Miracle-dz/UniFAR-FTUs huggingface dataset:
Advanced phosphocreatine-grafted chitosan hydrogel promote wound healing by macrophage modulation

Background: The repair of wounds usually caused by trauma or other chronic diseases remained challenging in clinics due to the potential risk of inflammation and inadequate tissue regenerative properties. Among them, the behaviour of immune cells, such as macrophages, is critical in tissue repair. Materials and methods: In this study, a water-soluble phosphocreatine-grafted methacryloyl chitosan (CSMP) was synthesized with a one-step lyophilization method, followed by the fabrication of CSMP hydrogel with a photocrosslinked method. The microstructure, water absorption and mechanical properties for the hydrogels were investigated. Then, the macrophages were co-cultured with hydrogels and the pro-inflammatory factors and polarization markers for these macrophages were detected through real-time quantitative polymerase chain reaction (RT-qPCR), Western blot (WB), and flow cytometry methods. Finally, the CSMP hydrogel was implanted in a wound defect area in mice to test its ability to promote wound healing. Results: The lyophilized CSMP hydrogel had a porous structure with pores ranging in size from 200 to 400 μm, which was larger than the CSM hydrogel’s. The lyophilized CSMP hydrogel possessed a higher water absorption rate compared with the CSM hydrogel. The compressive stress and modulus of these hydrogels were increased in the initial 7 days immersion and then gradually decreased during the in vitro immersion in PBS solution up to 21 days; the CSMP hydrogel showed a higher value in these parameters versus the CSM hydrogel. The CSMP hydrogel inhibited the expression of inflammatory factors such as interleukin-1β (IL-1β), IL-6, IL-12, and tumor necrosis factor-α (TNF-α) in an in vitro study cocultured with pro-inflammatory factors in pre-treated bone marrow-derived macrophages (BMM). The mRNA sequencing results showed that the CSMP hydrogel might inhibit the macrophages’ M1 type polarization through the NF-κB signaling pathway. Furthermore, when compared to the control group, the CSMP hydrogel promoted more skin area repair in the mouse wound defect area, and inflammatory factors such as IL-1β, IL-6, and TNF-α were lower in the repaired tissue for the CSMP group. Conclusion: This phosphate-grafted chitosan hydrogel showed great promise for wound healing through regulating the macrophage’s phenotype via the NF-κB signaling pathway.
When proprioceptive feedback enhances visual perception of self-body movement: rehabilitation perspectives

Introduction Rehabilitation approaches take advantage of vision’s important role in kinesthesia, using the mirror paradigm as a means to reduce phantom limb pain or to promote recovery from hemiparesis. Notably, it is currently applied to provide a visual reafferentation of the missing limb to relieve amputees’ pain. However, the efficiency of this method is still debated, possibly due to the absence of concomitant coherent proprioceptive feedback. We know that combining congruent visuo-proprioceptive signals at the hand level enhances movement perception in healthy people. However, much less is known about lower limbs, for which actions are far less visually controlled in everyday life than upper limbs. Therefore, the present study aimed to explore, with the mirror paradigm, the benefit of combined visuo-proprioceptive feedback from the lower limbs of healthy participants. Methods We compared the movement illusions driven by visual or proprioceptive afferents and tested the extent to which adding proprioceptive input to the visual reflection of the leg improved the resulting movement illusion. To this end, 23 healthy adults were exposed to mirror or proprioceptive stimulation and concomitant visuo-proprioceptive stimulation. In the visual conditions, participants were asked to voluntarily move their left leg in extension and look at its reflection in the mirror. In the proprioceptive conditions, a mechanical vibration was applied to the hamstring muscle of the leg hidden behind the mirror to simulate an extension of the leg, either exclusively or concomitantly, to the visual reflection of the leg in the mirror. Results (i) Visual stimulation evoked leg movement illusions but with a lower velocity than the actual movement reflection on the mirror; (ii) proprioceptive stimulation alone provided more salient illusions than the mirror illusion; and (iii) adding a congruent proprioceptive stimulation improved the saliency, amplitude, and velocity of the illusion. Conclusion The present findings confirm that visuo-proprioceptive integration occurs efficiently when the mirror paradigm is coupled with mechanical vibration at the lower limbs, thus providing promising new perspectives for rehabilitation.
A mathematical model and experimental procedure to analyze the cognitive effects of audio frequency magnetic fields

Audio frequency magnetic fields (20 Hz−20 kHz) are magnetic fields in extremely low frequency-very low frequency (ELF-VLF) bands that are present near audio equipment and acoustic transducers. These devices transform and operate the electrical signal from the recordings or other devices into acoustic and audio signals. The cognitive influence of sound and noise has been widely studied and recognized since the times of ancient Rome; however, the cognitive effects of the magnetic fields of these frequencies have not been studied. Due to the extensive use of audio devices that use this type of transducer near the temporal–parietal area, we believe that it is of interest to study their impact on short-term memory or working memory (WM) and to analyze their potential as they operate as a transcranial magnetic stimulation. In this study, a mathematical model and an experimental tool are introduced to analyze memory performance. The model dissociates the reaction time of a cognitive task. We analyze the model in data from a group of 65 young, healthy subjects. WM is assessed in our experimental setup by means of the Sternberg test (ST), whereby during the ST, one subgroup was exposed to an audio frequency magnetic stimulus, and the other subgroup received a sham stimulus. The magnetic stimulus was ~0.1 μT and was applied to both sides of the head at the frontal cortex near the temporal–parietal area, which is where WM is expected to be located. The ST records reaction times when determining whether an object displayed on the computer screen is one of the objects to be remembered. The results are analyzed within the mathematical model and changes are observed, including the deterioration of WM, which could affect 32% of its operability.
A novel precision-serology assay for SARS-CoV-2 infection based on linear B-cell epitopes of Spike protein

Introduction The COVID-19 pandemic illustrates the need for serology diagnostics with improved accuracy. While conventional serology based on recognition of entire proteins or subunits thereof has made significant contribution to the antibody assessment space, it often suffers from sub-optimal specificity. Epitope-based, high-precision, serology assays hold potential to capture the high specificity and diversity of the immune system, hence circumventing the cross-reactivity with closely related microbial antigens. Methods We herein report mapping of linear IgG and IgA antibody epitopes of the SARS-CoV-2 Spike (S) protein in samples from SARS-CoV-2 exposed individuals along with certified SARS-CoV-2 verification plasma samples using peptide arrays. Results We identified 21 distinct linear epitopes. Importantly, we showed that pre-pandemic serum samples contain IgG antibodies reacting to the majority of protein S epitopes, most likely as a result of prior infection with seasonal coronaviruses. Only 4 of the identified SARS-CoV-2 protein S linear epitopes were specific for SARS-CoV-2 infection. These epitopes are located at positions 278-298 and 550-586, just proximal and distal to the RBD, as well as at position 1134-1156 in the HR2 subdomain and at 1248-1271 in the C-terminal subdomain of protein S. To substantiate the applicability of our findings, we tested three of the high-accuracy protein S epitopes in a Luminex assay, using a certified validation plasma sample set from SARS-CoV-2 infected individuals. The Luminex results were well aligned with the peptide array results, and correlated very well with in-house and commercial immune assays for RBD, S1 and S1/S2 domains of protein S. Conclusion We present a comprehensive mapping of linear B-cell epitopes of SARS-CoV-2 protein S, that identifies peptides suitable for a precision serology assay devoid of cross-reactivity. These results have implications for development of highly specific serology test for exposure to SARS-CoV-2 and other members of the coronaviridae family, as well as for rapid development of serology tests for future emerging pandemic threats.
Effects of urbanization on the structure of plant-flower visitor network at the local and landscape levels in the northern Argentinian Yungas forest

Human population and cities are growing fast, with a concomitant modification of the land surface. Urbanization is driving biodiversity loss and biological homogenization, which impacts human wellbeing. In this study, we evaluated the influence of urbanization on flower visitor assemblage using an interaction network approach. We assessed the effect of different variables at the local and landscape scales on community parameters and network metrics along a gradient of urbanization located in a subtropical montane Yungas forest. We found that local variables affected the richness of flower visitors, which increased with greater flower coverage, high stability of floral resources, and the proportion of exotic plants. Moreover, local variables affected the diversity, nestedness (NODF), and specialization (H2) of the interaction network. Landscape variables, such as altitude and proportion of impervious surface (a proxy of urbanization), affected both the richness of flower visitors and specialization. The effect of urbanization on the richness of flower visitors differed across the altitudinal gradient, with higher impact at higher altitudes. In conclusion, our results indicate that local and landscape variables affect community parameters and the structure of plant-flower visitor networks to different extents and strengths.
An updated examination of the perception of barriers for pharmacogenomics implementation and the usefulness of drug/gene pairs in Latin America and the Caribbean

Pharmacogenomics (PGx) is considered an emergent field in developing countries. Research on PGx in the Latin American and the Caribbean (LAC) region remains scarce, with limited information in some populations. Thus, extrapolations are complicated, especially in mixed populations. In this paper, we reviewed and analyzed pharmacogenomic knowledge among the LAC scientific and clinical community and examined barriers to clinical application. We performed a search for publications and clinical trials in the field worldwide and evaluated the contribution of LAC. Next, we conducted a regional structured survey that evaluated a list of 14 potential barriers to the clinical implementation of biomarkers based on their importance. In addition, a paired list of 54 genes/drugs was analyzed to determine an association between biomarkers and response to genomic medicine. This survey was compared to a previous survey performed in 2014 to assess progress in the region. The search results indicated that Latin American and Caribbean countries have contributed 3.44% of the total publications and 2.45% of the PGx-related clinical trials worldwide thus far. A total of 106 professionals from 17 countries answered the survey. Six major groups of barriers were identified. Despite the region’s continuous efforts in the last decade, the primary barrier to PGx implementation in LAC remains the same, the “need for guidelines, processes, and protocols for the clinical application of pharmacogenetics/pharmacogenomics”. Cost-effectiveness issues are considered critical factors in the region. Items related to the reluctance of clinicians are currently less relevant. Based on the survey results, the highest ranked (96%–99%) gene/drug pairs perceived as important were CYP2D6/tamoxifen, CYP3A5/tacrolimus, CYP2D6/opioids, DPYD/fluoropyrimidines, TMPT/thiopurines, CYP2D6/tricyclic antidepressants, CYP2C19/tricyclic antidepressants, NUDT15/thiopurines, CYP2B6/efavirenz, and CYP2C19/clopidogrel. In conclusion, although the global contribution of LAC countries remains low in the PGx field, a relevant improvement has been observed in the region. The perception of the usefulness of PGx tests in biomedical community has drastically changed, raising awareness among physicians, which suggests a promising future in the clinical applications of PGx in LAC.
Cell-autonomous and differential endocannabinoid signaling impacts the development of presynaptic retinal ganglion cell axon connectivity in vivo

Cannabis exposure during gestation evokes significant molecular modifications to neurodevelopmental programs leading to neurophysiological and behavioral abnormalities in humans. The main neuronal receptor for Δ9-tetrahydrocannabinol (THC) is the type-1 cannabinoid receptor CB1R, one of the most abundant G-protein-coupled receptors in the nervous system. While THC is the major psychoactive phytocannabinoid, endocannabinoids (eCBs) are the endogenous ligands of CB1R and are known to act as retrograde messengers to modulate synaptic plasticity at different time scales in the adult brain. Accumulating evidence indicates that eCB signaling through activation of CB1R plays a central role in neural development. During development, most CB1R localized to axons of projection neurons, and in mice eCB signaling impacts axon fasciculation. Understanding of eCB-mediated structural plasticity during development, however, requires the identification of the precise spatial and temporal dynamics of CB1R-mediated modifications at the level of individual neurons in the intact brain. Here, the cell-autonomous role of CB1R and the effects of CB1R-mediated eCB signaling were investigated using targeted single-cell knockdown and pharmacologic treatments in Xenopus. We imaged axonal arbors of retinal ganglion cells (RGCs) in real time following downregulation of CB1R via morpholino (MO) knockdown. We also analyzed RGC axons with altered eCB signaling following treatment with URB597, a selective inhibitor of the enzyme that degrades Anandamide (AEA), or JZL184, an inhibitor of the enzyme that blocks 2-Arachidonoylglycerol (2-AG) hydrolysis, at two distinct stages of retinotectal development. Our results demonstrate that CB1R knockdown impacts RGC axon branching at their target and that differential 2-AG and AEA-mediated eCB signaling contributes to presynaptic structural connectivity at the time that axons terminate and when retinotectal synaptic connections are made. Altering CB1R levels through CB1R MO knockdown similarly impacted dendritic morphology of tectal neurons, thus supporting both pre- and postsynaptic cell-autonomous roles for CB1R-mediated eCB signaling.
Characteristics of intestinal microbiota in infants with late-onset breast milk jaundice

Introduction In this paper, microbiota analysis was determined to analyze the structure and difference of intestinal microbiota between LBMJ (late-onset breast milk jaundice) infants and healthy individuals. Methods We collected fresh fecal samples from 13 infants with LBMJ and 13 healthy individuals, then determined the intestinal microbiota by 16 s rRNA sequencing. The differences of microbiota structure, diversity and functional characteristics between the two groups were analyzed, and the correlation between dominant genus and TcB (transcutaneous bilirubin) value was calculated. Results In this study, there were no significant differences in maternal demographic characteristics, neonatal status and macronutrients in breast milk between the two groups (p > 0.05). There are differences in the structure of intestinal microbiota between LBMJ and the control group. At the genus level, the relative abundance of Klebsiella in the case group is high (p < 0.05). At the same time, correlation analysis indicates that the abundance of Klebsiella is positively correlated with TcB value. The intestinal microbiota richness and diversity (Alpha diversity and Beta diversity) of the two groups were significantly different (p < 0.05). LEfSe analysis showed that 25 genera including Klebsiella was significantly enriched in the LBMJ infants, and the other 17 species are enriched in the control group. Functional prediction analysis indicated that 42 metabolic pathways may be related to the occurrence of LBMJ. Conclusion In conclusion, characteristic changes are seen in intestinal microbiota compositions between LBMJ infants and the healthy controls. Klebsiella is closely associated with the severity of the disease, which may be due to enhanced β-glucuronidase activity.
Induction of Siglec-FhiCD101hi eosinophils in the lungs following murine hookworm Nippostrongylus brasiliensis infection

Helminth-induced eosinophils accumulate around the parasite at the site of infection, or in parasite-damaged tissues well after the helminth has left the site. The role of helminth-elicited eosinophils in mediating parasite control is complex. While they may contribute to direct parasite-killing and tissue repair, their involvement in long-term immunopathogenesis is a concern. In allergic Siglec-FhiCD101hi, eosinophils are associated with pathology. Research has not shown if equivalent subpopulations of eosinophils are a feature of helminth infection. In this study, we demonstrate that lung migration of rodent hookworm Nippostrongylus brasiliensis (Nb) results in a long-term expansion of distinct Siglec-FhiCD101hi eosinophil subpopulations. Nb-elevated eosinophil populations in the bone marrow and circulation did not present this phenotype. Siglec-FhiCD101hi lung eosinophils exhibited an activated morphology including nuclei hyper-segmentation and cytoplasm degranulation. Recruitment of ST2+ ILC2s and not CD4+ T cells to the lungs was associated with the expansion of Siglec-FhiCD101hi eosinophils. This data identifies a morphologically distinct and persistent subset of Siglec-FhiCD101hi lung eosinophils induced following Nb infection. These eosinophils may contribute to long-term pathology following helminth infection.
Social support and cognitive function in Chinese older adults who experienced depressive symptoms: is there an age difference?

Objective This study examined the moderating effect of overall social support and the different types of social support on cognitive functioning in depressed older adults. We also investigated whether the moderating effect varied according to age. Methods A total of 2,500 older adults (≥60 years old) from Shanghai, China were enrolled using a multistage cluster sampling method. Weighted linear regression and multiple linear regression was utilized to analyze the moderating effect of social support on the relationship between depressive symptoms and cognitive function and to explore its differences in those aged 60–69, 70–79, and 80 years and above. Results After adjusting for covariates, the results indicated that overall social support (β = 0.091, p = 0.043) and support utilization (β = 0.213, p < 0.001) moderated the relationship between depressive symptoms and cognitive function. Support utilization reduced the possibility of the cognitive decline in depressed older adults aged 60–69 years (β = 0.310, p < 0.001) and 80 years and above (β = 0.199, p < 0.001), while objective support increased the possibility of cognitive decline in depressed older people aged 70–79 years (β = −0.189, p < 0.001). Conclusion Our findings highlight the buffering effects of support utilization on cognitive decline in depressed older adults. We suggest that age-specific measures should be taken when providing social support to depressed older adults in order to reduce the deterioration of cognitive function.
Visual search and the inhibitions of return

In the early 1980's independent research streams were launched by two of the 20th century's leading attention researchers. Anne Treisman's research program is best-known for distinguishing empirically between serial and pop-out search and for proposing feature integration theory and the idea of an attentional operator, that sequentially inspects items or groups of items when search is difficult. Among his many contributions to psychological science, Michael Posner is well-known for pioneering simple model tasks that made the allocation of visual attention in space amenable to scientific inquiry. When one version of the Posner cuing paradigm was used to explore visuospatial orienting it was serendipitously discovered that an “inhibitory” effect occurred in the aftermath of events that captured visuospatial attention involuntarily. This “inhibitory” phenomenon became known as Inhibition of Return (IOR), and, as implied by its name, the underlying mechanisms were thought to bias attention away from previously explored places. These two research programs were linked in 1988 when Raymond Klein exploited the distinction between pop-out and serial search to test and verify Posner's proposal that this inhibition might be a novelty seeking mechanism that could improve search efficiency. Subsequent research has identified at least two different inhibitory mechanisms that bias attention toward novelty. We present evidence using several diagnostics (central vs. peripheral targets, joint consideration of speed and accuracy, and the locus of slack logic embedded in the psychological refractory period effect) to illustrate the dual natures of IOR. The input form operates on a salience map that influences what will capture our attention, while the output form operates on a priority map that influences what behaviors (including orienting) are likely to be executed. The input form is generated when the reflexive oculomotor system is suppressed while the output form is generated when this system is not suppressed. We believe that both forms of IOR can serve the novelty seeking (and search facilitating) function proposed by Posner and others. Yet, many questions remain unanswered. Some of the many remaining puzzles will be described and we hope that our review will stimulate research to solve them.
Biomarkers of delirium risk in older adults: a systematic review and meta-analysis

Delirium is a neuropsychiatric syndrome associated with increased morbidity and mortality in older patients. The aim of this study was to review predictive biomarkers of delirium in older patients to gain insights into the pathophysiology of this syndrome and provide guidance for future studies. Two authors independently and systematically searched MEDLINE, Embase, Cochrane Library, Web of Science and Scopus databases up to August 2021. A total of 32 studies were included. Only 6 studies were eligible for the meta-analysis, pooled results showed a significant increase in some serum biomarkers (C-reactive protein [CRP], tumour necrosis factor alpha [TNF-α] and interleukin-6 [IL-6]) among patients with delirium (odds ratio = 1.88, 95% CI 1.01 to 1.637; I2 = 76.75%). Although current evidence does not favour the use of any particular biomarker, serum CRP, TNF-α, and IL-6 were the most consistent biomarkers of delirium in older patients.