Miracle-dz/UniFAR-FTUs huggingface dataset:
Purines in Pain as a Gliopathy

In the last decades, the hypothesis of the role of purinergic receptors expressed by glial cells in the regulation of pain pathways has become a matter of fact. Although several painful conditions are undoubtedly of neuronal origin, the existence of an altered bidirectional signaling between neurons and activated glial cells has brought to the definition of pain as a “gliopathy” (Ji et al., 2013). In the central nervous system (CNS), neuronal excitability in pain pathways is enhanced by resident microglia, astrocytes, oligodendrocytes, and by infiltrating cells, such as T cells and macrophages, overall constituting the so-called “neuroimmune interface. ” Following peripheral nerve damage, spinal cord microglia sense a variety of neuron-derived stimuli leading to their transition toward a reactive state (Grace et al., 2014), whose inhibition through the antibiotic minocycline has proven anti-hyperalgesic and anti-allodynic (Wieseler et al., 2017). Microglia activation is followed by immune cell recruitment and by the appearance of a neurotoxic astrocyte subpopulation, the so-called A1 astrocytes (Liddelow et al., 2017). The extension of microglial and astrocytic processes into and near the synaptic space induces alterations to thousands of synapses, resulting in altered neural networks, maladaptive synaptic reorganization and generating a pro-inflammatory milieu, whose effects can extend for months after the initial nerve damage and guide the transition from acute to chronic pain (Gwak et al., 2017; Skaper et al., 2018). Neuronal firing is also significantly modulated at the sensory ganglion level, where neuronal bodies are surrounded and wrapped by resident satellite glial cells (SCGs), which become activated upon inflammation or nerve damage (Donegan et al., 2013; Magni et al., 2015), release neurotransmitters and chemical mediators and contribute to neuronal sensitization (Spray & Hanani, 2019). On the other way round, both CNS and PNS sensitized neurons increase their firing and release of neurotransmitters and neuromodulators that act paracrinally on glial cells, giving rise to a vicious and autoamplifying circle. Glial cells become permanently activated as demonstrated both in animal models of chronic pain and in patients (Loggia et al., 2015). In order to identify new potentially “druggable” targets, research is now focusing on the identification of the whole network of molecules involved in neuron-to-glia communication in pain. In this scenario, multiple adenosine and nucleotide receptors are expressed by glial cells involved in pain transmission (for review see Burnstock, 2017; Magni et al., 2018; Magni & Ceruti, 2019), and their pharmacological modulation could represent an innovative analgesic strategy. In the next sections we shall contribute with our point of view on the role of P2 nucleotide and P1 adenosine receptors expressed by glial cells in modulating pain transmission, with the aim of identifying new Edited by: Kjell Fuxe, Karolinska Institutet (KI), Sweden
Effectiveness of a Virtual Exercise Program During COVID-19 Confinement on Blood Pressure Control in Healthy Pregnant Women

Background The situation caused by COVID-19 has led to movement restrictions for the majority of the population due to the confinement established by the health authorities. This new situation has changed people’s habits and significantly affected the pregnant population. Decreased exercise and increased psychophysical stress are associated with excessive weight gain, diabetes, and gestational cardiovascular complications that affect the mother, fetus, and newborn. Recent research shows that the dynamics of maternal blood pressure is one of the most important control factors during pregnancy. Thus, prevention of these type of pathologies through interventions without maternal-fetal risks is important. Objectives To examine the influence of a virtual exercise program on maternal blood pressure during pregnancy. Materials and Methods A randomized clinical trial design was used (NCT04563065). Data from 72 pregnant women without obstetric contraindications under confinement conditions in the Madrid area were collected. Women were randomly assigned to the intervention (IG) or control group (CG). They previously signed informed consent forms. A moderate exercise program was performed as an intervention from 8–10 to 38–39 weeks of pregnancy. Systolic (SBP) and diastolic (DBP) maternal blood pressure were measured during the first, second and third trimesters of pregnancy, as well as before and immediately after delivery in both study groups. Results No differences in systolic and diastolic blood pressure during the first, second and third trimesters were found between groups. Significant differences in SBP were found immediately before delivery (IG = 119.83 ± 10.16 vs. CG = 125.6 ± 10.91; p = 0.047) and immediately after delivery (IG = 115.00 ± 11.18 vs. CG = 122.24 ± 15.71; p = 0.045). Conclusions Results show lower SBP values for the IG during delivery than CG. A virtual exercise program throughout pregnancy during COVID-19 confinement can help to control systolic blood pressure before and immediately after delivery in healthy pregnant women.
Hepatic Steatosis Predicts Higher Incidence of Recurrence in Colorectal Cancer Liver Metastasis Patients

Purpose: Colorectal liver metastasis (CRLM) is the major cause of death due to colorectal cancer. Although great efforts have been made in treatment of CRLM, about 60–70% of patients will develop hepatic recurrence. Hepatic steatosis was reported to provide fertile soil for metastasis. However, whether hepatic steatosis predicts higher incidence of CRLM recurrence is not clear. Therefore, we aimed to determine the role of hepatic steatosis in CRLM recurrence in the present study. Methods: Consecutive CRLM patients undergoing curative treatment were retrospectively enrolled and CT liver-spleen attenuation ratio was used to detect the presence of hepatic steatosis. In patients with hepatic steatosis, we also detected the presence of fibrosis. Besides, a systematic literature search was performed to do meta-analysis to further analyze the association between hepatic steatosis and CRLM recurrence. Results: A total of 195 eligible patients were included in our center. Patients with hepatic steatosis had a significantly worse overall (P = 0.0049) and hepatic recurrence-free survival (RFS) (P = 0.0012). Univariate and multivariate analysis confirmed its essential role in prediction of RFS. Besides, hepatic fibrosis is associated with worse overall RFS (P = 0.039) and hepatic RFS (P = 0.048). In meta-analysis, we included other four studies, with a total of 1,370 patients in the case group, and 3,735 patients in the control group. The odds ratio was 1.98 (95% CI: 1.25–3.14, P = 0.004), indicating that patients with steatosis had a significantly higher incidence of CRLM recurrence. Conclusion: In summary, patients with hepatic steatosis had a significantly worse overall and hepatic RFS and it's associated with higher incidence of CRLM recurrence.
Understanding Older Adults' Memory Distortion in the Light of Stereotype Threat

Numerous studies have documented the detrimental impact of age-based stereotype threat (ABST) on older adults' cognitive performance and especially on veridical memory. However, far fewer studies have investigated the impact of ABST on older adults' memory distortion. Here, we review the subset of research examining memory distortion and provide evidence for the role of stereotype threat as a powerful socio-emotional factor that impacts age-related susceptibility to memory distortion. In this review we define memory distortion as errors in memory that are associated with gist-based errors or source misattributions. Whereas, some of the reviewed experiments support the conclusion that ABST should be considered in the context of age-related differences in memory distortion, others reported little or no impact of stereotype threat. These discrepancies suggest that the role of ABST, and socio-emotional processes generally, in age-related changes in memory distortion are less clear. In this review, we argue that ABST does play an important role in age-related changes in memory distortion. We present evidence suggesting that discrepancies in the reviewed literature may be reconciled when evaluated in the context of the leading theories about stereotype threat: the Executive Resource Depletion hypothesis and the Regulatory Focus theory. We also discuss how differences in methodology and participant characteristics can account for a priori contradictory results in the literature. Finally, we propose some recommendations for researchers and practitioners when assessing memory in older adults.
Expression of a Bacterial Trehalose-6-phosphate Synthase otsA Increases Oil Accumulation in Plant Seeds and Vegetative Tissues

We previously demonstrated that exogenous trehalose 6-phosphate (T6P) treatment stabilized WRINKLED1 (WRI1), a master transcriptional regulator of fatty acid (FA) synthesis and increased total FA content in Brassica napus (B. napus) embryo suspension cell culture. Here, we explore Arabidopsis lines heterologously expressing the Escherichia coli T6P synthase (otsA) or T6P phosphatase (otsB) to refine our understanding regarding the role of T6P in regulating fatty acid synthesis both in seeds and vegetative tissues. Arabidopsis 35S:otsA transgenic seeds showed an increase of 13% in fatty acid content compared to those of wild type (WT), while seeds of 35:otsB transgenic seeds showed a reduction of 12% in fatty acid content compared to WT. Expression of otsB significantly reduced the level of WRI1 and expression of its target genes in developing seeds. Like Arabidopsis seeds constitutively expressing otsA, transient expression of otsA in Nicotiana benthamiana leaves resulted in strongly elevated levels of T6P. This was accompanied by an increase of 29% in de novo fatty acid synthesis rate, a 2.3-fold increase in triacylglycerol (TAG) and a 20% increase in total fatty acid content relative to empty vector (EV) controls. Taken together, these data support the heterologous expression of otsA as an approach to increasing TAG accumulation in plant seeds and vegetative tissues.
Case Report: Bayesian Statistical Inference of Experimental Parameters via Biomolecular Simulations: Atomic Force Microscopy

The atomic force microscopy (AFM) is a powerful tool for imaging structures of molecules bound on surfaces. To gain high-resolution structural information, one often superimposes structure models on the measured images. Motivated by high flexibility of biomolecules, we previously developed a flexible-fitting molecular dynamics (MD) method that allows protein structural changes upon superimposing. Since the AFM image largely depends on the AFM probe tip geometry, the fitting process requires accurate estimation of the parameters related to the tip geometry. Here, we performed a Bayesian statistical inference to estimate a tip radius of the AFM probe from a given AFM image via flexible-fitting molecular dynamics (MD) simulations. We first sampled conformations of the nucleosome that fit well the reference AFM image by the flexible-fitting with various tip radii. We then estimated an optimal tip parameter by maximizing the conditional probability density of the AFM image produced from the fitted structure.
4-Chlorothymol Exerts Antiplasmodial Activity Impeding Redox Defense System in Plasmodium falciparum

Malaria remains one of the major health concerns due to the resistance of Plasmodium species toward the existing drugs warranting an urgent need for new antimalarials. Thymol derivatives were known to exhibit enhanced antimicrobial activities; however, no reports were found against Plasmodium spp. In the present study, the antiplasmodial activity of thymol derivatives was evaluated against chloroquine-sensitive (NF-54) and -resistant (K1) strains of Plasmodium falciparum. Among the thymol derivatives tested, 4-chlorothymol showed potential activity against sensitive and resistant strains of P. falciparum. 4-Chlorothymol was found to increase the reactive oxygen species and reactive nitrogen species level. Furthermore, 4-chlorothymol could perturb the redox balance by modulating the enzyme activity of GST and GR. 4-Chlorothymol also showed synergy with chloroquine against chloroquine-resistant P. falciparum. 4-Chlorothymol was found to significantly suppress the parasitemia and increase the mean survival time in in vivo assays. Interestingly, in in vivo assay, 4-chlorothymol in combination with chloroquine showed higher chemosuppression as well as enhanced mean survival time at a much lower concentration as compared to individual doses of chloroquine and 4-chlorothymol. These observations clearly indicate the potential use of 4-chlorothymol as an antimalarial agent, which may also be effective in combination with the existing antiplasmodial drugs against chloroquine-resistant P. falciparum infection. In vitro cytotoxicity/hemolytic assay evidently suggests that 4-chlorothymol is safe for further exploration of its therapeutic properties.
Cognitive Impairment After Resolution of Hepatic Encephalopathy: A Systematic Review and Meta-Analysis

Hepatic encephalopathy (HE) is one of the most disabling metabolic diseases. It consists of a complication of liver disease through the action of neurotoxins, such as excessive production of ammonia from liver, resulting in impaired brain function. Its prevalence and incidence are not well known, although it has been established that up to 40% of cirrhotic patients may develop HE. Patients with HE episodes display a wide range of neurological disturbances, from subclinical alterations to coma. Recent evidence suggests that the resolution of hepatic encephalopathy does not fully restore cognitive functioning in cirrhotic patients. Therefore, the aim of this review was to evaluate the evidence supporting the presence of lingering cognitive deficits in patients with a history of HE compared to patients without HE history and how liver transplant affects such outcome in these patients. We performed two distinct meta-analysis of continuous outcomes. In both cases the results were pooled using random-effects models. Our results indicate that cirrhotic patients with a history of HE show clear cognitive deficits compared control cirrhotic patients (Std. Mean Difference (in SDs) = −0.72 [CI 95%: −0.94, −0.50]) and that these differences are not fully restored after liver transplant (Std. Mean Difference (in SDs) = −0.72 [CI 95%: −0.94, −0.50]).
Eye Movement Technique to Improve Executive Function in Patients With Stroke: A Randomized Controlled Trial

Objective: To investigate the efficacy of eye movement technique for the treatment of executive dysfunction of patients with stroke. Methods: This was a prospective, single-blinded, randomized, controlled, single-center clinical trial conducted from June 2018 to December 2019 in patients with stroke. The patients were randomized 1:1 to the routine (conventional management) and eye-move group (routine management plus eye movement technique: 5-min goal management training, 5-min computer-aided working memory, and 10 min of inhibitory control training and set conversion training). The intervention lasted 6 weeks, followed by a 4-week follow-up. The primary endpoint was the Behavioral Assessment of the Dysexecutive Syndrome (BADS) score. The secondary endpoints mainly included the Montreal Cognitive Assessment (MoCA), Wisconsin Card Sorting Test (WCST), and modified Barthel Index (MBI) scores. Results: Sixty-four patients were enrolled (32/group). After the 6-week intervention, the BADS and WCST scores of the eye-move group were significantly improved than those of the routine group (all P < 0.05), but the effects were attenuated in certain subscores after follow-up (all P > 0.05). The MoCA and MBI scores of the eye-move group were significantly higher, and the reaction time was significantly lower than those of the routine group at 4 weeks after the intervention (all P < 0.05). After follow-up, the MBI scores of the eye-move group were still higher than that of the routine group (P < 0.001), but there were no differences for MoCA scores and reaction time (both P > 0.05). Conclusion: The eye movement technique could improve the executive function of patients with stroke. These results have to be confirmed. This was a prospective, single-blinded, randomized, controlled, single-center clinical trial (ChiCTR2000036393). Clinical Trial Registration: [www.chictr. org.cn], identifier [ChiCTR2000036393].
Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in a Community-Based Cohort: Data From the Washington, D.C. Cardiovascular Health and Needs Assessment

Background: Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar 18Fluorodeoxyglucose (18FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort. Methods: Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including 18FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity. Results: AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, p = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, p = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (β = 0.41, p = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity. Conclusions: AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.
Self-Assembly of Hydrogen-Bonded Cage Tetramers of Phosphonic Acid

The self-association of phosphonic acids with general formula RP(O)(OH)2 in solution state remains largely unexplored. The general understanding is that such molecules form multiple intermolecular hydrogen bonds, but the stoichiometry of self-associates and the bonding motifs are unclear. In this work, we report the results of the study of self-association of tert-butylphosphonic acid using low temperature liquid-state 1H and 31P NMR spectroscopy (100 K; CDF3/CDF2Cl) and density functional theory (DFT) calculations. For the first time, we demonstrate conclusively that polar aprotic medium tert-butylphosphonic acid forms highly symmetric cage-like tetramers held by eight OHO hydrogen bonds, which makes the complex quite stable. In these associates. each phosphonic acid molecule is bonded to three other molecules by forming two hydrogen bonds as proton donor and two hydrogen bonds as proton acceptor. Though the structure of such cage-like tetramers is close to tetrahedral, the formal symmetry of the self-associate is C2.
Symmetry Based Material Optimization

Many man-made or natural objects are composed of symmetric parts and possess symmetric physical behavior. Although its shape can exactly follow a symmetry in the designing or modeling stage, its discretized mesh in the analysis stage may be asymmetric because generating a mesh exactly following the symmetry is usually costly. As a consequence, the expected symmetric physical behavior may not be faithfully reproduced due to the asymmetry of the mesh. To solve this problem, we propose to optimize the material parameters of the mesh for static and kinematic symmetry behavior. Specifically, under the situation of static equilibrium, Young’s modulus is properly scaled so that a symmetric force field leads to symmetric displacement. For kinematics, the mass is optimized to reproduce symmetric acceleration under a symmetric force field. To efficiently measure the deviation from symmetry, we formulate a linear operator whose kernel contains all the symmetric vector fields, which helps to characterize the asymmetry error via a simple ℓ2 norm. To make the resulting material suitable for the general situation, the symmetric training force fields are derived from modal analysis in the above kernel space. Results show that our optimized material significantly reduces the asymmetric error on an asymmetric mesh in both static and dynamic simulations.
Local Feature Extraction Network for Point Cloud Analysis

Geometric feature extraction of 3D point clouds plays an important role in many 3D computer vision applications such as region labeling, 3D reconstruction, object segmentation, and recognition. However, hand-designed features on point clouds lack semantic information, so cannot meet these requirements. In this paper, we propose local feature extraction network (LFE-Net) which focus on extracting local feature for point clouds analysis. Such geometric features learning from a relation of local points can be used in a variety of shape analysis problems such as classification, part segmentation, and point matching. LFE-Net consists of local geometric relation (LGR) module which aims to learn a high-dimensional local feature to express the relation between points and their neighbors. Benefiting from the additional singular values of local points and hierarchical neural networks, the learned local features are robust to permutation and rigid transformation so that they can be transformed into 3D descriptors. Moreover, we embed prior spatial information of the local points into the sub-features for combining features from multiple levels. LFE-Net achieves state-of-the-art performances on standard benchmarks including ModelNet40, ShapeNetPart.