Machine learning-based prediction of in-hospital mortality in patients with pneumonic chronic obstructive pulmonary disease exacerbations

While linear regression and LASSO models have been established for predicting in-hospital mortality, there is currently no validated clinical prediction algorithm to predict in-hospital mortality for patients with chronic obstructive pulmonary disease (COPD) exacerbations using machine learning. Thus, we will evaluate the BAP-65 and CURB-65, and construct a novel prediction model using the random forest (RF) technique. A dataset of 1,418 patients with COPD exacerbations was collected. Age, gender, mental status, vital signs, and laboratory results were all taken into account for predictors. The categorical outcome variable was hospital-based mortality of people over 65 years. The dataset was divided randomly into a training dataset (70%) and a testing dataset (30%). We trained three prediction models, BAP-65, CURB-65, and the RF model, estimated the area under the receiver operating characteristic curve (AUROC) for the entire dataset. We also conducted a comparison of the AUROC values using the Delong test. A total of 658 individuals with COPD acute exacerbations were enrolled. Our analysis using the receiver operating characteristic curve demonstrated that the RF model exhibited excellent performance, with an AUROC of 0.80 (95% confidence interval: 0.75-0.84). In comparison, the BAP-65 prediction model yielded an AUROC of 0.72 (0.68-0.75), while the CURB-65 prediction model achieved an AUROC of 0.69 (0.67-0.73). The RF model demonstrated superior predictive capabilities than the BAP-65 and CURB-65 models in predicting in-hospital mortality. The results further highlighted significant factors for predicting in-hospital mortality, including blood eosinophil count, systolic blood pressure, and prior history of asthma.</p

The paraffin section of formalin-fixed temporal lobe biopsy in low and high magnification view.

<p>(A) Low-magnification view of the paraffin portion of the formalin-fixed temporal lobe biopsy shows an immature <i>Schistosoma</i> egg surrounded by granuloma and glial cells. (B) High magnification shows two eggs with shells displaying the diagnostic acentric spine shape of immature <i>Schistosoma</i> eggs. Histiocytes near the eggs highlight that the nuclei of <i>Schistosoma</i> are smaller than those of the host’s cells.</p

Multifunctional Electrochemical Platforms Based on the Michael Addition/Schiff Base Reaction of Polydopamine Modified Reduced Graphene Oxide: Construction and Application

In this paper, a new strategy for the construction of multifunctional electrochemical detection platforms based on the Michael addition/Schiff base reaction of polydopamine modified reduced graphene oxide was first proposed. Inspired by the mussel adhesion proteins, 3,4-dihydroxyphenylalanine (DA) was selected as a reducing agent to simultaneously reduce graphene oxide and self-polymerize to obtain the polydopamine-reduced graphene oxide (PDA-rGO). The PDA-rGO was then functionalized with thiols and amines by the reaction of thiol/amino groups with quinine groups of PDA-rGO via the Michael addition/Schiff base reaction. Several typical compounds containing thiol and/or amino groups such as 1-[(4-amino)­phenylethynyl] ferrocene (Fc-NH₂), cysteine (cys), and glucose oxidase (GOx) were selected as the model molecules to anchor on the surface of PDA-rGO using the strategy for construction of multifunctional electrochemical platforms. The experiments revealed that the composite grafted with ferrocene derivative shows excellent catalysis activity toward many electroactive molecules and could be used for individual or simultaneous detection of dopamine hydrochloride (DA) and uric acid (UA), or hydroquinone (HQ) and catechol (CC), while, after grafting of cysteine on PDA-rGO, simultaneous discrimination detection of Pb²⁺ and Cd²⁺ was realized on the composite modified electrode. In addition, direct electron transfer of GOx can be observed when GOx-PDA-rGO was immobilized on glassy carbon electrode (GCE). When glucose was added into the system, the modified electrode showed excellent electric current response toward glucose. These results inferred that the proposed multifunctional electrochemical platforms could be simply, conveniently, and effectively regulated through changing the anchored recognition or reaction groups. This study would provide a versatile method to design more detection or biosensing platforms through a chemical reaction strategy in the future

Comparison of brain imaging before and after treatment.

<p>(A) MRI before surgery showing an intracranial occupying lesion in the left occipital lobe, with edema and mottled nodular linear enhancement in the surrounding region. (B) CT result three months after surgery showing the disappearance of the nidus and fading of the edema. CT, computed tomography.</p

The inhibition of GSK3β attenuates cell proliferation, induces apoptosis, arrests cells in GO/G1 phase and increases cell invasiveness.

<p>(<b>A</b>) The CCK-8 test showed that the inhibition of GSK3β suppressed the proliferation of the NSCLC cell lines <i>in vitro</i>. *<i>P</i><0.001. (<b>B</b>) <i>In vivo</i>: As described in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091231#pone-0091231-g003" target="_blank">Figure 3C</a>, the xenograft models were developed in nude mice. Each group consisted of 6 animals. Tumors were observed every 3 days for 4 weeks. The xenograft tumors of mice in the KD group grew significantly slower (as determined by the tumor volume) over the entire observation period. *<i>P</i><0.001. (<b>C</b>) Comparison of the isolated xenograft tumors. The image shows that tumors isolated from the KD group were smaller and lighter than the tumors from the control group. The data are expressed as the means ± SD, n = 6. *<i>P</i><0.001. (<b>D</b>) Representative image of Ki-67 IHC of a tumor xenograft viewed under a microscope. To calculate the Ki-67 LI, cells with brown-stained nuclei were considered positive, indicating active proliferation (magnification × 400). The data are expressed as the means ± SD, *<i>P</i><0.001. (<b>E</b>) Cell cycle analysis at 72 h after transfection. The results suggest that the inhibition of GSK3β resulted in G1/S arrest in A549 and SK-MES-1 cells and changed the proportions of the cell population in different phases of the cell cycle. The data are presented as the means ± S.D. from 3 independent experiments performed in triplicate. *<i>P</i><0.001. (<b>F</b>) By flow cytometry, the apoptotic analysis results indicated that the inhibition of GSK3β greatly increased the apoptotic rate of NSCLC cells (except for A549 cells) <i>in vitro</i>. *<i>P</i><0.001, ▴<i>P</i>>0.05. (<b>G</b>) The results of the TUNEL assay for xenograft tumors suggested that the inhibition of GSK3β increased the apoptotic rate of A549 cells <i>in vivo</i> (magnification × 400). The data are expressed as the means ± SD, *<i>P</i><0.001. (<b>H</b>) Transwell assays showing that the inhibition of GSK3β <i>in vitro</i> significantly decreased the invasiveness of NSCLC cells. The data are expressed as the means ± S.D. *<i>P</i><0.001.</p

GSK3β is overexpressed and active in NSCLC tumor tissues.

<p>(<b>A</b>) Typical IHC staining images of human NSCLC tumor and normal lung tissue (magnification × 200). (<b>B</b>) Western blotting assays confirmed that in paired normal/tumor tissues from NSCLC cancer patients, higher expression levels of GSK3β in tumors were found compared with their normal counterparts. The experiments were repeated 3 times, and the data are presented as the mean ± SD. *<i>P</i><0.001. (<b>C</b>) Phosphorylated glycogen synthase (pGS), a substrate of GSK3β, was detected in these NSCLC cell lines, except for H292.</p

Comprehensive Molecular Diagnosis of Bardet-Biedl Syndrome by High-Throughput Targeted Exome Sequencing

<div><p>Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder with significant genetic heterogeneity. BBS is linked to mutations in 17 genes, which contain more than 200 coding exons. Currently, BBS is diagnosed by direct DNA sequencing for mutations in these genes, which because of the large genomic screening region is both time-consuming and expensive. In order to develop a practical method for the clinic diagnosis of BBS, we have developed a high-throughput targeted exome sequencing (TES) for genetic diagnosis. Five typical BBS patients were recruited and screened for mutations in a total of 144 known genes responsible for inherited retinal diseases, a hallmark symptom of BBS. The genomic DNA of these patients and their families were subjected to high-throughput DNA re-sequencing. Deep bioinformatics analysis was carried out to filter the massive sequencing data, which were further confirmed through co-segregation analysis. TES successfully revealed mutations in BBS genes in each patient and family member. Six pathological mutations, including five novel mutations, were revealed in the genes <i>BBS2</i>, <i>MKKS</i>, <i>ARL6</i>, <i>MKS1</i>. This study represents the first report of targeted exome sequencing in BBS patients and demonstrates that high-throughput TES is an accurate and rapid method for the genetic diagnosis of BBS.</p></div

Stable silencing of GSK3β by shRNA in NSCLC cells.

<p>(<b>A</b>) GSK3β-specific shRNAs were transfected into NSCLC cells with lentiviral vector, and cells were harvested and counted 5 days after transfection. Real-time PCR indicated that interference by shRNA effectively knocked down the mRNA expression of GSK3β in NSCLC cells. (<b>B</b>) The cells were harvested and counted 7 days after transfection. Western blot shows the efficiency of protein silencing by shRNA. (<b>C</b>) After treatment with the GSK3 shRNA(KD group), the negative control shRNA (NC group) or normal saline (CON group), the A549 cells (1×10⁶/ml) were injected into the backs of nude mice. Four weeks later, xenograft tumors were isolated and immunohistochemical stained. The results verified the sustained reduced levels of GSK3β in the KD group relative to the control groups. Arrows indicate positive staining in the cytoplasm of tumor cells (magnification × 400). The experiments were repeated 3 times, and the data are expressed as the mean ± SD. *<i>P</i><0.001.</p

Positive expression of GSK3β is associated with poor prognosis for NSCLC.

<p>(<b>A</b>) In the entire group, patients with positive GSK3β expression had shorter survival times, <i>P</i> = 0.006. <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0091231#pone-0091231-g002" target="_blank">Figure 2B-D</a> shows the survival analysis for the subgroups. (<b>B</b>) In the lower differentiation subgroup, patients with positive GSK3β expression had significantly shorter survival times, <i>P</i> = 0.013. (<b>C</b>) In the T1+T2 subgroup, patients with positive GSK3β expression had significantly shorter survival times, <i>P</i> = 0.003. (<b>D</b>) In the N0+N1 subgroup, patients with positive GSK3β expression had significantly shorter survival times, <i>P</i> = 0.010. (E) Patients in the M0 subgroup with positive GSK3β expression had significantly shorter survival times, <i>P</i> = 0.008. Kaplan-Meier curves for the investigated proteins were used to compare the positive (<i>dashed lines</i>) and negative phenotypes (<i>solid lines</i>)<b>.</b></p

The Expressions of GSK3β in NSCLC and Normal Lung Tissue.

<p>Abbreviations: P, positive; N, negative. * Statistical significant.</p