Miracle-dz/UniFAR-FTUs huggingface dataset:
Modulatory activity of a bovine hydrolyzed collagen-hydroxyapatite food complex on human primary osteoblasts after simulating its gastrointestinal digestion and absorption.

INTRODUCTION osteoporosis is the most prevalent bone disease and one of the main causes of chronic disability in middle and advanced ages. Conventional pharmacological treatments are still limited, and their prolonged use can cause adverse effects that motivate poor adherence to treatment. Nutritional strategies are traditionally based on supplementing the diet with calcium and vitamin D. Recent studies confirm that the results of this supplementation are significantly improved if it is accompanied by the intake of oral hydrolyzed collagen. OBJECTIVE to evaluate the possible in vitro osteogenic activity of a peptide-mineral complex formed by bovine hydrolyzed collagen and bovine hydroxyapatite (Phoscollagen®, PHC®). METHODS the digestion and absorption of PHC® were simulated using the dynamic gastrointestinal digester of AINIA and Caco-2 cell model, respectively. Primary cultures of human osteoblasts were treated with the resulting fraction of PHC® and changes were evaluated in the proliferation of preosteoblasts and in the mRNA expression of osteogenic biomarkers at different stages of osteoblast maturation: Runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin (OC) and type I collagen (ColA1). RESULTS an increase in preosteoblastic proliferation was observed (p ≤ 0,05). No changes were detected in the biomarkers of osteoblasts with 5 days of differentiation, but were with 14 days, registering an increase in Runx2 (p = 0.0008), ColA1 (p = 0.035), OC (p = 0.027) and ALP (without significance). CONCLUSION these results show that the PHC® peptide-mineral complex stimulates the activity of mature osteoblasts, being capable of promoting bone formation.
Orientational disorder in sulfur hexafluoride: a neutron total scattering and reverse Monte Carlo study

The orientational disorder in crystalline sulfur hexafluoride, SF6, has been studied using a combination of neutron total scattering and the reverse Monte Carlo method. Analysis of the atomic configurations has shown the extent of the disorder through the evaluation of the S–F bond orientational distribution function, consistent with, but improving upon, the results of earlier neutron powder diffraction data. The correlations between orientations of neighbouring molecules have been studied through analysis of the distributions of F–F distances, showing that nearest-neighbour F–F close contacts are avoided, consistent with previous molecular dynamics simulation results. The results present a new case study of the application of neutron total scattering and the reverse Monte Carlo methods for the study of orientational disorder, where in this instance the disorder arises from orientational frustration rather than from a mismatch of molecular and site symmetries.
Feasibility of an Online Langerian Mindfulness Program for Stroke Survivors and Caregivers

Mindfulness is promising for individuals with neurological disorders and their caregivers to improve psychological well-being. The potential application of a Langerian mindfulness intervention, focused on attention to variability, however, is still unknown. The objective of the study was to determine the feasibility (usability, satisfaction, and potential effectiveness on psychological well-being) of an online mindfulness intervention for stroke survivors and caregivers. Using mixed methods, 11 stroke survivors and three caregivers participated in a 3-week, online, Langerian mindfulness intervention. A semi-structured interview assessed the intervention’s usability and gathered feedback. Self-reported measures about psychological well-being were documented remotely 3 times (preintervention, postintervention, and 1-month follow-up). Qualitatively, participants were highly satisfied with the intervention and reported subjective benefits, but the usability of the online platform was poor. None of the self-reported measures changed over time. This study provided evidence of feasibility of an online Langerian mindfulness intervention in a new population: stroke survivors and caregivers.
Momentary social interactions and affect in later life varied across the early stages of the COVID-19 pandemic

The COVID-19 pandemic has impacted many different facets of life. The infectious nature of the disease has led to significant changes in social interactions in everyday life. The present study examined how older adults’ patterns of everyday momentary social interactions (i.e., with no one, partner, family, and friends) and their affect varied across the early stages of the pandemic and whether the magnitude of affective benefits associated with social interactions changed across time. A total of 188 adults aged 50 or above (Mage = 62.05) completed momentary assessments in early March, late March, May, and July 2020. Overall, older adults spent more time in solitude and less time interacting with their friends after the declaration of the pandemic. Further, negative affect (NA) spiked after the pandemic declaration and then returned to pre-pandemic level. Finally, momentary interactions with close social ties were consistently associated with higher positive affect (PA) and lower NA whereas momentary solitude was associated with lower PA, but not related to NA. The magnitude of associations between specific social interactions (or solitude) and affect varied across time, and the onset of the pandemic appeared associated with this variation. During the presumably most stressful period, solitude was not associated with lower PA and family interaction was not associated with higher PA as they were at other times. Further, interactions with friends seemed to have diminished affective benefits following the onset of the pandemic.
Structural brain connectivity in patients with restless legs syndrome: a diffusion tensor imaging study.

STUDY OBJECTIVES To evaluate alterations of global and local structural brain connectivity in patients with restless legs syndrome (RLS). METHODS Patients with primary RLS and healthy controls were recruited at a sleep center where they underwent diffusion tensor imaging (DTI) of the brain. We calculated the network measures of global and local structural brain connectivity based on the DTI in both groups using DSI studio program and a graph theory. RESULTS A total of 69 patients with primary RLS and 51 healthy controls were included in the study. We found a significant difference in the global structural connectivity between the groups. The transitivity in the patients with RLS was lower than that in healthy controls (0.031 vs. 0.033, p=0.035). Additionally, there were significant differences in the local structural connectivity between the groups. The characteristic path length (r=0.283, p=0.018), radius of graph (r=0.260, p=0.030), and diameter of graph (r=0.280, p=0.019) were all positively correlated with RLS severity, whereas the mean clustering coefficient (r=-0.327, p=0.006), global efficiency (r=-0.272, p=0.023), small-worldness index (r=-0.325, p=0.006), and transitivity (r=-0.351, p=0.003) were negatively correlated with RLS severity. CONCLUSION We identified changes in the global structural connectivity of patients with RLS using graph theory based on DTI, which showed decreased segregation in the brain network compared to healthy controls. These changes are well-correlated with RLS severity. We also found changes in local structural connectivity, especially in regions involved in sensorimotor function, which suggests that these areas play a pivotal role in RLS. These findings contribute to a better understanding of the pathophysiology of RLS symptoms.
The dynamic effect of genetic variation on the in vivo ER stress transcriptional response in different tissues

Abstract The genetic regulation of gene expression varies greatly across tissue-type and individuals and can be strongly influenced by the environment. Many variants, under healthy control conditions, may be silent or even have the opposite effect under diseased stress conditions. This study uses an in vivo mouse model to investigate how the effect of genetic variation changes with cellular stress across different tissues. Endoplasmic reticulum stress occurs when misfolded proteins accumulate in the endoplasmic reticulum. This triggers the unfolded protein response, a large transcriptional response which attempts to restore homeostasis. This transcriptional response, despite being a conserved, basic cellular process, is highly variable across different genetic backgrounds, making it an ideal system to study the dynamic effects of genetic variation. In this study, we sought to better understand how genetic variation alters expression across tissues, in the presence and absence of endoplasmic reticulum stress. The use of different mouse strains and their F1s allow us to also identify context-specific cis- and trans- regulatory variation underlying variable transcriptional responses. We found hundreds of genes that respond to endoplasmic reticulum stress in a tissue- and/or genotype-dependent manner. The majority of the regulatory effects we identified were acting in cis-, which in turn, contribute to the variable endoplasmic reticulum stress- and tissue-specific transcriptional response. This study demonstrates the need for incorporating environmental stressors across multiple different tissues in future studies to better elucidate the effect of any particular genetic factor in basic biological pathways, like the endoplasmic reticulum stress response.
Lessons learned in adapting a lab-based measure of working memory capacity for the web

The purpose of this project was to document the challenges in adapting a measure of complex working memory span for delivery over the web. Automated operation span (AOSPAN; Unsworth, Heitz, Schrock, & Engle, 2005) is one of the most widely used tests for measuring working memory capacity. However, AOSPAN is a computer-based test that runs locally and thus is only suitable for lab-based studies. We have recently created a web-based version of AOSPAN that runs on a much wider variety of platforms (e.g., mobile phones and tablets). Conclusions and recommendations are applicable to researchers who are thinking of conducting studies online and developing web-based measures of which are traditionally used in the laboratory.
A Qualitative Analysis of Methotrexate Self-injection Education Videos on YouTube

Background Patients are increasingly turning to the Internet for health guidance, requiring awareness from clinicians of constantly changing resources and quality of available information. A previous study demonstrated a minority of YouTube videos were useful for teaching methotrexate (MTX) self-injection; however, YouTube content constantly evolves, and previous results may not represent current videos. This study provides an update on previous work from 2014 evaluating the quality of YouTube videos demonstrating self-administered subcutaneous MTX injections. Our aim was to evaluate how YouTube videos on MTX injection have changed and evaluate the current video quality. Methods “Methotrexate injection” was searched on YouTube. The first 75 videos were analyzed independently by 2 reviewers. Videos were classified as useful, misleading/irrelevant, or a personal patient view and rated for reliability, comprehensiveness, and quality. Results Of the 75 videos reviewed, 12 were classified as useful (16%), 43 misleading/irrelevant (57.3%), and 20 personal patient views (26.7%). Although this represents a substantial increase from previous results in the proportion of videos deemed misleading/irrelevant (57.3% vs. 27.5%) (p = 0.0011), their reliability and global quality scores were higher. Conclusions Concordant with the previous study, only a small proportion of the total videos were deemed useful videos for MTX injection specifically. However, reliability and global quality scores for all videos increased from the previous study, suggesting more videos provide reliable information with regard to MTX overall, even if it does not speak to self-injection directly. Logistics of the YouTube algorithm may still impede access to the “best” videos for patient teaching; therefore, clinicians should be prepared to recommend strategies for patients to find high-quality videos.
Development of melanoma clinical quality indicators for the Australian melanoma clinical outcomes registry (MelCOR): A modified Delphi study

Clinical quality registries aim to identify significant variations in care and provide anonymised feedback to institutions to improve patient outcomes. Thirty‐six Australian organisations with an interest in melanoma, raised funds through three consecutive Melanoma Marches, organised by Melanoma Institute Australia, to create a national Melanoma Clinical Outcomes Registry (MelCOR). This study aimed to formally develop valid clinical quality indicators for the diagnosis and early management of cutaneous melanoma as an important step in creating the registry.
Optimization of Atmospheric Cold Plasma Treatment with Different Gases for Reduction of Escherichia coli in Wheat Flour

In this study we aimed to derive the response surface models for Escherichia coli reduction in wheat flour using atmospheric cold plasma (ACP) with three types of gas. The jet-type atmospheric cold plasma wand system was used with a 30 W power supply, and three gases (argon, air, and nitrogen) were applied as the treatment gas. The operating parameters for process optimization considered were wheat flour mass (g), treatment time (min), and gas flow rate (L/min). The wheat flour samples were artificially contaminated with E. coli at a concentration of 9.25 ± 0.74 log CFU/g. ACP treatments with argon, air, and nitrogen resulted in 2.66, 4.21, and 5.55 log CFU/g reduction of E. coli, respectively, in wheat flour under optimized conditions. The optimized conditions to reduce E. coli were 0.5 g of the flour mass, 15 min of treatment time, and 0.20 L/min of nitrogen gas flow rate, and the predicted highest reduction level from modeling was 5.63 log CFU/g.
Ultrasonography as a diagnostic tool for Neural Pain in Leprosy

Leprosy is still a prevalent disease in Brazil, representing 93% of all occurrences in the Americas. Leprosy neuropathy is one of the most worrying manifestations of the disease. Acute neuropathy usually occurs during reaction episodes and is called neuritis. Twenty-two leprosy patients were included in this study. These patients had neural pain associated with ulnar sensory neuropathy, with or without adjunct motor involvement. The neurological picture began within thirty days of the clinical evaluation. The patients underwent a nerve conduction study and the demyelinating findings confirmed the diagnosis of neuritis. Ultrasonographic study (US) of the ulnar nerve was performed in all patients by a radiologist who was blinded to the clinical or neurophysiological results. Morphological characteristics of the ulnar nerve were analyzed, such as echogenicity, fascicular pattern, transverse cross-sectional area (CSA), aspect of the epineurium, as well as their anatomical relationships. The volume of selected muscles referring to the ulnar nerve, as well as their echogenicity, was also examined. Based on this analysis, patients with increased ulnar nerve CSA associated with loss of fascicular pattern, epineurium hyperechogenicity and presence of power Doppler flow were classified as neuritis. Therefore, patients initially classified by the clinical-electrophysiological criteria were reclassified by the imaging criteria pre-established in this study as with and without neuritis. Loss of fascicular pattern and flow detection on power Doppler showed to be significant morphological features in the detection of neuritis. In 38.5% of patients without clinical or neurophysiological findings of neuritis, US identified power Doppler flow and loss of fascicular pattern. The US is a method of high resolution and portability, and its low cost means that it could be used as an auxiliary tool in the diagnosis of neuritis and its treatment, especially in basic health units.
DSC Perfusion MRI–Derived Fractional Tumor Burden and Relative CBV Differentiate Tumor Progression and Radiation Necrosis in Brain Metastases Treated with Stereotactic Radiosurgery

BACKGROUND AND PURPOSE: Differentiation between tumor and radiation necrosis in patients with brain metastases treated with stereotactic radiosurgery is challenging. We hypothesized that MR perfusion and metabolic metrics can differentiate radiation necrosis from progressive tumor in this setting. MATERIALS AND METHODS: We retrospectively evaluated MRIs comprising DSC, dynamic contrast-enhanced, and arterial spin-labeling perfusion imaging in subjects with brain metastases previously treated with stereotactic radiosurgery. For each lesion, we obtained the mean normalized and standardized relative CBV and fractional tumor burden, volume transfer constant, and normalized maximum CBF, as well as the maximum standardized uptake value in a subset of subjects who underwent FDG-PET. Relative CBV thresholds of 1 and 1.75 were used to define low and high fractional tumor burden. RESULTS: Thirty subjects with 37 lesions (20 radiation necrosis, 17 tumor) were included. Compared with radiation necrosis, tumor had increased mean normalized and standardized relative CBV (P = .002) and high fractional tumor burden (normalized, P = .005; standardized, P = .003) and decreased low fractional tumor burden (normalized, P = .03; standardized, P = .01). The area under the curve showed that relative CBV (normalized = 0.80; standardized = 0.79) and high fractional tumor burden (normalized = 0.77; standardized = 0.78) performed the best to discriminate tumor and radiation necrosis. For tumor prediction, the normalized relative CBV cutoff of ≥1.75 yielded a sensitivity of 76.5% and specificity of 70.0%, while the standardized cutoff of ≥1.75 yielded a sensitivity of 41.2% and specificity of 95.0%. No significance was found with the volume transfer constant, normalized CBF, and standardized uptake value. CONCLUSIONS: Increased relative CBV and high fractional tumor burden (defined by a threshold relative CBV of ≥1.75) best differentiated tumor from radiation necrosis in subjects with brain metastases treated with stereotactic radiosurgery. Performance of normalized and standardized approaches was similar.
MEK1/2 inhibitor inhibits neointima formation by activating miR-126-3p/ C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine receptor 4 (CXCR4) axis

ABSTRACT Endothelial dysfunction is an initial and essential step in vascular-remodeling diseases, including atherosclerosis and neointima formation. During vascular remodeling, activated endothelial cells can release pro-inflammatory factors that promote phenotypic switching of vascular smooth muscle cells (VSMCs) to the proliferative phenotype. We previously reported that MEK1/2 inhibitor, U0126, has a protective effect on the development of atherosclerosis and vascular calcification. However, the effect of MEK1/2 inhibitors on neointimal formation and the underlying mechanism is not fully understood. We determined that MEK1/2 inhibitor reduced carotid artery ligation-induced neointimal formation, while increased collagen and elastin levels and vascular integrality. Mechanistically, MEK1/2 inhibitor or ERK1/2 siRNA increased miR-126-3p level in endothelial cells, thereby inhibiting expression of regular of G-protein signaling 16 (RGS16), a miR-126-3p target gene, to activate the C-X-C motif chemokine ligand 12 (CXCL12)/C-X-C motif chemokine receptor 4 (CXCR4) signaling pathway. Accordingly, miR-126-3p was also increased by U0126 in serum and carotid artery. RGS16 was inhibited while CXCR4 and CXCL12 was increased by U0126 in neointimal areas, especially in the endothelium. Moreover, similar results were observed in atherosclerotic plaques of high-fat diet-fed apolipoprotein E deficiency (apoE−/−) mice. In addition, vascular cell adhesion molecule 1 (VCAM-1), another miR-126-3p target gene, was reduced by U0126 in the neointimal areas, resulting reduced monocytes/macrophages accumulation. Taken together, our results indicate that MEK1/2 inhibitor can reduce neointima formation by activating endothelial miR-126-3p production to facilitate endothelium repair while reduce monocyte adhesion/infiltration. GRAPHICAL ABSTRACT
The Impact of Direct-Acting Antiviral Agents on Cytomegalovirus Reactivation in Chronic Hepatitis C Infection

Objective: The co-infection of HCV/CMV may accelerate the progression of liver diseases and worsen responsiveness to IFN treatment. The Direct-acting antiviral agents (DAAs), currently approved therapy for HCV, may cause a transient change in immune status, favoring the reactivation of other viruses. The current study aims to evaluate the impact of DAAs treatment on the reactivation of latent CMV in HCV patients. Methods: The serological IgG, IgM Abs against CMV were detected by ELISA on192 HCV patients. The seronegative CMV IgM patients received (sofosbuvir/daclatasvir) regimen, then the CMV reactivation was examined by measuring the CMV IgM by ELISA and CMV DNA by real-time PCR. Results: The serological data revealed that all patients were positive for CMV IgG (100%) while (64%) patients were positive for CMV IgM. The seronegative CMV IgM (36%) received the DAAs protocol. The sustained virological response was monitored by measuring the HCV RNA viremia in the patient sera. The serological data revealed that 28.6% of patients had a reactivation of CMV, while 18.5% of patients had detectable CMV DNA viremia. Moreover, there was a significant improvement in liver function as well as a decrease in FIB-4 and APRI scores at EOT. SVR was reached 97.4% among the total studied patients (N= 192). Conclusion: CMV co-infection has no impact on the response rate to DAAs. However, the CMV reactivation might have occurred after the complete eradication of HCV by DAAs.
Suboptimal Leader-to-Coordination Control for Nonlinear Systems With Switching Topologies: A Learning-Based Method

In the cooperative control for multiagent systems (MASs), the key issues of distributed interaction, nonlinear characteristics, and optimization should be considered simultaneously, which, however, remain intractable theoretically even to this day. Considering these factors, this article investigates leader-to-formation control and optimization for nonlinear MASs using a learning-based method. Under time-varying switching topology, a fully distributed state observer based on neural networks is designed to reconstruct the dynamics and the state trajectory of the leader signal with arbitrary precision under jointly connected topology assumption. Benefitted from the observers, formation for MASs under switching topologies is transformed into tracking control for each subsystem with continuous state generated by the observers. An augmented system with discounted infinite LQR performance index is considered to optimize the control effect. Due to the complexity of solving the Hamilton–Jacobi–Bellman equation, the optimal value function is approximated by a critic network via the integral reinforcement learning method without the knowledge of drift dynamics. Meanwhile, an actor network is also presented to assure stability. The tracking errors and estimation weighted matrices are proven to be uniformly ultimately bounded. Finally, two illustrative examples are given to show the effectiveness of this method.