Data_Sheet_1_Automated Machine Learning Model Development for Intracranial Aneurysm Treatment Outcome Prediction: A Feasibility Study.docx

Background: The prediction of aneurysm treatment outcomes can help to optimize the treatment strategies. Machine learning (ML) has shown positive results in many clinical areas. However, the development of such models requires expertise in ML, which is not an easy task for surgeons.Objectives: The recently emerged automated machine learning (AutoML) has shown promise in making ML more accessible to non-computer experts. We aimed to evaluate the feasibility of applying AutoML to develop the ML models for treatment outcome prediction.Methods: The patients with aneurysms treated by endovascular treatment were prospectively recruited from 2016 to 2020. Treatment was considered successful if angiographic complete occlusion was achieved at follow-up. A statistical prediction model was developed using multivariate logistic regression. In addition, two ML models were developed. One was developed manually and the other was developed by AutoML. Three models were compared based on their area under the precision-recall curve (AUPRC) and area under the receiver operating characteristic curve (AUROC).Results: The aneurysm size, stent-assisted coiling (SAC), and posterior circulation were the three significant and independent variables associated with treatment outcome. The statistical model showed an AUPRC of 0.432 and AUROC of 0.745. The conventional manually trained ML model showed an improved AUPRC of 0.545 and AUROC of 0.781. The AutoML derived ML model showed the best performance with AUPRC of 0.632 and AUROC of 0.832, significantly better than the other two models.Conclusions: This study demonstrated the feasibility of using AutoML to develop a high-quality ML model, which may outperform the statistical model and manually derived ML models. AutoML could be a useful tool that makes ML more accessible to the clinical researchers.</p

Additional file 3: of TSG-6 attenuates inflammation-induced brain injury via modulation of microglial polarization in SAH rats through the SOCS3/STAT3 pathway

Microglial phenotypic characteristics after SAH induction. Photomicrograph of microglia(red) and DAPI(blue) double immunostaining in a coronal section of the whole brain in sham and SAH groups. n = 5 in each group. Scale bar = 2000 μm. (TIF 1507 kb

Additional file 2: of TSG-6 attenuates inflammation-induced brain injury via modulation of microglial polarization in SAH rats through the SOCS3/STAT3 pathway

Effects of rh-TSG-6 on neuronal degenerating at 72 h after subarachnoid hemorrhage (SAH). Representative microphotographs and quantitative analysis of Fluoro-Jade C staining (FJC)-positive neurons in the sham, SAH, vehicle and rh-TSG-6 groups at 72 h following operation. n = 6 in each group. Data are expressed as mean ± SD. ***P < 0.001. Scale bar = 20 μm. (TIF 856 kb

Image_1_Silencing of SNHG12 Enhanced the Effectiveness of MSCs in Alleviating Ischemia/Reperfusion Injuries via the PI3K/AKT/mTOR Signaling Pathway.tif

Previous studies have reported that the long non-coding RNA SNHG12 (lncRNA SNHG12) plays a critical role in regulating the function of mesenchymal stem cells (MSCs); however, the effect of lncRNA SNHG12 on MSCs in injured brain tissue has rarely been reported. We studied the effect and mechanism of lncRNA SNHG12-modified mesenchymal stem cells (MSCs) in treating brain injuries caused by ischemia/reperfusion (I/R). I/R treated rat brain microvascular endothelial cells (BMECs) were co-cultured with MSCs or I/R pretreated MSCs. Next, BMEC proliferation was detected by using CCK-8 and EdU assays, and cell apoptosis was determined by using flow cytometry and the Hoechst staining method. Autophagy of BMECs was determined using immunofluorescence and expression of associated pathway proteins were measured by western blotting. Moreover, BMEC proliferation, apoptosis, and autophagy were also determined after the BMECs had been co-cultured with shSNHG12-MSCs. In addition, a rat model of middle cerebral artery occlusion (MCAO) was used to further confirm the findings obtained with cells. I/R treatment significantly decreased the proliferation of BMECs, but increased their levels of SNHG12 expression, apoptosis, and autophagy. However, co-culturing of BMECs with MSCs markedly alleviated the reduction in BMEC proliferation and the increases in BMEC apoptosis and autophagy, as well as the phosphorylation of PI3K, AKT, and mTOR proteins in BMECs that had been induced by I/R. Furthermore, shSNHG12 remarkably enhanced the effects of MSCs. In addition, an injection MSCs reduced the infarct areas and rates of cell apoptosis in MACO rats, and reduced the phosphorylation of PI3K, AKT, and mTOR proteins. Moreover, shSNHG12 enhanced the ameliorative effect of MSCs in treating brain injuries in the MACO rats. In conclusion, silencing of SNHG12 enhanced the effects of MSCs in reducing apoptosis and autophagy of BMECs by activating the PI3K/AKT/mTOR signaling pathway.</p

Data_Sheet_1_Class 1 integrons and multiple mobile genetic elements in clinical isolates of the Klebsiella pneumoniae complex from a tertiary hospital in eastern China.zip

BackgroundThe emergence of highly drug-resistant K. pneumoniae, has become a major public health challenge. In this work, we aim to investigate the diversity of species and sequence types (STs) of clinical Klebsiella isolates and to characterize the prevalence and structure of class 1 integrons.MethodsBased on the whole genome sequencing, species identification was performed by 16S rRNA gene homology and average nucleotide identity (ANI) analysis. STs were determined in accordance with the international MLST schemes for K. pneumoniae and K. variicola. Integron characterization and comparative genomic analysis were performed using various bioinformatic tools.ResultsSpecies identification showed that the 167 isolates belonged to four species: K. pneumoniae, K. variicola subsp. variicola, K. quasipneumoniae and K. aerogenes. Thirty-six known and 5 novel STs were identified in K. pneumoniae, and 10 novel STs were identified in K. variicola subsp. variicola. Class 1 integrons were found in 57.49% (96/167) of the isolates, and a total of 169 resistance gene cassettes encoding 19 types of resistance genes, including carbapenem resistance gene (blaIPM-4) and class D β-lactamases gene (blaOXA-1 and blaOXA-10), were identified. Among the 17 complete genomes, 29 class 1 integrons from 12 groups were found, only 1 group was encoded on chromosomes. Interestingly, one plasmid (pKP167-261) carrying two copies of approximately 19-kb IS26-Int1 complex resistance region that contains an integron and a multidrug resistance gene fragment.ConclusionThe results of this work demonstrated that the species and STs of the clinical Klebsiella isolates were more complex by the whole genome sequence analysis than by the traditional laboratory methods. Finding of the new structure of MGEs related to the resistance genes indicates the great importance of deeply exploring the molecular mechanisms of bacterial multidrug resistance.</p

Additional file 1: of Mesenchymal stem cells alleviate the early brain injury of subarachnoid hemorrhage partly by suppression of Notch1-dependent neuroinflammation: involvement of Botch

The experimental design and schematic diagram. Six experiments were conducted in our study. The schematic diagram showed the potential mechanism of BMSCs mediated anti-inflammatory effects on EBI after SAH. Briefly, Notch1 receptors are expressed on microglial cells. Following SAH ictus, Notch1 is activated by proteolytic cleavage, thus releasing NICD into the cytoplasm, which in turn enhances NF-ÎşB activation. In addition, NICD can translocate to the nucleus and combine with RBP-JÎş to generate co-activator complex to promote the transcription of NF-ÎşB and augment the inflammatory response. Botch efficiently antagonized the proteolytic cleavage and activation of the Notch1 receptor. BMSCs treatment upregulated Botch in brain tissue and alleviated the Notch1-driven microglia-mediated inflammatory response. (PDF 88 kb

Additional file 2: of Mesenchymal stem cells alleviate the early brain injury of subarachnoid hemorrhage partly by suppression of Notch1-dependent neuroinflammation: involvement of Botch

Co-staining of NeuN and CD68 as well as NueN and Iba1 at 24 h post-SAH. Representative images of double immunofluorescence staining for NeuN and CD68 or Iba1, results showed that Iba1- and CD68-positive cells were increased, but the numbers of NeuN-positive neurons were decreased in the cortex of left hemisphere after 24 h SAH. (TIF 8397 kb

Additional file 3: of Mesenchymal stem cells alleviate the early brain injury of subarachnoid hemorrhage partly by suppression of Notch1-dependent neuroinflammation: involvement of Botch

Effects of DAPT, Notch1 siRNA and BMSCs on (Nuclear factor-κB) NF-κB phosphorylation after SAH. DAPT administration inhibited p-NF-κB expression at 24 h post-SAH. Representative western blot bands (A) and quantification of p-NF-κB in the left cortex (B) indicate that DAPT inhibited NF-κB phosphorylation at 24 h post-SAH; n = 6 in each group; data are expressed as the mean ± SEM. *P < 0.05 versus Sham, ###P < 0.001 versus SAH + DMSO group. Notch1 siRNA injection inhibited phosphorylation of NF-κB at 24 h post-SAH. Representative western blot bands (C) and quantitative analyses of p-NF-κB expression in the left cortex (D) show that knockdown Notch1 inhibited NF-κB phosphorylation at 24 h post-SAH; n = 6 in each group; data are expressed as the mean ± SEM. *P < 0.05 versus Sham, ###P < 0.001 versus SAH + Scramble siRNA group. BMSCs treatment suppressed NF-κB phosphorylation at 24 and 72 h post-SAH. Western blot data showed that BMSCs significantly suppressed the phosphorylation of NF-κB (E and F) at 24 and 72 h post-SAH; n = 6 in each group; data are expressed as the mean ± SEM. *P < 0.05 versus Sham, #P < 0.05 versus SAH + PBS group. (TIF 4601 kb

Image_2_Adiponectin Ameliorates GMH-Induced Brain Injury by Regulating Microglia M1/M2 Polarization Via AdipoR1/APPL1/AMPK/PPARγ Signaling Pathway in Neonatal Rats.tif

Adiponectin (APN), a fat-derived plasma hormone, is a classic anti-inflammatory agent. Multiple studies have demonstrated the beneficial role of APN in acute brain injury, but the effect of APN in germinal matrix hemorrhage (GMH) is unclear, and the underlying molecular mechanisms remain largely undefined. In the current study, we used a GMH rat model with rh-APN treatment, and we observed that APN demonstrated a protective effect on neurological function and an inhibitory effect on neuroinflammation after GMH. To further explore the underlying mechanisms of these effects, we found that the expression of Adiponectin receptor 1 (AdipoR1) primarily colocalized with microglia and neurons in the brain. Moreover, AdiopR1, but not AdipoR2, was largely increased in GMH rats. Meanwhile, further investigation showed that APN treatment promoted AdipoR1/APPL1-mediated AMPK phosphorylation, further increased peroxisome proliferator-activated receptor gamma (PPARγ) expression, and induced microglial M2 polarization to reduce the neuroinflammation and enhance hematoma resolution in GMH rats. Importantly, either knockdown of AdipoR1, APPL1, or LKB1, or specific inhibition of AMPK/PPARγ signaling in microglia abrogated the protective effect of APN after GMH in rats. In all, we propose that APN works as a potential therapeutic agent to ameliorate the inflammatory response following GMH by enhancing the M2 polarization of microglia via AdipoR1/APPL1/AMPK/PPARγ signaling pathway, ultimately attenuating inflammatory brain injury induced by hemorrhage.</p

Image_3_Adiponectin Ameliorates GMH-Induced Brain Injury by Regulating Microglia M1/M2 Polarization Via AdipoR1/APPL1/AMPK/PPARγ Signaling Pathway in Neonatal Rats.tif

Adiponectin (APN), a fat-derived plasma hormone, is a classic anti-inflammatory agent. Multiple studies have demonstrated the beneficial role of APN in acute brain injury, but the effect of APN in germinal matrix hemorrhage (GMH) is unclear, and the underlying molecular mechanisms remain largely undefined. In the current study, we used a GMH rat model with rh-APN treatment, and we observed that APN demonstrated a protective effect on neurological function and an inhibitory effect on neuroinflammation after GMH. To further explore the underlying mechanisms of these effects, we found that the expression of Adiponectin receptor 1 (AdipoR1) primarily colocalized with microglia and neurons in the brain. Moreover, AdiopR1, but not AdipoR2, was largely increased in GMH rats. Meanwhile, further investigation showed that APN treatment promoted AdipoR1/APPL1-mediated AMPK phosphorylation, further increased peroxisome proliferator-activated receptor gamma (PPARγ) expression, and induced microglial M2 polarization to reduce the neuroinflammation and enhance hematoma resolution in GMH rats. Importantly, either knockdown of AdipoR1, APPL1, or LKB1, or specific inhibition of AMPK/PPARγ signaling in microglia abrogated the protective effect of APN after GMH in rats. In all, we propose that APN works as a potential therapeutic agent to ameliorate the inflammatory response following GMH by enhancing the M2 polarization of microglia via AdipoR1/APPL1/AMPK/PPARγ signaling pathway, ultimately attenuating inflammatory brain injury induced by hemorrhage.</p