Evaluating Learning-to-Rank Models for Prioritizing Code Review Requests using Process Simulation

In large-scale, active software projects, one of the main challenges with code review is prioritizing the many Code Review Requests (CRRs) these projects receive. Prior studies have developed many Learning-to-Rank (LtR) models in support of prioritizing CRRs and adopted rich evaluation metrics to compare their performances. However, the evaluation was performed before observing the complex interactions between CRRs and reviewers, activities and activities in real-world code reviews. Such a pre-review evaluation provides few indications about how effective LtR models contribute to code reviews. This study aims to perform a post-review evaluation on LtR models for prioritizing CRRs. To establish the evaluation environment, we employ Discrete-Event Simulation (DES) paradigm-based Software Process Simulation Modeling (SPSM) to simulate real-world code review processes, together with three customized evaluation metrics. We develop seven LtR models and use the historical review orders of CRRs as baselines for evaluation. The results indicate that employing LtR can effectively help to accelerate the completion of reviewing CRRs and the delivery of qualified code changes. Among the seven LtR models, LambdaMART and AdaRank are particularly beneficial for accelerating completion and delivery, respectively. This study empirically demonstrates the effectiveness of using DES-based SPSM for simulating code review processes, the benefits of using LtR for prioritizing CRRs, and the specific advantages of several LtR models. This study provides new ideas for software organizations that seek to evaluate LtR models and other artificial intelligence-powered software techniques

Development and Validation of a Prognostic Nomogram for Extremity Soft Tissue Leiomyosarcoma

Background: Extremity soft tissue leiomyosarcoma (LMS) is a rare disease with a poor prognosis. The aim of this study is to develop nomograms to predict the overall survival (OS) and cancer-specific survival (CSS) of patients with extremity soft tissue LMS.Methods: Based on the Surveillance, Epidemiology, and End Results (SEER) database, 1,528 cases of extremity soft tissue LMS diagnosed between 1983 and 2015 were included. Cox proportional hazards regression modeling was used to analyze prognosis and obtain independent predictors. The independent predictors were integrated to develop nomograms predicting 5- and 10-year OS and CSS. Nomogram performance was evaluated by a concordance index (C-index) and calibration plots using R software version 3.5.0.Results: Multivariate analysis revealed that age ≥60 years, high tumor grade, distant metastasis, tumor size ≥5 cm, and lack of surgery were significantly associated with decreased OS and CSS. These five predictors were used to construct nomograms for predicting 5- and 10-year OS and CSS. Internal and external calibration plots for the probability of 5- and 10-year OS and CSS showed excellent agreement between nomogram prediction and observed outcomes. The C-index values for internal validation of OS and CSS prediction were 0.776 (95% CI 0.752–0.801) and 0.835 (95% CI 0.810–0.860), respectively, whereas those for external validation were 0.748 (95% CI 0.721–0.775) and 0.814 (95% CI 0.785–0.843), respectively.Conclusions: The proposed nomogram is a reliable and robust tool for accurate prognostic prediction in patients with extremity soft tissue LMS

TERT promoter methylation is associated with high expression of TERT and poor prognosis in papillary thyroid cancer

The telomerase reverse transcriptase (TERT) is overexpressed and associated with poor prognosis in papillary thyroid cancer (PTC), the most common subtype of thyroid cancer. The overexpression of TERT in PTC was partially attributed to transcriptional activation by two hotspot mutations in the core promoter region of this gene. As one of the major epigenetic mechanisms of gene expression regulation, DNA methylation has been proved to regulate several tumor-related genes in PTC. However, the association of TERT promoter DNA methylation with TERT expression and PTC progression is still unclear. By treating PTC cell lines with demethylating agent decitabine, we found that the TERT promoter methylation and the genes’ expression were remarkably decreased. Consistently, PTC patients with TERT hypermethylation had significantly higher TERT expression than patients with TERT hypomethylation. Moreover, TERT hypermethylated patients showed significant higher rates of poor clinical outcomes than patients with TERT hypomethylation. Results from the cox regression analysis showed that the hazard ratios (HRs) of TERT hypermethylation for overall survival, disease-specific survival, disease-free interval (DFI) and progression-free interval (PFI) were 4.81 (95% CI, 1.61-14.41), 8.28 (95% CI, 2.14-32.13), 3.56 (95% CI, 1.24-10.17) and 3.32 (95% CI, 1.64-6.71), respectively. The HRs for DFI and PFI remained significant after adjustment for clinical risk factors. These data suggest that promoter DNA methylation upregulates TERT expression and associates with poor clinical outcomes of PTC, thus holds the potential to be a valuable prognostic marker for PTC risk stratification

Changes of cardiac function: cardiac adaptation in patients with hypothyroidism assessed by cardiac magnetic resonance-a meta-analysis

ObjectiveThe meta-analysis aimed to explore the cardiac adaptation in hypothyroidism patients by cardiac magnetic resonance.Research methods and proceduresDatabases including PubMed, Cochrane Library, Embase, CNKI, and Sinomed for clinical studies of hypothyroidism on cardiac function changes. Databases were searched from the earliest data to 15 June 2023. Two authors retrieved studies and evaluated their quality. Review Manager 5.4.1 and Stata18 were used to analyze the data. This study is registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY), 202440114.ResultsSix studies were selected for further analysis. Five of them reported differences in cardiac function measures between patients with hypothyroidism and healthy controls, and three studies reported cardiac function parameters after treatment in patients with hypothyroidism. The fixed-effect model combined WMD values for left ventricular ejection fraction (LVEF) had a pooled effect size of -1.98 (95% CI -3.50 to -0.44], P=0.01), implying that LVEF was lower in patients with hypothyroidism than in healthy people. Analysis of heterogeneity found moderate heterogeneity (P = 0.08, I² = 50%). WMD values for stroke volume (SV), cardiac index (CI), left ventricular end-diastolic volume index(LVEDVI), left ventricular end-systolic volume (LESVI), and left ventricular mass index(LVMI) were also analyzed, and pooled effect sizes showed the CI and LVEDVI of patients with hypothyroidism ware significantly decrease (WMD=-0.47, 95% CI [-0.93 to -0.00], P=0.05, WMD=-7.99, 95%CI [-14.01 to -1.96], P=0.009, respectively). Patients with hypothyroidism tended to recover cardiac function after treatment [LVEF (WMD = 6.37, 95%CI [2.05, 10.69], P=0.004), SV (WMD = 7.67, 95%CI [1.61, 13.74], P=0.01), CI (WMD = 0.40, 95%CI [0.01, 0.79], P=0.05)], and there was no difference from the healthy controls.ConclusionHypothyroidism could affect cardiac function, although this does not cause significant heart failure. It may be an adaptation of the heart to the hypothyroid state. There was a risk that this adaptation may turn into myocardial damage. Cardiac function could be restored after treatment in patients with hypothyroidism. Aggressive levothyroxine replacement therapy should be used to reverse cardiac function.Systematic review registrationhttps://inplasy.com, identifier (INPLASY202440114)

Efficacy and safety of lenvatinib combined with PD-1/PD-L1 inhibitors plus Gemox chemotherapy in advanced biliary tract cancer

BackgroundLenvatinib combined with anti-PD-1 antibodies and systemic chemotherapy has demonstrated a relatively high antitumor activity for intrahepatic cholangiocarcinoma in phase 2 clinical trials. However, its efficacy and safety in advanced biliary tract cancer (BTC) has not been reported in a real-world study.MethodsPatients with advanced BTC who received lenvatinib combined with PD-1/PD-L1 inhibitors plus oxaliplatin and gemcitabine (Gemox) chemotherapy were retrospectively screened. The overall survival, progression-free survival, objective response rate, disease control rate, clinical benefit rate, and safety were evaluated.ResultsFifty-seven patients with advanced BTC were included in the study. The median follow-up time was 15.1 (95% CI: 13.6–19.7) months. The median overall survival and progression-free survival were 13.4 (95% CI: 10.0–NA), and 9.27 (95% CI: 7.1–11.6) months, respectively. The objective response rate, disease control rate and clinical benefit rate were 43.9% (95% CI: 31.8%–56.7%), 91.2% (95% CI: 81.1%–96.2%), and 73.7% (95% CI: 61.0%–83.4%), respectively. Subgroup analysis revealed that the first-line treatment group had a longer median progression-free survival (12.13 vs. 6.77 months, P<0.01) and median overall survival (25.0 vs. 11.6 months, P=0.029) than the non-first-line treatment group. Moreover, three patients underwent conventional surgery after treatment. All patients (100%) experienced adverse events, and 45.6% (26/57) experienced grade 3 or 4 adverse events. The most commonly observed grade 3 or 4 adverse events was myelosuppression (7/57, 12.3%). No grade 5 adverse events were reported.ConclusionLenvatinib combined with PD-1/PD-L1 inhibitors and Gemox chemotherapy represents an effective and tolerable treatment option in patients with advanced BTC

Aryl Hydrocarbon Receptor Promotes IL-10 Expression in Inflammatory Macrophages Through Src-STAT3 Signaling Pathway

The aryl hydrocarbon receptor (AhR) is an important immune regulator with a role in inflammatory response. However, the role of AhR in IL-10 production by inflammatory macrophages is currently unknown. In this study, we investigated LPS-induced IL-10 expression in macrophages from AhR-KO mice and AhR-overexpressing RAW264.7 cells. AhR was highly expressed after LPS stimulation through NF-κB pathway. Loss of AhR resulted in reduced IL-10 expression in LPS-induced macrophages. Moreover, the IL-10 expression was elevated in LPS-induced AhR-overexpressing RAW264.7 cells. Maximal IL-10 expression was dependent on an AhR non-genomic pathway closely related to Src and STAT3. Furthermore, AhR-associated Src activity was responsible for tyrosine phosphorylation of STAT3 and IL-10 expression by inflammatory macrophages. Adoptive transfer of AhR-expressing macrophages protected mice against LPS-induced peritonitis associated with high IL-10 production. In conclusion, we identified the AhR-Src-STAT3-IL-10 signaling pathway as a critical pathway in the immune regulation of inflammatory macrophages, It suggests that AhR may be a potential therapeutic target in immune response

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Study on Strength of Slip Soil–Tuff Contact Surfaces in Tuff Landslide Based on Model Test

In the exploration tunnels of the Xiageliao landslide, slide failures were found not only inside the slip soil but also on the contact surface between the slip soil and the tuff. The undisturbed slip soil was collected from the exploration tunnel for testing to explore the pattern of slide failure occurrence. The surfaces of concrete blocks of different shapes were used to simulate slip soil–tuff contact surfaces of different roughness. The shear strength of these contact surfaces with different roughness was tested using a large-scale shear test system and analyzed through comparison with the shear strength of the slip soil. The test results showed that the interface roughness significantly affected the shear strength of the slip soil contact interface and determined the shear failure mode of the slip soil. When the roughness is below a certain level, the shear strength of the contact surface is less than the soil shear strength, and when the roughness reaches a certain level, the shear strength of the contact surface exceeds the strength of the slip soil itself. Thus, the strength of the slip soil itself sometimes differs from the strength of the slip surface. Based on the Moore–Cullen law, the test results found a formula for calculating the contact surface shear strength. These results provide some references for the risk evaluation of landslides

Review of Additive Manufacturing Techniques for Large-Scale Metal Functionally Graded Materials

Functionally graded materials (FGMs), which constitute a new type of composite material, have received considerable attention in industry because of the spatial gradient of their composition and the microstructure-induced gradient in their material performance, which make them better suited for high-performance multifunctional applications. Additive manufacturing (AM) has become one of the most promising techniques for the manufacture of materials and structures because of its high flexibility. The combination of advanced materials (FGMs) and advanced manufacturing methods (AM) is expected to facilitate the further development of such engineering materials. In this paper, the definition, historical development and material gradient types of FGMs are introduced. The classification, process principle and typical research results of the AM of metal FGMs are summarized and discussed. In particular, the research status of wire and arc additive manufacture (WAAM), which is more suitable for the preparation of large-scale metal FGMs, is reviewed in detail according to the types of FGMs, and a double-wire bypass plasma arc additive manufacturing technique, which is suitable for inducing a gradient along the direction of single-pass cladding, is proposed. On the basis of this summary of the important achievements made to date, future research is proposed

Review of Additive Manufacturing Techniques for Large-Scale Metal Functionally Graded Materials

Functionally graded materials (FGMs), which constitute a new type of composite material, have received considerable attention in industry because of the spatial gradient of their composition and the microstructure-induced gradient in their material performance, which make them better suited for high-performance multifunctional applications. Additive manufacturing (AM) has become one of the most promising techniques for the manufacture of materials and structures because of its high flexibility. The combination of advanced materials (FGMs) and advanced manufacturing methods (AM) is expected to facilitate the further development of such engineering materials. In this paper, the definition, historical development and material gradient types of FGMs are introduced. The classification, process principle and typical research results of the AM of metal FGMs are summarized and discussed. In particular, the research status of wire and arc additive manufacture (WAAM), which is more suitable for the preparation of large-scale metal FGMs, is reviewed in detail according to the types of FGMs, and a double-wire bypass plasma arc additive manufacturing technique, which is suitable for inducing a gradient along the direction of single-pass cladding, is proposed. On the basis of this summary of the important achievements made to date, future research is proposed