Dynamical order and many-body correlations in zebrafish show that three is a crowd.

Zebrafish constitute a convenient laboratory-based biological system for studying collective behavior. It is possible to interpret a group of zebrafish as a system of interacting agents and to apply methods developed for the analysis of systems of active and even passive particles. Here, we consider the effect of group size. We focus on two- and many-body spatial correlations and dynamical order parameters to investigate the multistate behavior. For geometric reasons, the smallest group of fish which can exhibit this multistate behavior consisting of schooling, milling and swarming is three. We find that states exhibited by groups of three fish are similar to those of much larger groups, indicating that there is nothing more than a gradual change in weighting between the different states as the system size changes. Remarkably, when we consider small groups of fish sampled from a larger group, we find very little difference in the occupancy of the state with respect to isolated groups, nor is there much change in the spatial correlations between the fish. This indicates that fish interact predominantly with their nearest neighbors, perceiving the rest of the group as a fluctuating background. Therefore, the behavior of a crowd of fish is already apparent in groups of three fish.

EphB3 receptor suppressor invasion, migration and proliferation in glioma by inhibiting EGFR-PI3K/AKT signaling pathway.

Eph receptors are the largest subfamily of receptor tyrosine kinases, and they have been shown to play a crucial role in glioma. The EphB3 receptor is a member of this family, and its effect on the invasion, migration and proliferation of glioma cells was examined in this study. It was found that the expression of EphB3 was decreased in glioma specimens with increasing tumor grade. Additionally, the U87MG and U251 cell lines showed low levels of EphB3 expression. This finding was consistent with the negative correlation between EphB3 expression in glioma tissues and tumor grade. Depletion of EphB3 gene in U87MG and U251 cell lines resulted in a substantial enhancement of their invasion, migration, and proliferation capacities in vitro. Furthermore, the knockdown of EphB3 led to an upregulation of EGFR, p-PI3K, and p-AKT protein levels. On the other hand, EphB3 overexpression reduced the invasiveness, proliferative capacity and migration rate of U87MG and U251 cells, and downregulated EGFR, p-PI3K and p-AKT. These findings indicate that EphB3 functions as a tumor suppressor in glioma, and its downregulation enhances the malignant potential of glioma cells by activating the EGFR-PI3K/AKT pathway. Thus, EphB3 is a promising diagnostic marker for glioma, and the EphB3-EGFR-PI3K / AKT axis deserves further investigation as a potential therapeutic target.

Understanding the Information Needs of Pharmacy Staff Using CancelRx: A Qualitative Study of the Use of Prescription E-cancellation.

Background: Although electronic prescription cancellation such as via CancelRx can facilitate critical communication between prescribers and pharmacy staff about discontinued medications, there is little work that explores whether CancelRx meets the needs of pharmacy staff users. Objective: This study leverages qualitative interviews with pharmacy staff to address the following question: When medication changes are made by a prescriber using CancelRx, what information is needed by pharmacy staff to make correct and effective decisions in their roles in medication management? Methods: We conducted an inductive thematic analysis of interviews with 11 pharmacy staff members (pharmacists and pharmacy technicians) across three outpatient community pharmacy sites within an academic health care system. Results: Three information needs themes were consistently identified by both pharmacists and pharmacy technicians: prescriber intent when initiating the CancelRx, clinical rationale for the medication change, and intended medication regimen. Notably, both pharmacists and pharmacy technicians often reported seeking multiple information needs not fully addressed by CancelRx in the electronic health record (EHR) to achieve the shared goals of correct dispensing of medications and supporting patient self-management. Conclusions: Our qualitative analysis reveals that outpatient community pharmacy staff in an academic health care system often seek additional information from the (EHR) following medication changes communicated by CancelRx to meet their information needs. Ideally, the prescriber would provide sufficient information through CancelRx to automatically identify all discontinued prescriptions. These limitations highlight the need for design features that support routine communication of needed information at the time of a medication change, such as structured data elements.

Dual-Path Information Fusion and Twin Attention-Driven Global Modeling for Solar Irradiance Prediction.

Accurate prediction of solar irradiance holds significant value for renewable energy usage and power grid management. However, traditional forecasting methods often overlook the time dependence of solar irradiance sequences and the varying importance of different influencing factors. To address this issue, this study proposes a dual-path information fusion and twin attention-driven solar irradiance forecasting model. The proposed framework comprises three components: a residual attention temporal convolution block (RACB), a dual-path information fusion module (DIFM), and a twin self-attention module (TSAM). These components collectively enhance the performance of multi-step solar irradiance forecasting. First, the RACB is designed to enable the network to adaptively learn important features while suppressing irrelevant ones. Second, the DIFM is implemented to reinforce the model's robustness against input data variations and integrate multi-scale features. Lastly, the TSAM is introduced to extract long-term temporal dependencies from the sequence and facilitate multi-step prediction. In the solar irradiance forecasting experiments, the proposed model is compared with six benchmark models across four datasets. In the one-step predictions, the average performance metrics RMSE, MAE, and MAPE of the four datasets decreased within the ranges of 0.463-2.390 W/m2, 0.439-2.005 W/m2, and 1.3-9.2%, respectively. Additionally, the average R2 value across the four datasets increased by 0.008 to 0.059. The experimental results indicate that the model proposed in this study exhibits enhanced accuracy and robustness in predictive performance, making it a reliable alternative for solar irradiance forecasting.

Fault Diagnosis of Wind Turbine Generators Based on Stacking Integration Algorithm and Adaptive Threshold.

Fault alarm time lag is one of the difficulties in fault diagnosis of wind turbine generators (WTGs), and the existing methods are insufficient to achieve accurate and rapid fault diagnosis of WTGs, and the operation and maintenance costs of WTGs are too high. To invent a new method for fast and accurate fault diagnosis of WTGs, this study constructs a stacking integration model based on the machine learning algorithms light gradient boosting machine (LightGBM), extreme gradient boosting (XGBoost), and stochastic gradient descent regressor (SGDRegressor) using publicly available datasets from Energias De Portugal (EDP). This model is automatically tuned for hyperparameters during training using Bayesian tuning, and the coefficient of determination (R2) and root mean square error (RMSE) were used to evaluate the model to determine its applicability and accuracy. The fitted residuals of the test set were calculated, the Pauta criterion (3σ) and the temporal sliding window were applied, and a final adaptive threshold method for accurate fault diagnosis and alarming was created. The model validation results show that the adaptive threshold method proposed in this study is better than the fixed threshold for diagnosis, and the alarm times for the GENERATOR fault type, GENERATOR_BEARING fault type, and TRANSFORMER fault type are 1.5 h, 5.8 h, and 3 h earlier, respectively.

Knockdown of FUT11 inhibits the progression of gastric cancer via the PI3K/AKT pathway.

Gastric cancer (GC) is a common and highly malignant tumor of the digestive tract. Members of the focused fucosyltransferase (FUT) family participate in the advancement of various types of cancer. However, research of FUT family members in the progression of GC known to be limited. The purpose of the research was to determine the function of important affiliates of the FUT family in GC and to explore its impacts on the proliferation and migration of GC cells and molecular mechanisms. For the study, fucosyltransferase11 (FUT11) was confirmed to be the only affiliate of the FUT family that was upmodulated in GC tissues and linked to poor survival according to GEPIA data. Furthermore, compared with adjacent noncancerous tissues, the expression of FUT11 was increased in GC tissues. The elevated FUT11 expression suggested that the overall survival (OS) rate of GC is low. Inhibition of FUT11 significantly reduced the proliferation and migration and suppressed the PI3K/AKT pathway by down-regulated collagen type VI alpha 3 chain (COL6A3) in GC cells. The present study has demonstrated that reinstating the expression of COL6A3 in gastric cancer (GC) cells can counteract the inhibitory impact of FUT11 knockdown on the proliferation and migration of GC cells. In conclusion, FUT11 may serve as a novel biomarker for GC, as it modulates GC cell proliferation and migration through the PI3K/AKT signaling pathway.

Building an Immune-Related Genes Model to Predict Treatment, Extracellular Matrix, and Prognosis of Head and Neck Squamous Cell Carcinoma.

Due to the considerable heterogeneity of head and neck squamous cell carcinoma (HNSCC), individuals with comparable TNM stages who receive the same treatment strategy have varying prognostic outcomes. In HNSCC, immunotherapy is developing quickly and has shown effective. We want to develop an immune-related gene (IRG) prognostic model to forecast the prognosis and response to immunotherapy of patients. In order to analyze differential expression in normal and malignant tissues, we first identified IRGs that were differently expressed. Weighted gene coexpression network analysis (WGCNA) was used to identify modules that were highly related, and univariate and multivariate Cox regression analyses were also used to create a predictive model for IRGs that included nine IRGs. WGCNA identified the four most noteworthy related modules. Patients in the model's low-risk category had a better chance of survival. The IRGs prognostic model was also proved to be an independent prognostic predictor, and the model was also substantially linked with a number of clinical characteristics. The low-risk group was associated with immune-related pathways, a low incidence of gene mutation, a high level of M1 macrophage infiltration, regulatory T cells, CD8 T cells, and B cells, active immunity, and larger benefits from immune checkpoint inhibitors (ICIs) therapy. The high-risk group, on the other hand, had suppressive immunity, high levels of NK and CD4 T-cell infiltration, high gene mutation rates, and decreased benefits from ICI therapy. As a result of our research, a predictive model for IRGs that can reliably predict a patient's prognosis and their response to both conventional and immunotherapy has been created.

An inflammation-associated ferroptosis signature optimizes the diagnosis, prognosis evaluation and immunotherapy options in hepatocellular carcinoma.

Inflammation and ferroptosis crosstalk complexly with immune microenvironment of hepatocellular carcinoma (HCC), thus affecting the efficacy of immunotherapy. Herein, our aim was to identify the inflammation-associated ferroptosis (IAF) biomarkers for contributing HCC. A total of 224 intersecting DEGs identified from different inflammation- and ferroptosis-subtypes were set as IAF genes. Seven of them including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 were used for construction of a risk model which classified HCC patients into two groups (high and low risk). HCC patients in the high-risk group exhibited shorter survival rate and higher immune score, and were predicted to have higher respond rate in immune checkpoint inhibition (ICI) therapy. Levels of the seven genes were significantly changed in HCC tissues in comparison to adjacent tissues. After inserting the gene expression into the risk model, we found that the risk model exhibited the higher diagnostic value for distinguish HCC tissues compared each single gene. Furthermore, HCC tissues from our research group with high-risk score exhibited more cases of microsatellite instability (MSI), heavier tumour mutational burden (TMB), higher expression level of PDL1 and cells with CD8. Knockdown of APOA5 reduced HCC cell proliferation combining with elevating inflammation and ferroptosis levels. In conclusion, we considered APOA5 maybe a novel target for suppressing HCC via simultaneously elevating inflammation and ferroptosis levels, and signature constructed by seven IAF genes including ADH4, APOA5, CFHR3, CXCL8, FTCD, G6PD and PON1 can act as a biomarker for optimising the diagnosis, prognosis evaluation and immunotherapy options in HCC patients.

USP10 deubiquitinates RUNX1 and promotes proneural-to-mesenchymal transition in glioblastoma.

The mesenchymal (MES) subtype of glioblastoma (GBM) is a highly aggressive, malignant and proliferative cancer that is resistant to chemotherapy. Runt-related transcription factor 1 (RUNX1) was shown to support MES GBM, however, its underlying mechanisms are unclear. Here, we identified USP10 as a deubiquitinating enzyme that regulates RUNX1 stabilization and is mainly expressed in MES GBM. Overexpression of USP10 upregulated RUNX1 and induced proneural-to-mesenchymal transition (PMT), thus maintaining MES properties in GBM. Conversely, USP10 knockdown inhibited RUNX1 and resulted in the loss of MES properties. USP10 was shown to interact with RUNX1, with RUNX1 being stabilized upon deubiquitylation. Moreover, we found that USP10 inhibitor Spautin-1 induced RUNX1 degradation and inhibited MES properties in vitro and in vivo. Furthermore, USP10 was strongly correlated with RUNX1 expression in samples of different subtypes of human GBM and had prognostic value for GBM patients. We identified USP10 as a key deubiquitinase for RUNX1 protein stabilization. USP10 maintains MES properties of GBM, and promotes PMT of GBM cells. Our study indicates that the USP10/RUNX1 axis may be a potential target for novel GBM treatments.

Intravoxel incoherent motion imaging used to assess tumor microvascular changes after transarterial chemoembolization in a rabbit VX2 liver tumor model.

Purpose: To evaluate the correlation between microvascular density (MVD) and intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) parameters and the effect of glycolytic flux after transarterial chemoembolization (TACE) in a rabbit VX2 liver tumor. Materials and methods: VX2 liver tumor allografts in 15 New Zealand white rabbits were treated with sterile saline (control group, n = 5) or lipiodol-doxorubicin emulsion (experimental group, n = 10). MRI was performed 2 weeks after the procedure to evaluate IVIM parameters, including apparent diffusion coefficient (ADC), pure diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (PF). All animal samples were taken of the tumor and surrounding liver. Immunostaining for CD31, CD34, CD105, and VEGF was used to evaluate MVD. The protein expression of Glut4, HK2, PKM2, LDHA, and MCT1 was determined using western blotting. Pearson correlation tests were used to analyze the relationship between MVD and IVIM parameters. Results: D* value in the peritumoral region was negatively correlated with CD34 (r = -0.71, P = 0.01). PF value positively correlated with CD34 (r = 0.68, P = 0.015), CD105 (r = 0.76, P = 0.004) and VEGF (r = 0.72, P = 0.008) in the peritumoral region. Glut4, HK2, PKM2, and MCT1 in the peritumoral regions were higher in the experimental group than in the control group (all P < 0.05). Conclusion: IVIM parameters were correlated with MVD in the intratumoral and peritumoral regions after TACE in a rabbit liver tumor model. The angiogenesis reflected by MVD may be related to changes of glycolytic flux.

Fluorine-Functionalized Triazine-Based Porous Organic Polymers for the Efficient Adsorption of Aflatoxins.

Food safety issue caused by aflatoxins has aroused widespread concern in society. Herein, a novel fluorine-functionalized triazine-based porous organic polymer (F-POP) was developed for the first time by the simple condensation polymerization of 2,2'-bis(trifluoromethyl)benzidine and cyanuric chloride. With in-built fluorine functional group (F) and imine group (-NH-), F-POP displayed significantly superior adsorption ability for aflatoxins, outperforming fluorine-free POP due to the multiple interaction mechanisms of hydrogen bond, F-O interaction, π-π interaction, F-π interaction, and hydrophobic interaction. Thus, magnetic F-POP was prepared by introducing Fe3O4 into F-POP and then utilized as a magnetic sorbent for the extraction of trace aflatoxins in peanut and rice samples prior to high-performance liquid chromatography-fluorescence detection. Under the optimal conditions, the proposed method presented high sensitivity with the limit of detections at 0.005-0.15 ng g-1. F-POP also exhibited outstanding adsorption capability for many other organic pollutants, revealing its great potential for analysis or adsorption applications.

Multi-Hazard Effects of Crosswinds on Cascading Failures of Conventional and Interspersed Railway Tracks Exposed to Ballast Washaway and Moving Train Loads.

The interspersed railway track is an enhanced timber railway track, spot-replacing damaged wooden sleepers with new concrete sleepers to improve the bearing capacity of existing railway lines. Although this interspersed solution is characterised by low cost and short maintenance time, the interspersed tracks have worse stability than concrete tracks and can deteriorate quickly when exposed to extreme weather conditions such as heavy rains and floods. In many cases, heavy rains and floods are accompanied by strong winds. Ballast washaway can often be observed under flood conditions while the mass of trains is unevenly distributed on two rails due to the effect of lateral wind load and rail irregularities. The current work is the first in the world to investigate the collective multi-hazard effects of ballast washway and uneven axle loads on the vulnerability of conventional and interspersed railway tracks using nonlinear FEM software, STRAND 7. The train bogie is modelled by two sets of point loads. The maximum displacement, bending moment and twists have been studied to evaluate the worst condition. The novel insights will help the railway industry develop proper operations of interspersed railway tracks against naturally hazardous conditions.

GOLPH3 Promotes Vasculogenic Mimicry via the Epithelial Mesenchymal Transition in Glioblastoma Cells.

AIM: To evaluate the relationship between Golgi phosphoprotein 3 (GOLPH3) and vasculogenic mimicry (VM) in glioblastoma cells. MATERIAL AND METHODS: Glioma tissues from 40 glioma patients with different pathological grades were collected. GOLPH3 and VM were evaluated by immunostaining in glioma tissues. Then, the correlation between GOLPH3 and VM were analyzed clinically. Additionally, a GOLPH3-downregulation lentivirus was constructed and transfected into the human primary glioblastoma cell line, U-87 MG. Afterwards, apoptosis, migration and invasion were assessed to determine the effects of downregulation GOLPH3. Then, E-cadherin and matrix metalloproteinase 2 (MMP2) were detected for assessment of the epithelial mesenchymal transition (EMT). RESULTS: GOLPH3 and VM were found to be positively correlated following clinical analysis (p < 0.01, r=0.788). Furthermore, GOLPH3 downregulation suppressed the migration and invasion of U87 MG cells (p < 0.05), followed by upregulation of E-cadherin and downregulation of MMP2. CONCLUSION: Collectively, our results demonstrate that GOLPH3 promoted VM in glioblastoma cells and that the corresponding mechanism was associated with the EMT. Our finding suggests that GOLPH3 may represent a promising therapeutic target for mitigating the recurrence and invasion of gliomas.

A novel immune cell signature for predicting osteosarcoma prognosis and guiding therapy.

Dysregulation of immune cell infiltration in the tumor microenvironment contributes to the progression of osteosarcoma (OS). In the present study, we explored genes related to immune cell infiltration and constructed a risk model to predict the prognosis of and guide therapeutic strategies for OS. The gene expression profile of OS was obtained from TARGET and Gene Expression Omnibus, which were set as the discovery and verification cohorts. CIBERSORT and Kaplan survival analyses were used to analyze the effects of immune cells on the overall survival rates of OS in the discovery cohort. Differentially expressed gene (DEG) analysis and protein-protein interaction (PPI) networks were used to analyze genes associated with immune cell infiltration. Cox regression analysis was used to select key genes to construct a risk model that classified OS tissues into high- and low-risk groups. The prognostic value of the risk model for survival and metastasis was analyzed by Kaplan-Meier survival analyses, receiver operating characteristic curves, and immunohistochemical experiments. Immunological characteristics and response effects of immune checkpoint blockade (ICB) therapy in OS tissues were analyzed using the ESTIMATE and Tumor Immune Dysfunction and Exclusion algorithms, while sensitivity for both targeted and chemotherapy drugs was analyzed using the OncoPredict algorithm. It was demonstrated that the high infiltration of resting dendritic cells in OS tissues was associated with poor prognosis. A total of 225 DEGs were found between the high- and low-infiltration groups of OS tissues, while 94 genes interacted with others. Through COX analyses, among these 94 genes, four genes (including AOC3, CDK6, COL22A1, and RNASE6) were used to construct a risk model. This risk model showed a remarkable prognostic value for survival rates and metastasis in both the discovery and verification cohorts. Even though a high microsatellite instability score was observed in the high-risk group, the ICB response in the high-risk group was poor. Furthermore, using OncoPredict, we found that the high-risk group OS tissues were resistant to seven drugs and sensitive to 25 drugs. Therefore, our study indicates that the resting dendritic cell signature constructed by AOC3, CDK6, COL22A1, and RNASE6 may contribute to predicting osteosarcoma prognosis and thus therapy guidance.

Discontinuation of outpatient medications: implications for electronic messaging to pharmacies using CancelRx.

Electronic communication of prescription discontinuation, or CancelRx, has the potential to improve medication safety. We aimed to describe the proportion of discontinued outpatient medications that would result in a CancelRx message to understand its impact on medication safety. We used a data report to identify all outpatient medications discontinued in the electronic health record (EHR) of an academic health system in 1 month (October 2018). Among all 63 485 medications discontinued, 23 118 (36.4%) were e-prescribed, 25 982 (40.9%) were patient-reported or reconciled, and the remainder prescribed nonelectronically. Discontinued high-risk medications were more likely to be e-prescribed (2768 of 5896, 47.0%). A discontinuation reason was specified in 37 353 (58.9%) of all discontinued medications. Approximately one-third to one-half of discontinued medications were e-prescribed within the same EHR and would result in a CancelRx message to the pharmacy. Extension of this functionality to medications reconciled in the EHR could significantly expand the impact of CancelRx on medication safety. In addition, complete and accurate discontinuation reasons are needed to optimize CancelRx implementation.

A specific immune signature for predicting the prognosis of glioma patients with IDH1-mutation and guiding immune checkpoint blockade therapy.

Isocitrate dehydrogenase (IDH1) is frequently mutated in glioma tissues, and this mutation mediates specific tumor-promoting mechanisms in glioma cells. We aimed to identify specific immune biomarkers for IDH1-mutation (IDH1mt) glioma. The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) were used to obtain RNA sequencing data and clinical characteristics of glioma tissues, while the stromal and immune scores of TCGA glioma tissues were determined using the ESTIMATE algorithm. Differentially expressed genes (DEGs), the protein-protein interaction(PPI) network, and least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were used to select hub genes associated with stroma and immune scores and the prognoses of patients and to construct the risk model. The practicability and specificity of the risk model in both IDH1mt and IDH1-wildtype (wtIDH1) gliomas in TCGA and CGGA were evaluated. Molecular mechanisms, immunological characteristics and benefits of immune checkpoint blockade therapy in glioma tissues with IDH1mt were analyzed using GSEA, immunohistochemical staining, CIBERSORT, and T-cell dysfunction and exclusion (TIDE) analysis. The overall survival rate for IDH1mt-glioma patients with high stroma/immune scores was lower than that for those with low stroma/immune scores. A total of 222 DEGs were identified in IDH1mt glioma tissues with high stroma/immune scores. Among them, 72 genes had interactions in the PPI network, while three genes, HLA-DQA2, HOXA3, and SAA2, were selected as hub genes and used to construct risk models classifying patients into high- and low-risk score groups, followed by LASSO and Cox regression analyses. This risk model showed prognostic value in IDH1mt glioma in both TCGA and CCGA; nevertheless, the model was not suitable for wtIDH1 glioma. The risk model may act as an independent prognostic factor for IDH1mt glioma. IDH1mt glioma tissues from patients with high-risk scores showed more infiltration of M1 and CD8 T cells than those from patients with low-risk scores. Moreover, TIDE analysis showed that immune checkpoint blockade(ICB) therapy was highly beneficial for IDH1mt patients with high-risk scores. The risk model showed specific potential to predict the prognosis of IDH1mt-glioma patients, as well as guide ICB, contributing to the diagnosis and therapy of IDH1mt-glioma patients.

The Impact of Electronic Communication of Medication Discontinuation (CancelRx) on Medication Safety: A Pilot Study.

OBJECTIVES: This study aimed to evaluate the impact of electronic communication of medication discontinuation from prescribers to pharmacies (CancelRx) on medication safety. METHODS: We used electronic health record (EHR) data to identify medications that were e-prescribed from a pilot practice to a health system pharmacy and subsequently discontinued before or after CancelRx implementation (January 16-April 15, 2018 versus 2019). We matched these EHR data to pharmacy management software data to identify medications that were sold to patients in the 6 months after discontinuation. As a surrogate for unintended cancellation, we also identified medications refilled within 120 days of discontinuation. We conducted a medical record review to identify documentation of prescriber intent to discontinue these medications. RESULTS: CancelRx implementation prevented prescriptions from being sold after discontinuation in the EHR (42 of 392 [10.7%] versus 0 of 387 [0.0%], P < 0.0001), but only 15 of 42 (35.7%) had documented intent to discontinue the medication (15 of 392, or 3.8% overall). There was a nonsignificant increase in the proportion of discontinued medications reordered within 120 days (10.0% versus 12.7%, P = 0.23). Medical record review of reordered prescriptions after CancelRx implementation found that 10 of 49 (10 of 387, or 2.6% overall) might have been unintentionally canceled. CONCLUSIONS: Implementation of CancelRx eliminated the sale of e-prescribed medications after discontinuation in the EHR but might result in the unintentional cancellation of some prescriptions. Strategies to increase situational awareness of providers and pharmacy staff, including increased visibility of CancelRx, clear distinctions between active and expired prescriptions, and transmission of the reason for discontinuation, might reduce the risk of unintentional cancellations.

A novel hypoxia-driven gene signature that can predict the prognosis of hepatocellular carcinoma.

Hypoxia environment exists in already started hepatocellular carcinoma (HCC) and promotes its progression by driving changes in the gene expression profiles of cells. However, the status of hypoxia-driven genes in HCC is largely unknown. In the present study, 368 HCC tissues from The Cancer Genome Atlas were divided into high and low hypoxia groups according to their hypoxia signatures. A total of 1,142 differentially expressed genes (DEGs) were identified between the two groups, and 34 of these DEGs were highly expressed in HCC tissues compared with adjacent tissues, especially in HCC tissues from patients with stage III-IV HCC. After constructing a protein-protein interaction network and applying the least absolute shrinkage and selection operator Cox regression method for 34 DEGs, a three-gene signature (complement factor H related 3 [CFHR3], egl-9 family hypoxia inducible factor 3 [EGLN3], and chromogranin A [CHGA]) was constructed and had prognostic value to predicted outcome of patients with HCC. This three-gene signature was suitable for classifying patients with HCC in the International Cancer Genome Consortium. CFHR3 shows remarkable diagnostic value in HCC. Hypoxia decreased CFHR3 expression, but increased HCC cell proliferation and motility. Overexpression of CFHR3 in HCC cells under hypoxia reversed the stimulatory effects of hypoxia and suppressed cell proliferation and metastasis in vivo. In conclusion, we identified a novel hypoxia-driven gene signature (CFHR3, EGLN3, and CHGA) for reliable prognostic prediction of HCC, and demonstrated that overexpression of CFHR3 may be a potential strategy to overcome hypoxia and treat HCC.

Dominating lengthscales of zebrafish collective behaviour.

Collective behaviour in living systems is observed across many scales, from bacteria to insects, to fish shoals. Zebrafish have emerged as a model system amenable to laboratory study. Here we report a three-dimensional study of the collective dynamics of fifty zebrafish. We observed the emergence of collective behaviour changing between ordered to randomised, upon adaptation to new environmental conditions. We quantify the spatial and temporal correlation functions of the fish and identify two length scales, the persistence length and the nearest neighbour distance, that capture the essence of the behavioural changes. The ratio of the two length scales correlates robustly with the polarisation of collective motion that we explain with a reductionist model of self-propelled particles with alignment interactions.

Preparing for the Improving Medicare Post-Acute Care Transformation Act: Incorporating A Sociotechnical Perspective to Enhance a Health Information Technology Evaluation Framework Applied to Post-Acute Care.

The Improving Medicare Post-Acute Care Transformation Act, which mandates electronic sharing of standardized patient data by post-acute care clinical settings, will likely spur further health information technology adoption and evaluation. To support evaluation, the study objective was to clarify components of an evidence-based health information technology evaluation framework, Health Information Technology Reference-based Evaluation Framework, by using the framework in home healthcare and incorporating a sociotechnical perspective in the health information technology evaluation. With 36 observations among three diverse home healthcare agencies, researchers conducted a recorded think-aloud process as nurses documented the home healthcare admission in the EHR. Thematic analysis revealed 15 themes that provided clarification for almost one-third of Health Information Technology Reference-based Evaluation Framework components and added a new concept. All themes reflected a sociotechnical perspective. The new theme added to the Health Information Technology Reference-based Evaluation Framework reflected the sociotechnical perspective: routine use. We anticipate the enhanced Health Information Technology Reference-based Evaluation Framework to be used by evaluators from diverse disciplines, to further facilitate context-dependent health information technology adoption in post-acute care settings.