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Healthcare vehicles such as ambulances are the key drivers for digital and pervasive remote care for elderly patients. Thus, Healthcare Vehicular Ad Hoc Network (H-VANET) plays a vital role to empower the digital and Intelligent Transportation System (ITS) for the smart medical world. Quality of Service (QoS) performance of vehicular communication can be improved through the development of a robust routing protocol having enhanced reliability and scalability. One of the most important issues in vehicular technology is allowing drivers to make trustworthy decisions, therefore building an efficient routing protocol that maintains an appropriate level of Quality of Service is a difficult task. Restricted mobility, high vehicle speeds, and continually changing topologies characterize the vehicular network environment. This paper contributes in four ways. First, it introduces adaptive, mobility-aware, and reliable routing protocols. The optimization of two routing protocols which are based on changing nature topologies of the network used for vehicular networks has been performed, amongst them, Optimized Link State Routing (Proactive) and Ad-hoc on Demand Distance Vector (Reactive) are considered for Packet Delivery Ratio (PDR) and throughput. Furthermore, Packet Loss Ratio (PLR), and end-to-end (E2E) delay parameters have also been calculated. Second, a healthcare vehicle system architecture for elderly patients is proposed. Third, a Platoon-based System model for routing protocols in VANET is proposed. Fourth, a dynamic channel model has been proposed for the vehicle to vehicle communication using IEEE8011.p. To optimize the QoS, the experimental setup is conducted in a discrete Network Simulator (NS-3) environment. The results reveal that the AODV routing protocol gives better performance for PDR as well as for PLR and the communication link established is also reliable for throughput. Where OLSR produces a large average delay. The adoptive mobility-aware routing protocols are potential candidates for providing Intelligent Transportation Systems with acceptable mobility, high reliability, high PDR, low PLR, and low E2E delay.

Device-to-Device (D2D) communications have recently attracted researchers, attention because of their numerous applications in industry verticals. It enables communications among devices without or with the partial involvement of a central system. To initiate a D2D communications device discovery and radio resource allocation is a critical task when devices have high mobility. Maintaining the quality-of-service and continuous connectivity requires a signaling burden. An efficient mobility management procedure is necessary to discover the neighboring devices in D2D communications systems. The Discovery of a massive number of devices requires an effective radio resource management procedure that causes signaling overhead. In 5G and beyond communication system, two mobility management methods exist; device discovery and beaconing. Since device density and traffic increases exponentially with high mobility, hence device discovery and beaconing increase the signaling overhead and energy consumption in power-limited devices. Thus, signaling overhead research needs much attention in 5G and beyond systems to meet the service requirements like accuracy, latency, and battery life. Therefore, the challenges and the techniques related to signaling overhead in D2D communications are presented.

Device to Device (D2D) communications is a candidate technology for the fifth-generation (5G) and beyond mobile networks and certainly that results in high throughput, less energy consumption, reduce delay, and data traffic offload. Proximity services are the key enablers of D2D communications. A D2D technology boosts the performance and capacity of a conventional cellular system through the proximity services. To initiate the proximity services, Device Discovery (DD) is one of the the primary tasks. A DD makes the decision for effective D2D communications in terms of accuracy, speed, and minimum energy consumption. To discover the neighbor devices, the discovery signal is transmitted directly or through some access points. The discovery signal is affected by invaders during transmission which causes inaccuracy, energy consumption, and latency. Therefore, security and privacy issues must be addressed, especially in discovery signal transmission. In this paper, security and privacy issues in DD are highlighted. It is comprehensive and proves that in-band is much better than out-band with practical and technological reasons. To enhance the scope of the research, network level, and system level Security and Privacy (S&P) issues in the distributed and centralized systems environment with or without central management are surveyed. Along with an extensive survey is provided for the most recent work on DD concerning security and privacy issues, and comparison among in-band and out-band DD is performed. In the end, open issues are identified as future work on DD security and privacy in D2D communications. It is a novel survey in terms of security and privacy aspects of DD with possible suggested solutions for readers' motivation.

Device to Device (D2D) communication was first considered in out-band to manage energy issues in the wireless sensor networks. The primary target was to secure information about system topology for successive communication. Now the D2D communication has been legitimated in in-band by the 3rd Generation Partnership Project (3GPP). To initiate D2D communication, Device Discovery (DD) is a primary task and every D2D application benefits from DD as an end to end link maintenance and data relay when the direct path is obstructed. The DD is facing new difficulties because of the mobility of the devices over static systems, and the mobility makes it more challenging for D2D communication. For in-band D2D, DD in a single cell and multi-cell, and dense area is not legitimated properly, causing latency, inaccuracy, and energy consumption. Among extensive studies on limiting energy consumption and latency, DD is one of the essential parts concentrating on access and communication. In this paper, a comprehensive survey on DD challenges, for example single cell/multi-cell and dense area DD, energy consumption during discovery, discovery delay, and discovery security, etc., has been presented to accomplish an effective paradigm of D2D networks. In order to undertake the device (user) needs, an architecture has been projected, which promises to overwhelm the various implementation challenges of DD. The paper mainly focuses on DD taxonomy and classification with an emphasis on discovery procedures and algorithms, a summary of advances and issues, and ways for potential enhancements. For ensuring a secure DD and D2D, auspicious research directions have been proposed, based on taxonomy.

Summary: Small cell lung cancers (SCLCs) have high mutational burden but are relatively unresponsive to immune checkpoint blockade (ICB). Using SCLC models, we demonstrate that inhibition of WEE1, a G2/M checkpoint regulator induced by DNA damage, activates the STING-TBK1-IRF3 pathway, which increases type I interferons (IFN-α and IFN-β) and pro-inflammatory chemokines (CXCL10 and CCL5), facilitating an immune response via CD8+ cytotoxic T cell infiltration. We further show that WEE1 inhibition concomitantly activates the STAT1 pathway, increasing IFN-γ and PD-L1 expression. Consistent with these findings, combined WEE1 inhibition (AZD1775) and PD-L1 blockade causes remarkable tumor regression, activation of type I and II interferon pathways, and infiltration of cytotoxic T cells in multiple immunocompetent SCLC genetically engineered mouse models, including an aggressive model with stabilized MYC. Our study demonstrates cell-autonomous and immune-stimulating activity of WEE1 inhibition in SCLC models. Combined inhibition of WEE1 plus PD-L1 blockade represents a promising immunotherapeutic approach in SCLC.

Summary: Concurrent loss-of-function mutations in STK11 and KEAP1 in lung adenocarcinoma (LUAD) are associated with aggressive tumor growth, resistance to available therapies, and early death. We investigated the effects of coordinate STK11 and KEAP1 loss by comparing co-mutant with single mutant and wild-type isogenic counterparts in multiple LUAD models. STK11/KEAP1 co-mutation results in significantly elevated expression of ferroptosis-protective genes, including SCD and AKR1C1/2/3, and resistance to pharmacologically induced ferroptosis. CRISPR screening further nominates SCD (SCD1) as selectively essential in STK11/KEAP1 co-mutant LUAD. Genetic and pharmacological inhibition of SCD1 confirms the essentiality of this gene and augments the effects of ferroptosis induction by erastin and RSL3. Together these data identify SCD1 as a selective vulnerability and a promising candidate for targeted drug development in STK11/KEAP1 co-mutant LUAD.