Calibrationless Reconstruction of Uniformly-Undersampled Multi-Channel MR Data with Deep Learning Estimated ESPIRiT Maps

Purpose: To develop a truly calibrationless reconstruction method that derives ESPIRiT maps from uniformly-undersampled multi-channel MR data by deep learning. Methods: ESPIRiT, one commonly used parallel imaging reconstruction technique, forms the images from undersampled MR k-space data using ESPIRiT maps that effectively represents coil sensitivity information. Accurate ESPIRiT map estimation requires quality coil sensitivity calibration or autocalibration data. We present a U-Net based deep learning model to estimate the multi-channel ESPIRiT maps directly from uniformly-undersampled multi-channel multi-slice MR data. The model is trained using fully-sampled multi-slice axial brain datasets from the same MR receiving coil system. To utilize subject-coil geometric parameters available for each dataset, the training imposes a hybrid loss on ESPIRiT maps at the original locations as well as their corresponding locations within the standard reference multi-slice axial stack. The performance of the approach was evaluated using publicly available T1-weighed brain and cardiac data. Results: The proposed model robustly predicted multi-channel ESPIRiT maps from uniformly-undersampled k-space data. They were highly comparable to the reference ESPIRiT maps directly computed from 24 consecutive central k-space lines. Further, they led to excellent ESPIRiT reconstruction performance even at high acceleration, exhibiting a similar level of errors and artifacts to that by using reference ESPIRiT maps. Conclusion: A new deep learning approach is developed to estimate ESPIRiT maps directly from uniformly-undersampled MR data. It presents a general strategy for calibrationless parallel imaging reconstruction through learning from coil and protocol specific data

Evaluation of the Effectiveness of Clinical Pharmacists’ Consultation in the Treatment of Infectious Diseases: A Single-Arm, Prospective Cohort Study

Background: With the implementation of Antimicrobial Stewardship Program, clinical pharmacists’ consultation (CPC) for infectious diseases (ID) is gradually adopted by many hospitals in China. We conducted a cohort study to evaluate the effectiveness of CPC in ID treatment on patient outcomes and potential determinants.Methods: Based on a registry database, a prospective cohort study was conducted in Guizhou Provincial People’s Hospital. The main exposure factor was whether clinician adopted the suggestion from clinical pharmacist. The outcome was effective response rate (ERR) of ID patients. The variables associated with the outcome (e.g., age, gender, severity of infection, liver function, and kidney function) were also prospectively recorded. A multilevel model was performed to analyze the factors related to ERR.Results: A total of 733 ID inpatients were included in the final analysis according to the predesigned inclusion and exclusion criteria. The proportion of clinical pharmacists’ suggestions adopted by clinicians and ERR were 88.13 and 69.03%, respectively. Significant data aggregation (P < 0.05) for individuals at the level of department was observed. According to the two-level variance component model, liver dysfunction (Adjusted Odds Ratio (AOR) = 0.649, 95%Credible Interval (CI): 0.432–0.976), severity of infection (AOR = 0.602, 95%CI: 0.464–0.781), and adopting the suggestion from pharmacist (AOR = 1.738, 95%CI: 1.028–2.940) had significant association with ERR.Conclusion: Our study suggests that the effect of CPC on ID treatment is significant. The policy/decision makers or hospital managers should be cognizant of the critical value of clinical pharmacists in ID treatment

RING finger 138 deregulation distorts NF-кB signaling and facilities colitis switch to aggressive malignancy

Prolonged activation of nuclear factor (NF)-кB signaling significantly contributes to the development of colorectal cancer (CRC). New therapeutic opportunities are emerging from targeting this distorted cell signaling transduction. Here, we discovered the critical role of RING finger 138 (RNF138) in CRC tumorigenesis through regulating the NF-кB signaling, which is independent of its Ubiquitin-E3 ligase activity involved in DNA damage response. RNF138(−/−) mice were hyper-susceptible to the switch from colitis to aggressive malignancy, which coincided with sustained aberrant NF-кB signaling in the colonic cells. Furthermore, RNF138 suppresses the activation of NF-кB signaling pathway through preventing the translocation of NIK and IKK-Beta Binding Protein (NIBP) to the cytoplasm, which requires the ubiquitin interaction motif (UIM) domain. More importantly, we uncovered a significant correlation between poor prognosis and the downregulation of RNF138 associated with reinforced NF-кB signaling in clinical settings, raising the possibility of RNF138 dysregulation as an indicator for the therapeutic intervention targeting NF-кB signaling. Using the xenograft models built upon either RNF138-dificient CRC cells or the cells derived from the RNF138-dysregulated CRC patients, we demonstrated that the inhibition of NF-кB signaling effectively hampered tumor growth. Overall, our work defined the pathogenic role of aberrant NF-кB signaling due to RNF138 downregulation in the cascade events from the colitis switch to colonic neoplastic transformation and progression, and also highlights the possibility of targeting the NF-кB signaling in treating specific subtypes of CRC indicated by RNF138-ablation

Use of MicroRNA Let-7 to Control the Replication Specificity of Oncolytic Adenovirus in Hepatocellular Carcinoma Cells

Highly selective therapy for hepatocellular carcinoma (HCC) remains an unmet medical need. In present study, we found that the tumor suppressor microRNA, let-7 was significantly downregulated in a proportion of primary HCC tissues (12 of 33, 36.4%) and HCC cell lines. In line with this finding, we have engineered a chimeric Ad5/11 fiber oncolytic adenovirus, SG7011let7T, by introducing eight copies of let-7 target sites (let7T) into the 3′ untranslated region of E1A, a key gene associated with adenoviral replication. The results showed that the E1A expression (both RNA and protein levels) of the SG7011let7T was tightly regulated according to the endogenous expression level of the let-7. As contrasted with the wild-type adenovirus and the control virus, the replication of SG7011let7T was distinctly inhibited in normal liver cells lines (i.e. L-02 and WRL-68) expressing high level of let-7 (>300 folds), whereas was almost not impaired in HCC cells (i.e. Hep3B and PLC/PRF/5) with low level of let-7. Consequently, the cytotoxicity of SG7011let7T to normal liver cells was successfully decreased while was almost not attenuated in HCC cells in vitro. The antitumor ability of SG7011let7T in vivo was maintained in mice with Hep3B xenograft tumor, whereas was greatly decreased against the SMMC-7721 xenograft tumor expressing a high level of let-7 similar with L-02 when compared to the wild-type adenovirus. These results suggested that SG7011let7T may be a promising anticancer agent or vector to mediate the expression of therapeutic gene, broadly applicable in the treatment for HCC and other cancers where the let-7 gene is downregulated

Non-Fourier Heat Conduction of a Functionally Graded Cylinder Containing a Cylindrical Crack

The present work investigates the problem of a cylindrical crack in a functionally graded cylinder under thermal impact by using the non-Fourier heat conduction model. The theoretical derivation is performed by methods of Fourier integral transform, Laplace transform, and Cauchy singular integral equation. The concept of heat flux intensity factor is introduced to investigate the heat concentration degree around the crack tip quantitatively. The temperature field and the heat flux intensity factor in the time domain are obtained by transforming the corresponding quantities from the Laplace domain numerically. The effects of heat conduction model, functionally graded parameter, and thermal resistance of crack on the temperature distribution and heat flux intensity factor are studied. This work is beneficial for the thermal design of functionally graded cylinder containing a cylindrical crack

Mechanical Properties, Curing Mechanism, and Microscopic Experimental Study of Polypropylene Fiber Coordinated Fly Ash Modified Cement–Silty Soil

Silty soil has the characteristics of low natural moisture content and poor viscosity, and the strength and deformation required for foundation engineering can be satisfied by reinforcing and improving the silt. In order to study the reinforcement and improvement effects of polypropylene (PP) fiber and fly ash (FA) on cement–silty soil, an unconfined compressive strength (UCS) test, scanning electron microscope (SEM) test, and X-ray diffraction (XRD) analysis test were carried out. Cement (mixed amounts are 4%, 8%, 12%, and 16% of dry soil mass) was used as the basic modifier, and PP fiber (mixed amounts are 0%, 0.15%, 0.3%, and 0.45% of dry soil mass) compounded with FA (adding amounts of 0%, 5%, 10%, and 15% of dry soil mass) were used as an external admixture of cement–silty soil to study the mechanical properties, curing mechanism, and microstructure of the modified soil in different ages of 7 d, 14 d, 28 d, and 60 d. The test results show that with the increase in cement and curing age, the UCS of the modified soil increases, and with the increase in the PP fiber and FA, the UCS of the modified soil first increases and then decreases; there is an optimal content of FA and PP fiber, which are 10 and 0.15%, respectively. A large amount of C-S-H and AFt substances are produced inside the modified soil to cover the surface of soil particles or fill in the pores between soil particles, forming a tight spatial network structure and improving the mechanical properties of the cement–soil. The intensity of the diffraction peaks of the mineral components within the modified soils is more influenced by the cement and age, and the effect of FA is weaker. The stress–strain curve of the modified soil is divided into elastic stage, plastic deformation stage, and strain-softening stage, and the specimens in each stage have corresponding deformation characteristics. By analyzing the behavioral characteristics and curing improvement mechanism of modified soil from the duo perspective of macro-mechanical properties and microstructural composition, it can provide some basis for the engineering application of silty soil

Chemical fingerprint analysis of Gentianae Radix et Rhizoma by high-performance liquid chromatography

Gentianae Radix et Rhizoma (also called “Longdan” in Chinese) is commonly used for eliminating damp-heat and quenching the fire of liver and gall bladder in traditional Chinese medicine. In this study, a novel and reliable method using high-performance liquid chromatography (HPLC) was developed both for quantitative analysis of four bioactive compounds (loganic acid, swertiamarin, gentiopicroside and sweroside) and chemical fingerprint analysis of “Longdan”. In quantitative analysis, four compounds showed good regressions (R2>0.9987) within the test ranges and the recovery of the method was in the range 97.61−102.49%. In fingerprint analysis, ten characteristic peaks were selected to evaluate the similarities of the crude drugs, and the HPLC chromatograms of twenty samples from different regions of China showed similar patterns. The results demonstrated that the combination of the quantitative and chromatographic fingerprint analyses offered an efficient way to evaluate the quality consistency of Gentianae Radix et Rhizoma

Radiotherapy Fraction in Limited-Stage Small Cell Lung Cancer in the Modern Era: A Systematic Review and Meta-Analysis of 8006 Reconstructed Individual Patient Data

The optimal thoracic radiotherapy (TRT) dose and fractionation for limited-stage small cell lung cancer (LS-SCLC) using modern techniques remain unclear. We conducted systematic review and meta-analyses of the efficacy and safety differences between definitive hypofractionated TRT (HypoTRT), conventional TRT (ConvTRT) and hyperfractionated TRT (HyperTRT), especially in the modern era. Eligible randomized controlled trials (RCTs), real-world cohorts, and single-arm trials published between 1990 and 2021 were identified. Two meta-analyses of overall survival (OS) were conducted: (i) a random-effects meta-analysis based on reconstructed individual-patient data (IPD) of all studies; and (ii) a Bayesian network meta-analysis based on study-level aggregated data (AD) of RCTs. The incidences of severe radiation-related toxicities were compared using the random-effects meta-regression model. Overall, 53 of the 30,031 publications met the inclusion criteria, and a total of 8006 IPD were reconstructed. After adjusting for key treatment variables and stratification by study type, there were no significant differences in the OS rates between the altered fractionation regimens (HypoTRT vs. HyperTRT, aHR [adjusted HR] = 1.05, 95% CI 0.93–1.19; ConvTRT vs. HyperTRT, aHR = 1.00, 95% CI 0·90–1.11; HypoTRT vs. ConvTRT, aHR = 1.05, 95% CI 0.91–1.20). In the modern era, the survival outcomes of all three schedules, while remaining comparable, have improved significantly. Results of the AD-based network meta-analysis were consistent with those of IPD analysis, and HypoTRT was ranked as the best regimen (SUCRA = 81%). There were no significant differences in toxicities between groups when using modern radiation techniques. In the modern era, no significant differences in OS or severe radiation-related toxicities were observed between altered schedules in LS-SCLC. HypoTRT may be associated with moderate and non-significant OS improvements, which should be further confirmed in prospective randomized phase III trials

Radiotherapy Fraction in Limited-Stage Small Cell Lung Cancer in the Modern Era: A Systematic Review and Meta-Analysis of 8006 Reconstructed Individual Patient Data.

Peer reviewed: TrueThe optimal thoracic radiotherapy (TRT) dose and fractionation for limited-stage small cell lung cancer (LS-SCLC) using modern techniques remain unclear. We conducted systematic review and meta-analyses of the efficacy and safety differences between definitive hypofractionated TRT (HypoTRT), conventional TRT (ConvTRT) and hyperfractionated TRT (HyperTRT), especially in the modern era. Eligible randomized controlled trials (RCTs), real-world cohorts, and single-arm trials published between 1990 and 2021 were identified. Two meta-analyses of overall survival (OS) were conducted: (i) a random-effects meta-analysis based on reconstructed individual-patient data (IPD) of all studies; and (ii) a Bayesian network meta-analysis based on study-level aggregated data (AD) of RCTs. The incidences of severe radiation-related toxicities were compared using the random-effects meta-regression model. Overall, 53 of the 30,031 publications met the inclusion criteria, and a total of 8006 IPD were reconstructed. After adjusting for key treatment variables and stratification by study type, there were no significant differences in the OS rates between the altered fractionation regimens (HypoTRT vs. HyperTRT, aHR [adjusted HR] = 1.05, 95% CI 0.93-1.19; ConvTRT vs. HyperTRT, aHR = 1.00, 95% CI 0·90-1.11; HypoTRT vs. ConvTRT, aHR = 1.05, 95% CI 0.91-1.20). In the modern era, the survival outcomes of all three schedules, while remaining comparable, have improved significantly. Results of the AD-based network meta-analysis were consistent with those of IPD analysis, and HypoTRT was ranked as the best regimen (SUCRA = 81%). There were no significant differences in toxicities between groups when using modern radiation techniques. In the modern era, no significant differences in OS or severe radiation-related toxicities were observed between altered schedules in LS-SCLC. HypoTRT may be associated with moderate and non-significant OS improvements, which should be further confirmed in prospective randomized phase III trials

Visualization and Analysis of Transport Accessibility Changes Based on Time Cartograms

Visualization of the spatial distribution pattern of transport accessibility and its changes can be crucial for understanding and assessing the performance of transportation systems. Compared to traditional maps representing geographic space, time cartograms modify geographic locations and spatial relationships to suit travelling times and thereby emphasize time–distance relationships in time-space. This study aims to facilitate a better understanding of the evolution of the spatial distribution pattern of accessibility by presenting a novel visualization and analysis methodology based on time cartograms. This is achieved by combining a visual qualitative display with a quantitative indicator analysis from multiple perspectives to show transport accessibility changes. Two indicators, namely, the shortest railway travel time (STRT) and spatiotemporal con-version parameter (STCP), are proposed to measure accessibility changes. Our work consists of the construction of time cartograms, the analysis of indicators, and the use of multiple views to show changes in transportation accessibility from multiple perspectives. The methodology is applied on the railway data of Beijing and selected 226 cities in China and to analyze changes in railway accessibility in 1996, 2003, 2009 and 2016. The results show that the development of transportation technology has continuously shortened the travel time, the time-space is gradually compressed, However, the difference in transport accessibility is getting bigger and bigger because of the uneven transportation development speeds between the regions