Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteomic and Transcriptional Profiles of Human Stem Cell-Derived β Cells Following Enteroviral Challenge

Enteroviral infections are implicated in islet autoimmunity and type 1 diabetes (T1D) pathogenesis. Significant β-cell stress and damage occur with viral infection, leading to cells that are dysfunctional and vulnerable to destruction. Human stem cell-derived β (SC-β) cells are insulin-producing cell clusters that closely resemble native β cells. To better understand the events precipitated by enteroviral infection of β cells, we investigated transcriptional and proteomic changes in SC-β cells challenged with coxsackie B virus (CVB). We confirmed infection by demonstrating that viral protein colocalized with insulin-positive SC-β cells by immunostaining. Transcriptome analysis showed a decrease in insulin gene expression following infection, and combined transcriptional and proteomic analysis revealed activation of innate immune pathways, including type I interferon (IFN), IFN-stimulated genes, nuclear factor-kappa B (NF-κB) and downstream inflammatory cytokines, and major histocompatibility complex (MHC) class I. Finally, insulin release by CVB4-infected SC-β cells was impaired. These transcriptional, proteomic, and functional findings are in agreement with responses in primary human islets infected with CVB ex vivo. Human SC-β cells may serve as a surrogate for primary human islets in virus-induced diabetes models. Because human SC-β cells are more genetically tractable and accessible than primary islets, they may provide a preferred platform for investigating T1D pathogenesis and developing new treatments.
Circulating Ficolin-2 and Ficolin-3 Form Heterocomplexes

Key Points Stable ficolin-2/-3 heterocomplexes exist in normal human serum and plasma. Concentrations of ficolin-2/-3 complexes correlate with ficolin-2 and -3 in plasma. Visual Abstract The complement system constitutes an important part of the innate immune system. The collectins and the ficolins are soluble pattern recognition molecules that contribute to complement activation via the lectin pathway. During previous experiments with ficolin-2 and ficolin-3, we have observed that the molecules may interact. We therefore hypothesized the existence of stable ficolin-2/-3 heterocomplexes. We could demonstrate ficolin-2/-3 heterocomplexes in normal human serum and plasma by ELISA using Abs specific for ficolin-2 and ficolin-3. The formation of heteromeric protein complexes were validated by coimmunoprecipitation and Western blot analysis. When recombinant ficolin-2 and recombinant ficolin-3 were mixed, no complexes were formed. However, when coexpressing ficolin-2 and ficolin-3 in Chinese hamster ovary cells, we could detect ficolin-2/-3 heterocomplexes in the supernatant. Furthermore, we measured concentration of the ficolin-2/-3 heterocomplexes in arbitrary units in 94 healthy individuals. We also established the relationship between the concentrations of ficolin-2, ficolin-3, and the ficolin-2/-3 heterocomplexes. We observed that the concentration of the ficolin-2/-3 heterocomplex correlated significantly with ficolin-2 (ρ: 0.24, p < 0.018) and ficolin-3 concentrations (ρ: 0.46, p < 0.0001). In conclusion, we describe a novel protein complex between ficolin-2 and ficolin-3 present in serum and plasma, which might be of additional biological relevance apart from the native ficolin-2 and ficolin-3 molecules.
CgSCD1 Is Essential for Melanin Biosynthesis and Pathogenicity of Colletotrichum gloeosporioides

Colletotrichum gloeosporioides, an important phytopathogenic fungus, mainly infects tropical fruits and results in serious anthracnose. Previous studies have shown that melanin biosynthesis inhibitor can inhibit the melanization of the appressoria of Magnaporthe grisea and Colletotrichum orbiculare, resulting in limited infection of the hosts. In this study, we identified and characterized a scytalone dehydratase gene (CgSCD1) from C. gloeosporioides which is involved in melanin synthesis. The CgSCD1 gene deletion mutant ΔCgscd1 was obtained using homologous recombination. The ΔCgscd1 mutant showed no melanin accumulation on appressoria formation and vegetative hyphae. Furthermore, the virulence of ΔCgscd1 was significantly reduced in comparison with the wild-type (WT) strain. Further investigations showed that the growth rate as well as germination and appressorium formation of ΔCgscd1 displayed no difference compared to the wild-type and complemented transformant Cgscd1com strains. Furthermore, we found that the appressorial turgor pressure in the ΔCgscd1 mutant showed no difference compared to that in the WT and Cgscd1com strains in the incipient cytorrhysis experiment. However, fewer infectious hyphae of ΔCgscd1 were observed in the penetration experiments, suggesting that the penetration ability of nonpigmented appressoria was partially impaired. In conclusion, we identified the CgSCD1 gene, which is involved in melanin synthesis and pathogenicity, and found that the melanization defect did not affect appressorial turgor pressure in C. gloeosporioides.
Functionalization of γ-Alumina and Magnesia Nanoparticles with a Fluorocarbon Surfactant to Promote Ultra Gas-Wet Surfaces: Experimental and Theoretical Approach.

A promising alternative to improve the ultra-gas-wet alteration process by the addition of nanoparticles was developed. This study is focused on studying the functionalization process of nanoparticles of gamma-alumina (γ-Al2O3) and magnesia (MgO) using a commercial fluorocarbon surfactant (SYLNYL®FSJ), from an experimental and theoretical approach. Different fluorocarbon surfactant concentrations were used in the functionalization process of the nanoparticles, and the materials obtained were characterized by Fourier-transform infrared spectroscopy (FTIR) and dynamic light scattering (DLS). The experimental setup of the interaction between the surfactant and nanoparticles was reproduced by molecular simulations in order to obtain physical insights into the adsorption process. Experimental results show a suitable functionalization for both nanoparticles with the fluorocarbon surfactant. The γ-Al2O3 nanoparticles showed better behavior based on the obtained non-frictional conditions, which lead the water and n-decane droplets to slide on the rock surface coated with the functionalized nanoparticles. The experimental contact angles on the functionalized γ-Al2O3 nanoparticles were reproduced by molecular dynamics simulations. From the interaction energies evaluation, it was also determined that alumina nanoparticles could reduce the adhesive energy to 0.01 kcal∙mol-1, regarding magnesia nanoparticles. Also, a significant difference was obtained for the surfactant-liquid interactions between the two nanoparticles evaluated, with changes of 17% for surfactant-water interactions and 28% for the surfactant-n-decane. The obtained results explain the pronounced increase for the contact angles of n-decane on the functionalized γ-Al2O3 nanoparticles.
Imaging of Monoclonal Gammapathy of Undetermined Significance and Smoldering Multiple Myeloma

Multiple myeloma (MM) is always preceded by an initial monoclonal gammopathy of undetermined significance (MGUS) that then develops into asymptomatic or smoldering multiple myeloma (SMM), which constitutes an intermediate clinical stage between MGUS and MM. According to a recent study, risk factors for faster MGUS to MM progression include an M protein of 1.5 g/dL or more and an abnormal free light chain ratio in patients with non-IgM MGUS. Therefore, the International Myeloma Working Group (IMWG) decided to recommend whole-body computed tomography (WBCT) for patients with high-risk MGUS in order to exclude early bone destruction. Studies evaluating magnetic resonance imaging (MRI) in SMM found an optimal cutoff of two or more focal lesions to be of prognostic significance for fast progression into symptomatic disease and considered this biomarker as a myeloma-defining event (MDE) needing to start therapy with the aim to avoid progression to harmful bone lesions. Moreover, studies assessing positron emission tomography (PET) with computed tomography (CT) using 18F-deoxyglucose (FDG) (FDG-PET/CT) in SMM showed that presence of focal bone lesion without underlying osteolysis is associated with a rapid progression to symptomatic MM. Latest IMWG guidelines recommended to perform WBCT (either CT alone or as part of an FDG-PET/CT protocol) as the first imaging technique at suspected SMM and, if these images are negative or inconclusive, to perform whole-body MRI. The goal of this paper is to clarify the role of different imaging modalities in MGUS and SMM workups.
Ultra-high-resolution fMRI of Human Ventral Temporal Cortex Reveals Differential Representation of Categories and Domains

Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. Human ventral temporal cortex (VTC) is critical for visual recognition. It is thought that this ability is supported by large-scale patterns of activity across VTC that contain information about visual categories. However, it is unknown how category representations in VTC are organized at the submillimeter scale and across cortical depths. To fill this gap in knowledge, we measured BOLD responses in medial and lateral VTC to images spanning 10 categories from five domains (written characters, bodies, faces, places, and objects) at an ultra-high spatial resolution of 0.8 mm using 7 Tesla fMRI in both male and female participants. Representations in lateral VTC were organized most strongly at the general level of domains (e.g., places), whereas medial VTC was also organized at the level of specific categories (e.g., corridors and houses within the domain of places). In both lateral and medial VTC, domain-level and category-level structure decreased with cortical depth, and downsampling our data to standard resolution (2.4 mm) did not reverse differences in representations between lateral and medial VTC. The functional diversity of representations across VTC partitions may allow downstream regions to read out information in a flexible manner according to task demands. These results bridge an important gap between electrophysiological recordings in single neurons at the micron scale in nonhuman primates and standard-resolution fMRI in humans by elucidating distributed responses at the submillimeter scale with ultra-high-resolution fMRI in humans. SIGNIFICANCE STATEMENT Visual recognition is a fundamental ability supported by human ventral temporal cortex (VTC). However, the nature of fine-scale, submillimeter distributed representations in VTC is unknown. Using ultra-high-resolution fMRI of human VTC, we found differential distributed visual representations across lateral and medial VTC. Domain representations (e.g., faces, bodies, places, characters) were most salient in lateral VTC, whereas category representations (e.g., corridors/houses within the domain of places) were equally salient in medial VTC. These results bridge an important gap between electrophysiological recordings in single neurons at a micron scale and fMRI measurements at a millimeter scale.
Food Retail Environments in Greater Melbourne 2008–2016: Longitudinal Analysis of Intra-City Variation in Density and Healthiness of Food Outlets

Obesity prevalence is inequitably distributed across geographic areas. Food environments may contribute to health disparities, yet little is known about how food environments are evolving over time and how this may influence dietary intake and weight. This study aimed to analyse intra-city variation in density and healthiness of food outlets between 2008 and 2016 in Melbourne, Australia. Food outlet data were classified by location, type and healthiness. Local government areas (LGAs) were classified into four groups representing distance from the central business district. Residential population estimates for each LGA were used to calculate the density of food outlets per 10,000 residents. Linear mixed models were fitted to estimate the mean density and ratio of ‘healthy’ to ‘unhealthy’ food outlets and food outlet ‘types’ by LGA group over time. The number of food outlets increased at a faster rate than the residential population, driven by an increasing density of both ‘unhealthy’ and ‘healthy’ outlets. Across all years, ratios of ‘unhealthy’ to ‘healthy’ outlets were highest in LGAs located in designated Growth Areas. Melbourne’s metropolitan food environment is saturated by ‘unhealthy’ and ‘less healthy’ food outlets, relative to ‘healthy’ ones. Melbourne’s urban growth areas had the least healthy food environments.
Chrono-Nutrition and Diet Quality in Adolescents with Delayed Sleep-Wake Phase Disorder

Background: Delayed sleep-wake phase disorder (DSPD), characterized by delayed sleep-onset and problems with awakening in the morning, is mostly prevalent in adolescents. Several studies have suggested chrono-nutrition could present a possible modifiable risk factor for DSPD. Objective: To describe differences in chrono-nutrition and diet quality in adolescents with DSPD compared to age-related controls. Methods: Chrono-nutrition and diet quality of 46 adolescents with DSPD, aged 13–20 years, and 43 controls were assessed via questionnaires. Diet quality included the Dutch Healthy Diet index (DHD-index) and Eating Choices Index (ECI). Results were analysed using logistic regression and Spearman’s partial correlation. Results: Compared with controls, DSPD patients consumed their first food of the day significantly later on weekdays (+32 ± 12 min, p = 0.010) and weekends (+25 ± 8 min, p = 0.005). They consumed their dinner more regularly (80.4% vs. 48.8%, p = 0.002) and consumed morning-snacks less frequently (3.0 ± 2.1 days vs. 4.2 ± 1.7 days, p = 0.006). No differences in clock times of breakfast, lunch, or dinner were found. Moreover, no significant differences in overall diet quality were observed. Conclusion: This descriptive study showed chrono-nutritional differences between adolescents with and without DPSD. Further studies are needed to explore features of chrono-nutrition as a possible treatment of DPSD.
Thyrotropin-Releasing Hormone (TRH) and Somatostatin (SST), but not Growth Hormone-Releasing Hormone (GHRH) nor Ghrelin (GHRL), Regulate Expression and Release of Immune Growth Hormone (GH) from Chicken Bursal B-Lymphocyte Cultures

It is known that growth hormone (GH) is expressed in immune cells, where it exerts immunomodulatory effects. However, the mechanisms of expression and release of GH in the immune system remain unclear. We analyzed the effect of growth hormone-releasing hormone (GHRH), thyrotropin-releasing hormone (TRH), ghrelin (GHRL), and somatostatin (SST) upon GH mRNA expression, intracellular and released GH, Ser133-phosphorylation of CREB (pCREBS133), intracellular Ca2+ levels, as well as B-cell activating factor (BAFF) mRNA expression in bursal B-lymphocytes (BBLs) cell cultures since several GH secretagogues, as well as their corresponding receptors (-R), are expressed in B-lymphocytes of several species. The expression of TRH/TRH-R, ghrelin/GHS-R1a, and SST/SST-Rs (Subtypes 1 to 5) was observed in BBLs by RT-PCR and immunocytochemistry (ICC), whereas GHRH/GHRH-R were absent in these cells. We found that TRH treatment significantly increased local GH mRNA expression and CREB phosphorylation. Conversely, SST decreased GH mRNA expression. Additionally, when added together, SST prevented TRH-induced GH mRNA expression, but no changes were observed in pCREBS133 levels. Furthermore, TRH stimulated GH release to the culture media, while SST increased the intracellular content of this hormone. Interestingly, SST inhibited TRH-induced GH release in a dose-dependent manner. The coaddition of TRH and SST decreased the intracellular content of GH. After 10 min. of incubation with either TRH or SST, the intracellular calcium levels significantly decreased, but they were increased at 60 min. However, the combined treatment with both peptides maintained the Ca2+ levels reduced up to 60-min. of incubation. On the other hand, BAFF cytokine mRNA expression was significantly increased by TRH administration. Altogether, our results suggest that TRH and SST are implicated in the regulation of GH expression and release in BBL cultures, which also involve changes in pCREBS133 and intracellular Ca2+ concentration. It is likely that TRH, SST, and GH exert autocrine/paracrine immunomodulatory actions and participate in the maturation of chicken BBLs.
Use of Supervised Machine Learning for GNSS Signal Spoofing Detection with Validation on Real-World Meaconing and Spoofing Data—Part I †

The vulnerability of the Global Navigation Satellite System (GNSS) open service signals to spoofing and meaconing poses a risk to the users of safety-of-life applications. This risk consists of using manipulated GNSS data for generating a position-velocity-timing solution without the user’s system being aware, resulting in presented hazardous misleading information and signal integrity deterioration without an alarm being triggered. Among the number of proposed spoofing detection and mitigation techniques applied at different stages of the signal processing, we present a method for the cross-correlation monitoring of multiple and statistically significant GNSS observables and measurements that serve as an input for the supervised machine learning detection of potentially spoofed or meaconed GNSS signals. The results of two experiments are presented, in which laboratory-generated spoofing signals are used for training and verification within itself, while two different real-world spoofing and meaconing datasets were used for the validation of the supervised machine learning algorithms for the detection of the GNSS spoofing and meaconing.
Awareness, Knowledge, Attitude and Preventive Practice of Leptospirosis Among Healthy Malaysian and Non-Malaysian Wet Market Workers in Selected Urban Areas in Selangor, Malaysia

Leptospirosis has been reported as an endemic in most tropical countries. Among high risk occupations, leptospirosis includes workers in agriculture and domestic animal industries. Environmental hygiene in the wet market has established a link between the presence of rodents with probability of leptospirosis infection. This study was aimed to compare the level of knowledge, attitude and preventive practice against leptospirosis between healthy Malaysian and non-Malaysian wet market workers in selected wet markets in urban areas of Selangor. A cross-sectional study in the determined area was conducted with the participation of 147 respondents. The respondents were randomly chosen from the list provided by the state agency that regulates these markets. A self-administered bilingual validated questionnaire (English and Bahasa Melayu) was distributed to the selected respondents. There were 68 (48.3%) Malaysian respondents and 79 (53.7%) non-Malaysian respondents. The majority of them were males, who attained formal education and were less than 40 years old. Meanwhile, the respondents earned less than RM3000. Among the Malaysian respondents, 80.9% were aware of leptospirosis as compared to 17.7% of the non-Malaysian colleagues (p < 0.05). All items of knowledge showed that the Malaysian respondents scored higher as compared to non-Malaysian respondents. On attitude towards infection prevention, most Malaysian respondents had a positive attitude, while most non-Malaysian respondents had undecided perception on the majority of crucial attitude items. In practicing preventive measures, there was a marked significant difference in proportion between Malaysian and non-Malaysian respondents for items on “Specific Protection and Isolation at Source. ” There was a significant gap on knowledge, attitude and preventive practice among Malaysian workers as compared to non-Malaysian workers. Therefore, it was highly recommended the health promotion implementation should also provide specific focus on non-Malaysian workers.
A Quasi-experimental Study Measuring the Effectiveness of Two Empathy Enhancement Programs on Caregivers Working with Older Adults Living Alone

ABSTRACT Objectives: This quasi-experimental study assessed the effectiveness of two empathy enhancement programs on direct care workers of older adults living alone in South Korea. Methods: A total of 104 direct care workers participated in either a simulation-based program or a lecture-based program. Data were collected prior to and 2 weeks after the program implementation using self-reported questionnaires. Results: The lecture-based group had significantly higher levels of empathy compared to the simulation-based group. Pretest-posttest differences were found in the lecture-based group only, including higher levels of empathy and caring efficacy and lower levels of secondary traumatic stress and burnout. Conclusions: More studies are needed to identify helpful components of empathy enhancement programs to direct care workers working with older adults living alone. Also, a further randomized controlled trial study is needed to assess programs’ effectiveness on older adults living alone and direct care workers. Clinical implications: A lecture-based empathy enhancement program can increase levels of empathy and caring efficacy of direct care workers working with older adults and decrease care workers’ levels of burnout and stress. Training for direct care workers of older adults is needed to improve the empathy of direct care workers while reducing their stress and burnout.
Extracellular Synthesis and Characterization of Silver Nanoparticles—Antibacterial Activity against Multidrug-Resistant Bacterial Strains

Herein, we report the use of a cell-free extract for the extracellular synthesis of silver nanoparticles (AgNPs) and their potential to address the growing threat of multidrug-resistant (MDR) pathogenic bacteria. The reproducibility of AgNP synthesis was good and AgNP formation kinetics were monitored as a function of various reaction factors via ultraviolet-visible absorption spectroscopy. This green method was dependent on the alkaline pH of the reaction mixture. With the addition of dilute sodium hydroxide, well-dispersed AgNPs could be produced in large quantities via the classical nucleation and growth route. The new biosynthetic route enabled the production of AgNPs within a narrow size range of 4 to 17 nm. The AgNPs were characterized using various techniques and their antibacterial activity against MDR pathogenic bacteria was evaluated. Field-emission scanning electron microscopic imaging revealed prominent morphological changes in Staphylococcus aureus cells due to mechanical damage, which led to cell death. Escherichia coli cells showed signs of contraction and intracellular fluid discharge as a consequence of disrupted cell membrane function. This new biologically-assisted extracellular strategy is potentially useful for the decontamination of surfaces and is expected to contribute to the development of new products containing AgNPs.