Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein A Modulates Neutrophil and Keratinocyte Signaling and Survival in Response to Staphylococcus aureus

The type 1 TNF-α receptor (TNFR1) has a central role in initiating both pro-inflammatory and pro-apoptotic signaling cascades in neutrophils. Considering that TNFR1 signals Staphylococcus aureus protein A (SpA), the aim of this study was to explore the interaction of this bacterial surface protein with neutrophils and keratinocytes to underscore the signaling pathways that may determine the fate of these innate immune cells in the infected tissue during staphylococcal skin infections. Using human neutrophils cultured in vitro and isogenic staphylococcal strains expressing or not protein A, we demonstrated that SpA is a potent inducer of IL-8 in neutrophils and that the induction of this chemokine is dependent on the SpA-TNFR1 interaction and p38 activation. In addition to IL-8, protein A induced the expression of TNF-α and MIP-1α highlighting the importance of SpA in the amplification of the inflammatory response. Protein A contributed to reduce neutrophil mortality prolonging their lifespan upon the encounter with S. aureus. Signaling initiated by SpA modulated the type of neutrophil cell death in vitro and during skin and soft tissue infections (SSTI) in vivo triggering the apoptotic pathway instead of necrosis. Moreover, SpA induced pro-inflammatory cytokines in keratinocytes, modulating their survival in vitro and preventing the exacerbated necrosis and ulceration of the epithelium during SSTI in vivo. Taken together, these results highlight the importance of the inflammatory signaling induced by protein A in neutrophils and skin epithelial cells. The ability of protein A to modulate the neutrophil/epithelial cell death program in the skin is of clinical relevance considering that lysis of neutrophils and epithelial cells will promote an intense inflammatory response and contribute to tissue damage, a non-desirable feature of complicated SSTI.
Feeding Hotspots and Distribution of Fin and Humpback Whales in the Norwegian Sea From 2013 to 2018

Fin whales (Balaenoptera physalus) and humpback whales (Megaptera novaeangliae) are commonly found in the Norwegian Sea during the summer months. Records from around 1995 to 2004 show that their distribution patterns were mainly associated with those of macro-zooplankton. More recent studies conducted from 2009 to 2012 demonstrate marked shifts, with fin whale distribution related to pelagic fish distribution, decreasing densities of humpbacks, and increased densities of toothed whales. During the same period, historically large abundances of pelagic planktivorous fish in the Norwegian Sea were reported. The goals of this study were to examine the summer distribution of fin and humpback whales from 2013 to 2018 and to assess the potential association between distribution and environmental impact factors. Results suggest a pronounced northerly shift in distribution for both species, a feeding hotspot for fin whales at the shelf area between Svalbard and Norway, and one near Bear Island for humpback whales. Fin whale distribution was associated with that of blue whiting (Micromesistius poutassou) and capelin (Mallotus villosus), whereas humpback whale distribution was associated with that of euphausiids (Meganyctiphanes norvegica, Thysanoessa longicaudata, and Thysanoessa inermis), capelin, and herring (Clupea harengus). However, a significant negative spatial correlation was found between whale occurrence and the widely expanding population of northeast Atlantic mackerel (Scomber scombrus). The results of this study suggest that the prey composition of fin and humpback whales in recent years contain a large proportion of fish. The apparent northerly shift in the distribution of these whale species is largely determined by the availability of prey, but it likely is also impacted by direct or indirect interspecific interactions, especially with killer whales (Orcinus orca). Such large-scale pronounced changes in distribution seem to confirm a high degree of plasticity in fin and humpback whale feeding in the Norwegian Sea.
The Analgesic Effect of Different Concentrations of Epidural Ropivacaine Alone or Combined With Sufentanil in Patients After Cesarean Section

Background: Patients experience moderate-high intensity postoperative pain after cesarean section (CS). The aim of this study was to investigate the optimal concentrations of ropivacaine and sufentanil for use in controlling pain after CS. Methods: One hundred and seventy-four women undergoing elective CS were randomly allocated to four groups. Epidural analgesia was administered with 0.1% ropivacaine in the R1 group, 0.15% ropivacaine in the R2 group, a combination of 0.1% ropivacaine and 0.5 μg/ml of sufentanil in the R1S group, and a combination of 0.15% ropivacaine and 0.5 μg/ml of sufentanil in the R2S group (at a basal rate of 4 ml/h, bolus dose of 4 ml/20 min as needed). Pain scores (numerical rating scale [NRS]: 0–10 cm) at rest (NRS-R), during movement (NRS-M), and when massaging the uterus (NRS-U) were documented at 6 and 24 h. We also recorded patient satisfaction scores, time to first flatus, motor deficits, and adverse drug reactions. Results: NRS (NRS-R, NRS-M, NRS-U) scores in the R2S group (2 [1–3], 4 [3–5], 6 [5–6], respectively) were lower than in the R1 group (3 [3–4], 5 [4–6], 7 [6–8], respectively) (p < 0.001, p < 0.05, p < 0.01, respectively) at 6 h; and patient satisfaction (9 [8–10]) was improved compared to the R1 group (8 [6–8]) (p < 0.01). The time to first flatus (18.7 ± 11.8 h) was reduced relative to the R1 group (25.9 ± 12.0 h) (p < 0.05). The time to first ambulation was not delayed (p > 0.05). However, the incidence of pruritus (4 [9.3%]) was increased compared to the R2 group (0 [0]) (p < 0.05) at 6 h, and the incidence of numbness (23 [53.5%], 23 [53.5%]) was increased compared to the R1 group (10 [23.3%], 10 [23.3%]) (all p < 0.01) at both 6 and 24 h. Conclusions: Although we observed a higher incidence of pruritus and numbness, co-administration of 0.15% ropivacaine and 0.5 μg/ml of sufentanil administered epidurally optimized pain relief after CS, with treated subjects exhibiting lower NRS scores, shorter time to first flatus, and higher patient-satisfaction scores.
Tetrazoles as PPARγ ligands: A Structural and Computational Investigation

Diabetes is an important chronic disease affecting about 10% of the adult population in the US and over 420 million people worldwide, resulting in 1.6 million deaths every year, according to the World Health Organization. The most common type of the disease, type 2 diabetes, can be pharmacologically managed using oral hypoglycemic agents or thiazolidinediones (TZDs), such as pioglitazone, which act by activating the Peroxisome Proliferated-Activated Receptor γ. Despite their beneficial effects in diabetes treatment, TZDs like rosiglitazone and troglitazone were withdrawn due to safety reasons, creating a void in the pharmacological options for the treatment of this important disease. Here, we explored a structure-based approach in the screening for new chemical probes for a deeper investigation of the effects of PPARγ activation. A class of tetrazole compounds was identified and the compounds named T1, T2 and T3 were purchased and evaluated for their ability to interact with the PPARγ ligand binding domain (LBD). The compounds were binders with micromolar range affinity, as determined by their IC50 values. A Monte Carlo simulation of the compound T2 revealed that the tetrazole ring makes favorable interaction with the polar arm of the receptor binding pocket. Finally, the crystal structure of the PPARγ-LBD-T2 complex was solved at 2.3 Å, confirming the binding mode for this compound. The structure also revealed that, when the helix H12 is mispositioned, an alternative binding conformation is observed for the ligand suggesting an H12-dependent binding conformation for the tetrazole compound.
Impact of Phosphate Availability on Membrane Lipid Content of the Model Strains, Streptomyces lividans and Streptomyces coelicolor

In this issue we demonstrated that the phospholipid content of Streptomyces lividans varies greatly with Pi availability being was much lower in Pi limitation than in Pi proficiency whereas that of Streptomyces coelicolor varied little with Pi availability. In contrast the content in phosphate free ornithine lipids was enhanced in both strains in condition of phosphate limitation. Ornithine lipids biosynthesis starts with the N-acylation of ornithine to form lyso-ornithine that is then O-acylated to yield ornithine lipid. The operon sco1222-23 was proposed to be involved in the conversion of specific amino acids into ornithine in condition of phosphate limitation whereas the sco0921-20 operon encoding N- and O-acyltransferase, respectively, was shown to be involved in the biosynthesis of these lipids. The expression of these two operons was shown to be under the positive control of the two components system PhoR/PhoP and thus induced in phosphate limitation. The expression of phoR/phoP being weak in S. coelicolor, the poor expression of these operons resulted into a fivefold lower ornithine lipids content in this strain compared to S. lividans. In the deletion mutant of the sco0921-20 operon of S. lividans, lyso-ornithine and ornithine lipids were barely detectable and TAG content was enhanced. The complementation of this mutant by the sco0921-20 operon or by sco0920 alone restored ornithine lipids and TAG content to wild type level and was correlated with a twofold increase in the cardiolipin content. This suggested that SCO0920 bears, besides its broad O-acyltransferase activity, an N-acyltransferase activity and this was confirmed by the detection of lyso-ornithine in this strain. In contrast, the complementation of the mutant by sco0921 alone had no impact on ornithine lipids, TAG nor cardiolipin content but was correlated with a high lyso-ornithine content. This confirmed that SCO0921 is a strict N-acyltransferase. However, interestingly, the over-expression of the sco0921-20 operon or of sco0921 alone in S. coelicolor, led to an almost total disappearance of phosphatidylinositol that was correlated with an enhanced DAG and TAG content. This suggested that SCO0921 also acts as a phospholipase C, degrading phosphatidylinositol to indirectly supply of phosphate in condition of phosphate limitation.
Language Dysfunction in Schizophrenia: Assessing Neural Tracking to Characterize the Underlying Disorder(s)?

Deficits in language production and comprehension are characteristic of schizophrenia. To date, it remains unclear whether these deficits arise from dysfunctional linguistic knowledge, or dysfunctional predictions derived from the linguistic context. Alternatively, the deficits could be a result of dysfunctional neural tracking of auditory information resulting in decreased auditory information fidelity and even distorted information. Here, we discuss possible ways for clinical neuroscientists to employ neural tracking methodology to independently characterize deficiencies on the auditory–sensory and abstract linguistic levels. This might lead to a mechanistic understanding of the deficits underlying language related disorder(s) in schizophrenia. We propose to combine naturalistic stimulation, measures of speech–brain synchronization, and computational modeling of abstract linguistic knowledge and predictions. These independent but likely interacting assessments may be exploited for an objective and differential diagnosis of schizophrenia, as well as a better understanding of the disorder on the functional level—illustrating the potential of neural tracking methodology as translational tool in a range of psychotic populations.
Integrating Causal and Evolutionary Analysis of Life-History Evolution: Arrival Date in a Long-Distant Migrant

In migratory species, the timing of arrival at the breeding grounds is a life-history trait with major fitness consequences. The optimal arrival date varies from year-to-year, and animals use cues to adjust their arrival dates to match this annual variation. However, which cues they use to time their arrival and whether these cues actually predict the annual optimal arrival date is largely unknown. Here, we integrate causal and evolutionary analysis by identifying the environmental variables used by a migratory songbird to time its arrival dates and testing whether these environmental variables also predicted the optimal time to arrive. We used 11 years of male arrival data of a pied flycatcher population. Specifically, we tested whether temperature and normalized difference vegetation index (NDVI) values from their breeding grounds in the Netherlands and from their wintering grounds in Ivory Coast explained the variation in arrival date, and whether these variables correlated with the position of the annual fitness peak at the breeding grounds. We found that temperature and NDVI, both from the wintering and the breeding grounds, explained the annual variation in arrival date, but did not correlate with the optimal arrival date. We explore three alternative explanations for this lack of correlation. Firstly, the date of the fitness peak may have been incorrectly estimated because a potentially important component of fitness (i.e., migration date dependent mortality en route or directly upon arrival) could not be measured. Secondly, we focused on male timing but the fitness landscape is also likely to be shaped by female timing. Finally, the correlation has recently disappeared because climate change disrupted the predictive value of the cues that the birds use to time their migration. In the latter case, birds may adapt by altering their sensitivity to temperature and NDVI.
CT Angiography-Based Radiomics for Classification of Intracranial Aneurysm Rupture

Background: Intracranial aneurysm rupture is a devastating medical event with a high morbidity and mortality rate. Thus, timely detection and management are critical. The present study aimed to identify the aneurysm radiomics features associated with rupture and to build and evaluate a radiomics classification model of aneurysm rupture. Methods: Radiomics analysis was applied to CT angiography (CTA) images of 393 patients [152 (38.7%) with ruptured aneurysms]. Patients were divided at a ratio of 7:3 into retrospective training (n = 274) and prospective test (n = 119) cohorts. A total of 1,229 radiomics features were automatically calculated from each aneurysm. The feature number was systematically reduced, and the most important classifying features were selected. A logistic regression model was constructed using the selected features and evaluated on training and test cohorts. Radiomics score (Rad-score) was calculated for each patient and compared between ruptured and unruptured aneurysms. Results: Nine radiomics features were selected from the CTA images and used to build the logistic regression model. The radiomics model has shown good performance in the classification of the aneurysm rupture on training and test cohorts [area under the receiver operating characteristic curve: 0.92 [95% confidence interval CI: 0.89–0.95] and 0.86 [95% CI: 0.80–0.93], respectively, p < 0.001]. Rad-score showed statistically significant differences between ruptured and unruptured aneurysms (median, 2.50 vs. −1.60 and 2.35 vs. −1.01 on training and test cohorts, respectively, p < 0.001). Conclusion: The results indicated the potential of aneurysm radiomics features for automatic classification of aneurysm rupture on CTA images.
Efficacy of BRAF Inhibitors in Combination With Stereotactic Radiosurgery for the Treatment of Melanoma Brain Metastases: A Systematic Review and Meta-Analysis

Background BRAF inhibitors have improved the outcome for patients with BRAF mutant metastatic melanoma and have shown intracranial responses in melanoma brain metastases. Stereotactic radiosurgery (SRS) is being used as a local treatment for melanoma brain metastasis (MBM) with better local control and survival. We searched for studies comparing the combination of two treatments with SRS alone to detect any clinical evidence of synergism. Materials and Methods PubMed, EMBASE, Medline, and Cochrane library were searched until May 2020 for studies with desired comparative outcomes. Outcomes of interest that were obtained for meta-analysis included survival as the primary, and local control as the secondary outcome. Results A total of eight studies involving 976 patients with MBM were selected. Survival was significantly improved for patients receiving BRAF inhibitor plus SRS in comparison to SRS alone as assessed from the time of SRS induction (SRS survival: hazard ratio [HR] 0.67 [0.58–0.79], p <0.00001), from the time of brain metastasis diagnosis (BM survival: HR 0.65 [0.54, 0.78], p < 0.00001), or from the time of primary diagnosis (PD survival: HR 0.74 [0.57–0.95], p = 0.02). Dual therapy was also associated with improved local control, indicating an additive effect of the two treatments (HR 0.53 [0.31–0.93], p=0.03). Intracranial hemorrhage was higher in patients receiving BRAF inhibitors plus SRS than in those receiving SRS alone (OR, 3.16 [1.43–6.96], p = 0.004). Conclusions BRAF inhibitors in conjunction with SRS as local treatment appear to be efficacious. Local brain control and survival improved in patients with MBM receiving dual therapy. Safety assessment would need to be elucidated further as the incidence of intracranial hemorrhage was increased.
Pseudomonas fluorescens DN16 Enhances Cucumber Defense Responses Against the Necrotrophic Pathogen Botrytis cinerea by Regulating Thermospermine Catabolism

Plants can naturally interact with beneficial rhizobacteria to mediate defense responses against foliar pathogen infection. However, the mechanisms of rhizobacteria-mediated defense enhancement remain rarely clear. In this study, beneficial rhizobacterial strain Pseudomonas fluorescens DN16 greatly increased the resistance of cucumber plants against Botrytis cinerea infection. RNA-sequencing analyses showed that several polyamine-associated genes including a thermospermine (TSpm) synthase gene (CsACL5) and polyamine catabolic genes (CsPAO1, CsPAO5, and CsCuAO1) were notably induced by DN16. The associations of TSpm metabolic pathways with the DN16-mediated cucumber defense responses were further investigated. The inoculated plants exhibited the increased leaf TSpm levels compared with the controls. Accordantly, overexpression of CsACL5 in cucumber plants markedly increased leaf TSpm levels and enhanced defense against B. cinerea infection. The functions of TSpm catabolism in the DN16-mediated defense responses of cucumber plants to B. cinerea were further investigated by pharmacological approaches. Upon exposure to pathogen infection, the changes of leaf TSpm levels were positively related to the enhanced activities of polyamine catabolic enzymes including polyamine oxidases (PAOs) and copper amine oxidases (CuAOs), which paralleled the transcription of several defense-related genes such as pathogenesis-related protein 1 (CsPR1) and defensin-like protein 1 (CsDLP1). However, the inhibited activities of polyamine catabolic enzymes abolished the DN16-induced cucumber defense against B. cinerea infection. This was in line with the impaired expression of defense-related genes in the inoculated plants challenged by B. cinerea. Collectively, our findings unraveled a pivotal role of TSpm catabolism in the regulation of the rhizobacteria-primed defense states by mediating the immune responses in cucumber plants after B. cinerea infection.
Optimal Model Mapping for Intravoxel Incoherent Motion MRI

In general, only one diffusion model would be applied to whole field-of-view voxels in the intravoxel incoherent motion-magnetic resonance imaging (IVIM-MRI) study. However, the choice of the applied diffusion model can significantly influence the estimated diffusion parameters. The quality of the diffusion analysis can influence the reliability of the perfusion analysis. This study proposed an optimal model mapping method to improve the reliability of the perfusion parameter estimation in the IVIM study. Six healthy volunteers (five males and one female; average age of 38.3 ± 7.5 years). Volunteers were examined using a 3.0 Tesla scanner. IVIM-MRI of the brain was applied at 17 b-values ranging from 0 to 2,500 s/mm2. The Gaussian model, the Kurtosis model, and the Gamma model were found to be optimal for the CSF, white matter (WM), and gray matter (GM), respectively. In the mean perfusion fraction (fp) analysis, the GM/WM ratios were 1.16 (Gaussian model), 1.80 (Kurtosis model), 1.94 (Gamma model), and 1.54 (Optimal model mapping); in the mean pseudo diffusion coefficient (D*) analysis, the GM/WM ratios were 1.18 (Gaussian model), 1.19 (Kurtosis model), 1.56 (Gamma model), and 1.24 (Optimal model mapping). With the optimal model mapping method, the estimated fp and D* were reliable compared with the conventional methods. In addition, the optimal model maps, the associated products of this method, may provide additional information for clinical diagnosis.
Rock My World: Rewind to a Better Transition to Remote Learning

Students and faculty alike found themselves in tumultuous times as they made the transition from face-to-face to remote learning. As faculty and administrators worked hard to overcommunicate with students in the hopes of keeping them engaged and focused on their academic pursuits, students found their attentions split among school, the Covid-19 health pandemic, and paying bills as many lost their employment. In some cases, the overcommunication led to students ignoring messages as they were completely overwhelmed; at the same time, some students found themselves reverting back to looking for the days of someone telling them what to do every minute of the day. Because faculty, and administrators, were not well prepared to handle the situation, an unevenness in how faculty communicated with students occurred. That is, some faculty withdrew in the same way that students did, and the term essentially ended with students turning in remaining assignments even though no further instruction occurred. Other faculty tried to move their face-to-face class online without taking into consideration the differences between these two channels. Still others tried to create an online course as they went from week to week. The inconsistencies across classes combined with the additional stress students were already experiencing became a recipe for exactly what the administration was trying to avoid—unsuccessful completion of courses and/or students unprepared for the courses that would come after the ones in which they were enrolled that term. The purpose of this study is to examine the experiences and perceptions of students when their classes pivoted from face-to-face to mediated, usually through video conferencing for synchronous or learning management systems for asynchronous. More specifically, we have collected qualitative data that addresses the communication students received from their instructors, what they believed instructors did successfully, what instructors could have done better, and the advice they would offer to instructors who found themselves in a similar crisis situation in the future.