A deep learning model for predicting multidrug-resistant organism infection in critically ill patients.

BACKGROUND: This study aimed to apply the backpropagation neural network (BPNN) to develop a model for predicting multidrug-resistant organism (MDRO) infection in critically ill patients. METHODS: This study collected patient information admitted to the intensive care unit (ICU) of the Affiliated Hospital of Qingdao University from August 2021 to January 2022. All patients enrolled were divided randomly into a training set (80%) and a test set (20%). The least absolute shrinkage and selection operator and stepwise regression analysis were used to determine the independent risk factors for MDRO infection. A BPNN model was constructed based on these factors. Then, we externally validated this model in patients from May 2022 to July 2022 over the same center. The model performance was evaluated by the calibration curve, the area under the curve (AUC), sensitivity, specificity, and accuracy. RESULTS: In the primary cohort, 688 patients were enrolled, including 109 (15.84%) MDRO infection patients. Risk factors for MDRO infection, as determined by the primary cohort, included length of hospitalization, length of ICU stay, long-term bed rest, antibiotics use before ICU, acute physiology and chronic health evaluation II, invasive operation before ICU, quantity of antibiotics, chronic lung disease, and hypoproteinemia. There were 238 patients in the validation set, including 31 (13.03%) MDRO infection patients. This BPNN model yielded good calibration. The AUC of the training set, the test set and the validation set were 0.889 (95% CI 0.852-0.925), 0.919 (95% CI 0.856-0.983), and 0.811 (95% CI 0.731-0.891), respectively. CONCLUSIONS: This study confirmed nine independent risk factors for MDRO infection. The BPNN model performed well and was potentially used to predict MDRO infection in ICU patients.

Research progress of LINE-1 in the diagnosis, prognosis, and treatment of gynecologic tumors.

The retrotransposon known as long interspersed nuclear element-1 (LINE-1), which is currently the sole autonomously mobile transposon in the human genome, can result in insertional mutations, chromosomal rearrangements, and genomic instability. In recent years, numerous studies have shown that LINE-1 is involved in the development of various diseases and also plays an important role in the immune regulation of the organism. The expression of LINE-1 in gynecologic tumors suggests that it is expected to be an independent indicator for early diagnosis and prognosis, and also, as a therapeutic target, LINE-1 is closely associated with gynecologic tumor prognosis. This article discusses the function of LINE-1 in the diagnosis, treatment, and prognosis of ovarian, cervical, and endometrial malignancies, as well as other gynecologic malignancies. It offers fresh perspectives on the early detection of tumors and the creation of novel anti-tumor medications.

Effects of the theory of planned behavior and nudge strategy-based intervention on the adherence to anticoagulation treatment in patients with non-valvular atrial fibrillation.

BACKGROUND: Non-valvular atrial fibrillation is associated with the incidence of thromboembolism. Current guidelines recommend preferential use of novel oral anticoagulants (NOAC) in patients with nonvalvular atrial fibrillation. Oral anticoagulation medication adherence rate was relatively low among discharged patients with non-valvular atrial fibrillation. AIM: To investigate the effects of the anticoagulation programs based on the theory of planned behavior and nudge strategy among patients with non-valvular atrial fibrillation. METHODS: 130 patients with non-valvular atrial fibrillation were randomized to the intervention group or control group, 72 patients in the intervention group, and 58 patients in the control group with a 6-month follow-up. Medication adherence, intention, attitude, perceived behavioral control and subjective norm and quality of life were assessed. RESULTS: There were significantly differences in the intention, attitude and subjective norm between the two groups at one month, three months and six months follow-up (P <0.01). There were significantly differences in the perceived behavioral control between the two groups at three months and six months follow-up (P <0.01). The medication adherence scale score was higher in the intervention group than in the control group at three months and six months follow-up. However, there were no differences in quality of life between the two groups at one month, three months and six months follow-up. CONCLUSIONS: The program based on the theory of planned behavior and nudge strategy can improve medication adherence in patients with non-valvular atrial fibrillation.

Hemostatic effects of FmocF-ADP hydrogel consisted of Fmoc-Phenylalanine and ADP.

During trauma and surgery, bleeding is a major concern. One of the crucial strategies for hemostasis is the use of biological hemostatic material. Herein, we reported an amino acid-based hydrogel FmocF-ADP hydrogel, which consisted of N-[(9H-fluoren-9-ylmethoxy) carbonyl]-3-phenyl-L-alanine (FmocF) and adenosine diphosphate (ADP) sodium solution. The hydrogel was created by FmocF self-assembling to nanofiber in ADP sodium solution and then cross-linking to hydrogel. FmocF-ADP hydrogel showed good in vitro coagulation activity as measured by whole blood clotting assays, platelet clotting assays, platelet activation assays, and platelet adhesion assays. Further, it was noted to reveal an exceptional in vivo hemostatic effect in a mouse liver bleeding model. Together with the previous report of the good biocompatibility and antimicrobial activity of FmocF hydrogel, our study would extend the biomedical application of FmocF hydrogel. In conclusion, the present study would provide a constructive strategy for the development of new antimicrobial and hemostatic materials or develop a potential hemostatic material.

Advances in Exosomal microRNAs and Proteins in Ovarian Cancer Diagnosis, Prognosis, and Treatment.

Late diagnosis, postoperative recurrence, and chemotherapy resistance are the main causes of the high mortality rate in ovarian cancer (OC). Understanding the molecular mechanisms in the pathogenesis and progression of OC may contribute to discovering new tumor biomarkers and therapeutic targets for OC. Exosomes are small extracellular vesicles derived from different types of cells that carry cargos, including nucleic acids, proteins, and lipids, and are pivotal mediators of intercellular communication in the tumor microenvironment. There is emerging evidence that exosomal proteins and nucleic acids play pivotal roles in facilitating the progression and drug resistance of OC. Identification of these factors may aid in the future diagnosis of OC. Furthermore, they also have promising value as OC therapeutic targets that can improve the prognosis. In the current review, we summarize the progress of exosomal research in OC, especially highlighting the most updated roles of exosomal microRNAs and proteins in the diagnosis, prognosis, therapy, and drug resistance of OC in order to facilitate future studies in this area.

Adeno-associated virus vector-mediated gene therapy for the treatment of ovarian cancer: a literature review.

Background and Objective: The adeno-associated virus (AAV) is a member of the Parvoviridae family and has emerged as one of the most popular and promising approaches for gene therapy due to its low toxicity, low immunogenicity, and excellent safety after optimization. Advances in gene therapy methods have allowed novel treatments such as using AAV to knock out or repair target genes. AAV-mediated gene therapy has been used in numerous tumor studies, including lymphatic metastasis of prostate cancer, liver cancer, and renal cell carcinoma in mice. Ovarian cancer is an extremely aggressive malignancy which is prone to recurrence, and AAV vector-based gene therapy may be a potential treatment strategy. Methods: Herein, we reviewed the current research to provide an update on the role of AAV-mediated gene therapy in tumor research, especially in ovarian cancer. To find recent developments in pertinent research, we examined the PubMed database. Key Content and Findings: AAV vectors may produce steady and effective gene expression without becoming harmful, making it a viable gene delivery technique. AAV-based gene therapy products have been widely used in preclinical research and some have achieved marketing approval. Conclusions: Due to its affinity for various organs, reliable integration, and long-lasting expression, certain AAV serotypes have been widely used in gene therapy. However, there are also some challenges. Extensive research on the role of AAV in disease and gene therapy has shown great potential. Herein, we examined the literature to better understand the function of the AAV in tumor research, particularly in ovarian cancer research.

GAN Compression: Efficient Architectures for Interactive Conditional GANs.

Conditional Generative Adversarial Networks (cGANs) have enabled controllable image synthesis for many vision and graphics applications. However, recent cGANs are 1-2 orders of magnitude more compute-intensive than modern recognition CNNs. For example, GauGAN consumes 281G MACs per image, compared to 0.44G MACs for MobileNet-v3, making it difficult for interactive deployment. In this work, we propose a general-purpose compression framework for reducing the inference time and model size of the generator in cGANs. Directly applying existing compression methods yields poor performance due to the difficulty of GAN training and the differences in generator architectures. We address these challenges in two ways. First, to stabilize GAN training, we transfer knowledge of multiple intermediate representations of the original model to its compressed model and unify unpaired and paired learning. Second, instead of reusing existing CNN designs, our method finds efficient architectures via neural architecture search. To accelerate the search process, we decouple the model training and search via weight sharing. Experiments demonstrate the effectiveness of our method across different supervision settings, network architectures, and learning methods. Without losing image quality, we reduce the computation of CycleGAN by 21×, Pix2pix by 12×, MUNIT by 29×, and GauGAN by 9×, paving the way for interactive image synthesis.

The effect of IL-10 genetic variation and interleukin 10 serum levels on Crohn's disease susceptibility in a New Zealand population.

Interleukin (IL)-10 has important effects in immunoregulation and inflammation, and previous studies have provided evidence for the involvement of IL-10 in the pathogenesis of Crohn's disease (CD). In this study, we investigated whether genetic variants of the IL-10 gene were associated with CD in a New Zealand population. Three single nucleotide polymorphisms (SNPs) in the promoter region of IL-10 (rs1800871, rs1800872, and rs1800896) and a flanking SNP, rs3024505, were genotyped in a well-characterized New Zealand dataset consisting of 342 CD cases and 610 controls. Furthermore, we measured serum IL-10 levels in a number of the CD patients and controls and examined whether a relationship existed between these polymorphisms and serum IL-10 levels. We demonstrated an association with CD for SNPs rs3024505 and rs1800896, and phenotypic analysis indicated an association of rs3024505 with an early age at first diagnosis, stricturing CD behavior, and requirement for bowel resection. We also observed that IL-10 concentration was significantly higher in CD patients than in the controls and that the T allele of rs1800896, the A allele of rs1800871, and the T allele of rs1800872 were associated with increased serum IL-10 levels.

Skeletal phenotype of the leptin receptor-deficient db/db mouse.

Leptin, a major hormonal product of the adipocyte, regulates appetite and reproductive function through its hypothalamic receptors. The leptin receptor is present in osteoblasts and chondrocytes, and previously we have shown leptin to be an anabolic bone factor in vitro, stimulating osteoblast proliferation and inhibiting osteoclastogenesis. Leptin increases bone mass and reduces bone fragility when administered peripherally but also can indirectly reduce bone mass when administered into the central nervous system. However, data from animal models deficient in either leptin (ob/ob) or its receptor (db/db) remain contradictory. We compared the bone phenotype of leptin receptor-deficient (db/db) and wild-type mice using micro-computed tomographic (µCT) analysis of the proximal tibias and vertebrae. In the tibia, db/db mice had reduced percent trabecular bone volume (13.0 ± 1.62% in wild-type versus 6.01 ± 0.601% in db/db mice, p = .002) and cortical bone volume (411 ± 21.5 µm(3) versus 316 ± 3.53 µm(3), p = .0014), trabecular thickness (48.4 ± 001.07 µm versus 45.1 ± 0.929 µm, p = .041) and trabecular number (2.68 ± 0.319 mm(-1) versus 1.34 ± 0.148 mm(-1), p = .0034). In the fifth lumbar vertebral body, the trabecular thickness and cortical thickness were decreased in the db/db versus wild-type mice (0.053 ± 0.0011 mm versus 0.047 ± 0.0013 mm, p = .0002 and 0.062 ± 0.00054 mm versus 0.056 ± 0.0009 mm, p = .0001), respectively, whereas the trabecular and cortical percent bone volume and trabecular number did not reach significance. The total (endosteal and periosteal) cortical perimeter (12.2 ± 0.19 mm versus 13.2 ± 0.30 mm, p = .01) was increased. The serum osteocalcin levels were reduced in the db/db mice, suggesting that bone formation rates are decreased. The material properties of db/db femurs were determined by three-point bending and nanoindentation, showing decreased bone strength (13.3 ± 0.280 N versus 7.99 ± 0.984 N, p = .0074) and material stiffness (28.5 ± 0.280 GPa versus 25.8 ± 0.281 GPa, p < .0001). These results demonstrate that bone mass and strength are reduced in the absence of leptin signaling, indicating that leptin acts in vivo as an anabolic bone factor. This concurs with results of in vitro studies and of peripheral leptin administration in vivo and suggests that leptin's direct effects on bone cells are likely to override its actions via the central nervous system.

The probiotic Escherichia coli Nissle 1917 reduces pathogen invasion and modulates cytokine expression in Caco-2 cells infected with Crohn's disease-associated E. coli LF82.

Increased numbers of adherent invasive Escherichia coli (AIEC) have been found in Crohn's disease (CD) patients. In this report, we investigate the potential of the probiotic Escherichia coli Nissle 1917 (EcN) to reduce features associated with AIEC pathogenicity in an already established infection with AIEC reference strain LF82.

Quinazolines as novel anti-inflammatory histone deacetylase inhibitors.

Histone deacetylase (HDAC) inhibitors regulate many biological responses, including anti-inflammatory and anti-cancer effects. We sought to identify novel classes of HDAC inhibitors from in-house compound libraries. Initially, compounds from 26 different structural classes that showed anti-inflammatory effects in a pre-screen in HEK293T cells were tested in vitro for HDAC inhibition, using a commercial fluorescence assay. The known HDAC inhibitors suberoylanilide hydroxamic acid (SAHA) and trichostatin A (TSA) were used as positive controls. Examples of three different structural classes (anilinoacridines, phenylpyrrolocarbazoles and benzofurylquinazolines) showed significant inhibition in the HDAC assay, and small subsets of these were also evaluated, seeking initial structure-activity relationships (SAR) for each class. Several of the most effective compounds from this HDAC screen were evaluated for their effects on the expression of the pro-inflammatory gene, IL1-alpha, and the cancer-related genes, p53, p21, E-cadherin and C-MYC. While the benzofurylquinazolines increased the expression level of the pro-inflammatory gene IL1-alpha as well as p21 and p53 in the PC3 cell line, a phenylpyrrolocarbazole had the converse effect on p53 expression. Several of the compounds showed in vitro HDAC inhibition ability in PC3, HCT116 and NIH-3T3 cell lines comparable to that of SAHA.