Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Prediction of Breast Cancer Recurrence for Patients Treated with Neoadjuvant Chemotherapy: A Transfer Learning Approach on DCE-MRIs

Simple Summary An early prediction of Breast Cancer Recurrence (BCR) for patients undergoing neoadjuvant chemotherapy (NACT) could better guide clinicians in the identification of the most suitable combination treatments for individual patient scenarios. We proposed a transfer learning approach to give an early prediction of three-year BCR for patients undergoing NACT, using DCE-MRI exams from I-SPY1 TRIAL and BREAST-MRI-NACT-Pilot public databases. Because no technical expertise is required in the extraction of meaningful features from images, the predictive model qualifies as a user-friendly tool for any medical expert in support of therapeutic choices. Only pre-treatment and early-treatment MRI examinations were analyzed to allow for potential therapy changes at a very early stage of treatment. We tested the strength of the model on an independent test. The best predictive performances (accuracy of 85.2%, sensitivity of 84.6%, and AUC of 0.83) were achieved by combining the extracted features with some clinical factors: age, ER, PgR, HER2+. Abstract Cancer treatment planning benefits from an accurate early prediction of the treatment efficacy. The goal of this study is to give an early prediction of three-year Breast Cancer Recurrence (BCR) for patients who underwent neoadjuvant chemotherapy. We addressed the task from a new perspective based on transfer learning applied to pre-treatment and early-treatment DCE-MRI scans. Firstly, low-level features were automatically extracted from MR images using a pre-trained Convolutional Neural Network (CNN) architecture without human intervention. Subsequently, the prediction model was built with an optimal subset of CNN features and evaluated on two sets of patients from I-SPY1 TRIAL and BREAST-MRI-NACT-Pilot public databases: a fine-tuning dataset (70 not recurrent and 26 recurrent cases), which was primarily used to find the optimal subset of CNN features, and an independent test (45 not recurrent and 17 recurrent cases), whose patients had not been involved in the feature selection process. The best results were achieved when the optimal CNN features were augmented by four clinical variables (age, ER, PgR, HER2+), reaching an accuracy of 91.7% and 85.2%, a sensitivity of 80.8% and 84.6%, a specificity of 95.7% and 85.4%, and an AUC value of 0.93 and 0.83 on the fine-tuning dataset and the independent test, respectively. Finally, the CNN features extracted from pre-treatment and early-treatment exams were revealed to be strong predictors of BCR.
Prescription strategy of antimalarials in cutaneous and systemic lupus erythematosus: an international survey

Background: Antimalarial agents (AMs), mainly hydroxychloroquine (HCQ) and chloroquine, are the cornerstone of treatment of cutaneous and systemic lupus erythematosus. However, many aspects of AM prescription remain empirical. The aim of this study was to assess the modalities of AM prescription among physicians treating patients with lupus and to verify the assumption that AM use is heterogeneous and frequently at variance with international guidelines. Methods: We performed an international cross-sectional study among physicians involved in lupus care, using a web-based survey (from September 2019 to July 2020) addressing the main controversial aspects of AM prescription. Results: A total of 298 physicians [median age: 42 (interquartile range: 17) years, mainly internists and rheumatologists] from 35 countries participated to the study. A total of 93% used HCQ as the first-line AM, 69.5% used fixed doses of AMs (mainly 400 mg/day for HCQ) and only 37.9% adjusted the dose in case of renal failure. The main reasons for measuring HCQ blood levels were suspected non-adherence (55.7%) and failure of AM treatment (34.1%). In case of AM failure, 58.0% added an immunosuppressive agent. In case of remission, 49.7% maintained the same dose of AM, whereas 48.3% reduced the dose. One-third of respondents reported not following the American screening guidelines on AM retinal toxicity and 40.9% started retinal screening from the first year of treatment. Conclusion: This study highlights the strong heterogeneity of AM prescription in lupus, as well as several key unmet needs regarding AMs. This may be improved by developing more comprehensive recommendations and favoring dissemination among physicians.
On Growth and Morphology of TiO2 Nanotubes on Ti6Al4V by Anodic Oxidation in Ethylene Glycol Electrolyte: Influence of Microstructure and Anodization Parameters

Different studies demonstrated the possibility to produce TiO2 nanotubes (TNTs) on Ti6Al4V alloy by electrochemical anodization. However, the anodizing behavior of α and β-phases in organic electrolytes is not yet clarified. This study reports on the anodizing behavior of the two phases in an ethylene glycol electrolyte using different applied potentials and anodizing times. Atomic force and scanning electron microscopies were used to highlight the anodic oxides differences in morphology. It was demonstrated that the initial compact oxide grew faster over the β-phase as the higher Al content of the α-phase caused its re-passivation, and the higher solubility of the V-rich oxide led to earlier pores formation over the β-phase. The trend was inverted once the pores formed over the compact oxide of the α-phase. The growth rate of the α-phase TNTs was higher than that of the β-phase ones, leading to the formation of long and well defined nanotubes with thin walls and a honeycomb tubular structure, while the ones grown over the β-phase were individual, shorter, and with thicker walls.
Exploring the Release of Toxic Oligomers from α-Synuclein Fibrils with Antibodies and STED Microscopy

α-Synuclein (αS) is an intrinsically disordered and highly dynamic protein involved in dopamine release at presynaptic terminals. The abnormal aggregation of αS as mature fibrils into intraneuronal inclusion bodies is directly linked to Parkinson’s disease. Increasing experimental evidence suggests that soluble oligomers formed early during the aggregation process are the most cytotoxic forms of αS. This study investigated the uptake by neuronal cells of pathologically relevant αS oligomers and fibrils exploiting a range of conformation-sensitive antibodies, and the super-resolution stimulated emission depletion (STED) microscopy. We found that prefibrillar oligomers promptly penetrate neuronal membranes, thus resulting in cell dysfunction. By contrast, fibril docking to the phospholipid bilayer is accompanied by αS conformational changes with a progressive release of A11-reactive oligomers, which can enter into the neurons and trigger cell impairment. Our data provide important evidence on the role of αS fibrils as a source of harmful oligomers, which resemble the intermediate conformers formed de novo during aggregation, underling the dynamic and reversible nature of protein aggregates responsible for α-synucleinopathies.
Genetic Relationship of Fall Armyworm (Spodoptera frugiperda) Populations That Invaded Africa and Asia

Simple Summary Since 2016, the fall armyworm, an important economic pest native to tropical and subtropical regions of the Western Hemisphere, has invaded Africa and further spread rapidly into most Asian countries. The fall armyworm is highly polyphagous, but two of its major strains, the corn and the rice strains, cause severe damage in the Western Hemisphere. However, the invaded populations in Africa and Asia mostly infested the corn fields. Studies on the genetic identity of the species using two molecular markers, one nuclear gene and one mitochondrial gene, showed that the major genetic group is a heterogeneous hybrid of males from the corn strain and females from the rice strain. Moreover, a minor group of homogenous individuals from the corn strain but no homogenous individuals from the rice strain were also detected. A geographic distribution analysis at the subpopulation level indicated similar genetic diversity in Africa and Asia, suggesting fall armyworm in Africa spread into Asia without significant genetic change. Abstract The fall armyworm, Spodoptera frugiperda, is an important agricultural pest native to tropical and subtropical regions of the Western Hemisphere, and has invaded Africa and further spread into most countries of Asia within two years. Here, we analyzed the genetic variation of invaded populations by comparing the nucleotide sequences of two genes: the nuclear Z-chromosome linked gene triose phosphate isomerase (Tpi) and the mitochondrial gene cytochrome oxidase subunit I (COI) of 27 specimens collected in Africa (DR Congo, Tanzania, Uganda, and Zimbabwe) and Asia (Bangladesh, Korea, Nepal, and Vietnam). The results revealed that 25 specimens were from a heterogeneous hybrid (Tpi-corn strain and COI-rice strain; Tpi-C/COI-R) of the corn strain male and rice strain female, but two specimens were from a homogenous corn strain (Tpi-corn strain and COI-corn strain; Tpi-C/COI-C). The further analysis of the fourth exon and the fourth intron sequences of the Tpi gene identified at least four subgroups of the corn strain. These four genetic subgroups were identified in Africa and Asia, suggesting no significant genetic change due to the rapid migration within two years. Our study provides essential information for understanding the genetic diversity of fall armyworm in new habitats.
Effects of Aging on the Physical and Rheological Properties of Trinidad Lake Asphalt Modified Bitumen

The application of various modifiers has emerged in recent years to improve conventional petroleum-based bitumen properties. The natural asphalt called Trinidad Lake Asphalt (TLA) has been applied very often due to its consistent properties, high viscosity and density, and superior rheological properties, and effective blending with other bitumen. However, most studies on TLA-modified binders always focused on physical and rheological properties in the original (unaged) condition, but the details about aging properties are often neglected. This study aimed to investigate the effect of short-term aging on the physical and rheological characteristics of the 35/50 base bitumen modified by the addition of two different TLA contents. The conventional physical tests and dynamic shear rheological tests were undertaken before and after aging to measure the penetration and softening point, complex shear modulus, and phase angle of the modified binders, as well as to calculate the zero shear viscosity using the Cross model fitting procedure. Based on the results of the above-mentioned comprehensive testing, the effect of aging on TLA-modified binder properties was evaluated using aging indices, as well as a direct comparison of results. The tests revealed that the short-term aging of TLA-modified binders did not worsen or reduce the pavement resistance to permanent deformation or the load-bearing capacity of the asphalt mixture.
A Fructan Exohydrolase from Maize Degrades Both Inulin and Levan and Co-Exists with 1-Kestotriose in Maize

Enzymes with fructan exohydrolase (FEH) activity are present not only in fructan-synthesizing species but also in non-fructan plants. This has led to speculation about their functions in non-fructan species. Here, a cell wall invertase-related Zm-6&1-FEH2 with no “classical” invertase motif was identified in maize. Following heterologous expression in Pichia pastoris and in Nicotiana benthamiana leaves, the enzyme activity of recombinant Zm-6&1-FEH2 displays substrate specificity with respect to inulin and levan. Subcellular localization showed Zm-6&1-FEH2 exclusively localized in the apoplast, and its expression profile was strongly dependent on plant development and in response to drought and abscisic acid. Furthermore, formation of 1-kestotriose, an oligofructan, was detected in vivo and in vitro and could be hydrolyzed by Zm-6&1-FEH2. In summary, these results support that Zm-6&1-FEH2 enzyme from maize can degrade both inulin-type and levan-type fructans, and the implications of the co-existence of Zm-6&1-FEH2 and 1-kestotriose are discussed.
Hunger and Health: Taking a Formative Approach to Build a Health Intervention Focused on Nutrition and Physical Activity Needs as Perceived by Stakeholders

The intersections between hunger and health are beginning to gain traction. New interventions emphasize collaboration between the health and social service sectors. This study aimed to understand the nutrition and physical activity (PA) needs as perceived by food pantry stakeholders to inform a health intervention approach. The study used formative research incorporating mixed methods through surveying and semi-structured interviews with three food pantry stakeholder groups: Clients (n = 30), staff (n = 7), and volunteers (n = 10). Pantry client participants reported; high rates of both individual (60%, n = 18) and household (43%, n = 13) disease diagnosis; low consumption (0–1 servings) of fruits (67%, n = 20) and vegetables (47%, n = 14) per day; and low levels (0–120 min) of PA (67%, n = 20) per week. Interviews identified five final convergent major themes across all three stakeholder groups including food and PA barriers, nutrition and PA literacy, health status and lifestyle, current pantry operations and adjustments, and suggestions for health intervention programming. High rates of chronic disease combined with low health literacy among pantry clients demonstrate the need to address health behaviors. Further research piloting the design and implementation of a comprehensive health behavior intervention program in the food pantry setting is needed.
Dysregulation of miR-15a-5p, miR-497a-5p and miR-511-5p Is Associated with Modulation of BDNF and FKBP5 in Brain Areas of PTSD-Related Susceptible and Resilient Mice

Post-traumatic stress disorder (PTSD) is a neuropsychiatric disorder occurring in susceptible individuals following a traumatic event. Understanding the mechanisms subserving trauma susceptibility/resilience is essential to develop new effective treatments. Increasing evidence suggests that non-coding RNAs, such as microRNAs (miRNAs), may play a prominent role in mediating trauma susceptibility/resilience. In this study, we evaluated the transcriptional expression of two key PTSD-related genes (FKBP5 and BDNF) and the relative targeting miRNAs (miR-15a-5p, miR-497a-5p, miR-511-5p, let-7d-5p) in brain areas of PTSD-related susceptible and resilient mice identified through our recently developed mouse model of PTSD (arousal-based individual screening (AIS) model). We observed lower transcript levels of miR-15a-5p, miR-497a-5p, and miR-511a-5p in the hippocampus and hypothalamus of susceptible mice compared to resilient mice, suggesting that the expression of these miRNAs could discriminate the two different phenotypes of stress-exposed mice. These miRNA variations could contribute, individually or synergically, to the inversely correlated transcript levels of FKBP5 and BDNF. Conversely, in the medial prefrontal cortex, downregulation of miR-15a-5p, miR-511-5p, and let-7d-5p was observed both in susceptible and resilient mice, and not accompanied by changes in their mRNA targets. Furthermore, miRNA expression in the different brain areas correlated to stress-induced behavioral scores (arousal score, avoidance-like score, social memory score and PTSD-like score), suggesting a linear connection between miRNA-based epigenetic modulation and stress-induced phenotypes. Pathway analysis of a miRNA network showed a statistically significant enrichment of molecular processes related to PTSD and stress. In conclusion, our results indicate that PTSD susceptibility/resilience might be shaped by brain-area-dependent modulation of miRNAs targeting FKBP5, BDNF, and other stress-related genes.
A Multidisciplinary Fingerprinting Approach for Authenticity and Geographical Traceability of Portuguese Wines

The interest in developing reliable wine authenticity schemes is a hot-topic, especially for wines with recognized added-value. In order to accomplish this goal, two dimensions need to be considered: the grapevine variety determination and the geographical provenance. The aim of this study was to develop a multidisciplinary approach applicable to wines from the sub region Melgaço and Monção of the demarcated Vinho Verde region and from the demarcated Douro region. The proposed scheme consists on the use of DNA-based assays to detect Single Nucleotide Polymorphisms (SNPs) on three genes of the anthocyanin pathway (UFGT, F3H and LDOX) coupled with High-resolution melting (HRM) analysis aiming the varietal identification. The Alvarinho wines revealed to have the same haplotype using this marker set, demonstrating its applicability for genetic identification. In addition, to assess their geographical provenance, a multi-elemental approach using Sr and Pb isotopic ratios of wine, soil and bedrock samples was used. The isotopic data suggest a relation between Sr and Pb uptake by vine roots and soil’s texture and clay content, rather than with the whole rock’s isotopic ratios, but also highlights the potential of a discriminating method based on the combination of selected isotopic signatures.
Glycolysis Metabolites and Risk of Atrial Fibrillation and Heart Failure in the PREDIMED Trial

The increased prevalence of atrial fibrillation (AF) and heart failure (HF) highlights the need to better understand the mechanisms underlying these cardiovascular diseases (CVDs). In the present study, we aimed to evaluate the association between glycolysis-related metabolites and the risk of AF and HF in a Mediterranean population at high risk of CVD. We used two case–control studies nested within the PREDIMED trial. A total of 512 incident AF cases matched to 734 controls, and 334 incident HF cases matched to 508 controls, were included. Plasma metabolites were quantified by using hydrophilic interaction liquid chromatography coupled with high-resolution negative ion mode MS detection. Conditional logistic regression analyses were performed. The results showed no association between baseline plasma glycolysis intermediates and other related metabolites with AF. Only phosphoglycerate was associated with a higher risk of HF (OR for 1 SD increase: 1.28; 95% CI: 1.06, 1.53). The present findings do not support a role of the glycolysis pathway in the pathogenesis of AF. However, the increased risk of HF associated with phosphoglycerate requires further studies.
Modeling Left Ventricle Perfusion in Healthy and Stenotic Conditions

A theoretical fluid mechanical model is proposed for the investigation of myocardial perfusion in healthy and stenotic conditions. The model hinges on Terzaghi’s consolidation theory and reformulates the related unsteady flow equation for the simulation of the swelling–drainage alternation characterizing the diastolic–systolic phases. When compared with the outcome of experimental in vivo observations in terms of left ventricle transmural perfusion ratio (T.P.R.), the analytical solution provided by the present study for the time-dependent blood pressure and flow rate across the ventricle wall proves to consistently reproduce the basic mechanisms of both healthy and ischemic perfusion. Therefore, it could constitute a useful interpretative support to improve the comprehension of the basic hemodynamic mechanisms leading to the most common cardiac diseases. Additionally, it could represent the mathematical basis for the application of inverse methods aimed at estimating the characteristic parameters of ischemic perfusion (i.e., location and severity of coronary stenoses) via downstream ventricular measurements, possibly inspiring their assessment via non-invasive myocardial imaging techniques.
Influence of equipment changes on MRI measures of brain atrophy and brain microstructure in a placebo-controlled trial of ibudilast in progressive multiple sclerosis

Background Hardware changes can be an unavoidable confound in imaging trials. Understanding the impact of such changes may play an important role in the analysis of imaging data. Objective To characterize the effect of equipment changes in a longitudinal, multi-site multiple sclerosis trial. Methods Using data from a clinical trial in progressive multiple sclerosis, we explored how major changes in imaging hardware affected data. We analyzed the extent to which these changes affected imaging biomarkers and the estimated treatment effects by including such changes as a time-dependent covariate. Results Significant differences whole brain atrophy (brain parenchymal fraction, BPF) and microstructure (transverse diffusivity, TD) between scans with and without changes were found and depended on the type of hardware change. A switch from GE HDxt to Siemens Skyra led to significant shifts in BPF (p < 0.04) and TD (p < 0.0001). However, we could not detect the influence of hardware changes on overall trial outcomes– differences between placebo and treatment arms in change over time of BPF and TD (p > 0.5). Conclusions The results suggest that differences among hardware types should be considered when planning and analyzing brain atrophy and diffusivity in a longitudinal clinical trial.
L2-CalSat: A Calibration Satellite for Ultra-Sensitive CMB Polarization Space Missions

In this work, the use of a calibration satellite (L2-CalSat) flying in formation with a Cosmic Microwave Background (CMB) polarization mission in an orbit located at the second Lagrange point, is proposed. The new generation of CMB telescopes are expected to reach unprecedented levels of sensitivity to allow a very precise measurement of the B-mode of polarization, the curl-like polarization component expected from gravitational waves coming from Starobinski inflationary models. Due to the CMB polarized signal weakness, the instruments must be subjected to very precise calibration processes before and after launching. Celestial sources are often used as external references for calibration after launch, but these sources are not perfectly characterized. As a baseline option, L2-CalSat is based on the CubeSat standard and serves as a perfectly known source of a reference signal to reduce polarization measurements uncertainty. A preliminary design of L2-CalSat is described and, according to the scanning strategy followed by the telescope, the influence of the relative position between the spacecrafts in the calibration process is studied. This new calibration element will have a huge impact on the performance of CMB space missions, providing a significant improvement in the measurements accuracy without requiring new and costly technological developments.