Miracle-dz/UniFAR-FTUs huggingface dataset:
Complement 3 and the Prognostic Nutritional Index Distinguish Kawasaki Disease from Other Fever Illness with a Nomogram

Objective: This study aimed to establish a model to distinguish Kawasaki disease (KD) from other fever illness using the prognostic nutritional index (PNI) and immunological factors. Method: We enrolled a total of 692 patients (including 198 with KD and 494 children with febrile diseases). Of those, 415 patients were selected to be the training group and 277 patients to be the validation group. Laboratory data, including the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the prognostic nutritional index (PNI), and immunological factors, were retrospectively collected for an analysis after admission. We used univariate and multivariate logistic regressions and nomograms for the analysis. Result: Patients with KD showed significantly higher C3 and a lower PNI. After a multivariate logistic regression, the total leukocyte count, PNI, C3, and NLR showed a significance (p < 0.05) and then performed well with the nomogram model. The areas under the ROC in the training group and the validation group were 0.858 and 0.825, respectively. The calibration curves of the two groups for the probability of KD showed a near agreement to the actual probability. Conclusions: Compared with children with febrile diseases, patients with KD showed increased C3 and a decreased nutritional index of the PNI. The nomogram established with these factors could effectively identify KD from febrile illness in children.
Faster Region-Based Convolutional Neural Network in the Classification of Different Parkinsonism Patterns of the Striatum on Maximum Intensity Projection Images of [18F]FP-CIT Positron Emission Tomography

The aim of this study was to compare the performance of a deep-learning convolutional neural network (Faster R-CNN) model to detect imaging findings suggestive of idiopathic Parkinson’s disease (PD) based on [18F]FP-CIT PET maximum intensity projection (MIP) images versus that of nuclear medicine (NM) physicians. The anteroposterior MIP images of the [18F]FP-CIT PET scan of 527 patients were classified as having PD (139 images) or non-PD (388 images) patterns according to the final diagnosis. Non-PD patterns were classified as overall-normal (ONL, 365 images) and vascular parkinsonism with definite defects or prominently decreased dopamine transporter binding (dVP, 23 images) patterns. Faster R-CNN was trained on 120 PD, 320 ONL, and 16 dVP pattern images and tested on the 19 PD, 45 ONL, and seven dVP patterns images. The performance of the Faster R-CNN and three NM physicians was assessed using receiver operating characteristics curve analysis. The difference in performance was assessed using Cochran’s Q test, and the inter-rater reliability was calculated. Faster R-CNN showed high accuracy in differentiating PD from non-PD patterns and also from dVP patterns, with results comparable to those of NM physicians. There were no significant differences in the area under the curve and performance. The inter-rater reliability among Faster R-CNN and NM physicians showed substantial to almost perfect agreement. The deep-learning model accurately differentiated PD from non-PD patterns on MIP images of [18F]FP-CIT PET, and its performance was comparable to that of NM physicians.
Ultrasensitive Biosensor with Hyperbolic Metamaterials Composed of Silver and Zinc Oxide

We propose a hyperbolic metamaterial-based surface plasmon resonance (HMM-SPR) sensor by composing a few pairs of alternating silver (Ag) and zinc oxide (ZnO) layers. Aiming to achieve the best design for the sensor, the dependence of the sensitivity on the incidence angle, the thickness of the alternating layer and the metal filling fraction are explored comprehensively. We find that the proposed HMM-SPR sensor achieves an average sensitivity of 34,800 nm per refractive index unit (RIU) and a figure of merit (FOM) of 470.7 RIU−1 in the refractive index ranging from 1.33 to 1.34. Both the sensitivity (S) and the FOM show great enhancement when compared to the conventional silver-based SPR sensor (Ag-SPR). The underlying physical reason for the higher performance is analyzed by numerical simulation using the finite element method. The higher sensitivity could be attributed to the enhanced electric field amplitude and the increased penetration depth, which respectively increase the interaction strength and the sensing volume. The proposed HMM-SPR sensor with greatly improved sensitivity and an improved figure of merit is expected to find application in biochemical sensing due to the higher resolution.
Dnmt3aa but Not Dnmt3ab Is Required for Maintenance of Gametogenesis in Nile Tilapia (Oreochromis niloticus)

Dnmt3a, a de novo methyltransferase, is essential for mammalian germ line DNA methylation. Only one Dnmt3a is identified in mammals, and homozygous mutants of Dnmt3a are lethal, while two Dnmt3a paralogs, dnmt3aa and dnmt3ab, are identified in teleosts due to the third round of genome duplication, and homozygous mutants of dnmt3aa and dnmt3ab are viable in zebrafish. The expression patterns and roles of dnmt3aa and dnmt3ab in gonadal development remain poorly understood in teleosts. In this study, we elucidated the precise expression patterns of dnmt3aa and dnmt3ab in tilapia gonads. Dnmt3aa was highly expressed in oogonia, phase I and II oocytes and granulosa cells in ovaries and spermatogonia and spermatocytes in testes, while dnmt3ab was mainly expressed in ovarian granulosa cells and testicular spermatocytes. The mutation of dnmt3aa and dnmt3ab was achieved by CRISPR/Cas9 in tilapia. Lower gonadosomatic index (GSI), increased apoptosis of oocytes and spermatocytes and significantly reduced sperm quality were observed in dnmt3aa−/− mutants, while normal gonadal development was observed in dnmt3ab−/− mutants. Consistently, the expression of apoptotic genes was significantly increased in dnmt3aa−/− mutants. In addition, the 5-methylcytosine (5-mC) level in dnmt3aa−/− gonads was decreased significantly, compared with that of dnmt3ab−/− and wild type (WT) gonads. Taken together, our results suggest that dnmt3aa, not dnmt3ab, plays important roles in maintaining gametogenesis in teleosts.
Multi-Target Actions of Acridones from Atalantia monophylla towards Alzheimer’s Pathogenesis and Their Pharmacokinetic Properties

Ten acridones isolated from Atalantia monophylla were evaluated for effects on Alzheimer’s disease pathogenesis including antioxidant effects, acetylcholinesterase (AChE) inhibition, prevention of beta-amyloid (Aβ) aggregation and neuroprotection. To understand the mechanism, the type of AChE inhibition was investigated in vitro and binding interactions between acridones and AChE or Aβ were explored in silico. Drug-likeness and ADMET parameters were predicted in silico using SwissADME and pKCSM programs, respectively. All acridones showed favorable drug-likeness and possessed multifunctional activities targeting AChE function, Aβ aggregation and oxidation. All acridones inhibited AChE in a mixed-type manner and bound AChE at both catalytic anionic and peripheral anionic sites. In silico analysis showed that acridones interfered with Aβ aggregation by interacting at the central hydrophobic core, C-terminal hydrophobic region, and the key residues 41 and 42. Citrusinine II showed potent multifunctional action with the best ADMET profile and could alleviate neuronal cell damage induced by hydrogen peroxide and Aβ1-42 toxicity.
Competing Bioaerosols May Influence the Seasonality of Influenza-Like Illnesses, including COVID-19. The Chicago Experience

Data from Chicago confirm the end of flu season coincides with the beginning of pollen season. More importantly, the end of flu season also coincides with onset of seasonal aerosolization of mold spores. Overall, the data suggest bioaerosols, especially mold spores, compete with viruses for a shared receptor, with the periodicity of influenza-like illnesses, including COVID-19, a consequence of seasonal factors that influence aerosolization of competing species.
Effectiveness of Information and Communication Technology (ICT) Interventions in Elderly’s Sleep Disturbances: A Systematic Review and Meta-Analysis

Sleep is a crucial factor for human health and is closely related to quality of life. Sleep disturbances constitute a health problem that should be solved, especially when it affects the elderly. This study aims to examine the effectiveness of information and communication technologies (ICT) interventions in managing sleep disturbances in the elderly. The study used a systematic review of three databases: Ovid-Medline, Ovid-EMBASE, and the Cochrane library database for papers published till 15 April 2021. Two authors independently selected and screened relevant studies based on predefined inclusion criteria. The meta-analysis of randomized controlled trials (RCTs) was carried out using Review Manager 5.4. Two authors independently screened the titles and abstracts of 4297 studies considering both inclusion and exclusion criteria. The complete texts of 47 articles were then evaluated, 31 articles were excluded, and finally, 16 articles were selected. Our meta-analysis showed that the cognitive-behavioral therapy for insomnia (CBT-I) group had a significantly reduced Insomnia Severity Index (ISI) compared to the control group (−4.81 [−5.56, −4.06], p < 0.00001, I2 = 83%) in RCTs, with a significant reduction in ISI (3.47 [1.58, 5.35], p = 0.0003) found in quasi-experimental studies. A significant improvement was found in total sleep time in the CBT-I group compared to the control group (29.24 [15.41, 43.07], p <0.0001) in RCTs, while the CBT-I group showed significantly reduced wake time after sleep onset compared to the control group (−20.50 [−26.60, −14.41], p < 0.00001). In addition, a significant reduction in depression was found in the CBT-I group compared to the control group (−2.11 [−2.85, −1.37], p < 0.00001, I2 = 0%) in RCTs. The quality of life–mental component score (5.75 [1.64, 9.87], p = 0.006, I2 = 0%) and the quality of life–physical component score (5.19 [0.76, 9.62], p = 0.02, I2 = 0%) showed significant improvement in the CBT-I group compared to the control group. ICT interventions showed positive effects on sleep disturbances of the elderly, specifically confirming the positive effect on depression and quality of life as well as the indicators directly related to sleep such as ISI and quality of sleep. Thus, the application of ICT in the healthcare sector will be greater in the future, with changes in the nursing education and practice guidelines so that nurses can play a pivotal role in promoting health behaviors such as sleep-related quality of life and daily activities of the elderly.
Evaluation of Plaque Vulnerability via Combination of Hemodynamic Analysis and Simultaneous Non-Contrast Angiography and Intraplaque Hemorrhage (SNAP) Sequence for Carotid Intraplaque Hemorrhage

The purpose of this study was to assess the vulnerability of plaque using a combination of simultaneous non-contrast angiography, intraplaque hemorrhage (SNAP) sequence, and local hemodynamic analysis in an intraplaque hemorrhage (IPH), and to evaluate the association between morphological and hemodynamic factors and IPH by comparing the IPH (presence of IPH) and non-IPH (plaque with absence of IPH) groups. In total, 27 IPH patients and 27 non-IPH patients were involved in this study, and baseline characteristics were collected. For morphological factors, diameters, and areas of the internal carotid artery (ICA), external carotid artery, and common carotid artery were measured, and bifurcation angle (α) and ICA angle (β) were also measured for comparison between the IPH group and non-IPH group. For hemodynamic factors, time-averaged wall shear stress (WSS), minimum WSS, maximum WSS, and oscillatory shear index were calculated using computational fluid dynamics (CFD) simulations. For the qualitative analysis, cross-sectional images with analyzed WSS and SNAP sequences were combined to precisely assess local hemodynamics. Bifurcation angle (α) was significantly different between the IPH and non-IPH groups (39.47 degrees vs. 47.60 degrees, p = 0.041). Significantly higher time-averaged WSS, minimum WSS, and maximum WSS were observed in the IPH group compared to the non-IPH group. In the IPH group, when using the combined analysis with SNAP sequences and WSS, the WSS of the region with IPH was significantly higher than the region without IPH (2.32 vs. 1.21 Pa, p = 0.005). A smaller bifurcation angle (α) and higher time-averaged WSS, minimum WSS, and maximum WSS were associated with IPH. The combined analysis of SNAP sequences and WSS might help to evaluate the risk of carotid IPH.
Interest in Humans: Comparisons between Riding School Lesson Equids and Assisted-Intervention Equids

Simple Summary Very little is known about the impact of equine-assisted interventions on equids’ perception of humans. Different factors can influence human–horse relationships: animal characteristics, daily interactions with the caretakers, and working and living conditions. In this study, 172 equids working in equine-assisted interventions, ‘classical’ riding school lessons, or both were submitted to a standardised human–horse relationship test in order to test if EAI had an impact on the equid reactions to humans. The possible influence of intrinsic (age, sex, type) or other extrinsic factors (housing and feeding conditions) was also considered. The results showed that the number (more than the type) of experimenter-directed behaviours varied significantly between individuals and that the activity was the most important factor of influence: Equids working in riding school lessons performed more interactive behaviours than those working in equine-assisted interventions or having mixed activity. Other factors such as daily hay quantity, the horses’ age, and sex also influenced secondarily the horse’s motivation to interact, although no interaction was found between factors. These results suggest that equine-assisted interventions do influence horses’ perception of humans outside work. Further studies are needed in order to understand the processes involved. Abstract Little is known about the impact of equine-assisted interventions (EAI) on equids’ perception of humans. In this study 172 equids, living in 12 riding centres, were submitted to a standardised human–horse relationship test: the motionless person test. Age, sex, type (horse/pony), housing, and feeding conditions of subjects were recorded. Overall, 17 equids worked in EAI, 95 in riding school lessons (RS), and 60 in both (EAI-RS). There were high inter-individual variations in the number of interactive behaviours directed towards the experimenter: negative binomial general linear models showed that activity was the most important factor: RS equids performed more interactive behaviours than EAI (p = 0.039) and EAI-RS (p < 0.001) equids. Daily quantity of hay appeared as the second most important factor (equids with more than 3 kg interacted more than equids with less than 3 kg, p = 0.013). Individual characteristics were also important as horses interacted more than ponies (p = 0.009), geldings more than mares (p = 0.032), and 3–15-year-old equids more than equids over 15 years (p = 0.032). However, there was no interaction between factors. The lower number of interactive behaviours of EAI equids leads to different hypotheses—namely, selection on temperament, specific training, or compromised welfare (apathy). In any case, our results raised new lines of questions on EAI.
A New Approach to Atopic Dermatitis Control with Low-Concentration Propolis-Loaded Cold Cream

Atopic dermatitis (AD) is a chronic inflammatory skin disease that is difficult to treat. Traditional cold cream, a water-in-oil emulsion made from beeswax, is used to alleviate AD symptoms in clinical practice, although its effectiveness has not been scientifically proven. The addition of propolis has the potential to impart anti-inflammatory properties to cold cream. However, in high concentrations, propolis can trigger allergic reactions. Thus, the objective of this work was to develop a cold cream formulation based on purified beeswax containing the same amount of green propolis present in raw beeswax. The impact of adding this low propolis concentration to cold cream on AD control was evaluated in patients compared to cold cream without added propolis (CBlank). Raw beeswax was chemically characterized to define the propolis concentration added to the propolis-loaded cold cream (CPropolis). The creams were characterized as to their physicochemical, mechanical, and rheological characteristics. The effect of CPropolis and CBlank on the quality of life, disease severity, and skin hydration of patients with AD was evaluated in a triple-blind randomized preclinical study. Concentrations of 34 to 120 ng/mL of green propolis extract reduced TNF-α levels in LPS-stimulated macrophage culture. The addition of propolis to cold cream did not change the cream’s rheological, mechanical, or bioadhesive properties. The preclinical study suggested that both creams improved the patient’s quality of life. Furthermore, the use of CPropolis decreased the disease severity compared to CBlank.
Identification of a Region in the Common Amino-terminal Domain of Hendra Virus P, V, and W Proteins Responsible for Phase Transition and Amyloid Formation

Henipaviruses are BSL-4 zoonotic pathogens responsible in humans for severe encephalitis. Their V protein is a key player in the evasion of the host innate immune response. We previously showed that the Henipavirus V proteins consist of a long intrinsically disordered N-terminal domain (NTD) and a β-enriched C-terminal domain (CTD). These terminals are critical for V binding to DDB1, which is a cellular protein that is a component of the ubiquitin ligase E3 complex, as well as binding to MDA5 and LGP2, which are two host sensors of viral RNA. Here, we serendipitously discovered that the Hendra virus V protein undergoes a liquid-to-hydrogel phase transition and identified the V region responsible for this phenomenon. This region, referred to as PNT3 and encompassing residues 200–310, was further investigated using a combination of biophysical and structural approaches. Congo red binding assays, together with negative-staining transmisison electron microscopy (TEM) studies, show that PNT3 forms amyloid-like fibrils. Fibrillation abilities are dramatically reduced in a rationally designed PNT3 variant in which a stretch of three contiguous tyrosines, falling within an amyloidogenic motif, were replaced by three alanines. Worthy to note, Congo red staining experiments provided hints that these amyloid-like fibrils form not only in vitro but also in cellula after transfection or infection. The present results set the stage for further investigations aimed at assessing the functional role of phase separation and fibrillation by the Henipavirus V proteins.
Identification and Characterization of 24-Dehydrocholesterol Reductase (DHCR24) in the Two-Spotted Cricket, Gryllus bimaculatus

Simple Summary DHCR24 (24-dehydrocholesterol reductase) is a key enzyme for producing cholesterol from desmosterol and that is also involved in the conversion of plant sterols to cholesterol in most plant-feeding insects. This study extensively examined the possibility of DHCR24 involved in the sterol conversion in omnivorous insects, which feed on multiple food origins. Homologs of DHCR24 (GbDHCR24-1 and -2) were identified and characterized by using the two-spotted cricket, Gryllus bimaculatus, as an experimental model. The quantitative expression analyses and RNA interference experiments revealed that GbDHCR24-1 rather than GbDHCR24-2 facilitates the desmosterol-to-cholesterol conversion in crickets. Our data suggested that the omnivorous species produced cholesterol from desmosterol in the same manner as the plant-feeding species do. Abstract Arthropods, including insects, convert sterols into cholesterol due to the inability to synthesise cholesterol de novo. 24-dehydrocholesterol reductase (DHCR24) plays an important role in the conversion. Not only involving the cholesterol biosynthesis in vertebrates, DHCR24 is required for the conversion of desmosterol into cholesterol in phytophagous insects. The current study extensively examined DHCR24 in omnivorous insects, which feed on both plants and animals, using Gryllus bimaculatus as the experimental model. We identified cDNAs encoding two homologues of DHCR24 from G. bimaculatus, which were designated as GbDHCR24-1 and GbDHCR24-2. Both homologues contained the flavin adenine dinucleotide binding domain, which is a feature of DHCR24. Quantitative polymerase chain reaction revealed that among tissues of adult crickets, fat body and anterior midgut expressed high levels of GbDHCR24s. Both fat body and anterior midgut demonstrated DHCR24 activities in which one of the functions is the conversion of desmosterol into cholesterol in vitro. Knockdown of GbDHCR24-1 significantly reduced the conversion activity in the anterior midgut while knockdown of the GbDHCR24-2 did not. Additionally, the accumulation of desmosterol was detected in a feeding experiment with a specific DHCR24 inhibitor, azacosterol. We finally concluded that GbDHCR24-1 is the major enzyme that facilitates the desmosterol-to-cholesterol-conversion in crickets.
Metabolic Reprogramming of Mammary Epithelial Cells during TGF-β-Induced Epithelial-to-Mesenchymal Transition

The cytokine transforming growth factor-β (TGF-β) can induce normal breast epithelial cells to take on a mesenchymal phenotype, termed epithelial-to-mesenchymal transition (EMT). While the transcriptional and proteomic changes during TGF-β-induced EMT have been described, the metabolic rewiring that occurs in epithelial cells undergoing EMT is not well understood. Here, we quantitively analyzed the TGF-β-induced metabolic reprogramming during EMT of non-transformed NMuMG mouse mammary gland epithelial cells using nuclear magnetic resonance (NMR) spectroscopy. We found that TGF-β elevates glycolytic and tricarboxylic acid (TCA)-cycle activity and increases glutaminolysis. Additionally, TGF-β affects the hexosamine pathway, arginine-proline metabolism, the cellular redox state, and strongly affects choline metabolism during EMT. TGF-β was found to induce phosphocholine production. A kinase inhibitor RSM-93A that inhibits choline kinase α (CHKα) mitigated TGF-β-induced changes associated with EMT, i.e., increased filamentous (F)-actin stress fiber formation and N-Cadherin mesenchymal marker expression.
Mass Spectrometry-Based Zebrafish Toxicometabolomics: A Review of Analytical and Data Quality Challenges

Metabolomics has achieved great progress over the last 20 years, and it is currently considered a mature research field. As a result, the number of applications in toxicology, biomarker, and drug discovery has also increased. Toxicometabolomics has emerged as a powerful strategy to provide complementary information to study molecular-level toxic effects, which can be combined with a wide range of toxicological assessments and models. The zebrafish model has gained importance in recent decades as a bridging tool between in vitro assays and mammalian in vivo studies in the field of toxicology. Furthermore, as this vertebrate model is a low-cost system and features highly conserved metabolic pathways found in humans and mammalian models, it is a promising tool for toxicometabolomics. This short review aims to introduce zebrafish researchers interested in understanding the effects of chemical exposure using metabolomics to the challenges and possibilities of the field, with a special focus on toxicometabolomics-based mass spectrometry. The overall goal is to provide insights into analytical strategies to generate and identify high-quality metabolomic experiments focusing on quality management systems (QMS) and the importance of data reporting and sharing.