Rainfall Reliability Evaluation for Stability of Municipal Solid Waste Landfills on Slope

[[abstract]]A method to assess the reliability for the stability of municipal solid waste (MSW) landfills on slope due to rainfall infiltration is proposed. Parameter studies are first done to explore the influence of factors on the stability of MSW. These factors include rainfall intensity, duration, pattern, and the engineering properties of MSW. Then 100 different combinations of parameters are generated and associated stability analyses of MSW on slope are performed assuming that each parameter is uniform distributed around its reason ranges. In the following, the performance of the stability of MSW is interpreted by the artificial neural network (ANN) trained and verified based on the aforementioned 100 analysis results. The reliability for the stability of MSW landfills on slope is then evaluated and explored for different rainfall parameters by the ANN model with first-order reliability method (FORM) and Monte Carlo simulation (MCS).[[incitationindex]]SCI[[booktype]]紙

Effect of adjunctive ranitidine for antipsychotic-induced weight gain: A systematic review of randomized placebo-controlled trials

This study was a meta-analysis of randomized controlled trials (RCTs) of ranitidine as an adjunct for antipsychotic-induced weight gain in patients with schizophrenia. RCTs reporting weight gain or metabolic side effects in patients with schizophrenia were included. Case reports/series, nonrandomized or observational studies, reviews, and meta-analyses were excluded. The primary outcome measures were body mass index (BMI) (kg/m2) and body weight (kg). Four RCTs with five study arms were identified and analyzed. Compared with the control group, adjunctive ranitidine was associated with marginally significant reductions in BMI and body weight. After removing an outlier study for BMI, the effect of ranitidine remained significant. Adjunctive ranitidine outperformed the placebo in the negative symptom score of the Positive and Negative Syndrome Scale. Although ranitidine was associated with less frequent drowsiness, other adverse events were similar between the two groups. Adjunctive ranitidine appears to be an effective an

High-Throughput Experimental Studies to Identify miRNA Targets Directly, with Special Focus on the Mammalian Brain

We review the pertinent literature on methods used in high-throughput experimental identification of microRNA (miRNA) targets with emphasis on neurochemical studies. miRNAs are short regulatory noncoding RNAs that play important roles in the mammalian brain. The functions of miRNAs are related to their binding of RNAs including mRNAs. Since mammalian miRNAs tend to bind to target mRNAs via imperfect complementarity, understanding exactly which target mRNAs are recognized by which specific miRNAs is a challenge. Based on early experimental evidence, a set of binding rules for miRNAs has been described. These have focused on the 5\u27 seed region of miRNAs binding to the 3\u27 untranslated region of targeted mRNAs. Bioinformaticians have applied these algorithms for theoretical miRNA target prediction. To date, the different computational methods are not in agreement with each other and do not explain all miRNA targets as defined using high-throughput experimental methods. We consider these latter techniques which identify putative miRNA targets directly. Each experimental approach involves specific assumptions and potential technical pitfalls. Some of these direct experimental methods for miRNA target identification have used co-immunoprecipitation (RIP-Chip and others) and transfection-based experimental design. Topics related to experimentally identified miRNA targets are discussed, with special emphasis on studies pertinent to the mammalian brain

Inferring genetic interactions via a nonlinear model and an optimization algorithm

<p>Abstract</p> <p>Background</p> <p>Biochemical pathways are gradually becoming recognized as central to complex human diseases and recently genetic/transcriptional interactions have been shown to be able to predict partial pathways. With the abundant information made available by microarray gene expression data (MGED), nonlinear modeling of these interactions is now feasible. Two of the latest advances in nonlinear modeling used sigmoid models to depict transcriptional interaction of a transcription factor (TF) for a target gene, but do not model cooperative or competitive interactions of several TFs for a target.</p> <p>Results</p> <p>An S-shape model and an optimization algorithm (GASA) were developed to infer genetic interactions/transcriptional regulation of several genes simultaneously using MGED. GASA consists of a genetic algorithm (GA) and a simulated annealing (SA) algorithm, which is enhanced by a steepest gradient descent algorithm to avoid being trapped in local minimum. Using simulated data with various degrees of noise, we studied how GASA with two model selection criteria and two search spaces performed. Furthermore, GASA was shown to outperform network component analysis, the time series network inference algorithm (TSNI), GA with regular GA (GAGA) and GA with regular SA. Two applications are demonstrated. First, GASA is applied to infer a subnetwork of human T-cell apoptosis. Several of the predicted interactions are supported by the literature. Second, GASA was applied to infer the transcriptional factors of 34 cell cycle regulated targets in <it>S. cerevisiae</it>, and GASA performed better than one of the latest advances in nonlinear modeling, GAGA and TSNI. Moreover, GASA is able to predict multiple transcription factors for certain targets, and these results coincide with experiments confirmed data in YEASTRACT.</p> <p>Conclusions</p> <p>GASA is shown to infer both genetic interactions and transcriptional regulatory interactions well. In particular, GASA seems able to characterize the nonlinear mechanism of transcriptional regulatory interactions (TIs) in yeast, and may be applied to infer TIs in other organisms. The predicted genetic interactions of a subnetwork of human T-cell apoptosis coincide with existing partial pathways, suggesting the potential of GASA on inferring biochemical pathways.</p

Influence of Crohn’s disease related polymorphisms in innate immune function on ileal microbiome

We have previously identified NOD2 genotype and inflammatory bowel diseases (IBD) phenotype, as associated with shifts in the ileal microbiome (“dysbiosis”) in a patient cohort. Here we report an integrative analysis of an expanded number of Crohn's disease (CD) related genetic defects in innate immune function (NOD2, ATG16L1, IRGM, CARD9, XBP1, ORMDL3) and composition of the ileal microbiome by combining the initial patient cohort (Batch 1, 2005–2010, n = 165) with a second consecutive patient cohort (Batch 2, 2010–2012, n = 118). These combined patient cohorts were composed of three non-overlapping phenotypes: 1.) 106 ileal CD subjects undergoing initial ileocolic resection for diseased ileum, 2.) 88 IBD colitis subjects without ileal disease (predominantly ulcerative colitis but also Crohn’s colitis and indeterminate colitis, and 3.) 89 non-IBD subjects. Significant differences (FDR C. difficile infection, and NOD2 genotype on ileal dysbiosis in the expanded analysis. The relative abundance of the Proteobacteria phylum was positively associated with ileal CD and colitis phenotypes, but negatively associated with NOD2R genotype. Additional associations with ORMDL3 and XBP1 were detected at the phylum/subphylum level. IBD medications, such as immunomodulators and anti-TNFα agents, may have a beneficial effect on reversing dysbiosis associated with the IBD phenotype. Exploratory analysis comparing microbial composition of the disease unaffected region of the resected ileum between 27 ileal CD patients who subsequently developed endoscopic recurrence within 6–12 months versus 34 patients who did not, suggested that microbial biomarkers in the resected specimen helped stratify patients with respect to risk of post-surgical recurrence.</div

WangLab at MEDIQA-Chat 2023: Clinical Note Generation from Doctor-Patient Conversations using Large Language Models

This paper describes our submission to the MEDIQA-Chat 2023 shared task for automatic clinical note generation from doctor-patient conversations. We report results for two approaches: the first fine-tunes a pre-trained language model (PLM) on the shared task data, and the second uses few-shot in-context learning (ICL) with a large language model (LLM). Both achieve high performance as measured by automatic metrics (e.g. ROUGE, BERTScore) and ranked second and first, respectively, of all submissions to the shared task. Expert human scrutiny indicates that notes generated via the ICL-based approach with GPT-4 are preferred about as often as human-written notes, making it a promising path toward automated note generation from doctor-patient conversations.Comment: Camera-ready submission to ClinicalNLP @ ACL 202

Novel C-terminal heat shock protein 90 inhibitors target breast cancer stem cells and block migration, self-renewal, and epithelial–mesenchymal transition

In patients with triple-negative breast cancer (TNBC), evidence suggests that tumor-initiating cells (TIC) have stem cell-like properties, leading to invasion and metastasis. HSP90 plays a critical role in the conformational maintenance of many client proteins in TIC development. Therefore, we hypothesize that the novel C-terminal HSP90 inhibitors KU711 and KU758 can target TIC and represent a promising strategy for overcoming metastasis. Human breast cancer cells (MDA-MB-468LN, MDA-MB-231) treated with the HSP90 inhibitors KU711, KU758, and 17-AAG showed a 50–80% decrease in TIC markers CD44 and aldehyde dehydrogenase (P < 0.01) as assessed by flow cytometry. A decrease in sphere formation, which was used to assess self-renewal, was observed after the treatment of TNBC cells starting at 2.5 µm KU711 and 0.31 µm KU758. KU compounds also blocked the invasion and migration of TNBC cells in a dose-dependent manner. The knockdown of HSP90 clients was observed without any change in prosurvival HSP70 levels. In vivo, in a murine orthotopic breast cancer model, treatment with KU758 and KU711 yielded an approximately twofold and a fourfold reduction in tumor volumes versus control, respectively, without demonstrated toxicity. In conclusion, C-terminal HSP90 inhibitors are potent novel therapeutics against TNBC in vitro and in vivo as they target TICs and block invasion, EMT transition, and self-renewal

Atomic Structure and Dynamics of Single Platinum Atom Interactions with Monolayer MoS

We have studied atomic level interactions between single Pt atoms and the surface of monolayer MoS₂ using aberration-corrected annular dark field scanning transmission electron microscopy at an accelerating voltage of 60 kV. Strong contrast from single Pt atoms on the atomically resolved monolayer MoS₂ lattice enables their exact position to be determined with respect to the MoS₂ lattice, revealing stable binding sites. In regions of MoS₂ free from surface contamination, the Pt atoms are localized in S vacancy sites and exhibit dynamic hopping to nearby vacancy sites driven by the energy supplied by the electron beam. However, in areas of MoS₂ contaminated with carbon surface layers, the Pt atoms appear at various positions with respect to the underlying MoS₂ lattice, including on top of Mo and in off-axis positions. These variations are due to the Pt bonding with the surrounding amorphous carbon layer, which disrupts the intrinsic Pt-MoS₂ interactions, leading to more varied positions. Density functional theory (DFT) calculations reveal that Pt atoms on the surface of MoS₂ have a small barrier for migration and are stabilized when bound to either a single or double sulfur vacancies. DFT calculations have been used to understand how the catalytic activity of the MoS₂ basal plane for hydrogen evolution reaction is influenced by Pt dopants by variation of the hydrogen adsorption free energy. This strong dependence of catalytic effect on interfacial configurations is shown to be common for a series of dopants, which may provide a means to create and optimize reaction centers

A Case of Novel Coronavirus Disease 19 in a Chronic Hemodialysis Patient Presenting with Gastroenteritis and Developing Severe Pulmonary Disease.

Novel coronavirus disease 2019 (COVID-19) is a highly infectious, rapidly spreading viral disease with an alarming case fatality rate up to 5%. The risk factors for severe presentations are concentrated in patients with chronic kidney disease, particularly patients with end-stage renal disease (ESRD) who are dialysis dependent. We report the first US case of a 56-year-old nondiabetic male with ESRD secondary to IgA nephropathy undergoing thrice-weekly maintenance hemodialysis for 3 years, who developed COVID-19 infection. He has hypertension controlled with angiotensin receptor blocker losartan 100 mg/day and coronary artery disease status-post stent placement. During the first 5 days of his febrile disease, he presented to an urgent care, 3 emergency rooms, 1 cardiology clinic, and 2 dialysis centers in California and Utah. During this interval, he reported nausea, vomiting, diarrhea, and low-grade fevers but was not suspected of COVID-19 infection until he developed respiratory symptoms and was admitted to the hospital. Imaging studies upon admission were consistent with bilateral interstitial pneumonia. He was placed in droplet-eye precautions while awaiting COVID-19 test results. Within the first 24 h, he deteriorated quickly and developed acute respiratory distress syndrome (ARDS), requiring intubation and increasing respiratory support. Losartan was withheld due to hypotension and septic shock. COVID-19 was reported positive on hospital day 3. He remained in critical condition being treated with hydroxychloroquine and tocilizumab in addition to the standard medical management for septic shock and ARDS. Our case is unique in its atypical initial presentation and highlights the importance of early testing