Miracle-dz/UniFAR-FTUs huggingface dataset:
Profiling of fatty acid metabolism in the dorsal root ganglion after peripheral nerve injury

Peripheral nerve injury (PNI) induces neuronal hyperexcitability, which underlies neuropathic pain. The emergence of RNA sequencing technologies has enabled profiling of transcriptional changes in pathological conditions. However, these approaches do not provide information regarding metabolites such as lipids that are not directly encoded by genes. Fatty acids (FAs) are some of the essential lipids in mammalian organisms and are mainly stored as membrane phospholipids. In response to various biological stimuli, FAs are rapidly released and converted into several mediators, such as eicosanoids and docosanoids. FAs themselves or their metabolites play important roles in physiology and pathology. In this study, using a comprehensive lipidomic analysis of FA metabolites, 152 species were measured in the dorsal root ganglia of mice at multiple time points after PNI. We found that PNI increased the ω-6 FA metabolites produced by cyclooxygenases but not those produced by lipoxygenases or cytochrome P450 enzymes in the dorsal root ganglia. In contrast, ω-3 FA metabolites biosynthesized by any enzyme transiently increased after nerve injury. Overall, these findings provide a new resource and valuable insights into PNI pathologies, including pain and nerve regeneration.
Whole-genome/exome analysis of circulating tumor DNA and comparison to tumor genomics from patients with heavily pre-treated ovarian cancer: subset analysis of the PERMED-01 trial

Introduction The poor prognosis of ovarian carcinoma (OvC) is due to the advanced stage at diagnosis, a high risk of relapse after first-line therapies, and the lack of efficient treatments in the recurrence setting. Circulating tumor DNA (ctDNA) analysis is a promising tool to assess treatment-resistant OvC and may avoid iterative tissue biopsies. We aimed to evaluate the genomic profile of recurrent heavily pre-treated OvC. Methods We performed tumor panel-based sequencing as well as low-coverage whole-genome sequencing (LC-WGS) of tumor and plasma collected in patients with ovarian cancer included in the PERMED-01 trial. Whole-exome sequencing (WES) data of plasma samples were also analyzed and compared to mutation and copy number alteration (CNA) tumor profiles. The prognostic value [progression-free survival (PFS)] of these alterations was assessed in an exploratory analysis. Results Tumor and plasma genomic analyses were done for 24 patients with heavily pretreated OvC [67% high-grade serous carcinoma (HGSC)]. Tumor mutation burden was low (median 2.04 mutations/Mb) and the most frequent mutated gene was TP53 (94% of HGSC). Tumor CNAs were frequent with a median of 50% of genome altered fraction. Plasma LC-WGS and WES detected ctDNA in 21/24 cases (88%) with a median tumor fraction of 12.7%. We observed a low correlation between plasma and tumor CNA profiles. However, this correlation was significant in cases with the highest circulating tumor fraction. Plasma genome altered fraction and plasma mutation burden (p = 0.011 and p = 0.041, respectively, log-rank tests) were associated with PFS. Conclusions Combination of LC-WGS and WES can detect ctDNA in most pre-treated OvCs. Some ctDNA characteristics, such as genome altered fraction and plasma mutation burden, showed prognostic value. ctDNA assessment with LC-WGS may be a promising and non-expansive tool to evaluate disease evolution in this disease with high genomic instability. Clinical Trial Registration https://clinicaltrials.gov/ct2/show/NCT02342158, identifier NCT02342158.
FoxP3+ CD8 T-cells in acute HIV infection and following early antiretroviral therapy initiation

Objectives Besides CD4 regulatory T-cells (Tregs), immunosuppressor FoxP3+ CD8 T-cells are emerging as an important subset of Tregs, which contribute to immune dysfunction and disease progression in HIV infection. However, FoxP3+ CD8 T-cell dynamics in acute HIV infection and following early antiretroviral therapy (ART) initiation remain understudied. Methods Subsets of FoxP3+ CD8 T-cells were characterized both prospectively and cross-sectionally in PBMCs from untreated acute (n=26) and chronic (n=10) HIV-infected individuals, early ART-treated in acute infection (n=10, median of ART initiation: 5.5 months post-infection), ART-treated in chronic infection (n=10), elite controllers (n=18), and HIV-uninfected controls (n=21). Results Acute and chronic infection were associated with increased total, effector memory, and terminally differentiated FoxP3+ CD8 T-cells, while early ART normalized only the frequencies of total FoxP3+ CD8 T-cells. We observed an increase in FoxP3+ CD8 T-cell immune activation (HLADR+/CD38+), senescence (CD57+/CD28-), and PD-1 expression during acute and chronic infection, which were not normalized by early ART. FoxP3+ CD8 T-cells in untreated participants expressed higher levels of immunosuppressive LAP(TGF-β1) and CD39 than uninfected controls, whereas early ART did not affect their expression. The expression of gut-homing markers CCR9 and Integrin-β7 by total FoxP3+ CD8 T-cells and CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cells increased in untreated individuals and remained higher than in uninfected controls despite early ART. Elite controllers share most of the FoxP3+ CD8 T-cell characteristics in uninfected individuals. Conclusions Although early ART normalized total FoxP3+ CD8 T-cells frequencies, it did not affect the persistent elevation of the gut-homing potential of CD39+ and LAP(TGF-β1)+ FoxP3+ CD8 T-cell, which may contribute to immune dysfunction.
Effects of vaccination, new SARS-CoV-2 variants and reinfections on post-COVID-19 complications

Post-COVID-19 complications involve a variety of long-lasting health complications emerging in various body systems. Since the prevalence of post-COVID-19 complications ranges from 8–47% in COVID-19 survivors, it represents a formidable challenge to COVID-19 survivors and the health care system. Post-COVID-19 complications have already been studied in the connection to risk factors linked to their higher probability of occurrence and higher severity, potential mechanisms underlying the pathogenesis of post-COVID-19 complications, and their functional and structural correlates. Vaccination status has been recently revealed to represent efficient prevention from long-term and severe post-COVID-19 complications. However, the exact mechanisms responsible for vaccine-induced protection against severe and long-lasting post-COVID-19 complications remain elusive. Also, to the best of our knowledge, the effects of new SARS-CoV-2 variants and SARS-CoV-2 reinfections on post-COVID-19 complications and their underlying pathogenesis remain to be investigated. This hypothesis article will be dedicated to the potential effects of vaccination status, SARS-CoV-2 reinfections, and new SARS-CoV-2 variants on post-COVID-19 complications and their underlying mechanisms Also, potential prevention strategies against post-COVID complications will be discussed.
Imagining interceptions: Eye movements as an online indicator of covert motor processes during motor imagery

The analysis of eye movements during motor imagery has been used to understand the influence of covert motor processes on visual-perceptual activity. There is evidence showing that gaze metrics seem to be affected by motor planning often dependent on the spatial and temporal characteristics of a task. However, previous research has focused on simulated actions toward static targets with limited empirical evidence of how eye movements change in more dynamic environments. The study examined the characteristics of eye movements during motor imagery for an interception task. Twenty-four participants were asked to track a moving target over a computer display and either mentally simulate an interception or rest. The results showed that smooth pursuit variables, such as duration and gain, were lower during motor imagery when compared to passive observation. These findings indicate that motor plans integrate visual-perceptual information based on task demands and that eye movements during imagery reflect such constraint.
CircRNA-mediated regulation of brown adipose tissue adipogenesis

Adipose tissue represents a candidate target for the treatment of metabolic illnesses, such as obesity. Brown adipose tissue (BAT), an important heat source within the body, promotes metabolic health through fat consumption. Therefore, the induction of white fat browning may improve lipid metabolism. Currently, the specific roles of circRNA in BAT and white adipose tissue (WAT) remain elusive. Herein, we conducted circRNA expression profiling of mouse BAT and WAT using RNA-seq. We identified a total of 12,183 circRNAs, including 165 upregulated and 79 downregulated circRNAs between BAT and WAT. Differentially expressed (DE) circRNAs were associated with the mitochondrion, mitochondrial part, mitochondrial inner membrane, mitochondrial envelope, therefore, these circRNAs may affect the thermogenesis and lipid metabolism of BAT. Moreover, DE circRNAs were enriched in browning- and thermogenesis-related pathways, including AMPK and HIF-1 signaling. In addition, a novel circRNA, circOgdh, was found to be highly expressed in BAT, formed by back-splicing of the third and fourth exons of the Ogdh gene, and exhibited higher stability than linear Ogdh. circOgdh was mainly distributed in the cytoplasm and could sponge miR-34a-5p, upregulating the expression of Atgl, a key lipolysis gene, which enhanced brown adipocyte lipolysis and suppressed lipid droplet accumulation. Our findings offer in-depth knowledge of the modulatory functions of circRNAs in BAT adipogenesis.
Inequality in abundance

With technological advance has come the possibility of a new era of abundance. Technologies like 3D printing and robotics promise to lower the costs of production and distribution of goods and services, presumably making these goods and services readily available to those across income and wealth spectrums. This undoubtedly is a good thing. But what will be the effect of these technologies on existing wealth inequalities and the psychological and societal burdens they impose? Can we expect that this newfound abundance will help remedy the current historic levels of inequality in the U.S. and other western countries? Unfortunately, the answer is likely no, for two reasons. First, history suggests that inequality often persists even under conditions of abundance due to dynamics of power and politics and ongoing impacts of structural inequalities. Having more than enough of a particular good or service to go around does not guarantee that all will have access to this good or service. Second, even if the new abundance enabled by technology extends into all levels of the socioeconomic spectrum, enabling individuals to access goods and services (and their attendant benefits) previously beyond their reach, the harms that attend unequal societies will persist. Increasing evidence suggests that these harms, including increased violence and decreased health, arise not from access (or a lack thereof) to particular goods and services, but from the adverse psychological consequences of living in an unequal society. This is a psychological burden shared not just by those at the losing end of the inequality equation, but also those who enjoy a relative advantage in society. Unequal societies are psychologically harmful to all who live in them, regardless of where these individuals fall on the socioeconomic spectrum, and largely independent of the particular goods and services they enjoy. The upshot is that society cannot rely on new abundance technologies to automatically solve problems of inequality and the social and psychological burdens that plague those who live in unequal societies. Indeed, depending on how society responds to questions of access to these technologies, their introduction might exacerbate various forms of inequality. In light of this, it is crucial to address conditions of inequality head-on, so that the new era of abundance promised by technological advance can lead to real gains in individual and societal wellbeing.
Using 2D and 3D pluripotent stem cell models to study neurotropic viruses

Understanding the impact of viral pathogens on the human central nervous system (CNS) has been challenging due to the lack of viable human CNS models for controlled experiments to determine the causal factors underlying pathogenesis. Human embryonic stem cells (ESCs) and, more recently, cellular reprogramming of adult somatic cells to generate human induced pluripotent stem cells (iPSCs) provide opportunities for directed differentiation to neural cells that can be used to evaluate the impact of known and emerging viruses on neural cell types. Pluripotent stem cells (PSCs) can be induced to neural lineages in either two- (2D) or three-dimensional (3D) cultures, each bearing distinct advantages and limitations for modeling viral pathogenesis and evaluating effective therapeutics. Here we review the current state of technology in stem cell-based modeling of the CNS and how these models can be used to determine viral tropism and identify cellular phenotypes to investigate virus-host interactions and facilitate drug screening. We focus on several viruses (e.g., human immunodeficiency virus (HIV), herpes simplex virus (HSV), Zika virus (ZIKV), human cytomegalovirus (HCMV), SARS-CoV-2, West Nile virus (WNV)) to illustrate key advantages, as well as challenges, of PSC-based models. We also discuss how human PSC-based models can be used to evaluate the safety and efficacy of therapeutic drugs by generating data that are complementary to existing preclinical models. Ultimately, these efforts could facilitate the movement towards personalized medicine and provide patients and physicians with an additional source of information to consider when evaluating available treatment strategies.
Development and initial validation of a clinical measure to assess symptoms of post-stroke depression in stroke patients at the rehabilitation stage

Background The high incidence of post-stroke depression (PSD) during rehabilitation exerts a negative effect on the treatment and functional recovery of patients with stroke and increases the risk of mortality. It is necessary to screen PSD in the rehabilitation stage and thus provide effective intervention strategies. However, existing measurements used to assess PSD in the rehabilitation stage in patients with stroke lack specificity. This study aimed to develop a clinical measure to assess symptoms of PSD in the rehabilitation stage. Methods The research team created the initial items through a literature review and semi-structured interviews of patients with stroke. Then, the symptom-related items were estimated by three panels: healthcare professionals (N = 41), Delphi experts (N = 15), and patients with stroke in the rehabilitation stage (N = 30). Results The literature review and semi-structured interview produced 51 symptom-related items including six domains, and the items were reduced to 47 by the healthcare professionals. The symptom-related items were further reduced to 33 items by a two-round Delphi consultation. The initiative coefficients of the two Delphi rounds were 71.4 and 100%, the expert authority coefficients were both 0.85, Kendall’s W were 0.152 and 0.408 (p < 0.01), and the coefficient of variation (CV) were 0.05–0.32 and 0.00–0.18, respectively. The item-level content validity index (I-CVI) was 0.53–1.00, the scale-level CVI/universal agreement (S-CVI/UA) was 0.26, and the S-CVI/average (S -CVI/Ave) was 0.85 for the first found Delphi consultation; the I-CVI was 0.67–1.00, the S-CVI/UA was 0.61, and the S-CVI/Ave was 0.97 for the second round Delphi consultation. All content validity indicators have been significantly improved compared with the first round. Using mean ≥ 4 and full score ≥ 0.5, combined with CV ≤ 0.16 as the item criteria, a clinical measure of PSD with 33 items and 6 dimensions (cognition, sleep, behavior, emotion, body, and guilt) was finally formed after two rounds. The patients with stroke made no further revisions after evaluation. Conclusion The research team developed a specific tool with good content validity to assess the symptoms of PSD in the rehabilitation stage.
p53 as a biomarker and potential target in gastrointestinal stromal tumors

KIT and PDGFRA play a major role in the oncogenic process in gastrointestinal stroma tumors (GIST) and small molecules have been employed with great success to target the KIT and PDGFRA pathways in this cancer. However, approximately 10% of patients with GIST are resistant to current targeted drug therapy. There is a need to explore other potential targets. Although p53 alterations frequently occur in most cancers, studies regarding p53 in GIST have been limited. The CDKN2A/MDM2/p53 axis regulates cell cycle progression and DNA damage responses, which in turn control tumor growth. This axis is the major event required for transformation from low- to high-risk GIST. Generally, p53 mutation is infrequent in GIST, but p53 overexpression has been reported to be associated with high-risk GIST and unfavorable prognosis, implying that p53 should play a critical role in GIST. Also, Wee1 regulates the cell cycle and the antitumor activity of Wee1 inhibition was reported to be p53 mutant dependent. In addition, Wee1 was reported to have potential activity in GIST through the regulation of KIT protein and this mechanism may be dependent on p53 status. In this article, we review previous reports regarding the role of p53 in GIST and propose targeting the p53 pathway as a novel additional treatment strategy for GIST.
Combining electro- and magnetoencephalography data using directional archetypal analysis

Metastable microstates in electro- and magnetoencephalographic (EEG and MEG) measurements are usually determined using modified k-means accounting for polarity invariant states. However, hard state assignment approaches assume that the brain traverses microstates in a discrete rather than continuous fashion. We present multimodal, multisubject directional archetypal analysis as a scale and polarity invariant extension to archetypal analysis using a loss function based on the Watson distribution. With this method, EEG/MEG microstates are modeled using subject- and modality-specific archetypes that are representative, distinct topographic maps between which the brain continuously traverses. Archetypes are specified as convex combinations of unit norm input data based on a shared generator matrix, thus assuming that the timing of neural responses to stimuli is consistent across subjects and modalities. The input data is reconstructed as convex combinations of archetypes using a subject- and modality-specific continuous archetypal mixing matrix. We showcase the model on synthetic data and an openly available face perception event-related potential data set with concurrently recorded EEG and MEG. In synthetic and unimodal experiments, we compare our model to conventional Euclidean multisubject archetypal analysis. We also contrast our model to a directional clustering model with discrete state assignments to highlight the advantages of modeling state trajectories rather than hard assignments. We find that our approach successfully models scale and polarity invariant data, such as microstates, accounting for intersubject and intermodal variability. The model is readily extendable to other modalities ensuring component correspondence while elucidating spatiotemporal signal variability.
Can dog-assisted and relaxation interventions boost spatial ability in children with and without special educational needs? A longitudinal, randomized controlled trial

Children's spatial cognition abilities are a vital part of their learning and cognitive development, and important for their problem-solving capabilities, the development of mathematical skills and progress in Science, Technology, Engineering and Maths (STEM) topics. As many children have difficulties with STEM topic areas, and as these topics have suffered a decline in uptake in students, it is worthwhile to find out how learning and performance can be enhanced at an early age. The current study is the first to investigate if dog-assisted and relaxation interventions can improve spatial abilities in school children. It makes a novel contribution to empirical research by measuring longitudinally if an Animal-Assisted Intervention (AAI) or relaxation intervention can boost children's development of spatial abilities. Randomized controlled trials were employed over time including dog intervention, relaxation intervention and no treatment control groups. Interventions were carried out over 4 weeks, twice a week for 20 min. Children were tested in mainstream schools (N = 105) and in special educational needs (SEN) schools (N = 64) before and after interventions, after 6 weeks, 6 months and 1 year. To assess intervention type and to provide advice for subsequent best practice recommendations, dog-assisted interventions were run as individual or small group interventions. Overall, children's spatial abilities improved over the year with highest increases in the first 4 months. In Study 1, typically developing children showed higher scores and more continuous learning overall compared to children with special educational needs. Children in the dog intervention group showed higher spatial ability scores immediately after interventions and after a further 6 weeks (short-term). Children in the relaxation group also showed improved scores short-term after relaxation intervention. In contrast, the no treatment control group did not improve significantly. No long-term effects were observed. Interestingly, no gender differences could be observed in mainstream school children's spatial skills. In study 2, children in SEN schools saw immediate improvements in spatial abilities after relaxation intervention sessions. No changes were seen after dog interventions or in the no treatment control group. Participants' pet ownership status did not have an effect in either cohort. These are the first findings showing that AAI and relaxation interventions benefit children's spatial abilities in varied educational settings. This research represents an original contribution to Developmental Psychology and to the field of Human-Animal Interaction (HAI) and is an important step towards further in-depth investigation of how AAI and relaxation interventions can help children achieve their learning potential, both in mainstream schools and in schools for SEN.