The multicenter, phase Ib CC-122-DLBCL-001 dose-expansion study (NCT02031419) explored the cereblon E3 ligase modulator (CELMoD) agent avadomide (CC-122) plus rituximab in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL). Patients received avadomide 3 mg/day 5 days on/2 days off plus rituximab 375 mg/m 2 on day 8 of cycle 1, day 1 of cycles 2 through 6, and day 1 of every third subsequent cycle for 2 years. Primary endpoints were safety and tolerability; preliminary efficacy was a secondary endpoint. A total of 68 patients were enrolled (DLBCL [ n  = 27], FL [ n  = 41; 31 lenalidomide-naïve, 10 lenalidomide-treated]). Median age was 62 years (range, 33–84 years), and patients had received a median of 3 (range, 1–8) prior regimens. Among patients with DLBCL, 66.7% had primary refractory disease (partial response or less to initial therapy). Among patients with FL, 65.9% were rituximab-refractory at study entry and 10.0% were lenalidomide-refractory. The most common any-grade avadomide-related adverse events (AEs) were neutropenia (63.2%), infections/infestations (23.5%), fatigue (22.1%), and diarrhea (19.1%). The most common grade 3/4 avadomide-related AEs were neutropenia (55.9%) infections/infestations (8.8%), and febrile neutropenia (7.4%). In patients with DLBCL, overall response rate (ORR) was 40.7% and median duration of response (mDOR) was 8.0 months. In patients with FL, ORR was 80.5% and mDOR was 27.6 months; response rates were similar in lenalidomide-naïve and -treated patients. Avadomide plus rituximab was well tolerated, and preliminary antitumor activity was observed in patients with R/R DLBCL and FL, including subgroups with typically poor outcomes. These results support further investigation of novel CELMoD agents in combination with rituximab in R/R DLBCL and FL.

Early prognosis of clinical efficacy is an urgent need for oncology drug development. Herein, we systemically examined the quantitative approach of tumor growth inhibition (TGI) and survival modeling in the space of relapsed and refractory multiple myeloma (MM), aiming to provide insights into clinical drug development. Longitudinal serum M-protein and progression-free survival (PFS) data from three phase III studies ( N  = 1367) across six treatment regimens and different patient populations were leveraged. The TGI model successfully described the longitudinal M-protein data in patients with MM. The tumor inhibition and growth parameters were found to vary as per each study, likely due to the patient population and treatment regimen difference. Based on a parametric time-to-event model for PFS, M-protein reduction at week 4 was identified as a significant prognostic factor for PFS across the three studies. Other factors, including Eastern Cooperative Oncology Group performance status, prior anti-myeloma therapeutics, and baseline serum ß2-microglobulin level, were correlated with PFS as well. In conclusion, patient disease characteristics (i.e., baseline tumor burden and treatment lines) were important determinants of tumor inhibition and PFS in MM patients. M-protein change at week 4 was an early prognostic biomarker for PFS.

Transportation is regarded as an industry with high energy consumption and high CO 2 emissions. Little attention has been paid to the environmental performance improvement of China’s transportation industry, especially in a stepwise improvement way. In this study, we first apply the closest targets DEA method to evaluate the environmental performance in the transportation industry of 30 provincial-level regions in China’s mainland from 2010 to 2017. Then, we incorporate the closest targets and context-dependent DEA model and thus conform a stepwise projection path for each inefficient province to improve environmental performance with less effort by the way of identifying a sequence of intermediate closest targets. The empirical study shows that the environmental performance of the transportation industry obtained from the closest targets model is greater than that obtained from the SBM model for each province. Among the three areas, the eastern area performs the best in environmental performance followed by the central region and western region. Shanghai has the best environmental performance. Additionally, compared with conventional DEA models, the proposed stepwise improvement method can generate easier and closer achieved targets for the inefficient provinces. Hainan, Yunnan, and Xinjiang provinces have the lowest environmental performance, which need four steps to achieve efficiency.

The work state of a launch vehicle is generally interpreted automatically on software. However, the sheer number of target parameters makes it difficult to realize real-time interpretation, and abnormal interpretation result does not necessarily mean that the vehicle is in abnormal state. This paper introduces the edge computing to achieve on-line interpretation and real-time diagnosis of a single launch vehicle. Firstly, the parameters to be interpreted were subjected to thresholding, leaving only those with high interpretation value. Next, the interpretation server layer of the real-time diagnosis model was built based on the attribute and value reduction algorithm of variable precision rough set (VPRS). Moreover, the higher-grade criteria were written in criterion modeling language (CML) and used to interpret the various higher-grade interpretation data pushed by the edge layer in real time. On this basis, the outputs of the edge layer and interpretation server layer were integrated to achieve the real-time diagnosis of single vehicle faults. Finally, the proposed model was proved feasible through the application in a launch vehicle.

Background: Helicobacter pylori infection is a common infection that affects human beings. This infection also affects children. Different diagnostic methods such as serology, stool antigen detection, rapid urease test and histology are used to detect this microorganism. Objectives: The aim of this study was to determine the correlation between serology and histology/rapid urease test. Patients and Methods: In this study, two groups (case and control) were selected and matched for age and sex. The case group comprised of 77 children with confirmed H. pylori infection, as they had positive rapid urease test and histology results. The control group included 77 healthy children. Both case and control groups were checked serologically for detection of anti H. pylori IgM, IgG and IgA antibody titers. Receiver operating characteristic (ROC)-analysis software was used for data analysis. Results: Amongst the case group 54.6% were female and 45.4% were male. The most common complaints were abdominal pain (96%) and anorexia (82%). Using ROC-analysis method three cut-off points for IgG, IgM and IgA were obtained. These points were 3.3 U/ML for IgA, 6.4 U/ML for IgM and 9.9 U/ML for IgG. Considering cut-off points for each antibody, higher levels were considered as positive and lower levels as negative. Antibody titers were compared with gold standard methods including histologic and rapid urease tests. IgA level had a sensitivity of 64%, specificity of 58%, accuracy of 59.3%, positive predictive value of 31.5% and negative predictive value of 76.9%. IgM level had a sensitivity of 76%, specificity of 36.1%, accuracy of 74.2%, positive predictive value of 31.5% and negative predictive value of 76.9%. IgG level had a sensitivity of 58.6%, specificity of 61.3%, accuracy of 60.6%, positive predictive value of 36.9% and negative predictive value of 79.3%. Conclusions: Therefore, these antibodies have a relatively high negative predictive value and a low positive predictive value. Thus, their negative results are more valuable. The most sensitive antibody is IgM and most specific antibody is IgG. However, the performances of all serological tests for H. pylori are poor in children and these tests should not be used for diagnosis of H. pylori infection and treatment decisions for the pediatric age group.

Background . The mainstay of treatment for advanced ovarian cancer is debulking surgery followed by chemotherapy that includes carboplatin and paclitaxel, but the prognosis is poor. This study is aimed at evaluating the efficacy and safety of cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (CRS+HIPEC) as first-line surgical treatment in patients with advanced ovarian cancer (AOC). Methods . FIGO stage III/IV AOC patients underwent CRS+HIPEC as first-line surgical treatment at our center from December 2007 to January 2020. The primary endpoint was survival, and the secondary endpoint was safety. Results . Among 100 patients, the median Karnofsky performance status (KPS) score was 80 (50-100), median peritoneal cancer index (PCI) was 19 (1-39), median completeness of cytoreduction (CC) score was 1 (0-3), number of organ regions removed was 4 (3-9), number of peritoneal regions removed was 4 (1-9), and number of anastomoses was 1 (0-4). The median follow-up was 36.8 months; 75 (75.0%) patients were still alive, and 25 (25.0%) had died. The median overall survival (mOS) was 87.6 (95% CI: 72.1-103.0) months, and the 1-, 2-, 3-, 4-, and 5-year survival rates were 94.1%, 77.2%, 68.2%, 64.2%, and 64.2%, respectively. Univariate analysis showed that better mOS correlated with an age ≤, ,  ml, , and CC score 0-1. Multivariate Cox analysis showed that CC was an independent factor for OS; patients who underwent CRS with a CC score 0-1 had a mPFS of 67.8 (95% CI: 48.3-87.4) months. The perioperative serious adverse event and morbidity rates were 4.0% and 2.0%, respectively. Conclusions . CRS+HIPEC improves survival for AOC patients with acceptable safety at experienced high-volume centers. Stringent patient selection and complete CRS are key factors for better survival.