Miracle-dz/UniFAR-FTUs huggingface dataset:
Combined analysis of finite element model and audiometry provides insights into the pathogenesis of conductive hearing loss

The middle ear transmits sound to the inner ear via vibrations in the eardrum and ossicles, and damage to the middle ear results in conductive hearing loss. Although conductive hearing loss can be corrected by surgery, the currently available clinical investigations cannot always diagnose the ossicular chain pathology underlying the conductive hearing loss, and even intraoperative findings can be equivocal. Acoustic analysis using finite element models (FEMs) can simulate the sound pressure change at an arbitrary site for each frequency. FEMs are used in acoustic engineering to simulate the frequency-dependent sound pressure distribution at discrete cells in a simulated model and analyze the effects of specific parameters on the audiogram. However, few reports have compared the numerical results obtained using FEMs with data from clinical cases. We used FEMs to simulate audiograms of the air-bone gap (ABG) for various ossicular chain defects and compared these with preoperative audiograms obtained from 44 patients with a normal tympanic membrane who had otosclerosis, middle ear malformations or traumatic ossicular disruption. The simulated audiograms for otosclerosis and attic fixation of the malleus-incus complex both exhibited an up-slope but could be distinguished from each other based on the ABG at 1000 Hz. The simulated audiogram for incudostapedial joint discontinuity exhibited a peak at around 750 Hz and a down-slope above 1000 Hz. In general, the simulated audiograms for otosclerosis, attic fixation and incudostapedial joint discontinuity were consistent with those obtained from clinical cases. Additional simulations indicated that changes in ossicular mass had relatively small effects on ABG. Furthermore, analyses of combination pathologies suggested that the effects of one defect on ABG were added to those of the other defect. These FEM-based findings provide insights into the pathogenesis of conductive hearing loss due to otosclerosis, middle ear malformations and traumatic injury.
Colivelin, a synthetic derivative of humanin, ameliorates endothelial injury and glycocalyx shedding after sepsis in mice

Endothelial dysfunction plays a central role in the pathogenesis of sepsis-mediated multiple organ failure. Several clinical and experimental studies have suggested that the glycocalyx is an early target of endothelial injury during an infection. Colivelin, a synthetic derivative of the mitochondrial peptide humanin, has displayed cytoprotective effects in oxidative conditions. In the current study, we aimed to determine the potential therapeutic effects of colivelin in endothelial dysfunction and outcomes of sepsis in vivo. Male C57BL/6 mice were subjected to a clinically relevant model of polymicrobial sepsis by cecal ligation and puncture (CLP) and were treated with vehicle or colivelin (100-200 µg/kg) intraperitoneally at 1 h after CLP. We observed that vehicle-treated mice had early elevation of plasma levels of the adhesion molecules ICAM-1 and P-selectin, the angiogenetic factor endoglin and the glycocalyx syndecan-1 at 6 h after CLP when compared to control mice, while levels of angiopoietin-2, a mediator of microvascular disintegration, and the proprotein convertase subtilisin/kexin type 9, an enzyme implicated in clearance of endotoxins, raised at 18 h after CLP. The early elevation of these endothelial and glycocalyx damage biomarkers coincided with lung histological injury and neutrophil inflammation in lung, liver, and kidneys. At transmission electron microscopy analysis, thoracic aortas of septic mice showed increased glycocalyx breakdown and shedding, and damaged mitochondria in endothelial and smooth muscle cells. Treatment with colivelin ameliorated lung architecture, reduced organ neutrophil infiltration, and attenuated plasma levels of syndecan-1, tumor necrosis factor-α, macrophage inflammatory protein-1α and interleukin-10. These therapeutic effects of colivelin were associated with amelioration of glycocalyx density and mitochondrial structure in the aorta. At molecular analysis, colivelin treatment was associated with inhibition of the signal transducer and activator of transcription 3 and activation of the AMP-activated protein kinase in the aorta and lung. In long-term outcomes studies up to 7 days, co-treatment of colivelin with antimicrobial agents significantly reduced the disease severity score when compared to treatment with antibiotics alone. In conclusion, our data support that damage of the glycocalyx is an early pathogenetic event during sepsis and that colivelin may have therapeutic potential for the treatment of sepsis-associated endothelial dysfunction.
Targeting immunometabolism mediated by the IDO1 Pathway: A new mechanism of immune resistance in endometrial cancer

Immunotherapy is acquiring a primary role in treating endometrial cancer (EC) with a relevant benefit for many patients. Regardless, patients progressing during immunotherapy or those who are resistant represent an unmet need. The mechanisms of immune resistance and escape need to be better investigated. Here, we review the major mechanisms of immune escape activated by the indolamine 2,3-dioxygenase 1 (IDO1) pathway in EC and focus on potential therapeutic strategies based on IDO1 signaling pathway control. IDO1 catalyzes the first rate-limiting step of the so-called “kynurenine (Kyn) pathway”, which converts the essential amino acid l-tryptophan into the immunosuppressive metabolite l-kynurenine. Functionally, IDO1 has played a pivotal role in cancer immune escape by catalyzing the initial step of the Kyn pathway. The overexpression of IDO1 is also associated with poor prognosis in EC. These findings can lead to advantages in immunotherapy-based approaches as a rationale for overcoming the immune escape. Indeed, besides immune checkpoints, other mechanisms, including the IDO enzymes, contribute to the EC progression due to the immunosuppression induced by the tumor milieu. On the other hand, the IDO1 enzyme has recently emerged as both a promising therapeutic target and an unfavorable prognostic biomarker. This evidence provides the basis for translational strategies of immune combination, whereas IDO1 expression would serve as a potential prognostic biomarker in metastatic EC.
Combined effects of nanoplastics and heavy metal on antioxidant parameters of juvenile tri-spine horseshoe crabs

Juvenile tri-spine horseshoe crabs (Tachypleus tridentatus) were exposed to determine the effects of single and combined stresses of polystyrene nanoplastics (nano-PS) and heavy metal (Cu2+) on antioxidant enzyme parameters. The juveniles were exposed to a 21-day 100-nm polystyrene concentration (104 particles l-1) and a concentration of Cu2+ (10 µg l-1) followed by a recovery period of 7 days. The in vivo antioxidant activity for whole horseshoe crab was analyzed. The results revealed that all antioxidant parameters, i.e., superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA), and lipid peroxidation (LPO), showed both increased and decreased levels in different experimental groups of horseshoe crabs having different experimental conditions compared to the control group at three time points, i.e., on days 7, 14, and 21. Similarly during the recovery period, SOD, CAT, and MDA showed decreased levels in all experimental groups, while GSH and LPO showed increased levels in all experimental groups of horseshoe crabs under the influence of different experimental conditions of nanoplastics and heavy metals compared to the control group on day 28. These results showed that the exposure of nano-PS and Cu2+ had precise effects on juvenile horseshoe crabs. Integrated biomarker responses showed that nano-PS and Cu2+ had adverse effects on juvenile horseshoe crabs. By principal component analysis, the potentially toxic effects of nano-PS and Cu2+ on horseshoe crabs were obtained.
Normed dataset for novel metaphors, novel similes, literal and anomalous sentences in Chinese

COPYRIGHT © 2022 Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Normed dataset for novel metaphors, novel similes, literal and anomalous sentences in Chinese
Cross-talk of four types of RNA modification proteins with adenosine reveals the landscape of multivariate prognostic patterns in breast cancer

Background: Breast cancer (BC) is the most common malignant tumour, and its heterogeneity is one of its major characteristics. N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing constitute the four most common adenosine-associated RNA modifications and represent the most typical and critical forms of epigenetic regulation contributing to the immunoinflammatory response, tumorigenesis and tumour heterogeneity. However, the cross-talk and potential combined profiles of these RNA-modified proteins (RMPs) in multivariate prognostic patterns of BC remain unknown. Methods: A total of 48 published RMPs were analysed and found to display significant expression alterations and genomic mutation rates between tumour and normal tissues in the TCGA-BRCA cohort. Data from 4188 BC patients with clinical outcomes were downloaded from the Gene Expression Omnibus (GEO), the Cancer Genome Atlas (TCGA), and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), normalized and merged into one cohort. The prognostic value and interconnections of these RMPs were also studied. The four prognosis-related genes (PRGs) with the greatest prognostic value were then selected to construct diverse RMP-associated prognostic models through univariate Cox (uniCox) regression analysis, differential expression analysis, Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox (multiCox) regression. Alterations in biological functional pathways, genomic mutations, immune infiltrations, RNAss scores and drug sensitivities among different models, as well as their prognostic value, were then explored. Results: Utilizing a large number of samples and a comprehensive set of genes contributing to adenosine-associated RNA modification, our study revealed the joint potential bio-functions and underlying features of these diverse RMPs and provided effective models (PRG clusters, gene clusters and the risk model) for predicting the clinical outcomes of BC. The individuals with higher risk scores showed poor prognoses, cell cycle function enrichment, upregulation of stemness scores, higher tumour mutation burdens (TMBs), immune activation and specific drug resistance. This work highlights the significance of comprehensively examining post-transcriptional RNA modification genes. Conclusion: Here, we designed and verified an advanced forecasting model to reveal the underlying links between BC and RMPs and precisely predict the clinical outcomes of multivariate prognostic patterns for individuals.
Metabolomic analysis in spondyloarthritis: A systematic review

Spondyloarthritis (SpA) is a group of rheumatic diseases that cause joint inflammation. Accumulating studies have focused on the metabolomic profiling of SpA in recent years. We conducted a systematic review to provide a collective summary of previous findings on metabolomic profiling associated with SpA. We systematically searched PubMed, Medline, Embase and Web of Science for studies on comparisons of the metabolomic analysis of SpA patients and non-SpA controls. The Newcastle–Ottawa Scale (NOS) was used to assess the quality of the included articles. From 482 records identified, 31 studies were included in the analysis. A number of metabolites were differentially distributed between SpA and non-SpA cases. SpA patients showed higher levels of glucose, succinic acid, malic acid and lactate in carbohydrate metabolism, higher glycerol levels and lower fatty acid (especially unsaturated fatty acid) levels in lipid metabolism, and lower levels of tryptophan and glutamine in amino acid metabolism than healthy controls. Both conventional and biological therapy of SpA can insufficiently reverse the aberrant metabolism state toward that of the controls. However, the differences in the results of metabolic profiling between patients with SpA and other inflammatory diseases as well as among patients with several subtypes of SpA are inconsistent across studies. Studies on metabolomics have provided insights into etiological factors and biomarkers for SpA. Supplementation with the metabolites that exhibit decreased levels, such as short-chain fatty acids (SCFAs), has good treatment prospects for modulating immunity. Further studies are needed to elucidate the role of disordered metabolic molecules in the pathogenesis of SpA.
The impact of mindfulness meditation on social and moral behavior: Does mindfulness enhance other-oriented motivation or decrease monetary reward salience?

This perspective article provides an overview of the impact of mindfulness meditation (MM) on social and moral behavior. In mindfulness research, prosocial behavior has been operationalized as helping behavior, altruistic redistribution of funds, reparative behavior, or monetary donation. Studies concerning moral behavior are still scarce. Despite inconsistent evidence, several studies found a beneficial effect of mindfulness on prosocial outcomes (i.e., a higher propensity to spend or give away money for the sake of other individuals). However, since the employed tasks were reward-based, participants’ decisions also directly affected their own payoff by reducing it. Crucially, MM also affects self-control circuitry and reduces reward-seeking behaviors and reward salience by making rewards less tempting. We have discussed evidence suggesting how challenging it may be to dissociate the specific weight of enhanced other-oriented motivation from one of the decreased monetary reward salience in explaining meditators’ behavior. Future higher-quality studies are needed to address this open issue.
Vertical ground reaction force oscillation during standing on hard and compliant surfaces: The “postural rhythm”

When a person stands upright quietly, the position of the Centre of Mass (CoM), the vertical force acting on the ground and the geometrical configuration of body segments is accurately controlled around to the direction of gravity by multiple feedback mechanisms and by integrative brain centres that coordinate multi-joint movements. This is not always easy and the postural muscles continuously produce appropriate torques, recorded as ground reaction force by a force platform. We studied 23 young adults during a 90 s period, standing at ease on a hard (Solid) and on a compliant support (Foam) with eyes open (EO) and with eyes closed (EC), focusing on the vertical component of the ground reaction force (VGRF). Analysis of VGRF time series gave the amplitude of their rhythmic oscillations (the root mean square, RMS) and of their frequency spectrum. Sway Area and Path Length of the Centre of Pressure (CoP) were also calculated. VGRF RMS (as well as CoP sway measures) increased in the order EO Solid ≈ EC Solid < EO Foam < EC Foam. The VGRF frequency spectra featured prevailing frequencies around 4–5 Hz under all tested conditions, slightly higher on Solid than Foam support. Around that value, the VGRF frequencies varied in a larger range on hard than on compliant support. Sway Area and Path Length were inversely related to the prevailing VGRF frequency. Vision compared to no-vision decreased Sway Area and Path Length and VGRF RMS on Foam support. However, no significant effect of vision was found on VGRF mean frequency for either base of support condition. A description of the VGRF, at the interface between balance control mechanisms and sway of the CoP, can contribute information on how upright balance is maintained. Analysis of the frequency pattern of VGRF oscillations and its role in the maintenance of upright stance should complement the traditional measures of CoP excursions in the horizontal plane.
The pattern of expression and prognostic value of key regulators for m7G RNA methylation in hepatocellular carcinoma

N7-methylguanosine (m7G) modification on internal RNA positions plays a vital role in several biological processes. Recent research shows m7G modification is associated with multiple cancers. However, in hepatocellular carcinoma (HCC), its implications remain to be determined. In this place, we need to interrogate the mRNA patterns for 29 key regulators of m7G RNA modification and assess their prognostic value in HCC. Initial, the details from The Cancer Genome Atlas (TCGA) database concerning transcribed gene data and clinical information of HCC patients were inspected systematically. Second, according to the mRNA profiles of 29 m7G RNA methylation regulators, two clusters (named 1 and 2, respectively) were identified by consensus clustering. Furthermore, robust risk signature for seven m7G RNA modification regulators was constructed. Last, we used the Gene Expression Omnibus (GEO) dataset to validate the prognostic associations of the seven-gene risk signature. We figured out that 24/29 key regulators of m7G RNA modification varied remarkably in their grades of expression between the HCC and the adjacent tumor control tissues. Cluster one compared with cluster two had a substandard prognosis and was also positively correlated with T classification (T), pathological stage, and vital status (fustat) significantly. Consensus clustering results suggested the expression pattern of m7G RNA modification regulators was correlated with the malignancy of HCC strongly. In addition, cluster one was extensively enriched in metabolic-related pathways. Seven optimal genes (METTL1, WDR4, NSUN2, EIF4E, EIF4E2, NCBP1, and NCBP2) were selected to establish the risk model for HCC. Indicating by further analyses and validation, the prognostic model has fine anticipating command and this probability signature might be a self supporting presage factor for HCC. Finally, a new prognostic nomogram based on age, gender, pathological stage, histological grade, and prospects were established to forecast the prognosis of HCC patients accurately. In essence, we detected association of HCC severity and expression levels of m7G RNA modification regulators, and developed a risk score model for predicting prognosis of HCC patients’ progression.
Use of remote data collection methodology to test for an illusory effect on visually guided cursor movements

Investigating the influence of perception on the control of visually guided action typically involves controlled experimentation within the laboratory setting. When appropriate, however, behavioral research of this nature may benefit from the use of methods that allow for remote data collection outside of the lab. This study tested the feasibility of using remote data collection methods to explore the influence of perceived target size on visually guided cursor movements using the Ebbinghaus illusion. Participants completed the experiment remotely, using the trackpad of their personal laptop computers. The task required participants to click on a single circular target presented at either the left or right side of their screen as quickly and accurately as possible (Experiment 1), or to emphasize speed (Experiment 2) or accuracy (Experiment 3). On each trial the target was either surrounded by small or large context circles, or no context circles. Participants’ judgments of the targets’ perceived size were influenced by the illusion, however, the illusion failed to produce differences in click-point accuracy or movement time. Interestingly, the illusion appeared to affect participants’ movement of the cursor toward the target; more directional changes were made when clicking the Perceived Large version of the illusion compared to the Perceived Small version. These results suggest the planning of the cursor movement may have been influenced by the illusion, while later stages of the movement were not, and cursor movements directed toward targets perceived as smaller required less correction compared to targets perceived as larger.
Leaf elemental composition analysis in spider plant [Gynandropsis gynandra L. (Briq.)] differentiates three nutritional groups

Understanding the genetic variability within a plant species is paramount in implementing a successful breeding program. Spider plant (Gynandropsis gynandra) is an orphan leafy vegetable and an extraordinary source of vitamins, secondary metabolites and minerals, representing an important resource for combatting malnutrition. However, an evaluation of the leaf elemental composition, using a worldwide germplasm collection to inform breeding programs and the species valorization in human nutrition is still lacking. The present study aimed to profile the leaf elemental composition of G. gynandra and depict any potential geographical signature using a collection of 70 advanced lines derived from accessions originating from Asia and Eastern, Southern and West Africa. The collection was grown in a greenhouse using a 9 × 8 alpha lattice design with two replications in 2020 and 2021. Inductively coupled plasma–optical emission spectrometry was used to profile nine minerals contents. A significant difference (p < 0.05) was observed among the lines for all nine minerals. Microelements such as iron, zinc, copper and manganese contents ranged from 12.59–430.72, 16.98–166.58, 19.04–955.71, 5.39–25.10 mg kg−1 dry weight, respectively, while the concentrations of macroelements such as potassium, calcium, phosphorus and magnesium varied in the ranges of 9992.27–49854.23, 8252.80–33681.21, 3633.55–14216.16, 2068.03–12475.60 mg kg−1 dry weight, respectively. Significant and positive correlations were observed between iron and zinc and calcium and magnesium. Zinc, calcium, phosphorus, copper, magnesium, and manganese represented landmark elements in the genotypes. Eastern and Southern African genotypes were clustered together in group 1 with higher phosphorus, copper and zinc contents than Asian and West African lines, which clustered in group 2 and were characterized by higher calcium, magnesium and manganese contents. An additional outstanding group 3 of six genotypes was identified with high iron, zinc, magnesium, manganese and calcium contents and potential candidates for cultivar release. The genotype × year interaction variance was greater than the genotypic variance, which might translate to phenotypic plasticity in the species. Broad-sense heritability ranged from low to high and was element-specific. The present results reveal the leaf minerals diversity in spider plant and represent a baseline for implementing a minerals-based breeding program for human nutrition.