Miracle-dz/UniFAR-FTUs huggingface dataset:
Identification of KIF23 as a Prognostic Biomarker Associated With Progression of Clear Cell Renal Cell Carcinoma

About 3% of adult cancers are caused by renal cell carcinoma (RCC) and its pathogenesis remains elusive. Among RCC, clear cell renal cell carcinoma (ccRCC) is the predominant histological subtype. Resistance to conventional treatments leaves few treatment options for advanced ccRCC. Although the transcriptome profile of primary ccRCC has been comprehensively summarized, the transcriptome profile of metastatic ccRCC is still lacking. In this study we identified a list of metastasis-related genes and constructing a metastasis-associated prognostic gene signature. By analyzing data from GSE85258 and GSE105288 datasets, 74 genes were identified as metastasis-related genes. To construct prognostic features, we downloaded the expression data of ccRCC from the Cancer Genome Atlas (TCGA). Metastasis-associated genes were initially selected through the LASSO Cox regression analysis and 12 metastasis-related were included to construct prognostic model. Transcriptome profile, patient prognosis, and immune cell infiltration characteristics differed between low- and high-risk groups after grouping according to median risk score. Through explored the functions of differentially expressed genes (DEGs) between the two groups. Kinesin family member 23 (KIF23) was identified as a prognostic marker in ccRCC patients. Furthermore, inhibition of KIF23 expression reduced the proliferation, migration and invasion of ccRCC cells. We further demonstrated that KIF23 promote nuclear translocation of β-catenin in ccRCC cells, which provides novel insight into the functions and molecular machinery of KIF23 in ccRCC.
Aspartate Transaminase AST2 Involved in Sporulation and Necrotrophic Pathogenesis in the Hemibiotrophs Magnaporthe oryzae and Colletotrichum graminicola

Aspartate family includes five additional amino acids other than aspartate, among which most except aspartate have been reported for their action in pathogenesis by amino acid biosynthesis. However, how aspartate, the initial substrate of this family metabolic pathway, is involved in pathogenesis remains unknown. Here, we focused on aspartate transaminase (AST) that catalyzes transamination reaction between glutamate-aspartate in Magnaporthe oryzae. Three MoAST genes were bioinformatically analyzed, of which MoAST2 was uniquely upregulated when invasive hyphae switched to necrotrophic pathogenesis. MoAST2 deletion (ΔMoast2) caused a drastic reduction in conidiogenesis and appressorium formation. Particularly, ΔMoast2 was observed to be proliferated at the biotrophic phase but inhibited at the necrotrophic stage, and with invisible symptoms detected, suggesting a critical role in necrotrophic phase. Glutamate family restored the ΔMoast2 defects but aspartate family did not, inferring that transamination occurs from aspartate to glutamine. MoAST2 is cytosolic and possessed H2O2 stress tolerance. In parallel, Colletotrichum graminicola AST2, CgAST2 was proven to be a player in necrotrophic anthracnose development. Therefore, conserved AST2 is qualified to be a drug target for disease control.
Activation of the Mesencephalic Trigeminal Nucleus Contributes to Masseter Hyperactivity Induced by Chronic Restraint Stress

Psychological stress is commonly accepted to be closely associated with masticatory muscle disorder, which is the main symptom of temporomandibular disorder (TMD). Previous studies have confirmed that exposure to stress may cause masticatory muscle hyperactivity. However, the central mechanism underlying this process remains unclear. The mesencephalic trigeminal nucleus (Vme), which resides in the brainstem, is the primary afferent center for masticatory proprioception and plays a key role in oral–motor movements by projecting to the trigeminal motor nucleus (Vmo). Therefore, the present study was designed to examine the role of Vme neurons in masseter overactivity induced by chronic stress. We found that subjecting mice to restraint stress (6 h/day) for 14 days caused significant anxiety-like behavior, obvious masseter overactivity, and markedly enhanced electrophysiological excitability of Vme neurons. By using anterograde tract tracing combined with immunofluorescence staining methods, we observed vesicular glutamate transporter 1 (VGLUT1)-positive glutamatergic projections from the Vme to the Vmo. Moreover, chronic restraint stress (CRS) elevated the expression of VGLUT1 and choline acetyltransferase (ChAT) in Vmo. Furthermore, administration of VGLUT1-targeted short hairpin RNA (shRNA) into the bilateral Vme significantly suppressed the enhanced overexcitability of Vme neurons, downregulated the overexpression of VGLUT1 and ChAT in the Vmo, and attenuated the elevated overactivity of the masseter caused by CRS. Taken together, we showed that CRS can excite neurons in the Vme, enhancing glutamatergic excitatory projections from the Vme to the Vmo and resulting in masseter muscle overactivity. These findings provide us with a novel central mechanism underlying the correlation between psychological factors and TMD.
Sociometric Status in Bullying Perpetrators: A Systematic Review

Numerous studies have analyzed the relationship between sociometric status and bullying but it is difficult to reach a consensus regarding this issue. Objective The present study carried out a systematic review on the sociometric status of adolescent bullies. Design The bibliographic search was carried out in the mainly databases. Results The findings of 29 studies selected defend three positions. First, bullying is associated with the popular status in their peer group. Second, rejected or unpopular adolescents tend to perpetrate bullying as a response to the frustration generated by their status. Finally, other group the perpetrators of bullying is among these two poles. Conclusions The students' sociometric status is necessary for designing bullying intervention programs at school.
Reduction of Phosphorus Using Electric Arc Furnace Slag Filters in the Macatawa Watershed (Michigan)

Eutrophication is a major problem in lakes and rivers throughout the world. One such system is Lake Macatawa, located in West Michigan, which hydrologically connects to Lake Michigan. Lake Macatawa and its watershed suffer from excess phosphorus and sediment loads. The total maximum daily load for the lake calls for a total phosphorus (TP) reduction of 75%, which would reduce the water column total phosphorus concentration from 125 μg/L to 50 μg/L. Understanding how P moves through this landscape, into Lake Macatawa, and ultimately to Lake Michigan and the St. Lawrence Seaway, is critical to managing and controlling P runoff. A potentially significant source of P to Lake Macatawa occurs through agricultural tile drainage. Various best management practices (BMPs) have been implemented in the Macatawa watershed to reduce P loading, especially surface runoff, but their overall effectiveness has been limited. Electric arc furnace (EAF) slag, a waste product from the steel industry, can chemically bind P and has been used previously in agricultural settings. Three iron slag filters were installed at the end of agricultural tile lines in the Macatawa watershed and evaluated to assess their effectiveness in removing P, while also monitoring for the presence of potentially toxic chemicals leaching from the slag. After 1 year of slag filter performance, both SRP (soluble reactive phosphorus) and TP decreased in the tile drain effluent: percent reductions of soluble reactive phosphorus and TP ranged from 7.4% to 57.3% and 59.5–76.5%, respectively. Absolute concentrations of TP were reduced to between 100 and 329 μg/L, which still exceeds the 50 μg/L goal for Lake Macatawa. Concentrations of toxic metals, polycyclic aromatic hydrocarbons compounds, and cyanide all were at levels below drinking water standards. Our preliminary conclusions are that the installation of these filters should be targeted to areas where tile drain effluent P levels are very high (SRP > 250 μg/L) to obtain an optimal cost/benefit ratio. While they are not a panacea, when installed in combination with other BMPs (Best Management Practices), EAF slag filters may play an important localized role in reducing P to Lake Macatawa and farther downstream.
Structural Characterization of the Full-Length Anti-CD20 Antibody Rituximab

Rituximab, a murine–human chimera, is the first monoclonal antibody (mAb) developed as a therapeutic agent to target CD20 protein. Its Fab domain and its interaction with CD20 have been extensively studied and high-resolution atomic models obtained by X-ray diffraction or cryo-electron microscopy are available. However, the structure of the full-length antibody is still missing as the inherent protein flexibility hampers the formation of well-diffracting crystals and the reconstruction of 3D microscope images. The global structure of rituximab from its dilute solution is here elucidated by small-angle X-ray scattering (SAXS). The limited data resolution achievable by this technique has been compensated by intensive computational modelling that led to develop a new and effective procedure to characterize the average mAb conformation as well as that of the single domains. SAXS data indicated that rituximab adopts an asymmetric average conformation in solution, with a radius of gyration and a maximum linear dimension of 52 Å and 197 Å, respectively. The asymmetry is mainly due to an uneven arrangement of the two Fab units with respect to the central stem (the Fc domain) and reflects in a different conformation of the individual units. As a result, the Fab elbow angle, which is a crucial determinant for antigen recognition and binding, was found to be larger (169°) in the more distant Fab unit than that in the less distant one (143°). The whole flexibility of the antibody has been found to strongly depend on the relative inter-domain orientations, with one of the Fab arms playing a major role. The average structure and the amount of flexibility has been studied in the presence of different buffers and additives, and monitored at increasing temperature, up to the complete unfolding of the antibody. Overall, the structural characterization of rituximab can help in designing next-generation anti-CD20 antibodies and finding more efficient routes for rituximab production at industrial level.
A Virtual Navigation Training Promotes the Remapping of Space in Allocentric Coordinates: Evidence From Behavioral and Neuroimaging Data

Allocentric space representations demonstrated to be crucial to improve visuo-spatial skills, pivotal in every-day life activities and for the development and maintenance of other cognitive abilities, such as memory and reasoning. Here, we present a series of three different experiments: Experiment 1, Discovery sample (23 young male participants); Experiment 2, Neuroimaging and replicating sample (23 young male participants); and Experiment 3 (14 young male participants). In the experiments, we investigated whether virtual navigation stimulates the ability to form spatial allocentric representations. With this aim, we used a novel 3D videogame (MindTheCity! ), focused on the navigation of a virtual town. We verified whether playing at MindTheCity! enhanced the performance on spatial representational tasks (pointing to a specific location in space) and on a spatial memory test (asking participant to remember the location of specific objects). Furthermore, to uncover the neural mechanisms underlying the observed effects, we performed a preliminary fMRI investigation before and after the training with MindTheCity! Results show that our virtual training enhances the ability to form allocentric representations and spatial memory (Experiment 1). Experiments 2 and 3 confirmed the behavioral results of Experiment 1. Furthermore, our preliminary neuroimaging and behavioral results suggest that the training activates brain circuits involved in higher-order mechanisms of information encoding, triggering the activation of broader cognitive processes and reducing the working load on memory circuits (Experiments 2 and 3).
Improved Mobilome Delineation in Fragmented Genomes

The mobilome of a microbe, i.e., its set of mobile elements, has major effects on its ecology, and is important to delineate properly in each genome. This becomes more challenging for incomplete genomes, and even more so for metagenome-assembled genomes (MAGs), where misbinning of scaffolds and other losses can occur. Genomic islands (GIs), which integrate into the host chromosome, are a major component of the mobilome. Our GI-detection software TIGER, unique in its precise mapping of GI termini, was applied to 74,561 genomes from 2,473 microbial species, each species containing at least one MAG and one isolate genome. A species-normalized deficit of ∼1.6 GIs/genome was measured for MAGs relative to isolates. To test whether this undercount was due to the higher fragmentation of MAG genomes, TIGER was updated to enable detection of split GIs whose termini are on separate scaffolds or that wrap around the origin of a circular replicon. This doubled GI yields, and the new split GIs matched the quality of single-scaffold GIs, except that highly fragmented GIs may lack central portions. Cross-scaffold search is an important upgrade to GI detection as fragmented genomes increasingly dominate public databases. TIGER2 better captures MAG microdiversity, recovering niche-defining GIs and supporting microbiome research aims such as virus-host linking and ecological assessment.
Antibacterial Activity of an Anodized TiNbSn Alloy Prepared in Sodium Tartrate Electrolyte

In this study, we anodized a TiNbSn alloy with low Young’s modulus in an electrolyte of sodium tartrate with and without hydrogen peroxide (H2O2). The photo-induced characteristics of the anodized alloy were analyzed for crystallinity and electrochemical conditions with comparisons to the effect with the addition of H2O2. The antibacterial activity was evaluated using methicillin-resistant Staphylococcus aureus and other pathogenic bacteria according to ISO 27447, and time decay antibacterial tests were also conducted. The anodized oxide had a porous microstructure with anatase- and rutile-structured titanium dioxide (TiO2). In contrast, the peaks of rutile-structured TiO2 were accelerated in the anodized TiNbSn alloy with H2O2. The formation of hydroxyl radicals and methylene blue breaching performance under ultraviolet irradiation was confirmed in the anodic oxide on TiNbSn alloy with and without H2O2. The anodic oxide on TiNbSn alloy had a robust antibacterial activity, and no significant difference was detected with or without H2O2. We conclude that anodized TiNbSn alloy with sodium tartrate electrolyte may be a functional biomaterial with a low Young’s modulus and an antibacterial function.
Comparative Analysis of Lateral Preferences in Patients With Resistant Schizophrenia

Background Schizophrenia is a chronic brain disorder of diverse etiology and clinical presentation. Despite the expansion of treatment methods, between 30 and 50% of cases remain resistant to treatment. In patients with schizophrenia, specifics in the dominant lateralization in the brain function have been discovered. This gave a reason to seek the relation between functional lateralization and the effect of treatment. Methods Of the 105 people observed with schizophrenia, 45 (42.9%) were treatment resistant, and 60 (57.1%) were considered responders. We compared functional lateralization (hand, foot, and eye) between the two groups. Handedness was ascertained by using the Edinburgh Handedness Inventory. The assessment was made at 12 weeks of treatment. Results Of all patients with schizophrenia, 41.89% have mixed lateralization, 53.34% are right winged, and 4.76% of the patients are left winged. Resistance of the symptoms shows that 26 (57.78%) are cross-dominated, 18 (40%) are right winged, and 1 (2.22%) is left winged. In patients with clinical remission, 18 (30%) are of mixed dominance, 38 (63.33%) are right winged, and 4 (6.66%) are left winged. From the results for the separate lateralization of the hand, foot, and eye, we found a significant difference only in terms of the dominance of the eye. In 44 (41.9%) of the patients, we found dominance of the left eye. In patients with resistance, the percentage established by us is higher—at 26 (57.8%). These results indicate that the increased percentage of mixed dominance in patients with schizophrenia is mainly due to left-sided lateralization of the eye, especially in those with resistance to treatment. Conclusion We find an increased number of patients with cross-dominance left eye dominance in patients with schizophrenia. Cross-dominance and left eye dominance are associated with a higher probability of symptom resistance than other forms of lateralization (left-handed or right-handed). The high percentage of cross-dominance is due to the high percentage of left-sided dominance of the eye.
Effects of a Multi-Suckling System Combined With Enriched Housing Post-Weaning on Response and Cognitive Resilience to Isolation

Improving welfare is still a critical issue in pig husbandry. Upgrades of the housing environment seem to be a promising solution to optimise resilience as a whole, and therefore improve animal welfare. The objective of this study was to evaluate the effect of an alternative housing system to enhance cognitive resilience and also to promote the pigs' welfare. A total of 96 piglets from two contrasted housing systems [alternative housing system (AHS) vs. conventional system (CONV)] was used. The major upgrades of the alternative system were multi-litter housing during lactation, delayed weaning, extra space allowance, and environmental enrichment from birth onwards. To estimate welfare, weight, and feed intake (as a general indicator of performances), the tear staining area (as a chronic stress indicator), behavioural postures, heart rate traits, and saliva cortisol concentration were measured over a 21 h-isolation. To assess cognitive resilience, the pigs were subjected to a maze with a social reward both before and after the isolation challenge and indicators of cognitive abilities were followed. The AHS pigs showed lower cortisol levels and tear staining area before the challenge, demonstrating overall better welfare due to the alternative housing conditions. During the challenge, AHS pigs had a lower heart rate, higher heart rate variability, and higher vagal activity than the CONV pigs, which might indicate a reduced sensitivity to the stressor. AHS pigs appeared to have a better long-term memory tested in a maze. Providing social and environmental enrichments, that fit the satisfaction of the essential needs of the pigs better, appears to be beneficial for pig welfare as a whole. Its effects on cognitive resilience still need to be proven.
Sevoflurane and Hypercapnia Blunt the Physiological Variability of Spontaneous Breathing: A Comparative Interventional Study

Background: Although spontaneous breathing is known to exhibit substantial physiological fluctuation that contributes to alveolar recruitment, changes in the variability of the respiratory pattern following inhalation of carbon dioxide (CO2) and volatile anesthetics have not been characterized. Therefore, we aimed at comparing the indices of breathing variability under wakefulness, sleep, hypercapnia and sedative and anesthetic concentrations of sevoflurane. Methods: Spontaneous breathing pattern was recorded on two consecutive days in six rabbits using open whole-body plethysmography under wakefulness and spontaneous sleep and following inhalation of 5% CO2, 2% sevoflurane (0.5 MAC) and 4% (1 MAC) sevoflurane. Tidal volume (VT), respiratory rate (RR), minute ventilation (MV), inspiratory time (TI) and mean inspiratory flow (VT/TI) were calculated from the pressure fluctuations in the plethysmograph. Means and coefficients of variation were calculated for each measured variable. Autoregressive model fitting was applied to estimate the relative contributions of random, correlated, and oscillatory behavior to the total variance. Results: Physiological sleep decreased MV by lowering RR without affecting VT. Hypercapnia increased MV by elevating VT. Sedative and anesthetic concentrations of sevoflurane increased VT but decreased MV due to a decrease in RR. Compared to the awake stage, CO2 had no effect on VT/TI while sevoflurane depressed significantly the mean inspiratory flow. Compared to wakefulness, the variability in VT, RR, MV, TI and VT/TI were not affected by sleep but were all significantly decreased by CO2 and sevoflurane. The variance of TI originating from correlated behavior was significantly decreased by both concentrations of sevoflurane compared to the awake and asleep conditions. Conclusions: The variability of spontaneous breathing during physiological sleep and sevoflurane-induced anesthesia differed fundamentally, with the volatile agent diminishing markedly the fluctuations in respiratory volume, inspiratory airflow and breathing frequency. These findings may suggest the increased risk of lung derecruitment during procedures under sevoflurane in which spontaneous breathing is maintained.
Prevalence, Associated Factors, and Survival Outcomes of Small-Cell Neuroendocrine Carcinoma of the Gynecologic Tract: A Large Population-Based Analysis

Small-cell carcinomas are highly malignant tumors with neuroendocrine function and which often occur in the lungs. Primary small-cell neuroendocrine carcinomas of the gynecologic tract are extremely rare. This study aimed to evaluate the prevalence of independent predictors related to the prognosis and overall survival of patients with small-cell neuroendocrine carcinomas of the gynecologic tract. Patients with gynecologic small-cell neuroendocrine carcinomas diagnosed between 1973 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox risk regression analyses were performed to determine the independent predictors of overall survival. Overall survival was calculated using the Kaplan–Meier method, and the log-rank test was used for comparison. We included 5,15,393 eligible carcinomas in the present study; the prevalence of gynecologic small-cell neuroendocrine carcinomas was 0.121% (N = 622). Multivariate analysis indicated that advanced age, stage III and IV cancer, and no chemotherapy treatment may be predictors of poor small-cell neuroendocrine cervical carcinoma prognosis. Stage III and IV cancer and lack of surgery, radiotherapy, or chemotherapy were identified as potential predictors of poor prognosis in patients with ovarian small-cell neuroendocrine carcinoma. Kaplan–Meier analysis suggested that the median survival was 19, 11, and 12 months for cervical, ovarian, and endometrial small-cell neuroendocrine carcinomas, respectively. The 1-, 3-, and 5-year overall survival rates were as follows: 58.8, 31.4, and 26.1%, respectively, for small-cell neuroendocrine cervical carcinoma; 46.3, 23.5, and 22.0%, respectively, for ovarian small-cell neuroendocrine carcinoma; and 49.4, 29.4, and 25.9%, respectively, for endometrial small-cell neuroendocrine carcinoma. Our findings indicate that comprehensive and individualized treatment of small-cell neuroendocrine carcinomas of the gynecologic tract may prolong patient survival, although further studies are required.