Miracle-dz/UniFAR-FTUs huggingface dataset:
The synthetic cannabinoid dehydroxylcannabidiol restores the function of a major GABAA receptor isoform in a cell model of hyperekplexia

The functions of the glycine receptor (GlyR) and GABAA receptor (GABAAR) are both impaired in hyperekplexia, a neurological disorder usually caused by GlyR mutations. Although emerging evidence indicates that cannabinoids can directly restore normal GlyR function, whether they affect GABAAR in hyperekplexia remains unknown. Here we show that dehydroxylcannabidiol (DH-CBD), a synthetic nonpsychoactive cannabinoid, restores the GABA- and glycine-activated currents (IGABA and IGly, respectively) in HEK293 cells coexpressing a major GABAAR isoform (α1β2γ2) and GlyRα1 carrying a human hyperekplexia-associated mutation (GlyRα1R271Q). Using coimmunoprecipitation and FRET assays, we found that DH-CBD disrupts the protein interaction between GABAAR and GlyRα1R271Q. Furthermore, a point mutation of GlyRα1, changing Ser-296 to Ala-296, which is critical for cannabinoid binding on GlyR, significantly blocked DH-CBD-induced restoration of IGABA and IGly currents. This S296A substitution also considerably attenuated DH-CBD-induced disruption of the interaction between GlyRα1R271Q and GABAAR. These findings suggest that, because it restores the functions of both GlyRα1 and GABAAR, DH-CBD may represent a potentially valuable candidate drug to manage hyperekplexia.
Importance of Cx43 for Right Ventricular Function

In the heart, connexins form gap junctions, hemichannels, and are also present within mitochondria, with connexin 43 (Cx43) being the most prominent connexin in the ventricles. Whereas the role of Cx43 is well established for the healthy and diseased left ventricle, less is known about the importance of Cx43 for the development of right ventricular (RV) dysfunction. The present article focusses on the importance of Cx43 for the developing heart. Furthermore, we discuss the expression and localization of Cx43 in the diseased RV, i.e., in the tetralogy of Fallot and in pulmonary hypertension, in which the RV is affected, and RV hypertrophy and failure occur. We will also introduce other Cx molecules that are expressed in RV and surrounding tissues and have been reported to be involved in RV pathophysiology. Finally, we highlight therapeutic strategies aiming to improve RV function in pulmonary hypertension that are associated with alterations of Cx43 expression and function.
Sensitive Mercury Speciation Analysis in Water by High-Performance Liquid Chromatography-Atomic Fluorescence Spectrometry Coupling with Solid-Phase Extraction

An efficient method based on high-performance liquid chromatography coupled with atomic fluorescence spectrometry (HPLC-AFS) was successfully developed for the simultaneous determination of four mercury species including Hg2+, methylmercury (MeHg), ethylmercury (EtHg), and phenylmercury (PhHg) in water. Samples were enriched and cleaned up with a solid-phase extraction (SPE) pretreatment using a thiol cartridge. Some key parameters including the selection of a SPE cartridge, eluent type, eluent volume, and interference factors were systematically investigated. Chromatographic separation was achieved on a C18 column using a mobile phase consisting of methanol and 60 mmol L−1 ammonium acetate with 10 mmol L−1l-cysteine by gradient elution. Under the optimized conditions, good linearity (r ≥ 0.9991) was observed between 0.20 to 10.0 μg L−1. The limits of detection were in the range of 0.001–0.002 μg L−1. High recoveries (87.2 to 111%) and good reproducibility (1.1–6.5%) were obtained. Such a method is sensitive, selective and accurate, which can be applied to the quantification of mercury species in water samples.
Spinal PAR2 Activation Contributes to Hypersensitivity Induced by Peripheral Inflammation in Rats

The mechanisms of inflammatory pain need to be identified in order to find new superior treatments. Protease-activated receptors 2 (PAR2) and transient receptor potential vanilloid 1 (TRPV1) are highly co-expressed in dorsal root ganglion neurons and implicated in pain development. Here, we examined the role of spinal PAR2 in hyperalgesia and the modulation of synaptic transmission in carrageenan-induced peripheral inflammation, using intrathecal (i.t.) treatment in the behavioral experiments and recordings of spontaneous, miniature and dorsal root stimulation-evoked excitatory postsynaptic currents (sEPSCs, mEPSCs and eEPSCs) in spinal cord slices. Intrathecal PAR2-activating peptide (AP) administration aggravated the carrageenan-induced thermal hyperalgesia, and this was prevented by a TRPV1 antagonist (SB 366791) and staurosporine i.t. pretreatment. Additionally, the frequency of the mEPSC and sEPSC and the amplitude of the eEPSC recorded from the superficial dorsal horn neurons were enhanced after acute PAR2 AP application, while prevented with SB 366791 or staurosporine pretreatment. PAR2 antagonist application reduced the thermal hyperalgesia and decreased the frequency of mEPSC and sEPSC and the amplitude of eEPSC. Our findings highlight the contribution of spinal PAR2 activation to carrageenan-induced hyperalgesia and the importance of dorsal horn PAR2 and TRPV1 receptor interactions in the modulation of nociceptive synaptic transmission.
Natural Marine and Terrestrial Compounds as Modulators of Matrix Metalloproteinases-2 (MMP-2) and MMP-9 in Alzheimer’s Disease

Several studies have reported neuroprotective effects by natural products. A wide range of natural compounds have been investigated, and some of these may play a beneficial role in Alzheimer’s disease (AD) progression. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases, have been implicated in AD. In particular, MMP-2 and MMP-9 are able to trigger several neuroinflammatory and neurodegenerative pathways. In this review, we summarize and discuss existing literature on natural marine and terrestrial compounds, as well as their ability to modulate MMP-2 and MMP-9, and we evaluate their potential as therapeutic compounds for neurodegenerative and neuroinflammatory diseases, with a focus on Alzheimer’s disease.
Determination of Yeast DNA Based on Its Quenching the Fluorescence Emission of Norfloxacin

Abstract The interaction between norfloxacin and yeast double-stranded DNA (dsDNA) was studied using UV spectrometry and fluorescence spectrometry. Norfloxacin exhibited a fluorescence excitation at 272 nm and a fluorescence emission at 415 nm in pH 7.0 phosphate buffer solution. The addition of yeast dsDNA to the norfloxacin solution resulted in a strong static fluorescence quenching due to the binding of the norfloxacin by yeast dsDNA. The binding constant was (2.90 ± 0.03) × 104 M−1 (15°C). Based on the fluorescence quenching, a novel method for sensitive determination of yeast dsDNA concentration ranging from 77 nM to 43.2 µM was developed. The relative standard deviation for eleven detections of 28.8 µM dsDNA was 3.0%. The fluorescence spectrum of the norfloxacin bound covalently to single-stranded DNA (ssDNA) showed an obvious change after the ssDNA hybridized with its complementary DNA, producing a qualitative detection method for DNA sequence.
Cognitive differences between adults with traumatic brain injury and specific learning disorder

ABSTRACT Background: Impaired working memory, attention, and processing speed are common in individuals with traumatic brain injury (TBI) and specific learning disorder (SLD). Yet, there is a paucity of research that has examined cognitive differences between these groups. Objective: The current study examined potential group differences between individuals with TBI and SLD on performance-based tests of working memory, attention, and processing speed. Subsequently, the study examined whether just processing speed tests could discriminate persons with TBI versus SLD. Method: The authors analyzed archival data to assess differences between 39 adult participants with moderate-severe TBI versus 57 adult participants with SLD on the Trail Making Test Part A, Trail Making Test Part B, Digit Span test, and Symbol Search test. Results: 95% confidence intervals revealed that participants with TBI performed significantly worse on the Trail Making Test Part A and Symbol Search test. Logistic regression analysis procedures revealed that Trail Making Test Part A was the most sensitive discriminator. Conclusion: Diagnosis of moderate-severe TBI compared to SLD can be determined by poor performance on measures of visual scanning and processing speed. These findings may be used for diagnostic interpretation and treatment planning by clinicians.
Increased Serum Complement C3 Levels Are Associated With Adverse Clinical Outcomes After Ischemic Stroke.

BACKGROUND AND PURPOSE Complement C3 has been implicated in inflammation and ischemia/reperfusion injury, but its impact on the prognosis of ischemic stroke remains unclear. Aim of this study was to prospectively investigate the association between serum complement C3 and adverse clinical outcomes after ischemic stroke. METHODS We measured serum complement C3 levels for 3474 patients with ischemic stroke in 26 participating hospitals and collected data of clinical outcomes at 3 months after ischemic stroke. The primary outcome was composite outcome of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke onset and secondary outcomes included major disability, death, and vascular events. RESULTS During 3 months of follow-up, 866 participants (25.4%) developed primary outcome. After multivariate adjustment, elevated serum complement C3 levels were associated with increased risk of primary outcome (odds ratio, 1.30 [95% CI, 1.02-1.65]; Ptrend=0.038) when 2 extreme tertiles were compared. Each SD increase of log-transformed complement C3 was associated with 13% (95% CI, 2%-25%) increased risk of primary outcome. Multivariable-adjusted spline regression model showed a linear relationship between serum complement C3 and the risk of primary outcome (Plinearity=0.022). Addition of serum complement C3 to conventional risk factors significantly improved the risk prediction of primary outcome (net reclassification index: 8.87%, P=0.028; integrated discrimination index: 0.19%, P=0.029). CONCLUSIONS High serum complement C3 levels at baseline were associated with increased risks of adverse clinical outcomes at 3 months after ischemic stroke, suggesting that serum complement C3 may be a valuable prognostic biomarker for ischemic stroke.
A Grid-Based Framework for Collective Perception in Autonomous Vehicles

Today, perception solutions for Automated Vehicles rely on sensors on board the vehicle, which are limited by the line of sight and occlusions caused by any other elements on the road. As an alternative, Vehicle-to-Everything (V2X) communications allow vehicles to cooperate and enhance their perception capabilities. Besides announcing its own presence and intentions, services such as Collective Perception (CPS) aim to share information about perceived objects as a high-level description. This work proposes a perception framework for fusing information from on-board sensors and data received via CPS messages (CPM). To that end, the environment is modeled using an occupancy grid where occupied, and free and uncertain space is considered. For each sensor, including V2X, independent grids are calculated from sensor measurements and uncertainties and then fused in terms of both occupancy and confidence. Moreover, the implementation of a Particle Filter allows the evolution of cell occupancy from one step to the next, allowing for object tracking. The proposed framework was validated on a set of experiments using real vehicles and infrastructure sensors for sensing static and dynamic objects. Results showed a good performance even under important uncertainties and delays, hence validating the viability of the proposed framework for Collective Perception.
Hybrid surgery for symptomatic chronic near-total or total occlusion of the internal carotid artery

Stroke is the second leading cause of death globally and accounts for an estimated 5.5 million deaths each year worldwide. Revascularization of the carotid artery is one of the key procedures to reduce the incidence of stroke. Chronic total occlusion (TO) and near-total occlusion (NO) of the carotid artery are rare. Treatment for TO and NO is controversial with potential complications, including periprocedural stroke, intracranial hemorrhage, and carotid-cavernous fistula (CCF). There have been attempts to implement carotid artery endarterectomy (CEA) and endovascular treatment, but the success rates were far from satisfactory. For patients with TO, the success rate of revascularization is around 40% and 60%, respectively, for CEA and endovascular technique. For patients with NO, the morbidity and mortality rates are 3% and 9%, respectively.
Short-term outcomes of pyeloplasty vs. nephrectomy in adult patients with ureteropelvic junction obstruction and differential renal function ≤15%

Abstract Objectives To compare symptom resolution and short-term renal function after pyeloplasty or nephrectomy in adults with ureteropelvic junction obstruction (UPJO) in poorly functioning renal units (PFRU). Methods Retrospective analysis of adult patients with UPJO and differential renal function (DRF) ≤ 15% who underwent laparoscopic pyeloplasty or nephrectomy. Primary endpoints included symptom resolution and estimated glomerular filtration rate (eGFR) at 12 months. Surgical complications were compared between groups. A secondary analysis was performed comparing baseline and postoperative DRF to evaluate the PFRU recovery potential after pyeloplasty. Results Sixty-three patients were included; 19 underwent pyeloplasty and 44 underwent nephrectomy. The mean age of the cohort was 39.5 ± 13.8 years. Nephrectomy was associated with significantly higher intra-operative blood loss (p = 0.02). Operative time and length of hospital stay were not significantly different between groups. There were three complications in the nephrectomy group, and none in the pyeloplasty group (p = 0.34). Symptom resolution rates were equivalent between groups (73% vs. 76%; p = 0.78). The eGFR variation was not statistically different after pyeloplasty or nephrectomy (+6.2 vs. +0.1 mL/min/1.73m2, respectively; p = 0.18). Patients undergoing pyeloplasty had no significant change in the mean DRF (baseline 9.5 vs. 10%; p = 0.99). Conclusion Pyeloplasty can be considered for selected patients with UPJO in PFRU as an organ-sparing alternative to nephrectomy. Although there was no significant gain in mean DRF, pyeloplasty prevented further functional loss and relieved symptoms in most cases in the short-term with at least the same complication rates of nephrectomy.
Bridging executive function and disinhibited eating among youth: A network analysis.

OBJECTIVE Poorer executive function (EF) has been linked to disinhibited eating in youth, suggesting poor EF predisposes toward obesity, yet the specific nature and extent of interconnections between facets of these domains is unclear. Network analysis provides a promising framework for elucidating the relationship between poor EF and disinhibited eating, and offers insights into potential maintenance processes. METHOD Among youth ages 8-17 years, a regularized partial correlation network of EF and disinhibited eating facets was estimated to examine expected influence centrality and bridge expected influence. Computerized neurocognitive tasks assessed EF variables, including decision-making, general and food-related inhibitory control, delayed gratification, cognitive flexibility, and working memory. Disinhibited eating variables included total carbohydrate-fat intake at a laboratory test meal and self-reported eating in the absence of hunger, emotional eating, and loss-of-control eating severity. RESULTS In the current sample (N = 248; Mage = 12.5; 54.8% female; 43.5% non-Hispanic White; 25.8% non-Hispanic Black; BMI %ile = 65.8 ± 27.8), emotional eating in response to depressive symptoms emerged as a central symptom in the network. Carbohydrate-fat intake had the highest bridge expected influence and was most strongly connected to general inhibitory control (part r = .14). DISCUSSION The link between general inhibitory control and objective palatable food intake may be particularly salient in maintaining maladaptive eating behavior. Interventions targeting behavioral disinhibition may disrupt associations among a network of disinhibited eating facets in youth and should be targets for longitudinal research.
Harnessing liver-resident memory T cells for protection against malaria

ABSTRACT Introduction Tissue-resident memory T cells (TRM cells) are powerful mediators of protracted adaptive immunity to infection in peripheral organs. Harnessing TRM cells through vaccination hence promises unprecedented potential for protection against infection. A paramount example of this is malaria, a major infectious disease for which immunity through traditional vaccination strategies remains challenging. Liver TRM cells appear to be highly protective against malaria, and recent developments in our knowledge of the biology of these cells have defined promising, novel strategies for their induction. Areas covered Here, we describe the path that led to the discovery of TRM cells and discuss the importance of liver TRM cells in immunity against Plasmodium spp. infection; we summarize current knowledge on TRM cell biology and discuss the current state and potential of TRM-based vaccination against malaria. Expert opinion TRM based vaccination has emerged as a promising means to achieve efficient protection against malaria. Recent advances provide a solid basis for continuing the development of this area of research. Deeper understanding of the mechanisms that mediate TRM formation and maintenance and identification of immunogenic and protective target epitopes suitable for human vaccination remain the main challenges for translation of these discoveries.
EFFECTS OF FLOW RATE AND TEMPERATURE ON THE DISSOLUTION OF POLYCYCLIC AROMATIC HYDROCARBONS TRANSFERRING FROM A NONAQUEOUS PHASE LIQUID TO NONIONIC SURFACTANT SOLUTIONS

The effects of flow rate and temperature on the dissolution of two polycyclic aromatic hydrocarbon (PAH) compounds, naphthalene and phenanthrene, transferring from a synthesized nonaqueous phase liquid (NAPL) comprised of hexadecane and the 2 PAHs into different nonionic surfactant solutions were investigated using a reactor with a spinning cell. The variation of the flow rate was possible by changing the angular velocity of the spinning cell. The flow rate generally increased the values of the mass transfer coefficients and the rates of mass transferred for both aromatics in the absence and presence of a surfactant in the aqueous phase. In comparison to the pure aqueous solution the results suggest that the addition of a surfactant at all doses investigated enhanced the rates of mass transfer for both PAHs. As the temperature increased the rates of mass transfer for both PAHs in the solutions of surfactants increased. The increase in the temperature has a much greater effect on the rates of mass transfer for both PAHs in solutions of the surfactant Triton X-100 than in Brij 35. In solutions of the surfactant Triton X-100 a decrease in the mass transfer coefficient for both PAHs with surfactant concentration was observed for the temperatures investigated.
Hip displacement in children with cerebral palsy.

AIMS The migration percentage (MP) is one criterion used for surgery in dislocated or displaced hips in children with cerebral palsy (CP). The MP at which a displaced hip can no longer return to normal is unclear. The aim of this paper was to identify the point of no return of the MP through a large population-based study. METHODS All children registered on the Cerebral Palsy Integrated Pathway Scotland surveillance programme undergo regular pelvic radiographs. Any child who had a MP measuring over 35% since the programme's inception in 2013, in at least one hip and at one timepoint, was identified. The national radiography database was then interrogated to identify all pelvic radiographs for each of these children from birth through to the date of analysis. A minimum of a further two available radiographs following the initial measurement of MP ≥ 35% was required for inclusion. RESULTS A total of 239 children (346 hips) were identified as suitable for analysis at a mean of 6.5 years (2.0 to 14.8) follow-up. In all, 1,485 radiographs taken both prior to and after a hip had a MP ≥ 35% were examined and the MP measured to identify any progression of displacement. Interrogation of the data identified that hips with a MP up to 46% returned to a MP below 40% without intervention, and all hips with a MP equal to or greater than 46% displaced further and the MP did not return to the normal range. Statistical analysis showed the result to be 98% specific with this degree of certainty that hips reaching a MP ≥ 46% would not spontaneously regress. CONCLUSION These findings are clinically relevant in showing that it may be reasonable to continue to monitor hips with a MP not exceeding 46%. This threshold will also guide referral for further management of a displacing hip. Cite this article: Bone Joint J 2021;103-B(2):411-414.
A Highly Contiguous Genome Assembly of a Polyphagous Predatory Mite Stratiolaelaps scimitus (Womersley) (Acari: Laelapidae)

Abstract As a polyphagous soil-dwelling predatory mite, Stratiolaelaps scimitus (Womersley) (Acari: Laelapidae), formerly known as Stratiolaelaps miles (Berlese), is native to the Northern hemisphere and preys on soil invertebrates, including fungus gnats, springtails, thrips nymphs, nematodes, and other species of mites. Already mass-produced and commercialized in North America, Europe, Oceania and China, S. scimitus will highly likely be introduced to other countries and regions as a biocontrol agent against edaphic pests in the near future. The introduction, however, can lead to unexpected genetic changes within populations of biological control agents, which might decrease the efficacy of pest management or increase the risks to local environments. To better understand the genetic basis of its biology and behavior, we sequenced and assembled the draft genome of S. scimitus using the PacBio Sequel platform II. We generated ∼150× (64.81 Gb) PacBio long reads with an average read length of 12.60 kb. Reads longer than 5 kb were assembled into contigs, resulting in the final assembly of 158 contigs with an N50 length of 7.66 Mb, and captured 93.1% of the BUSCO (Benchmarking Universal Single-Copy Orthologs) gene set (n = 1,066). We identified 16.39% (69.91 Mb) repetitive elements, 1,686 noncoding RNAs, and 13,305 protein-coding genes, which represented 95.8% BUSCO completeness. Combining analyses of genome family evolution and function enrichment of gene ontology and pathway, a total of 135 families experienced significant expansions, which were mainly involved in digestion, detoxification, immunity, and venom. Major expansions of the detoxification enzymes, that is, P450s and carboxylesterases, suggest a possible genetic mechanism underlying polyphagy and ecological adaptions. Our high-quality genome assembly and annotation provide new insights on the evolutionary biology, soil ecology, and biological control for predaceous mites.