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Combination treatment with erlotinib plus bevacizumab has the potential to become a standard treatment regimen for patients with epidermal growth factor receptor mutation-positive (Systematic review and meta-analysis.The PubMed, Embase, Web of Science and Cochrane Library databases were searched, from inception to 15 January 2022.We included randomised controlled trials (RCTs), reported in English, assessing the efficacy of erlotinib plus bevacizumab versus erlotinib monotherapy in patients withThe main objective was to assess overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and adverse events (AEs). Two independent reviewers extracted data and assessed the risk of bias. A random-effects model was used where there was evidence for homogeneous effects.Four RCTs (reported across six publications) were included in the meta-analysis, with a total of 775 patients included in the pooled analyses of PFS, OS and ORR (387 in the erlotinib plus bevacizumab intervention group and 388 in the erlotinib group). Compared with the erlotinib alone group, the erlotinib plus bevacizumab group achieved a significantly prolonged PFS (HR: 0.59; 95% CI 0.49 to 0.72; p0.00001; IErlotinib plus bevacizumab for the treatment of patients with

A retrospective review of 9 patients diagnosed with empyema caused by

Although the inhibitory roles of ursolic acid (UA) have been established in various tumors, its effects on the stemness of non-small cell lung cancer (NSCLC) cells are still unclear. Here, we constructed NSCLC cells with paclitaxel resistance (A549-PR) and showed that A549-PR exhibited a remarkably stronger stemness than the parental A549 cells, which is evident by the increase of spheroid formation capacity, stemness marker expression, and ALDH1 activity. Additionally, UA significantly reduced the stemness and paclitaxel resistance of A549-PR cells. Mechanistic investigations revealed that UA inhibited the miR-149-5p/MyD88 signaling, which is responsible for UA-mediated effects on the stemness of A549-PR cells. Notably, miR-149-5p/MyD88 axis promoted the stemness of A549 cells, while inhibition of this axis attenuated the stemness of A549-PR cells. Therefore, these results suggest that UA could attenuate the stemness and chemoresistance of NSCLC cells through targeting miR-149-5p/MyD88 axis.

Silica/Cu composites generally fail to achieve the high strength due to the weak interfacial bonding between SiO2 and Cu. In the current work, the first use of silica quantum dots (SiO2 QDs) as a copper-based composite reinforcement. Silicon quantum dots (Si QDs) and copper acetate are employed as raw materials for spray pyrolysis to obtain an interconnected structure of SiO2 QDs/Cu2O, which achieve well-dispersion of the reinforcement and good interface combination in one step. The SiO2 QDs/Cu2O composite block is obtained by ball milling, hydrogen reduction, and SPS sintering. Micro interface structure and strengthening mechanism of the composites are investigated and presented in detail. Microstructural analysis discovers the Cu2O transition layer between SiO2 QDs and Cu matrix and well-dispersed SiO2 QDs in the Cu matrix. The good bonding of grain interface can significantly enhance the mechanical properties. The 1.2 wt% SiO2 QDs/Cu composite block exhibits an excellent ultimate tensile strength of 456.63 MPa, which is 101.68% higher than that of unreinforced Cu (227.39 MPa). Furthermore, the composite block maintains the high conductivity (83.27% IACS) and elongation (8.86%). Moreover, this work can promote the development of Cu matrix composites using ceramic reinforcement with an improved interface bonding.

The promise of strong physical unclonable functions (PUF) is to utilize the manufacturing variations of circuit elements to produce an independent and unpredictable response to any input challenge vector. Attacks on PUFs that predict the responses to input challenge vectors offer an interesting research problem. An attacking approach based on the optimization theory and side-channel information is proposed where we estimate the manufacturing variations of the circuit elements and predict the PUF’s responses to challenge vectors whose actual responses are not known. We apply this attacking approach on some popular PUF designs, including the Arbiter PUFs, the Memristor Crossbar PUFs, and the XOR Arbiter PUFs. Simulations show a substantial reduction in attack complexity compared with previously proposed machine-learning (ML)-based attacks: we achieve an average reduction of 66% in attack time compared with the ML approach. Despite some overhead, our approach is also applicable when the PUF responses are noisy.

To combat security threats to integrated circuit (IC) fabrication outsourcing, 2.5D integration can obfuscate the outsourced design by lifting a portion of the wires into an interposer layer. A security-aware physical design flow for 2.5D IC technology can then help defend against attacks by increasing the layout and functionality obfuscation.

Background: Anti-bacterial drugs are thought to be associated with several malignancies. Objective: We conducted a systematic review and meta-analysis to assess the association between antibacterial drug exposure and the risk of digestive system neoplasms. Methods: Relevant publications reporting a relationship between antibiotic use and the risk of cancer were identified in PubMed, EMBASE, and Cochrane Central Register through June 2018. The random-effects model was selected to pool the risk ratios (RRs) and determine 95% confidence intervals (95% CIs). We performed subgroup analyses by tumor organ site, individual antibacterial drug class, and drug dose accumulation. Results: A total of 17 eligible studies (four randomized trials and 13 observational studies) involving 77,284 cancer patients were included in our analyses. Anti-bacterial drug exposure slightly increased the risk of overall digestive system cancer (RR, 1.12; 95% CI, 1.10-1.14), stomach and small intestine (RR, 1.12; 95% CI, 1.07-1.17), anorectocolonic (RR, 1.08; 95% CI, 1.05-1.12), and hepatobiliary and pancreatic cancers (RR, 1.18; 95% CI, 1.14-1.22). For different anti-bacterial drugs classes, nitroimidazoles (RR, 1.17; 95% CI, 1.09-1.26) and quinolones (RR, 1.18; 95% CI, 1.11-1.26) showed a modest association with the risk of cancers incidence. The risks of digestive system cancers increased with the rise of drug dose accumulation: low (RR, 1.08; 95% CI, 1.05-1.11), intermediate (RR, 1.15; 95% CI, 1.12-1.18), and high (RR, 1.22; 95% CI, 1.18-1.26). Conclusions: Anti-bacterial drug exposure was associated with the risks of digestive system cancer occurrence in our analysis.

Physical limit of transistor miniaturization has driven chip design into the third dimension. 3D integration technology emerges as a viable option to improve chip performance and increase device density in a direction orthogonal to costly device scaling. As 3D integration is becoming a promising technology for next-generation chip design, recent years have seen a huge proliferation of research literature exploiting it from a security perspective. This paper presents a survey on the current state of 3D integration technology from a security perspective and summarizes its security opportunities and challenges. We report current research work on 3D integration based security in three major applications: supply chain attack prevention, side-channel attack mitigation, and trustworthy computing system design. The security advantages and opportunities of 3D integration in these security applications are highlighted. Besides, the paper discusses new vulnerabilities risen by 3D integration that require researchers’ attention. Based on the survey result, we summarize the distinct characteristics of 3D ICs and investigate their impacts on security-aware 3D IC designs.

Objective: CircPVT1 was identified as a tumor-promoted circRNA that is upregulated in several cancers. We researched clinical significance of circPVT1 in patients with non-small cell lung cancer (NSCLC) who received cisplatin combined with gemcitabine chemotherapy. Methods: Reverse transcriptase polymerase chain reaction assays were performed to detect circPVT1 expression in 96 patients with NSCLC. In addition, Kaplan-Meier methods were performed to analyze survival of patients with NSCLC. Results: There is no significant difference between circPVT1 and age, sex, histologic type, lymphatic invasion, or vascular invasion in patients with NSCLC and there is significant difference between circPVT1 and differentiation or p-TNM stage in patients with NSCLC. In addition, after cisplatin combined with gemcitabine chemotherapy, circPVT1 expression was decreased, and circPVT1 expression in the chemotherapy-resistant group was higher than in the chemotherapy-sensitive group. Survival of patients with NSCLC was associated with high circPVT1 expression. Conclusions: Our study revealed the clinical significance of circPVT1 in NSCLC after cisplatin combined with gemcitabine chemotherapy. After treatment, circPVT1 expression was decreased and circPVT1 expression in chemotherapy-resistant patients was higher than in chemotherapy-sensitive patients. Decreased circPVT1 expression in chemotherapy-sensitive patients is more notable than in chemotherapy-resistant patients. Therefore, it is possible to determine the effect of therapy after receiving chemotherapy by detecting the expression of circRNA in serum.

The hardware Trojan threat has motivated development of Trojan detection schemes at all stages of the integrated circuit (IC) lifecycle. While the majority of existing schemes focus on ICs at test-time, there are many unique advantages offered by post-deployment/run-time Trojan detection. However, run-time approaches have been underutilized with prior work highlighting the challenges of implementing them with limited hardware resources. In this paper, we propose three innovative low-overhead approaches for run-time Trojan detection which exploit the thermal sensors already available in many modern systems to detect deviations in power/thermal profiles caused by Trojan activation. The first one is a local sensor-based approach that uses information from thermal sensors together with hypothesis testing to make a decision. The second one is a global approach that exploits correlation between sensors and maintains track of the ICs thermal profile using a Kalman filter (KF). The third approach incorporates leakage power into the system dynamic model and apply extended KF (EKF) to track ICs thermal profile. Simulation results using state-of-the-art tools on ten publicly available Trojan benchmarks verify that all three proposed approaches can detect active Trojans quickly and with few false positives. Among three approaches, EKF is flawless in terms of the ten benchmarks tested but would require the most overhead.

In contrast to other studies in IC supply chain security where foundries are classified as either untrusted or trusted, a more realistic threat model is that the foundries are legally and economically obliged to perform trustworthy service, and it is the individual employees that introduce security risks. We call the above as the trusted foundry and untrusted employee (TFUE) model. Based on this model, we investigate new opportunities of establishing trustworthy operations in foundries made possible by double patterning lithography (DPL). DPL is used to setup two independent mask development lines which do not need to share any information. Under this setup, we consider the attack model where the untrusted employee(s) may try to insert Trojans into the circuit. As a countermeasure, we customize DPL to decompose the layout into two sub-layouts in such a way that each sub-layout individually expose minimum information to the untrusted employee.

Device scaling has increased interconnect power and delay to an extent that it is presenting a bottleneck to further performance gain. 3D/2.5D integration technology emerges as a viable option to improve chip performance in a direction orthogonal to costly device scaling. While the technology was originally proposed to enhance performance, it has unlocked new opportunities to thwart security threats in a global IC supply chain. Various obfuscation techniques based on 3D/2.5D IC technology have been proposed to protect IC designs from being pirated or tampered during outsourced fabrication. This chapter presents the current state of 3D/2.5D IC-based obfuscation techniques and highlights potential security opportunities and challenges of this technology in hardware intellectual property (IP) protection.

Attacks on hardware can take on many forms. As modern chips are designed and fabricated in a global supply chain, circuit designs are subject to counterfeiting, piracy, and malicious modification by untrusted foundries, which are known as supply chain attacks. In this paper, we first survey existing circuit obfuscation techniques that are proposed to thwart the aforementioned attacks. Then, we investigate the application of 2.5D/3D integration technologies in circuit obfuscation. We introduce a security-aware design flow that utilizes the 2.5D IC and logic locking technique to counter the supply chain attacks. Opportunities and challenges in the 2.5D/3D IC based security applications are highlighted.

Physical unclonable functions (PUFs) utilize manufacturing variations of circuit elements to produce unpredictable response to any challenge vector. The attack on PUF aims to predict the PUF response to all challenge vectors while only a small number of challenge-response pairs (CRPs) are known. The target PUFs in this paper include the Arbiter PUF (ArbPUF) and the Memristor Crossbar PUF (MXbarPUF). The manufacturing variations of the circuit elements in the targeted PUF can be characterized by a weight vector. An optimization-theoretic attack on the target PUFs is proposed. The feasible space for a PUF's weight vector is described by a convex polytope confined by the known CRPs. The centroid of the polytope is chosen as the estimate of the actual weight vector, while new CRPs are adaptively added into the original set of known CRPs. The linear behavior of both ArbPUF and MXbarPUF is proven which ensures that the feasible space for their weight vectors is convex. Simulation shows that our approach needs 71.4% fewer known CRPs and 86.5% less time than the state-of-the-art machine learning based approach.

Background Cyclin-dependent kinase 5 (CDK5) is an atypical CDK which plays a vital role in several cancers via regulating migration and motility of cancer cells. However, the clinicopathological impact and function of CDK5 in lung cancer remain poorly understood. The present study was aimed at exploring expression and clinicopathological significance of CDK5 in lung cancer. Methods There were 395 samples of lung tissue including 365 lung tumors (339 non-small cell lung cancers and 26 small cell lung cancers) and 30 samples of normal lung. CDK5 expression was detected by immunohistochemistry on lung tissue microarrays. Results Over expression was detected in lung cancer compared with normal lung tissues (P = 0.001). Furthermore, area under curve (AUC) of receiver operating characteristic (ROC) of CDK5 was 0.685 (95 % CI 0.564~0.751, P = 0.004). In lung cancer, we also discovered close correlations between CDK5 and pathological grading (r = 0.310, P

The increasing trend of outsourced fabrication in integrated circuit (IC) supply chain makes IC designs vulnerable to Intellectual Property (IP) piracy by untrusted foundries. 2.5D IC technology has shown the capability to counter this threat. By limiting the interposer layer of a 2.5D IC that contains inter-chip connections to be fabricated in a trusted foundry, the complete exposure of original design to an untrusted foundry is prevented. In this paper, we propose a security-aware physical design flow for 2.5D IC technology to prevent IP piracy based on IC testing rules and metrics. The partitioning phase utilizes the concepts of controllability and observability to conceal the functionality of a design and the placement phase generates obfuscated chip layouts that can withstand layout-geometry based attacks such as proximity attack. Simulation results show that our design flow is effective for producing secure chip layouts for outsourcing whose original netlist and functionality cannot be reverse-engineered based on layout-geometry information.

Due to the trend of outsourcing designs to foundries overseas, there has been an increasing threat of malicious modifications to the original integrated circuits (ICs), also known as hardware Trojans. Numerous countermeasures have been proposed. However, very little effort has been made to design-time strategies that help to make test-time or run-time detection of Trojans easier. In this paper, we characterize each cell's sensitivity to malicious modifications and develop an algorithm to select a subset of standard cells for a given circuit such that Trojans are easily detected using [1] when the circuit is synthesized on it. Experiments on 8 publicly available benchmarks show that using our method, we could detect on average 16.87% more Trojans with very small power/area overhead and no timing violations.

The problem of ordering task executions has been well studied under power, performance, and thermal constraints. However, it has been pursued less under security concerns. We have observed that different orders of task executions have different side-channel information leakage, thus having different security levels. In this paper, we first model the behavior of the attacker and then propose a secure algorithm for ordering aperiodic tasks that have soft deadlines. Our algorithm can keep a good balance between side-channel information leakage and total lateness. Experimental results show that the attacker could make 38.65% more error inferring the state of chip through side-channel analysis if tasks are scheduled using our algorithm as compared to using algorithms without security consideration (like EDF algorithm).