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A three-phase multilevel inverter (MLI), synthesized with 31 levels in regard to its output voltage, is used to provide the AC supply to a three-phase, squirrel cage induction motor. The gating angles required for the 30 power switches on the MLI are optimized using both the genetic algorithm (GA) and the grey wolf optimizer (GWO), in which the optimal angles are determined through solving the trigonometric equations taken from Fourier analysis to target the minimum total harmonic distortion (THD) at the MLI output. A simulation model and an experimental prototype are developed for performance analysis and validation. The results demonstrate that the MLI is effectively able to produce 31 levels of three-phase AC output voltage, with the THD not exceeding 5% when loaded with a resistive load and a three-phase induction motor. The voltage and current are measured and recorded for different loads and operating conditions, including the amount of energy consumed by the load. The results of the frequency analysis demonstrate that most of the triple harmonics, which can harm the efficiency of the inverter, are cancelled. [ABSTRACT FROM AUTHOR]

Tracing disinfectant (e.g., chlorine) and contaminants evolution in water networks requires the solution of one-dimensional (1D) advection-reaction (AR) partial differential equations (PDEs). With the absence of analytical solutions in many scenarios, numerical solutions require high-resolution time and space discretizations, resulting in large model dimensions. This adds complexity to the water quality control problem. In addition, considering multispecies water quality dynamics rather than the single-species dynamics produces a more accurate description of the reaction dynamics under abnormal hazardous conditions (e.g., contamination events). Yet, these dynamics introduce a nonlinear reaction formulation to the model. To that end, solving nonlinear 1D AR PDEs in real time is critical to achieving monitoring and control goals for various scaled networks with a high computational burden. In this work, we propose a novel comprehensive framework to overcome the large-dimensionality issue by introducing different approaches for applying model order reduction (MOR) algorithms to the nonlinear system followed by applying a real-time water quality regulation algorithm that is based on an advanced model to maintain desirable disinfectant levels in water networks under multispecies dynamics. The performance of this framework is validated using rigorous numerical case studies under a wide range of scenarios demonstrating the challenges associated with regulating water quality under such conditions. [ABSTRACT FROM AUTHOR]

The Δ133p53β isoform is increased in many primary tumors and has many tumor-promoting properties that contribute to increased proliferation, migration and inflammation. Here we investigated whether Δ133p53β contributed to some of the most aggressive tumors that had metastasized to the brain. Δ133p53β mRNA expression was measured in lung, breast, melanoma, colorectal metastases and, where available, the matched primary tumor. The presence of Δ133p53β expression was associated with the time for the primary tumor to metastasize and overall survival once the tumor was detected in the brain. Δ133p53β was present in over 50% of lung, breast, melanoma and colorectal metastases to the brain. It was also increased in the brain metastases compared with the matched primary tumor. Brain metastases with Δ133p53β expressed were associated with a reduced time for the primary tumor to metastasize to the brain compared with tumors with no Δ133p53β expression. In-vitro-based analyses in Δ133p53β-expressing cells showed increased cancer-promoting proteins on the cell surface and increased downstream p-AKT and p-MAPK signaling. Δ133p53β-expressing cells also invaded more readily across a mock blood–brain barrier. Together these data suggested that Δ133p53β contributes to brain metastases by making cells more likely to invade the brain. [ABSTRACT FROM AUTHOR]

Wireless sensing is the state-of-the-art technique for next generation health activity monitoring. Smart homes and healthcare centres have a demand for multi-subject health activity monitoring to cater for future requirements. 5G-sensing coupled with deep learning models has enabled smart health monitoring systems, which have the potential to classify multiple activities based on variations in channel state information (CSI) of wireless signals. Proposed is the first 5G-enabled system operating at 3.75 GHz for multi-subject, in-home health activity monitoring, to the best of the authors' knowledge. Classified are activities of daily life performed by up to 4 subjects, in 16 categories. The proposed system combines subject count and activities performed in different classes together, resulting in simultaneous identification of occupancy count and activities performed. The CSI amplitudes obtained from 51 subcarriers of the wireless signal are processed and combined to capture variations due to simultaneous multi-subject movements. A deep learning convolutional neural network is engineered and trained on the CSI data to differentiate multi-subject activities. The proposed system provides a high average accuracy of 91.25% for single subject movements and an overall high multi-class accuracy of 83% for 4 subjects and 16 classification categories. The proposed system can potentially fulfill the needs of future in-home health activity monitoring and is a viable alternative for monitoring public health and well being. [ABSTRACT FROM AUTHOR]

A robust observer for performing power system dynamic state estimation (DSE) of a synchronous generator is proposed. The observer is developed using the concept of $\mathcal {L}_{\infty }$ stability for uncertain, nonlinear dynamic generator models. We use this concept to (i) design a simple, scalable, and robust dynamic state estimator and (ii) obtain a performance guarantee on the state estimation error norm relative to the magnitude of uncertainty from unknown generator inputs, and process and measurement noises. Theoretical methods to obtain upper and lower bounds on the estimation error are also provided. Numerical tests validate the performance of the $\mathcal {L}_{\infty }$ -based estimator in performing DSE under various scenarios. The case studies reveal that the derived theoretical bounds are valid for a variety of case studies and operating conditions, while yielding better performance than existing power system DSE methods. [ABSTRACT FROM AUTHOR]

Background Laparoscopic appendectomy (LA) is performed worldwide in the treatment of acute appendicitis (AP), even if complicated by localized peritonitis. However, the role of the LA in the treatment of AP complicated by generalized peritonitis (GP) is yet controversial. The present study aimed to highlight the efficacy and safety of the laparoscopic approach in AP complicated with GP. Settings This study took place in Mansura University Hospital, Faculty of Medicine. Patients and methods From September 2010 to May 2019, the patients were randomly assigned to undergo either an LA or exploratory open appendectomy (EOA). The demographics of the patient and preoperative parameters, including radiological evaluation, intraoperative finding, and postoperative complications, were evaluated. The follow-up period was 8 months to 2 years (mean: 18 months). Main outcomes The primary outcome of this study was early postoperative complications. Results A total of 120 patients, aged 38±11 years, were analyzed. Of these, 69 (57.5%) patients underwent LA, whereas two (2.9%) were converted to open surgery. All patients presented with diffuse peritonitis. The duration of operation was longer in the laparoscopic group than in the EOA group (P=0.001). No differences were detected in the preoperative patient comorbidities. The rate of postoperative surgical infection and intra-abdominal abscess was similar in the laparoscopic and EOA groups (P=0.3040 and 0.0754, respectively). However, the length of hospital stay was shorter in the laparoscopic group than that in the EOA group (P=0.001). Conclusions The laparoscopic approach for appendicitis complicated by GP is better than the open approach, and hence, it must be the first choice for surgery in the case of clear preoperative diagnosis. [ABSTRACT FROM AUTHOR]

The problem of placing or selecting sensors and control nodes plays a pivotal role in the operation of dynamic networks. This paper proposes optimal algorithms and heuristics to solve the Simultaneous Sensor and Actuator Selection Problem (SSASP) in linear dynamic networks. In particular, a sufficiency condition of static output feedback stabilizability is used to obtain the minimal set of sensors and control nodes needed to stabilize an unstable network. We then show that SSASP can be written as a mixed-integer nonconvex problem. To solve this nonconvex combinatorial problem, three methods based on (i) mixed-integer nonlinear programming, (ii) binary search algorithms, and (iii) simple heuristics are proposed. The first method yields optimal solutions to SSASP—given that some constants are appropriately selected. The second method requires a database of binary sensor/actuator combinations, returns optimal solutions, and necessitates no tuning parameters. The third approach is a heuristic that yields suboptimal solutions but is computationally attractive. The theoretical properties of these methods are discussed and numerical tests on dynamic networks showcase the trade-off between optimality and computational time. [ABSTRACT FROM AUTHOR]

The power grid is rapidly transforming, and while recent grid innovations increased the utilization of advanced control methods, the next-generation grid demands technologies that enable the integration of distributed energy resources (DERs)—and consumers that both seamlessly buy and sell electricity. This paper develops an optimization model and blockchain-based architecture to manage the operation of crowdsourced energy systems (CESs), with peer-to-peer (P2P) energy trading transactions (ETTs). An operational model of CESs in distribution networks is presented considering various types of ETT and crowdsourcees. Then, a two-phase operation algorithm is presented: Phase I focuses on the day-ahead scheduling of generation and controllable DERs, whereas Phase II is developed for hour-ahead or real-time operation of distribution networks. The developed approach supports seamless P2P energy trading between individual prosumers and/or the utility. The presented operational model can also be used to operate islanded microgrids. The CES framework and the operation algorithm are then prototyped through an efficient blockchain implementation, namely, the IBM Hyperledger Fabric. This implementation allows the system operator to manage the network users to seamlessly trade energy. Case studies and prototype illustration are provided. [ABSTRACT FROM AUTHOR]

Background: Both low volume interscalene and infraclavicular-subomohyoid blocks were suggested to provide shoulder analgesia with low risk of phrenic nerve block. The aim of this study was to compare the frequency of the phrenic nerve block between these two techniques.Method: Seventy-two patients scheduled for shoulder arthroscopy were included in this randomized controlled blind study. Before induction of general anesthesia, patients received low volume interscalene block using 5 mL of ropivacaine 0.5% (LVS group) or infraclavicular-subomohyoid block using 25 mL of ropivacaine 0.5% (ISO group). The diaphragmatic excursion was measured (using ultrasound) before the block and after surgery. If the ratio of postoperative to pre-block excursions was <25%, a phrenic nerve block was concluded. Secondary outcomes were: the duration of analgesia, the 24-hour morphine requirement, and patient satisfaction.Results: The phrenic nerve was blocked in 88.9% of patients in LVS group vs 5.6% in ISO group (P < 0.001). There was no significant difference between the two groups with regard to the duration of analgesia, the morphine consumption, and the patient satisfaction.Conclusion: Compared with the low volume interscalene block, the infraclavicular subomohyoid block resulted in a significantly less frequent phrenic nerve block and with no difference in postoperative analgesia. Therefore, it may be relevant to consider for patients who cannot tolerate a phrenic nerve block. [ABSTRACT FROM AUTHOR]

Algorithms are developed for the quickest detection of a change in statistically periodic processes. These are processes in which the statistical properties are nonstationary but repeat after a fixed time interval. It is assumed that the pre-change law is known to the decision maker but the post-change law is unknown. In this framework, three families of problems are studied: robust quickest change detection, joint quickest change detection and classification, and multi-slot quickest change detection. In the multi-slot problem, the exact slot within a period where a change may occur is unknown. Algorithms are proposed for each problem, and either exact optimality or asymptotic optimality in the low false alarm regime is proved for each of them. The developed algorithms are then used for anomaly detection in traffic data and arrhythmia detection and identification in electrocardiogram (ECG) data. The effectiveness of the algorithms is also demonstrated on simulated data. [ABSTRACT FROM AUTHOR]

The cadastral maps in Palestine were produced before 1967 by the Jordanians and British Mandate authorities. Most surveyors, as well as the different governmental and local authorities are using these maps as they are without some processing, as if these maps were free of errors and problems. Even though good for some applications, it was found that these maps suffer serious shortcomings concerning geometric accuracy and content (as they have not been updated). This paper aims to assess the internal geometric accuracy of the scanned Jordanian block maps using different georeferencing techniques. Based on the achieved results, it was found that the 2nd order polynomial looks to be the most promising one, especially when supported with directly measured field data. [ABSTRACT FROM AUTHOR]

The combination of decentralized control and networked control where control loops are closed through a network is called decentralized networked control system (DNCS). This paper introduces a general framework that converts a generic decentralized control configuration of non-networked systems to the general setup of networked control systems (NCS). Two design methods from the literature of decentralized control for non-networked systems were chosen as a base for the design of a controller for the networked systems, the first being an observer-based decentralized control, while the second is the well-known Luenberger combined observer-controller. The main idea of our design is to formulate the DNCS in the general form and then map the resulting system to the general form of the NCS. First, a method for designing decentralized observer-based controller is discussed. Second, an implementation using a network is analyzed for the two designs. Third, two methods to analyze the stability of the DNCS are also introduced. Fourth, perturbation bounds for stability of the DNCS have been derived. Finally, examples and simulation results are shown and discussed. [ABSTRACT FROM AUTHOR]

The insertion of communication networks in the feedback loops of control systems is a defining feature of modern control systems. These systems are often subject to unknown inputs in a form of disturbances, perturbations, or attacks. The objective of this paper is to design and analyse an observer for networked dynamical systems with unknown inputs. The network effect can be viewed as either a perturbation or time-delay to the exchanged signals. In this paper, we (1) review an unknown input observer (UIO) design for a non-networked system, (2) derive the networked unknown input observer (NetUIO) dynamics, (3) design a NetUIO such that the effect of higher delay order terms are nullified and (4) establish stability-guaranteeing bounds on the networked-induced time-delay and perturbation. The formulation and results derived in this paper can be generalised to scenarios and applications where the signals are perturbed due to a different source of perturbation or delay. [ABSTRACT FROM PUBLISHER]

Traditional control and monitoring of water quality in drinking water distribution networks (WDNs) rely on mostly model- or toolbox-driven approaches, where the network topology and parameters are assumed to be known. In contrast, system identification (SysID) algorithms for generic dynamic system models seek to approximate such models using only input-output data without relying on network parameters. The objective of this paper is to investigate SysID algorithms for water quality model approximation. This research problem is challenging due to (1) complex water quality and reaction dynamics; and (2) the mismatch between the requirements of SysID algorithms and the properties of water quality dynamics. In this paper, we present the first attempt to identify water quality models in WDNs using only input-output experimental data and classical SysID methods without knowing any WDN parameters. Properties of water quality models are introduced, the ensuing challenges caused by these properties when identifying water quality models are discussed, and remedial solutions are given. Through case studies, we demonstrate the applicability of SysID algorithms, show the corresponding performance in terms of accuracy and computational time, and explore the possible factors impacting water quality model identification. [ABSTRACT FROM AUTHOR]

Energy systems are complex systems consisting of different decision making entities: policy makers (or system operators), generation companies, utility companies, and consumers. In this paper, the focus is on the decisions made by different market competitors, such as the energy generation companies (GENCOs) and their interactions with the policy makers. The goals of the independent system operators (ISOs) in a deregulated market are to minimize the policy cost and to maximize renewable energy penetration. The problem formulation presented in this paper is aimed toward helping the ISO in modeling the lower-level GENCOs' decision problems. GENCOs compete in energy production, while maximizing their net present values and minimizing their capital investments. The market players' decisions result in a lower-level market equilibrium problem, which is formulated as a complementarity problem. The existence and uniqueness of the solution for the lower-level problem are shown. The main aims of the paper are to study the effect of stakeholders' preferences on the solution of the complementarity problem, to analyze the effect of the ISO's design parameters on the generation equilibrium quantities, and to simulate the stochastic complementarity problem using different techniques. The applications of the proposed decision-making framework include computational modeling of policy design scenarios, such as in feed-in-tariff policies. [ABSTRACT FROM AUTHOR]

Background: Major lower limb nerve blocks are relatively safe techniques. However, their efficacy for hip hemiarthroplasty is unknown. The objective of this study was to determine the effectiveness of combined femoral, sciatic, obturator and lateral femoral cutaneous (LFC) nerve blocks in providing adequate anesthesia for hip hemiarthroplasty. Materials and Methods: A total of 20 patients with fracture neck femur; who underwent hip hemiarthroplasty, participated in this observational study. In the induction room, all patients received ultrasound-guided femoral, proximal obturator, LFC and parasacral sciatic nerve blocks in addition to local infiltration at the proximal site of the skin incision. Anesthesia was considered to be adequate only if the surgery was completed without any requirement for opioid administration. Results: All patients (100% [95% confidence interval, 86-100%]) had adequate anesthesia. Seventeen patients (85% [95% confidence interval, 63-96%] had mild discomfort during the reduction of the prosthetic femur head back into the hip socket; however, no supplementary analgesics were required. Conclusion: The combined femoral, sciatic, obturator and LFC nerve blocks in addition to local infiltration at the proximal site of skin incision could provide adequate anesthesia for hip hemiarthroplasty. Light sedation before reduction of the prosthetic femur head back into the hip socket is advisable. [ABSTRACT FROM AUTHOR]

Sensor and actuator selection problems (SASPs) are some of the core problems in dynamic systems design and control. These problems correspond to determining the optimal selection of sensors (measurements) or actuators (control nodes) such that certain estimation/control objectives can be achieved. While the literature on SASPs are indeed inveterate, the vast majority of the work focuses on linear(ized) representation of the network dynamics, resulting in the placements of sensors or actuators (SAs) that are valid for confined operating regions. As an alternative, herein we propose a new general framework for addressing SASPs in nonlinear dynamic systems (NDSs), assuming that the inputs and outputs are linearly coupled with the nonlinear dynamics. This is investigated through (i) classifying and parameterizing the NDSs into various nonlinear function sets, (ii) utilizing rich Lyapunov theoretic formulations, and (iii) designing a new customized branch-and-bound (BnB) algorithm that exploits problem structure of the SASPs. The newly designed BnB routines are computationally more attractive than the standard one and also directly applicable to solve SASPs for linear systems. In contrast with contemporary approaches from the literature, our approach is suitable for finding the optimal SAs combination for stable/unstable NDSs that ensures stabilization of estimation error and closed-loop dynamics through a simple linear feedback control policy. [ABSTRACT FROM AUTHOR]

Chlorine is a widely used disinfectant and proxy for water quality (WQ) monitoring in water distribution networks (WDN). Chlorine-based WQ regulation and control aim to maintain pathogen-free water. Chlorine residual evolution within WDN is commonly modeled using the typical single-species decay and reaction dynamics that account for network-wide, spatiotemporal chlorine concentrations only. Prior studies have proposed more advanced and accurate descriptions via multi-species dynamics. This paper presents a host of novel state-space, control-theoretic representations of multi-species water quality dynamics. These representations describe decay, reaction, and transport of chlorine and a fictitious reactive substance to reflect realistic complex scenarios in WDN. Such dynamics are simulated over space- and time-discretized grids of the transport partial differential equation and the nonlinear reaction ordinary differential equation. To that end, this paper (i) provides a full description on how to formulate a high fidelity model-driven state-space representation of the multi-species water quality dynamics and (ii) investigates the applicability and performance of different Eulerian-based schemes (Lax–Wendroff, backward Euler, Crank–Nicolson, and Implicit Upwind) and Lagrangian-based schemes (Method of Characteristics) in contrast with EPANET and its EPANET-MSX extension. Numerical case studies reveal that the Implicit Upwind scheme, Method of Characteristics, and Lax–Wendroff scheme outperform other schemes with reliable results under reasonable assumptions and limitations. [ABSTRACT FROM AUTHOR]

The increasing access to inexpensive sensors, computing power, and more accurate forecasting of storm events provides unique opportunities to shift flood management practices from static approaches to an optimization-based real-time control (RTC) of urban drainage systems. Recent studies have addressed a plethora of strategies for flood control in stormwater reservoirs; however, advanced control theoretic techniques are not yet fully investigated and applied to these systems. In addition, there is an absence of a coupled integrated control model for systems composed of watersheds, reservoirs, and channels for flood mitigation. To this end, we developed a novel nonlinear state-space model of hydrologic and hydrodynamic processes in watersheds, reservoirs, and one-dimensional channels. The model was tested under different types of reservoir control strategies based on real-time measurements (reactive control) and predictions of the future behavior of the system (predictive control) using rainfall forecastings. We applied the modeling approach in a system composed of a single watershed, reservoir, and channel connected in series for the observed rainfall data in San Antonio. Results indicate that for flood mitigation, the predictive control strategy outperforms the reactive controls not only when applied for synthetic design storm events, but also for a continuous simulation. Moreover, the predictive control strategy requires smaller valve operations while still guaranteeing efficient hydrological performance. From the results, we recommend the use of the nonlinear model predictive control strategy to control stormwater systems because of the ability to handle different objective functions, which can be altered according to rainfall forecasting and shift the reservoir operation from flood-based control to strategies focused on increasing detention times, depending on the forecasting. [ABSTRACT FROM AUTHOR]

Abstract: An improved post-deposition treatment for CdS/CdTe photovoltaic devices has been developed. Aqueous solutions containing pyrrole and sodium chloride provide a treatment of the CdTe surface when the device is illuminated with visible light. Evaporating gold metal on the CdTe surface completes the device structure. Comparison of the JV characteristics of the device treated with illumination to those not illuminated reveals a significant enhancement in device output. While most of the electronic properties (J sc, FF, R s and R sh) are very similar the V oc for the treated sample is higher (circa 0.79V versus 0.71V) leading to a higher efficiency of 12.3% for the treated cell versus 11.0% for the untreated cell. The performance of this treatment is very much the same as that observed when the photochemically induced treatment employs aniline, the benefit of the herein described method is the decreased level of toxicity associated with pyrrole relative to that of aniline. Characterization of the CdTe surface with SEM does not reveal any noticeable features and could be interpreted as indicating that treatment leads to a very thin coating of material. The GIXRD data reveal the presence of elemental tellurium on the surface of the CdTe. [Copyright &y& Elsevier]

Transformers have become the state-of-the-art architectures for various tasks in Natural Language Processing (NLP) and Computer Vision (CV); however, their space and computational complexity present significant challenges for real-world applications. A promising approach to address these issues is the introduction of sparsity, which involves the deliberate removal of certain parameters or activations from the neural network. In this systematic literature review, we aimed to provide a comprehensive overview of current research on sparsity in transformers. We analyzed the different sparsity techniques applied to transformers, their impact on model performance, and their efficiency in terms of time and space complexity. Moreover, we identified the major gaps and challenges in the existing literature. Our study also highlighted the importance of investigating sparsity in transformers for computational efficiency, reduced resource requirements, scalability, environmental impact, and hardware-algorithm co-design. By synthesizing the current state of research on sparsity in transformer-based models, we also provided valuable insights into their efficiency, impact on model performance, and potential trade-offs, contributing to advancing the field further. [ABSTRACT FROM AUTHOR]

• Bayesian optimization is applied for water quality control in distribution networks. • Coupling BO with EPANET to optimize the scheduling of multiple chlorine boosters. • Systematic testing of acquisition functions, covariance kernels, and BO parameters. • Results revealed substantial variability in the performance of different BO methods. • Choice of acquisition function more influential than choice of covariance kernel. Chlorine remains the most widely used disinfectant in drinking water treatment and distribution systems worldwide. To maintain a minimum residual throughout the distribution network, chlorine dosage needs to be regulated by optimizing the locations of chlorine boosters and their scheduling (i.e., chlorine injection rates). Such optimization can be computationally expensive since it requires numerous evaluations of water quality (WQ) simulation models. In recent years, Bayesian optimization (BO) has garnered considerable attention due to its efficiency in optimizing black-box functions in a wide range of applications. This study presents the first attempt to implement BO for the optimization of WQ in water distribution networks. The developed python-based framework couples BO with EPANET-MSX to optimize the scheduling of chlorine sources, while ensuring the delivery of water that satisfies water quality standards. Using Gaussian process regression to build the BO surrogate model, a comprehensive analysis was conducted to evaluate the performance of different BO methods. To that end, systematic testing of different acquisition functions, including the probability of improvement, expected improvement, upper confidence bound, and entropy search, in conjunction with different covariance kernels, including Matérn, squared-exponential, gamma-exponential, and rational quadratic, was conducted. Additionally, a thorough sensitivity analysis was performed to understand the influence of different BO parameters, including the number of initial points, covariance kernel length scale, and the level of exploration vs exploitation. The results revealed substantial variability in the performance of different BO methods and showed that the choice of the acquisition function has a more profound influence on the performance of BO than the covariance kernel. [ABSTRACT FROM AUTHOR]

The purpose of this Special Section is to provide an account of the state-of-the-art and perspectives for future research in the design and analysis of monitoring and control methods for smart water systems. This paper provides an overview of the six articles in the special section. Specifically, the special section consists of four review articles, as well as one vision and one tutorial article. These articles provide a review of leakage detection and isolation, a review of contamination event diagnosis, a review of state- space modelling of multiple reacting species in drinking water systems, a review of the application of model predictive control in Water Systems, a vision of optimizing pressure management and self-cleaning, as well as a tutorial for leakage detection and mitigation of potential contamination risk. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Our case report demonstrates extremely uncommon data associated with MIS‐A, such as cholestatic jaundice, anemia, and quickly progressing pneumonia. IVIG and pulse steroid medications are the best treatments for improving clinical outcomes. We report a case of multiple organ dysfunctions due to MIS‐A in an adult with a history of suspected COVID‐19. Our case demonstrates extremely uncommon data associated with MIS‐A, such as cholestatic jaundice, anemia, and quickly progressing pneumonia. IVIG and pulse steroid medications are the best treatments for improving clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a common complex genetic condition of women in the reproductive age. PCOS is a heterogeneous syndrome characterized by clinical/biochemical androgen excess, ovulatory dysfunction and polycystic ovaries. Metformin therapy has been proved to improve fertility in patients with PCOS, inducing not only high ovulation and pregnancy rates, but also reducing the incidence of miscarriages. Aim of the Work: This study was aimed to evaluate the effects of metformin therapy on hormonal profile and endometrial tissue, including pattern of immunohistochemical expression of androgen receptors (AR), in patients with PCOS. Patients and Methods: 100 patients with PCOS were included in this study. Each investigated case was submitted to detailed medical history, clinical examination that included body hair distribution, body weight, height and body mass index (BMI), transvaginal ultrasound, laboratory investigations ( included fasting insulin, free testosterone, LH and FSH levels). Endometrial pipelle samples were taken for histopathological evaluation and assessment of androgen receptor expression. These investigations were done before and after three months of metformin treatment. Results: A significant decrease of BMI of the investigated cases after metformin therapy was observed (P value <0.003). There was a significant decrease of LH level after metformin therapy from 9.17±2.84 Miu/ml to 6.18±3.6 Miu/ml and of fasting insulin level from 14.3±4.3 to 8.2±5.9. Insignificant increase of FSH level from 3.87±1.8 to 4.85±2.6 and also insignificant decrease of free testosterone level from 1.58±o.83 to 1.38±1.4 were also observed. Histopathological results of the endometrial specimens before metformin therapy revealed histologic features of early proliferative endometrium in 64 cases, 20 cases with a late proliferative endometrium and examination of the remaining 16 cases revealed features of simple endometrial hyperplasia. Among the 64 cases diagnosed as early proliferative endometrium before the therapy, 60 cases showed features of a late proliferative endometrium after treatment and the remaining 4 cases showed no histomorphologic changes. Among the 20 cases diagnosed as a late proliferative endometrium before therapy, 6 cases showed features of early secretory phase after therapy, 6 cases showed features of mid-secretory endometrium while the remaining 8 cases showed a late secretory endometrium that indicate successful ovulation after therapy. Regression of hyperplasia after therapy was noted in 6 of the 16 cases diagnosed as simple endometrial hyperplasia. Immunohistochemical (IHC) results revealed marked increase in endometrial AR expression in patients with PCOS compared to the normal fertile controls (p<0.004). Also, a significant decrease of AR expression in endometrial epithelial and stromal cells after metformin administration in patients with PCOS was noted (p<0.003). Conclusion: Metformin therapy restores normal menstrual cyclicity in patients with PCOS, induces ovulation and showing significant decrease in endometrial AR expression. [ABSTRACT FROM AUTHOR]

Buildings-to-grid (BtG) integration simulations are becoming prevalent due to the development of smart buildings and smart grid. Buildings are the major energy consumers of the total electricity production worldwide. There is an urgent need to integrate buildings with smart grid operation to accommodate the needs of flexible load controls due to the increasing of renewable energy resources. In the imminent future, smart buildings can contribute to grid stability by changing their overall demand patterns in response to grid operations. Meanwhile, building thermal energy consumption is also maintained by building operators to satisfy occupants’ thermal comforts. However, explicit large-scale demonstrations based on a simulation platform that integrates building occupancy, building physics, and grid physics at community level have not been explored. This study develops an occupancy behavior driven BtG optimization platform that can simulate, predict and optimize indoor temperature and energy consumption of buildings, generator setpoint and deviation while maintaining acceptable grid frequency. Authors have tested the framework on two standard power networks. The results show that the integrated framework can provide potential cost savings up to 60% comparing with the decoupled operation. [ABSTRACT FROM AUTHOR]

Wireless communication has become an integral part of modern vehicles. However, securing the information exchanged between interconnected terminals poses a significant challenge. Effective security solutions should be computationally inexpensive, ultra-reliable, and capable of operating in any wireless propagation environment. Physical layer secret key generation has emerged as a promising technique, which leverages the inherent randomness of wireless-channel responses in amplitude and phase to generate high-entropy symmetric shared keys. The sensitivity of the channel-phase responses to the distance between network terminals makes this technique a viable solution for secure vehicular communication, given the dynamic behavior of these terminals. However, the practical implementation of this technique in vehicular communication is hindered by fluctuations in the communication link between line-of-sight (LoS) and non-line-of-sight (NLoS) conditions. This study introduces a key-generation approach that uses a reconfigurable intelligent surface (RIS) to secure message exchange in vehicular communication. The RIS improves the performance of key extraction in scenarios with low signal-to-noise ratios (SNRs) and NLoS conditions. Additionally, it enhances the network's security against denial-of-service (DoS) attacks. In this context, we propose an efficient RIS configuration optimization technique that reinforces the signals received from legitimate users and weakens the signals from potential adversaries. The effectiveness of the proposed scheme is evaluated through practical implementation using a 1-bit RIS with 64 × 64 elements and software-defined radios operating within the 5G frequency band. The results demonstrate improved key-extraction performance and increased resistance to DoS attacks. The hardware implementation of the proposed approach further validated its effectiveness in enhancing key-extraction performance in terms of the key generation and mismatch rates, while reducing the effect of the DoS attacks on the network. [ABSTRACT FROM AUTHOR]

Cerebral arteriovenous malformations (AVMs) can be treated by microsurgery, stereotactic radiosurgery (SRS) as a stand-alone procedure, or combining embolization and conservative management. This single-center, retrospective review explored the outcomes of patients treated with SRS alone, embolization before SRS (ESRS), or conservative management for cerebral AVMs. Demographic details, Spetzler-Martin grade, SRS dose, obliteration, time to obliteration, imaging modality, rebleed, disease-specific mortality, and post-SRS complications were collected. Chi-square tests of independence and 1-way analysis of variance/Kruskal-Wallis tests were performed. Two-hundred and thirty-nine patients were treated with SRS alone, 37 were treated with ESRS, and 83 were conservatively managed. Obliteration rates were 78% (SRS alone) and 70% (ESRS). Rebleed rates were comparable among SRS alone (4%), ESRS (0%), and conservative management (8%). Disease-specific mortality rates were significantly lower for SRS alone (1%) and ESRS (0%) compared with conservative management (6%, X2 [2, n = 358] = 7.50, P = 0.024). Post-SRS complications occurred with SRS alone only and included radiation necrosis (n = 5), cavernous malformations (n = 2), and stroke (n = 1). Obliteration, rebleed, and disease-specific mortality rates were comparable among pediatric (<18 years), nonelderly (18−59 years), and elderly (≥60 years) age groups. Findings suggest that SRS and ESRS are safe and effective treatments for cerebral AVM (when quantified by obliteration, rebleed, and disease-specific mortality rates). With multinational, prospective, randomized controlled trials with long follow-up periods, the effectiveness and safety of SRS and ESRS compared with conservative management for AVM will be further clarified. [ABSTRACT FROM AUTHOR]

Background: The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis. Methods: PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression. Results: Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death. Conclusions: PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas. [ABSTRACT FROM AUTHOR]

Background The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis Methods PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression Results Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death. Conclusions PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas. [ABSTRACT FROM AUTHOR]

This study focuses on improving the sustainability of electrical supply in the healthcare system in the UK, to contribute to current efforts made towards the 2050 net-zero carbon target. As a case study, we propose a grid-connected hybrid renewable energy system (HRES) for a hospital in the south-east of England. Electrical consumption data were gathered from five wards in the hospital for a period of one year. PV-battery-grid system architecture was selected to ensure practical execution through the installation of PV arrays on the roof of the facility. Selection of the optimal system was conducted through a novel methodology combining multi-objective optimisation and data forecasting. The optimisation was conducted using a genetic algorithm with two objectives (1) minimisation of the levelised cost of energy and (2) CO 2 emissions. Advanced data forecasting was used to forecast grid emissions and other cost parameters at two year intervals (2023 and 2025). Several optimisation simulations were carried out using the actual and forecasted parameters to improve decision making. The results show that incorporating forecasted parameters into the optimisation allows to identify the subset of optimal solutions that will become sub-optimal in the future and, therefore, should be avoided. Finally, a framework for choosing the most suitable subset of optimal solutions was presented. [ABSTRACT FROM AUTHOR]

Dynamic state estimation (DSE) accurately tracks the dynamics of a power system and provides the evolution of the system state in real-time. This paper focuses on the control and protection applications of DSE, comprehensively presenting different facets of control and protection challenges arising in modern power systems. It is demonstrated how these challenges are effectively addressed with DSE-enabled solutions. As precursors to these solutions, reformulation of DSE considering both synchrophasor and sampled value measurements and comprehensive comparisons of DSE and observers have been presented. The usefulness and necessity of DSE based solutions in ensuring system stability, reliable protection and security, and resilience by revamping of control and protection methods are shown through examples, practical applications, and suggestions for further development. [ABSTRACT FROM AUTHOR]

The molecular structure of the carotenoid lactoside P457, (3 S,5 R,6 R,3′ S,5′ R,6′ S)-13′- cis-5,6-epoxy-3′,5′-dihydroxy-3-(β- d-galactosyl-(1→4)-β- d-glucosyl)oxy-6′,7′-didehydro-5,6,7,8,5′,6′-hexahydro-β,β-caroten-20-al, was confirmed by spectroscopic methods using Symbiodinium sp. strain NBRC 104787 cells isolated from a sea anemone. Among various algae, cyanobacteria, land plants, and marine invertebrates, the distribution of this unique diglycosyl carotenoid was restricted to free-living peridinin-containing dinoflagellates and marine invertebrates that harbor peridinin-containing zooxanthellae. Neoxanthin appeared to be a common precursor for biosynthesis of peridinin and P457, although neoxanthin was not found in peridinin-containing dinoflagellates. Fucoxanthin-containing dinoflagellates did not possess peridinin or P457; green dinoflagellates, which contain chlorophyll a and b, did not contain peridinin, fucoxanthin, or P457; and no unicellular algae containing both peridinin and P457, other than peridinin-containing dinoflagellates, have been observed. Therefore, the biosynthetic pathways for peridinin and P457 may have been coestablished during the evolution of dinoflagellates after the host heterotrophic eukaryotic microorganism formed a symbiotic association with red alga that does not contain peridinin or P457. [ABSTRACT FROM AUTHOR]

Background: Systemic lupus erythematosus (SLE) has been associated with excess cardiovascular morbidity and mortality. The underlying causes of this phenomenon are still relatively unknown, but it is believed that a combination of classic and new cardiovascular risk factors including chronic low-grade inflammation may be involved. Objective: This study was designed to assess the relationship between serum uric acid level and the CVD complications in SLE patients. Patients and methods: This clinical-based prospective study was carried out on 60 patients. This study was conducted in Sohag University Hospital. The patients in the study were divided into two equal groups: Group (A) included patients with normal S.UA in between (2.4-6.0 mg/dl) for females and (3.4-7.0) for males and group (B) that included patients with elevated S.UA higher than the upper limit. Results: Serum uric acid was significantly increased in patients with pulmonary hypertension than those who didn’t develop pulmonary hypertension (P = 0.02). serum uric acid level was insignificantly different as regards ECG and ECH findings except for segmental wall motion abnormality (SWMA) and pulmonary hypertension. There was a positive mild significant correlation between serum uric acid and cholesterol level (r = 0.35 and P = 0.01) and duration of treatment (r = 0.29 and P = 0.03), but insignificant with triglyceride level (r = 0.22 and P = 0.08) and EULAR\ACR2019 score (r = 0.01 and P = 093). Conclusion: Higher serum uric acid levels are associated with global damage in patients with SLE. Serum uric acid was associated with arterial stiffness. Nevertheless, serum uric acid might be an ancillary indicator of subclinical atherosclerosis in SLE women with clinically evident atherosclerotic cardiovascular disease. [ABSTRACT FROM AUTHOR]

The prognosis for people with the high-grade brain tumor glioblastoma is very poor, due largely to low cell death in response to genotoxic therapy. The transcription factor BCL6, a protein that normally suppresses the DNA damage response during immune cell maturation, and a known driver of B-cell lymphoma, was shown to mediate the survival of glioblastoma cells. Expression was observed in glioblastoma tumor specimens and cell lines. When BCL6 expression or activity was reduced in these lines, increased apoptosis and a profound loss of proliferation was observed, consistent with gene expression signatures suggestive of anti-apoptotic and pro-survival signaling role for BCL6 in glioblastoma. Further, treatment with the standard therapies for glioblastoma—ionizing radiation and temozolomide—both induced BCL6 expression in vitro, and an in vivo orthotopic animal model of glioblastoma. Importantly, inhibition of BCL6 in combination with genotoxic therapies enhanced the therapeutic effect. Together these data demonstrate that BCL6 is an active transcription factor in glioblastoma, that it drives survival of cells, and that it increased with DNA damage, which increased the survival rate of therapy-treated cells. This makes BCL6 an excellent therapeutic target in glioblastoma—by increasing sensitivity to standard DNA damaging therapy, BCL6 inhibitors have real potential to improve the outcome for people with this disease. [ABSTRACT FROM AUTHOR]

This paper introduces the time synchronization attack rejection and mitigation (TSARM) technique for time synchronization attacks over the global positioning system (GPS). The technique estimates the clock bias and drift of the GPS receiver along with the possible attack contrary to previous approaches. Having estimated the time instants of the attack, the clock bias and drift of the receiver are corrected. The proposed technique is computationally efficient and can be easily implemented in real time in a fashion complementary to standard algorithms for position, velocity, and time estimation in off-the-shelf receivers. The performance of this technique is evaluated on a set of collected data from a real GPS receiver. Our method renders excellent time recovery consistent with the application requirements. The numerical results demonstrate that the TSARM technique outperforms competing approaches in the literature. [ABSTRACT FROM PUBLISHER]

Intelligent transportation systems are an emerging technology that facilitates real-time vehicle-to-everything communication. Hence, securing and authenticating data packets for intra- and inter-vehicle communication are fundamental security services in vehicular ad-hoc networks (VANETs). However, public-key cryptography (P K C) is commonly used in signature-based authentication, which consumes significant computation resources and communication bandwidth for signatures generation and verification, and key distribution. Therefore, physical layer-based secret key extraction has emerged as an effective candidate for key agreement, exploiting the randomness and reciprocity features of wireless channels. However, the imperfect channel reciprocity generates discrepancies in the extracted key, and existing reconciliation algorithms suffer from significant communication costs and security issues. In this paper, P K C -based authentication is used for initial legitimacy detection and exchanging authenticated probing packets. Accordingly, we propose a blockchain-based reconciliation technique that allows the trusted third party (T T P) to publish the correction sequence of the mismatched bits through a transaction using a smart contract. The smart contract functions enable the T T P to map the transaction address to vehicle-related information and allow vehicles to obtain the transaction contents securely. The obtained shared key is then used for symmetric key cryptography (S K C)-based authentication for subsequent transmissions, saving significant computation and communication costs. The correctness and security robustness of the scheme are proved using Burrows–Abadi–Needham (BAN)-logic and Automated Validation of Internet Security Protocols and Applications (AVISPA) simulator. We also discussed the scheme's resistance to typical attacks. The scheme's performance in terms of packet delay and loss ratio is evaluated using the network simulator (OMNeT++). Finally, the computation analysis shows that the scheme saves ∼ 99 % of the time required to verify 1000 messages compared to existing P K C -based schemes. [ABSTRACT FROM AUTHOR]

Ultraviolet (UV) radiation induces DNA damage, oxidative stress, and inflammatory processes in skin, resulting in photoaging. Natural botanicals have gained considerable attention due to their beneficial protection against the harmful effects of UV irradiation. The present study aimed to evaluate the ability of curcumin (Cur) to protect human dermal fibroblasts (HDFs) against ultraviolet A (UVA)‑induced photoaging. HDFs were treated with 0‑10 μM Cur for 2 h and subsequently exposed to various intensities of UVA irradiation. The cell viability and apoptotic rate of HDFs were investigated by MTT and flow cytometry assays, respectively. The effect of UVA and Cur on the formation of reactive oxygen species (ROS), malondialdehyde levels, which are an indicator of ROS, and the levels/activity of antioxidative defense proteins, including glutathione, superoxide dismutase and catalase, were evaluated using 2',7'‑dichlorofluorescin diacetate and commercial assay kits. Furthermore, western blotting was performed to determine the levels of proteins associated with endoplasmic reticulum (ER) stress, the apoptotic pathway, inflammation and the collagen synthesis pathway. The results demonstrated that Cur reduced the accumulation of ROS and restored the activity of antioxidant defense enzymes, indicating that Cur minimized the damage induced by UVA irradiation in HDFs. Furthermore, western blot analysis demonstrated that Cur may attenuate UVA‑induced ER stress, inflammation and apoptotic signaling by downregulating the protein expression of glucose‑regulated protein 78, C/EBP‑homologous protein, nuclear factor‑κB and cleaved caspase‑3, while upregulating the expression of Bcl‑2. Additionally, it was demonstrated that Cur may regulate collagen metabolism by decreasing the protein expression of matrix metalloproteinase (MMP)‑1 and MMP‑3, and may promote the repair of cells damaged as a result of UVA irradiation through increasing the protein expression of transforming growth factor‑β (TGF‑β) and Smad2/3, and decreasing the expression of the TGF‑β inhibitor, Smad7. In conclusion, the results of the present study indicate the potential benefits of Cur for the protection of HDFs against UVA‑induced photoaging and highlight the potential for the application of Cur in skin photoprotection. [ABSTRACT FROM AUTHOR]

This paper presents a novel system design that considerably improves the entrapment of terrestrial ultraviolet (UV) irradiance in a customized honeycomb structure to produce hydrogen at a standard rate of 7.57 slpm for places with a UV index > 11. Thermolysis of high salinity water is done by employing a solid oxide electrolyzer cell (SOEC), which comprises three customized, novel active optical subsystems to filter, track, and concentrate terrestrial UV solar irradiance by Fresnel lenses. The output of systems is fed to a desalinator, a photovoltaic system to produce electrical energy, and a steam generator with modified surface morphology to generate the required superheated steam for the SOEC. A simulation in COMSOL Multiphysics ver. 5.6 has shown that a customized honeycomb structure, when incorporated on the copper–nickel surface of a steam generator, improves its absorptance coefficient up to 93.43% (48.98%—flat case). This results in generating the required superheated steam of 650 °C with a designed active optical system comprising nine Fresnel lenses (7 m2) that offer the concentration of 36 suns on the honeycomb structure of the steam generator as input. The required 1.27 kW of electrical power is obtained by concentrating the photovoltaic system using In0.33Ga0.67N/Si/InN solar cells. This production of hydrogen is sustainable and cost effective, as the estimated cost over 5 years by the proposed system is 0.51 USD/kg, compared to the commercially available system, which costs 3.18 USD/kg. [ABSTRACT FROM AUTHOR]

Background: The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis.Methods: PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression.Results: Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death.Conclusions: PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas. [ABSTRACT FROM AUTHOR]

Objective: To report on the clinical presentation, etiology, and laboratory features of acute and chronic atrial fibrillation (AF) in a tertiary hospital in Riyadh, Saudi Arabia. Materials and Methods: We retrospectively studied records of 720 patients with AF seen in outpatients and inpatients departments at King Abdulaziz Medical City, Riyadh, during the period of 1 January 2002 to 31 August 2008. Results: Documented acute and chronic AF was present in 157 (21.8%) and 563 (78.1%) patients, respectively. Palpitations, dizziness and syncope were the most frequent symptoms in acute AF, while dyspnea and palpitations were the most common symptoms in the chronic type. Acute respiratory problems and acute myocardial infarction were significantly more common in acute AF, while congestive heart failure and acute respiratory problems (chest infection, bronchial asthma, and pulmonary embolism) were significantly more common in chronic AF. The most common causes of both types of AF were diabetes mellitus (DM) in 68.8%, hypertension (HTN) in 59.3%, chronic lung diseases (bronchial asthma, chronic obstructive pulmonary disease and interstitial lung disease) in 31.8%, valvular heart disease in 23.6%, and ischemic heart disease (IHD) in 23.1%. In 9 (1.3%) patients, no cause was detected. The echocardiographic findings of let ventricular hypertrophy, valve lesions, and depressed let ventricular function were significantly more common in chronic AF (P<0.01). Conclusions: Nowadays, DM, HTN, and IHD are becoming the most common predisposing factors for AF in the central region of Saudi Arabia and require prevention and control [ABSTRACT FROM AUTHOR]

Simple Summary: We investigated the influence of genetic variants, called single nucleotide polymorphisms (SNP) in the TP53 tumour suppressor gene, on cancer risk, clinical features and TP53 isoform levels. These SNPs were significantly over-represented in cohorts of mixed cancers versus controls, suggesting they confer increased cancer risk. Heterozygosity at rs1042522(GC) and either of the two SNPs rs9895829(TC) and rs2909430(AG) confer up to a 5-fold greater risk of developing cancer. The SNP combinations were associated with high Δ133TP53 and TP53β messenger RNA levels, elevated infiltrating immune cells and shorter patient survival for glioblastoma and prostate cancer. The data suggest that ∆133p53β protein levels are increased by the SNPs resulting in increased inflammation which contributes to more aggressive cancers. We investigated the influence of selected TP53 SNPs in exon 4 and intron 4 on cancer risk, clinicopathological features and expression of TP53 isoforms. The intron 4 SNPs were significantly over-represented in cohorts of mixed cancers compared to three ethnically matched controls, suggesting they confer increased cancer risk. Further analysis showed that heterozygosity at rs1042522(GC) and either of the two intronic SNPs rs9895829(TC) and rs2909430(AG) confer a 2.34–5.35-fold greater risk of developing cancer. These SNP combinations were found to be associated with shorter patient survival for glioblastoma and prostate cancer. Additionally, these SNPs were associated with tumor-promoting inflammation as evidenced by high levels of infiltrating immune cells and expression of the Δ133TP53 and TP53β transcripts. We propose that these SNP combinations allow increased expression of the Δ133p53 isoforms to promote the recruitment of immune cells that create an immunosuppressive environment leading to cancer progression. [ABSTRACT FROM AUTHOR]