Miracle-dz/UniFAR-FTUs huggingface dataset:
Thermal Liquid Biopsy (TLB) of Blood Plasma as a Potential Tool to Help in the Early Diagnosis of Multiple Sclerosis

Background: Multiple sclerosis (MS) is frequently characterized by a variety of clinical signs, often exhibiting little specificity. The diagnosis requires a combination of medical observations and instrumental tests, and any support for its objective assessment is helpful. Objective: Herein, we describe the application of thermal liquid biopsy (TLB) of blood plasma samples, a methodology for predicting the occurrence of MS with a noninvasive, quick blood test. Methods: TLB allows one to define an index (TLB score), which provides information about overall real-time alterations in plasma proteome that may be indicative of MS. Results: This pilot study, based on 85 subjects (45 MS patients and 40 controls), showed good performance indexes (sensitivity and specificity both around 70%). The diagnostic methods better discriminate between early stage and low-burden MS patients, and it is not influenced by gender, age, or assumption of therapeutic drugs. TLB is more accurate for patients having low disability level (≤ 3.0, measured by the expanded disability status scale, EDSS) and a relapsing–remitting diagnosis. Conclusion: Our results suggest that TLB can be applied to MS, especially in an initial phase of the disease when diagnosis is difficult and yet more important (in such cases, accuracy of prediction is close to 80%), as well as in personalized patient periodic monitoring. The next step will be determining its utility in differentiating between MS and other disorders, in particular in inflammatory diseases.
Synthesis of Polyanionic C5-Modified 2′-Deoxyuridine and 2′-Deoxycytidine-5′-Triphosphates and Their Properties as Substrates for DNA Polymerases

Modified 2′-deoxyribonucleotide triphosphates (dNTPs) have widespread applications in both existing and emerging biomolecular technologies. For such applications it is an essential requirement that the modified dNTPs be substrates for DNA polymerases. To date very few examples of C5-modified dNTPs bearing negatively charged functionality have been described, despite the fact that such nucleotides might potentially be valuable in diagnostic applications using Si-nanowire-based detection systems. Herein we have synthesised C5-modified dUTP and dCTP nucleotides each of which are labelled with an dianionic reporter group. The reporter group is tethered to the nucleobase via a polyethylene glycol (PEG)-based linkers of varying length. The substrate properties of these modified dNTPs with a variety of DNA polymerases have been investigated to study the effects of varying the length and mode of attachment of the PEG linker to the nucleobase. In general, nucleotides containing the PEG linker tethered to the nucleobase via an amide rather than an ether linkage proved to be the best substrates, whilst nucleotides containing PEG linkers from PEG6 to PEG24 could all be incorporated by one or more DNA polymerase. The polymerases most able to incorporate these modified nucleotides included Klentaq, Vent(exo-) and therminator, with incorporation by Klenow(exo-) generally being very poor.
Internet Usage Habits and Experienced Levels of Psychopathology: A Pilot Study on Association with Spontaneous Eye Blinking Rate

Increasing availability of the internet has resulted in the increased prevalence of problematic online behaviors. Reliable and affordable neurobiological and psychological biomarkers that distinguish problematic internet use (PIU) from functional online activities are of utmost importance. Previous studies have shown a relationship between spontaneous eye blinking rate (sEBR) and changes in dopamine regulation in neurological and psychiatric disorders, including substance use disorders. In this study, we utilized sEBR to examine the potential link between individual differences in dopaminergic neurotransmission and PIU. In sum, 62 subjects participated in this study (median age 25, IQR 6 years, 34 females). The Problematic Internet Use Questionnaire (PIUQ-9), Beck Depression Inventory (BDI-II), Beck Anxiety Inventory (BAI), Clark–Beck Obsessive–Compulsive Inventory (CBOCI) and Barratt Impulsiveness Scale (BIS-11) were used for psychological assessment. The sEBRs were assessed with an electrooculogram recorded from above and below the left eye and from the right and left outer canthi. The group with PIU (PIUQ-9 > 20) expressed higher levels of impulsivity and compulsive behavior symptoms than the control group. In the group with PIU, impulsivity levels were inversely related to sEBR, and a trend of negative association of sEBR with compulsive behavior was observed. Future research should enroll subjects with high levels of PIU and strongly expressed psychopathology levels to further address the utility of sEBR as a potential biomarker.
Biocide Use in the Antimicrobial Era: A Review

Biocides are widely used in healthcare and industry to control infections and microbial contamination. Ineffectual disinfection of surfaces and inappropriate use of biocides can result in the survival of microorganisms such as bacteria and viruses on inanimate surfaces, often contributing to the transmission of infectious agents. Biocidal disinfectants employ varying modes of action to kill microorganisms, ranging from oxidization to solubilizing lipids. This review considers the main biocides used within healthcare and industry environments and highlights their modes of action, efficacy and relevance to disinfection of pathogenic bacteria. This information is vital for rational use and development of biocides in an era where microorganisms are becoming resistant to chemical antimicrobial agents.
Mechanisms of Venoarteriolar Reflex in Type 2 Diabetes with or without Peripheral Neuropathy

Simple Summary Postural changes induce arteriolar vasoconstriction in response to an increase in venous pressure in the limbs known as the venoarteriolar reflex (VAR). Previous studies reported that skin blood perfusion is impaired during the VAR in persons with type 2 diabetes mellitus (T2DM) with or without peripheral neuropathy, compared to control subjects. The aim of this study is to investigate the underlying mechanisms of the VAR in T2DM, with and without peripheral neuropathy. This study provides evidence that confirmed neuropathy alters the VAR by an alteration of the neurogenic response to leg dependency. Abstract The aim of this study is to investigate the underlying mechanisms of the venoarteriolar reflex (VAR) in type 2 diabetes mellitus (T2DM), with and without peripheral neuropathy. Laser Doppler flowmetry (LDF) recordings were performed on the medial malleus and dorsal foot skin, before and during leg dependency in healthy controls, in persons with obesity, in those with T2DM, in those with T2DM and subclinical neuropathy, and in those with T2DM and confirmed neuropathy. LDF recordings were analyzed with the wavelet transform to evaluate the mechanisms controlling the flowmotion (i.e., endothelial nitric oxide-independent and -dependent, neurogenic, myogenic, respiratory and cardiac mechanisms). Skin blood perfusion decreased throughout leg dependency at both sites. The decrease was blunted in persons with confirmed neuropathy compared to those with T2DM alone and the controls. During leg dependency, total spectral power increased in all groups compared to rest. The relative contribution of the endothelial bands increased and of the myogenic band decreased, without differences between groups. Neurogenic contribution decreased in controls, in persons with obesity and in those with T2DM, whereas it increased in subclinical- and confirmed neuropathy. In conclusion, this study provides evidence that confirmed diabetic neuropathy alters the VAR through the neurogenic response to leg dependency.
Recent Developments in Effective Antioxidants: The Structure and Antioxidant Properties

Since the last few years, the growing interest in the use of natural and synthetic antioxidants as functional food ingredients and dietary supplements, is observed. The imbalance between the number of antioxidants and free radicals is the cause of oxidative damages of proteins, lipids, and DNA. The aim of the study was the review of recent developments in antioxidants. One of the crucial issues in food technology, medicine, and biotechnology is the excess free radicals reduction to obtain healthy food. The major problem is receiving more effective antioxidants. The study aimed to analyze the properties of efficient antioxidants and a better understanding of the molecular mechanism of antioxidant processes. Our researches and sparing literature data prove that the ligand antioxidant properties complexed by selected metals may significantly affect the free radical neutralization. According to our preliminary observation, this efficiency is improved mainly by the metals of high ion potential, e.g., Fe(III), Cr(III), Ln(III), Y(III). The complexes of delocalized electronic charge are better antioxidants. Experimental literature results of antioxidant assays, such as diphenylpicrylhydrazyl (DPPH) and ferric reducing activity power assay (FRAP), were compared to thermodynamic parameters obtained with computational methods. The mechanisms of free radicals creation were described based on the experimental literature data. Changes in HOMO energy distribution in phenolic acids with an increasing number of hydroxyl groups were observed. The antioxidant properties of flavonoids are strongly dependent on the hydroxyl group position and the catechol moiety. The number of methoxy groups in the phenolic acid molecules influences antioxidant activity. The use of synchrotron techniques in the antioxidants electronic structure analysis was proposed.
Autosegmentation of Prostate Zones and Cancer Regions from Biparametric Magnetic Resonance Images by Using Deep-Learning-Based Neural Networks

The accuracy in diagnosing prostate cancer (PCa) has increased with the development of multiparametric magnetic resonance imaging (mpMRI). Biparametric magnetic resonance imaging (bpMRI) was found to have a diagnostic accuracy comparable to mpMRI in detecting PCa. However, prostate MRI assessment relies on human experts and specialized training with considerable inter-reader variability. Deep learning may be a more robust approach for prostate MRI assessment. Here we present a method for autosegmenting the prostate zone and cancer region by using SegNet, a deep convolution neural network (DCNN) model. We used PROSTATEx dataset to train the model and combined different sequences into three channels of a single image. For each subject, all slices that contained the transition zone (TZ), peripheral zone (PZ), and PCa region were selected. The datasets were produced using different combinations of images, including T2-weighted (T2W) images, diffusion-weighted images (DWI) and apparent diffusion coefficient (ADC) images. Among these groups, the T2W + DWI + ADC images exhibited the best performance with a dice similarity coefficient of 90.45% for the TZ, 70.04% for the PZ, and 52.73% for the PCa region. Image sequence analysis with a DCNN model has the potential to assist PCa diagnosis.
Characterisation of the Filler Fraction in CAD/CAM Resin-Based Composites

The performance of dental resin-based composites (RBCs) heavily depends on the characteristic properties of the individual filler fraction. As specific information regarding the properties of the filler fraction is often missing, the current study aims to characterize the filler fractions of several contemporary computer-aided design/computer-aided manufacturing (CAD/CAM) RBCs from a material science point of view. The filler fractions of seven commercially available CAD/CAM RBCs featuring different translucency variants were analysed using Scanning Electron Microscopy (SEM) with Energy Dispersive X-ray Spectroscopy (EDS), Micro-X-ray Computed Tomography (µXCT), Thermogravimetric Analysis (TG) and X-ray Diffractometry (XRD). All CAD/CAM RBCs investigated included midifill hybrid type filler fractions, and the size of the individual particles was clearly larger than the individual specifications of the manufacturer. The fillers in Shofu Block HC featured a sphericity of ≈0.8, while it was <0.7 in all other RBCs. All RBCs featured only X-ray amorphous phases. However, in Lava Ultimate, zircon crystals with low crystallinity were detected. In some CAD/CAM RBCs, inhomogeneities (X-ray opaque fillers or pores) with a size <80 µm were identified, but the effects were minor in relation to the total volume (<0.01 vol.%). The characteristic parameters of the filler fraction in RBCs are essential for the interpretation of the individual material’s mechanical and optical properties.
The Relationship between Oscillations in Brain Regions and Functional Connectivity: A Critical Analysis with the Aid of Neural Mass Models

Propagation of brain rhythms among cortical regions is a relevant aspect of cognitive neuroscience, which is often investigated using functional connectivity (FC) estimation techniques. The aim of this work is to assess the relationship between rhythm propagation, FC and brain functioning using data generated from neural mass models of connected Regions of Interest (ROIs). We simulated networks of four interconnected ROIs, each with a different intrinsic rhythm (in θ, α, β and γ ranges). Connectivity was estimated using eight estimators and the relationship between structural connectivity and FC was assessed as a function of the connectivity strength and of the inputs to the ROIs. Results show that the Granger estimation provides the best accuracy, with a good capacity to evaluate the connectivity strength. However, the estimated values strongly depend on the input to the ROIs and hence on nonlinear phenomena. When a population works in the linear region, its capacity to transmit a rhythm increases drastically. Conversely, when it saturates, oscillatory activity becomes strongly affected by rhythms incoming from other regions. Changes in functional connectivity do not always reflect a physical change in the synapses. A unique connectivity network can propagate rhythms in very different ways depending on the specific working conditions.
Comparison of Cost-Effectiveness between Inpatient and Home-Based Post-Acute Care Models for Stroke Rehabilitation in Taiwan

Stroke rehabilitation focuses on alleviating post-stroke disability. Post-acute care (PAC) offers an intensive rehabilitative program as transitional care following acute stroke. A novel home-based PAC program has been initiated in Taiwan since 2019. Our study aimed to compare the current inpatient PAC model with a novel home-based PAC model in cost-effectiveness and functional recovery for stroke patients in Taiwan. One hundred ninety-seven stroke patients eligible for the PAC program were divided into two different health interventional groups. One received rehabilitation during hospitalization, and the other received rehabilitation by therapists at home. To evaluate the health economics, we assessed the total medical expenditure on rehabilitation using the health system of Taiwan national health insurance and performed cost-effectiveness analyses using improvements of daily activity in stroke patients based on the Barthel index (BI). Total rehabilitative duration and functional recovery were also documented. The total rehabilitative cost was cheaper in the home-based PAC group (p < 0.001), and the cost-effectiveness is USD 152.474 ± USD 164.661 in the inpatient group, and USD 48.184 ± USD 35.018 in the home group (p < 0.001). Lesser rehabilitative hours per 1-point increase of BI score was noted in the home-PAC group with similar improvements in daily activities, life quality and nutrition in both groups. Home-based PAC is more cost-effective than inpatient PAC for stroke rehabilitation.
Genetic Analysis Reveals Rare Variants in T-Cell Response Gene MR1 Associated with Poor Overall Survival after Urothelial Cancer Diagnosis

Simple Summary The objectives of this study were to identify rare germline variant associations in urothelial carcinoma of the bladder (UC) incidence and to determine its association with clinical outcomes. Our analysis reveals that individuals with MR1 rare germline variants had significantly worse OS than those without any, and those with ADGRL2 variants were slightly more likely to have UC compared to a control cohort matched for age, sex, and smoking status. These associations, using models incorporating known environmental covariates and using well-defined clinical phenotypes, highlight several candidates for prognostic indicator genes for the differential presentation of UC. These associations highlight several candidate genes that have the potential to explain clinical disparities in UC and predict UC outcomes. Abstract Urothelial carcinoma of the bladder (UC) is the fifth most common cancer in the United States. Germline variants, especially rare germline variants, may account for a portion of the disparity seen among patients in terms of UC incidence, presentation, and outcomes. The objectives of this study were to identify rare germline variant associations in UC incidence and to determine its association with clinical outcomes. Using exome sequencing data from the DiscovEHR UC cohort (n = 446), a European-ancestry, North American population, the complex influence of germline variants on known clinical phenotypes were analyzed using dispersion and burden metrics with regression tests. Outcomes measured were derived from the electronic health record (EHR) and included UC incidence, age at diagnosis, and overall survival (OS). Consequently, key rare variant association genes were implicated in MR1 and ADGRL2. The Kaplan–Meier survival analysis reveals that individuals with MR1 germline variants had significantly worse OS than those without any (log-rank p-value = 3.46 × 10−7). Those with ADGRL2 variants were found to be slightly more likely to have UC compared to a matched control cohort (FDR q-value = 0.116). These associations highlight several candidate genes that have the potential to explain clinical disparities in UC and predict UC outcomes.
Considerations to Model Heart Disease in Women with Preeclampsia and Cardiovascular Disease

Preeclampsia is a multifactorial cardiovascular disorder diagnosed after 20 weeks of gestation, and is the leading cause of death for both mothers and babies in pregnancy. The pathophysiology remains poorly understood due to the variability and unpredictability of disease manifestation when studied in animal models. After preeclampsia, both mothers and offspring have a higher risk of cardiovascular disease (CVD), including myocardial infarction or heart attack and heart failure (HF). Myocardial infarction is an acute myocardial damage that can be treated through reperfusion; however, this therapeutic approach leads to ischemic/reperfusion injury (IRI), often leading to HF. In this review, we compared the current in vivo, in vitro and ex vivo model systems used to study preeclampsia, IRI and HF. Future studies aiming at evaluating CVD in preeclampsia patients could benefit from novel models that better mimic the complex scenario described in this article.
Quality of Gerontological Nursing and Ageism: What Factors Influence on Nurses’ Ageism in South Korea?

With the aging of the population, age-related problems are emerging, which has caused age discrimination. Particularly, most nurses care for a large number of old patients in the clinical setting. Nurses’ attitude toward the clients has a significant effect on the quality of nursing, so it is time to identify their perspective to the aged. The quality of nursing could greatly depend on who provides and how to provide care. If older patients meet nursing staff with an ageist perspective, whether intentionally or unintentionally, they experience negative attitudes toward them during served health care, and trust cannot be formed, resulting in a deterioration in the quality of medical services. This study aimed to identify factors influencing nurses’ ageism attitudes. A total of 162 general hospital nurses completed a questionnaire consisting of the Wong and Law Emotional Intelligence Scale (WLEIS), the Contact with Elderly People (CEP), the Anxiety about Aging Scale (AAS), and the Fraboni Scale of Ageism (FSA). Data were analyzed by descriptive statistics, t-test, one-way ANOVA, Scheffé post hoc, Pearson’s correlation coefficients, and stepwise multiple regression using SPSS/WIN 26.0 program. The average score of FSA was 2.63 ± 0.36 (range 1–4); FSA showed a statistical difference according to cohabitation with an old adult in the past (t = 2.42, p = 0.017). Factors influencing FSA were the fear of old people (β = 0.34, p < 0.001) and fear of loss (β = 0.28, p < 0.001) of the AAS; and these variables explained 21.1% of FSA (F = 22.56, p < 0.001). Based on these results, the development and application of nursing education focused on intergenerational contact is needed in order to reduce the anxiety about aging and to acquire a high quality of gerontological nursing with a reduction of ageism.
Kinetically Equivalent Functionality and Reactivity of Commonly Used Biocompatible Polyurethane Crosslinking Agents

In this paper, the kinetics of the reaction of phenyl isocyanate with crosslinking agents such as sucrose, sorbitol, and glycerol are reported. Crosslinking agents were used in high molar excess to isocyanate to obtain pseudo-first-order rate dependencies, and the reaction products were separated by high-performance liquid chromatography and detected by UV spectroscopy and mass spectrometry. It was found that the glycerol’s primary hydroxyl groups were approximately four times reactive than the secondary ones. However, in the case of sorbitol, the two primary OH groups were found to be the most reactive, and the reactivity of hydroxyl groups decreased in the order of kOH(6)(8.43) > kOH(1)(6.91) > kOH(5)(1.19) > kOH(2)(0.98) > kOH(3)(0.93) > kOH(4)(0.64), where the numbers in the subscript and in the brackets denote the position of OH groups and the pseudo-first-order rate constants, respectively. The Atomic Polar Tenzor (APT) charges of OH groups and dipole moments of monosubstituted sorbitol derivatives calculated by density functional theory (DFT) also confirmed the experimental results. On the other hand, the reactions of phenyl isocyanate with crosslinking agents were also performed using high excess isocyanate in order to determine the number of OH-groups participating effectively in the crosslinking process. However, due to the huge number of derivatives likely formed in these latter reactions, a simplified reaction scheme was introduced to describe the resulting product versus reaction time distributions detected by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS). Based on the results, the kinetically equivalent functionality (fk) of each crosslinking agent was determined and found to be 2.26, 2.6, and 2.96 for glycerol, sorbitol, and sucrose, respectively.