death than the control group (Hazard ratio 1.509, 95% CI 1.197–1.902). Conclusion: Analysis of the nationwide health insurance data revealed that anemia is one of the risk factors for the development of ischemic stroke, and also an independent prognostic factor affecting post-stroke mortality.
Contrasts in Glioblastoma—Venous Thromboembolism versus Bleeding Risk

Glioblastoma is among the tumor entities with an extreme thrombogenic potential and patients are at very high risk of developing a venous thromboembolism (VTE) over the course of the disease, with an incidence of up to 30% per year. Major efforts are currently being made to understand and gain novel insights into the underlying pathomechanisms of the development of VTE in patients with glioblastoma and to find appropriate biomarkers. Yet, patients with glioblastoma not only face a high thromboembolic risk but are also at risk of bleeding events. In the case of VTE, a therapeutic anticoagulation with low molecular weight heparin or, in the case of low bleeding risk, treatment with a direct oral anticoagulant, is recommended, according to recently published guidelines. With respect to an elevated bleeding risk in glioblastoma patients, therapeutic anticoagulation remains challenging in this patient group and prospective data for this vulnerable patient group are scarce, particularly with regard to direct oral anticoagulants.
Fatal Neonatal Sepsis Associated with Human Adenovirus Type 56 Infection: Genomic Analysis of Three Recent Cases Detected in the United States

Background: Human adenovirus (HAdV)-D56 was first described in 2011 by genomics analysis of a strain isolated in France in 2008 from a fatal case of neonatal infection. Since then, it has been reported in cases of keratoconjunctivitis and male urethritis. Three epidemiologically unrelated fatal cases of neonatal sepsis associated with infection by HAdV-D strains with a similar genetic makeup were documented in the United States between 2014 and 2020. Methods: Whole genome sequences were obtained for the isolated strains, and genomics analyses were conducted to compare them to phylogenetically related HAdV-D genomic sequences available in GenBank. Results: The three new US strains were indistinguishable by in silico restriction enzyme analysis. Their genome sequences were 99.9% identical to one another and to the prototype strain isolated in 2008 from a similar context of disease. The phylogenetic reconstruction revealed a highly supported clustering of all HAdV-D56 strains isolated in various countries since 1982. Our comparison to serologically intermediate strains 15/H9 described in the literature indicated that HAdV-D56-like viruses have circulated worldwide since the late 1950s. Conclusion: As with other HAdV-D genotypes with the ability to infect ocular and genital mucosae, the risk of severe prenatal or perinatal HAdV-D56 infection must be considered.
Rhodotorula kratochvilovae CCY 20-2-26—The Source of Multifunctional Metabolites

Multifunctional biomass is able to provide more than one valuable product, and thus, it is attractive in the field of microbial biotechnology due to its economic feasibility. Carotenogenic yeasts are effective microbial factories for the biosynthesis of a broad spectrum of biomolecules that can be used in the food and feed industry and the pharmaceutical industry, as well as a source of biofuels. In the study, we examined the effect of different nitrogen sources, carbon sources and CN ratios on the co-production of intracellular lipids, carotenoids, β–glucans and extracellular glycolipids. Yeast strain R. kratochvilovae CCY 20-2-26 was identified as the best co-producer of lipids (66.7 ± 1.5% of DCW), exoglycolipids (2.42 ± 0.08 g/L), β-glucan (11.33 ± 1.34% of DCW) and carotenoids (1.35 ± 0.11 mg/g), with a biomass content of 15.2 ± 0.8 g/L, by using the synthetic medium with potassium nitrate and mannose as a carbon source. It was shown that an increased C/N ratio positively affected the biomass yield and production of lipids and β-glucans.
Exploring Viral Diversity in a Gypsum Karst Lake Ecosystem Using Targeted Single-Cell Genomics

Little is known about the diversity and distribution of viruses infecting green sulfur bacteria (GSB) thriving in euxinic (sulfuric and anoxic) habitats, including gypsum karst lake ecosystems. In this study, we used targeted cell sorting combined with single-cell sequencing to gain insights into the gene content and genomic potential of viruses infecting sulfur-oxidizing bacteria Chlorobium clathratiforme, obtained from water samples collected during summer stratification in gypsum karst Lake Kirkilai (Lithuania). In total, 82 viral contigs were bioinformatically identified in 62 single amplified genomes (SAGs) of C. clathratiforme. The majority of viral gene and protein sequences showed little to no similarity with phage sequences in public databases, uncovering the vast diversity of previously undescribed GSB viruses. We observed a high level of lysogenization in the C. clathratiforme population, as 87% SAGs contained intact prophages. Among the thirty identified auxiliary metabolic genes (AMGs), two, thiosulfate sulfurtransferase (TST) and thioredoxin-dependent phosphoadenosine phosphosulfate (PAPS) reductase (cysH), were found to be involved in the oxidation of inorganic sulfur compounds, suggesting that viruses can influence the metabolism and cycling of this essential element. Finally, the analysis of CRISPR spacers retrieved from the consensus C. clathratiforme genome imply persistent and active virus–host interactions for several putative phages prevalent among C. clathratiforme SAGs. Overall, this study provides a glimpse into the diversity of phages associated with naturally occurring and highly abundant sulfur-oxidizing bacteria.
Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).