bluuebunny/crossref_metadata_2025 huggingface dataset:
Designing and Encapsulation of Inorganic Al12N12 Nanoclusters with Be, Mg, and Ca Metals for Efficient Hydrogen Adsorption: A Step Forward Towards Hydrogen Storage Materials
Authors: Mehboob Muhammad Yasir , Hussain Riaz , Irshad Zobia , Farwa Ume , Adnan Muhammad , Muhammad Shabbir
Published: October 2021

Nanoclusters such as [Formula: see text][Formula: see text] have received increased attention due to their diverse applications in the fields of optoelectronics and energy storage. In this paper, we have investigated a series of alkaline earth metal (AEM)-encapsulated [Formula: see text][Formula: see text] nanoclusters for hydrogen adsorption. Thermodynamic adsorption parameters, optical and nonlinear optical properties were investigated using density functional theory (DFT) at the B3LYP/6-31G(d,p) level of theory. Encapsulation of AEMs (Be, Mg and Ca) is an effective strategy to improve the NLO reaction and thermodynamic and adsorption properties of [Formula: see text][Formula: see text] nanoclusters. The adsorption energies ranging from [Formula: see text]26.57[Formula: see text]kJ/mol to [Formula: see text]213.33[Formula: see text]kJ/mol for the three guests (Be, Mg and Ca) capsulated [Formula: see text][Formula: see text] nanoclusters are observed. The adsorption energy is affected by the size of the nanocage. Therefore, Ca- and Mg-encapsulated cages show higher values of adsorption energy. Overall, an increase in adsorption energy ([Formula: see text][Formula: see text]kJ/mol to [Formula: see text]91.06[Formula: see text]kJ/mol) is observed for (Be, Mg and Ca) encapsulated [Formula: see text][Formula: see text] nanoclusters compared to untreated [Formula: see text][Formula: see text] and H2-[Formula: see text][Formula: see text] cages. Moreover, adsorption of hydrogen on AEMs encapsulated in [Formula: see text][Formula: see text] leads to a decrease in the HOMO-LUMO energy gap with an enhancement of linear and nonlinear hyperpolarizability. All hydrogen-adsorbed AEMs [Formula: see text][Formula: see text] nanocages exhibit large [Formula: see text] and [Formula: see text] values, suggesting that these systems are potential candidates for optical materials. Various geometrical parameters such as frontier molecular orbitals (FMOs), partial density of states, global quantum descriptor of reactivity, natural bond orbital testing and molecular electrostatic strength analyses were performed to investigate the thermodynamic stability of all the studied systems. The results obtained confirmed that the designed systems are suitable for hydrogen storage. Therefore, we recommend that these systems be investigated for their hydrogen storage and optical properties.
Screen Content Quality Assessment: Overview, Benchmark, and Beyond
Authors: Min Xiongkuo , Gu Ke , Zhai Guangtao , Yang Xiaokang , Zhang Wenjun , Le Callet Patrick , Chen Chang Wen
Published: October 2021

Screen content, which is often computer-generated, has many characteristics distinctly different from conventional camera-captured natural scene content. Such characteristic differences impose major challenges to the corresponding content quality assessment, which plays a critical role to ensure and improve the final user-perceived quality of experience (QoE) in various screen content communication and networking systems. Quality assessment of such screen content has attracted much attention recently, primarily because the screen content grows explosively due to the prevalence of cloud and remote computing applications in recent years, and due to the fact that conventional quality assessment methods can not handle such content effectively. As the most technology-oriented part of QoE modeling, image/video content/media quality assessment has drawn wide attention from researchers, and a large amount of work has been carried out to tackle the problem of screen content quality assessment. This article is intended to provide a systematic and timely review on this emerging research field, including (1) background of natural scene vs. screen content quality assessment; (2) characteristics of natural scene vs. screen content; (3) overview of screen content quality assessment methodologies and measures; (4) relevant benchmarks and comprehensive evaluation of the state-of-the-art; (5) discussions on generalizations from screen content quality assessment to QoE assessment, and other techniques beyond QoE assessment; and (6) unresolved challenges and promising future research directions. Throughout this article, we focus on the differences and similarities between screen content and conventional natural scene content. We expect that this review article shall provide readers with an overview of the background, history, recent progress, and future of the emerging screen content quality assessment research.
FPGA/GPU-based Acceleration for Frequent Itemsets Mining: A Comprehensive Review
Authors: Bustio-Martínez Lázaro , Cumplido René , Letras Martín , Hernández-León Raudel , Feregrino-Uribe Claudia , Hernández-Palancar José
Published: October 2021

In data mining, Frequent Itemsets Mining is a technique used in several domains with notable results. However, the large volume of data in modern datasets increases the processing time of Frequent Itemset Mining algorithms, making them unsuitable for many real-world applications. Accordingly, proposing new methods for Frequent Itemset Mining to obtain frequent itemsets in a realistic amount of time is still an open problem. A successful alternative is to employ hardware acceleration using Graphics Processing Units (GPU) and Field Programmable Gates Arrays (FPGA). In this article, a comprehensive review of the state of the art of Frequent Itemsets Mining hardware acceleration is presented. Several approaches (FPGA and GPU based) were contrasted to show their weaknesses and strengths. This survey gathers the most relevant and the latest research efforts for improving the performance of Frequent Itemsets Mining regarding algorithms advances and modern development platforms. Furthermore, this survey organizes the current research on Frequent Itemsets Mining from the hardware perspective considering the source of the data, the development platform, and the baseline algorithm.
Computing Graph Neural Networks: A Survey from Algorithms to Accelerators
Authors: Abadal Sergi , Jain Akshay , Guirado Robert , López-Alonso Jorge , Alarcón Eduard
Published: October 2021

Graph Neural Networks (GNNs) have exploded onto the machine learning scene in recent years owing to their capability to model and learn from graph-structured data. Such an ability has strong implications in a wide variety of fields whose data are inherently relational, for which conventional neural networks do not perform well. Indeed, as recent reviews can attest, research in the area of GNNs has grown rapidly and has lead to the development of a variety of GNN algorithm variants as well as to the exploration of ground-breaking applications in chemistry, neurology, electronics, or communication networks, among others. At the current stage research, however, the efficient processing of GNNs is still an open challenge for several reasons. Besides of their novelty, GNNs are hard to compute due to their dependence on the input graph, their combination of dense and very sparse operations, or the need to scale to huge graphs in some applications. In this context, this article aims to make two main contributions. On the one hand, a review of the field of GNNs is presented from the perspective of computing. This includes a brief tutorial on the GNN fundamentals, an overview of the evolution of the field in the last decade, and a summary of operations carried out in the multiple phases of different GNN algorithm variants. On the other hand, an in-depth analysis of current software and hardware acceleration schemes is provided, from which a hardware-software, graph-aware, and communication-centric vision for GNN accelerators is distilled.
A Survey on Client Throughput Prediction Algorithms in Wired and Wireless Networks
Authors: Schmid Josef , Höss Alfred , Schuller Björn W.
Published: October 2021

Network communication has become a part of everyday life, and the interconnection among devices and people will increase even more in the future. Nevertheless, prediction of Quality of Service parameters, particularly throughput, is quite a challenging task. In this survey, we provide an extensive insight into the literature on Transmission Control Protocol throughput prediction. The goal is to provide an overview of the used techniques and to elaborate on open aspects and white spots in this area. We assessed more than 35 approaches spanning from equation-based over various time smoothing to modern learning and location smoothing methods. In addition, different error functions for the evaluation of the approaches as well as publicly available recording tools and datasets are discussed. To conclude, we point out open challenges especially looking in the area of moving mobile network clients. The use of throughput prediction not only enables a more efficient use of the available bandwidth, the techniques shown in this work also result in more robust and stable communication.
Service Computing for Industry 4.0: State of the Art, Challenges, and Research Opportunities
Authors: Siqueira Frank , Davis Joseph G.
Published: October 2021

Recent advances in the large-scale adoption of information and communication technologies in manufacturing processes, known as Industry 4.0 or Smart Manufacturing, provide us a window into how the manufacturing sector will evolve in the coming decades. As a result of these initiatives, manufacturing firms have started to integrate a series of emerging technologies into their processes that will change the way products are designed, manufactured, and consumed. This article provides a comprehensive review of how service-oriented computing is being employed to develop the required software infrastructure for Industry 4.0 and identifies the major challenges and research opportunities that ensue. Particular attention is paid to the microservices architecture, which is increasingly recognized as offering a promising approach for developing innovative industrial applications. This literature review is based on the current state of the art on service computing for Industry 4.0 as described in a large corpus of recently published research papers, which helped us to identify and explore a series of challenges and opportunities for the development of this emerging technology frontier, with the goal of facilitating its widespread adoption.
Opportunities and Challenges in Code Search Tools
Authors: Liu Chao , Xia Xin , Lo David , Gao Cuiyun , Yang Xiaohu , Grundy John
Published: October 2021

Code search is a core software engineering task. Effective code search tools can help developers substantially improve their software development efficiency and effectiveness. In recent years, many code search studies have leveraged different techniques, such as deep learning and information retrieval approaches, to retrieve expected code from a large-scale codebase. However, there is a lack of a comprehensive comparative summary of existing code search approaches. To understand the research trends in existing code search studies, we systematically reviewed 81 relevant studies. We investigated the publication trends of code search studies, analyzed key components, such as codebase, query, and modeling technique used to build code search tools, and classified existing tools into focusing on supporting seven different search tasks. Based on our findings, we identified a set of outstanding challenges in existing studies and a research roadmap for future code search research.
GECCO 2021
Authors: Chicano Francisco
Published: October 2021

The 2021 Genetic and Evolutionary Computation Conference (GECCO 2021) was planned to be held in hybrid mode in Lille, France, on July 10th-14th, 2021. After a careful analysis of the evolution of the pandemic and the results of a poll to frequent attendees on the preferred form of attendance, a decision was made in mid-December to run GECCO'21 in online/virtual mode only. This report provides statistics about submissions and authorship, and some comments about the evolution and growth of GECCO.
Cell Wall Biology of Vibrio cholerae
Authors: Alvarez Laura , Hernandez Sara B. , Cava Felipe
Published: October 2021

Most bacteria are protected from environmental offenses by a cell wall consisting of strong yet elastic peptidoglycan. The cell wall is essential for preserving bacterial morphology and viability, and thus the enzymes involved in the production and turnover of peptidoglycan have become preferred targets for many of our most successful antibiotics. In the past decades, Vibrio cholerae, the gram-negative pathogen causing the diarrheal disease cholera, has become a major model for understanding cell wall genetics, biochemistry, and physiology. More than 100 articles have shed light on novel cell wall genetic determinants, regulatory links, and adaptive mechanisms. Here we provide the first comprehensive review of V. cholerae’s cell wall biology and genetics. Special emphasis is placed on the similarities and differences with Escherichia coli, the paradigm for understanding cell wall metabolism and chemical structure in gram-negative bacteria.
Deciphering the Chitin Code in Plant Symbiosis, Defense, and Microbial Networks
Authors: Khokhani Devanshi , Carrera Carriel Cristobal , Vayla Shivangi , Irving Thomas B. , Stonoha-Arther Christina , Keller Nancy P. , Ané Jean-Michel
Published: October 2021

Chitin is a structural polymer in many eukaryotes. Many organisms can degrade chitin to defend against chitinous pathogens or use chitin oligomers as food. Beneficial microorganisms like nitrogen-fixing symbiotic rhizobia and mycorrhizal fungi produce chitin-based signal molecules called lipo-chitooligosaccharides (LCOs) and short chitin oligomers to initiate a symbiotic relationship with their compatible hosts and exchange nutrients. A recent study revealed that a broad range of fungi produce LCOs and chitooligosaccharides (COs), suggesting that these signaling molecules are not limited to beneficial microbes. The fungal LCOs also affect fungal growth and development, indicating that the roles of LCOs beyond symbiosis and LCO production may predate mycorrhizal symbiosis. This review describes the diverse structures of chitin; their perception by eukaryotes and prokaryotes; and their roles in symbiotic interactions, defense, and microbe-microbe interactions. We also discuss potential strategies of fungi to synthesize LCOs and their roles in fungi with different lifestyles.
Optimal Time‐Consistent Investment Strategy for a Random Household Expenditure with Default Risk under Relative Performance
Authors: Guan Wenjin , Yuan Wei , Li Sheng
Published: October 2021

Considering the mind of rivalry between families, each family focuses not only on its own wealth but also on other families, especially neighbors. In this paper, we investigate the non‐zero‐sum mean‐variance game between two families with a random household expenditure under the default risk and relative performance. Applying the stochastic control theory within the framework of the game theory, the extended Hamilton–Jacobi–Bellman equation equations are derived. By solving this equation, we obtain the Nash equilibrium strategies of the two families and the corresponding equilibrium value functions. We also provide a numerical example to analyze the effects of relevant parameters on Nash equilibrium strategy and on the utility loss due to the mind of rivalry.
Intrapleural Tenecteplase for Complicated Parapneumonic Pleural Effusion
Authors: Kadhem Husain , Sridharan Kannan , Naser Naser
Published: October 2021

Intrapleural thrombolytics have shown promising results in complicated parapneumonic pleural effusions reducing the need for surgical interventions. Until now, studies have evaluated primarily streptokinase, urokinase, and recently, alteplase. In this case series, we share our experience with tenecteplase—a tissue-specific plasminogen activator in 15 patients. We observed that tenecteplase is effective in 14/15 (93.3%) of our patients, and none of them had any bleeding episodes.
Blockchain‐Envisioned Secure Authentication Approach in AIoT: Applications, Challenges, and Future Research
Authors: Wazid Mohammad , Das Ashok Kumar , Park Youngho
Published: October 2021

The Artificial Intelligence of Things (AIoT) is the amalgamation of Artificial Intelligence (AI) methods and the Internet of Things (IoT) infrastructure, which are deployed there to improve the overall performance of the system. AIoT can be deployed to achieve more efficient IoT operations; thereby can improve human‐machine interactions and provide better data analysis. AI methods can be used to transform IoT data into useful information for the better decision‐making processes, and it further increases the overall usability of the system. AIoT frameworks are very useful and applicable in a variety of applications, like security and surveillance system, smart home, intelligent transportation system, smart farming, secure and safe healthcare monitoring, industrial automation and control, eCommerce, logistics operations and control, and many more. However, AIoT frameworks may have issues related to data security and privacy as they are vulnerable to various types of information security‐related attacks. These issues further cause the serious consequences, like the unauthorized data leakage and data update. Blockchain is a specific type of database. It is a digital ledger of transactions, which is duplicated and distributed across the entire network of computer systems. It stores data in the form of some blocks, which are then chained together. Blockchain is tamper proof and provides more security as compared to the traditional security mechanisms. Hence, blockchain can be integrated in various AIoT applications to provide more security. A generalized blockchain‐envisioned secure authentication framework for AIoT has been proposed. The adversary model of blockchain‐envisioned secure authentication framework for AIoT is also highlighted that covers most of the potential threats of a kind of communication environment. Various applications of the proposed framework are also discussed. Furthermore, different issues and challenges of the proposed framework are highlighted. In the end, we also provide some future research directions relevant to the proposed framework.
Existence of Best Proximity Point with an Application to Nonlinear Integral Equations
Authors: Sharma Shagun , Chandok Sumit
Published: October 2021

Using the idea of modified

ϱ

-proximal admissible mappings, we derive some new best proximity point results for

ϱ
−
ϑ

-contraction mappings in metric spaces. We also provide some illustrations to back up our work. As a result of our findings, several fixed-point results for such mappings are also found. We obtain the existence of a solution for nonlinear integral equations as an application.
Short‐Term Traffic Flow Prediction of Expressway: A Hybrid Method Based on Singular Spectrum Analysis Decomposition
Authors: Shuai Chunyan , Pan Zhengyang , Gao Lun , Zuo HongWu
Published: October 2021

Real‐time expressway traffic flow prediction is always an important research field of intelligent transportation, which is conducive to inducing and managing traffic flow in case of congestion. According to the characteristics of the traffic flow, this paper proposes a hybrid model, SSA‐LSTM‐SVR, to improve forecasting accuracy of the short‐term traffic flow. Singular Spectrum Analysis (SSA) decomposes the traffic flow into one principle component and three random components, and then in terms of different characteristics of these components, Long Short‐Term Memory (LSTM) and Support Vector Regression (SVR) are applied to make prediction of different components, respectively. By fusing respective forecast results, SSA‐LSTM‐SVR obtains the final short‐term predictive value. Experiments on the traffic flows of Guizhou expressway in January 2016 show that the proposed SSA‐LSTM‐SVR model has lower predictive errors and a higher accuracy and fitting goodness than other baselines. This illustrates that a hybrid model for traffic flow prediction based on components decomposition is more effective than a single model, since it can capture the main regularity and random variations of traffic flow.
A Two‐Sided Stable Matching Model of Cloud Manufacturing Tasks and Services considering the Nonlinear Relationship between Satisfaction and Expectations
Authors: Zheng Yujie , Li Meiyan , Liu Jiakun
Published: October 2021

To improve the satisfaction of both service demanders (SDs) and service providers (SPs) in the matching of cloud manufacturing (CMfg) tasks and services, a two‐sided stable matching model of CMfg tasks and service considering the nonlinear relationship between satisfaction and expectations is proposed. As the expectations of SDs and SPs are difficult to be quantified directly, an evaluation method based on interval‐valued hesitant fuzzy linguistic sets (IVHFLSs) is first presented. Next, a nonlinear model of satisfaction and expectations is built to quantify the satisfaction, which achieves accurate quantification of satisfaction. Then, a two‐sided stable matching model of CMfg tasks and service is built, which takes the satisfaction of SDs and SPs as the optimization goals and considers the individual rationalities and blocking pairs. Finally, an adaptive genetic algorithm (AGA) is designed to solve the proposed two‐sided matching model. A practical application and comparison analysis is used to verify the effectiveness and superiority of the research.
Segmentation of Prefrontal Lobe Based on Improved Clustering Algorithm in Patients with Diabetes
Authors: Zhao Na , Zhao Qingzhen , Wang Liang , Wu Xiuqing , Zhang Rui , Feng Haijun
Published: October 2021

Diabetics are prone to postoperative cognitive dysfunction (POCD). The occurrence may be related to the damage of the prefrontal lobe. In this study, the prefrontal lobe was segmented based on an improved clustering algorithm in patients with diabetes, in order to evaluate the relationship between prefrontal lobe volume and COPD. In this study, a total of 48 diabetics who underwent selective noncardiac surgery were selected. Preoperative magnetic resonance imaging (MRI) images of the patients were segmented based on the improved clustering algorithm, and their prefrontal volume was measured. The correlation between the volume of the prefrontal lobe and

Z

-score or blood glucose was analyzed. Qualitative analysis shows that the gray matter, white matter, and cerebrospinal fluid based on the improved clustering algorithm were easy to distinguish. Quantitative evaluation results show that the proposed segmentation algorithm can obtain the optimal Jaccard coefficient and the least average segmentation time. There was a negative correlation between the volume of the prefrontal lobe and the

Z

-score. The cut-off value of prefrontal lobe volume for predicting POCD was <179.8, with the high specificity. There was a negative correlation between blood glucose and volume of the prefrontal lobe. From the results, we concluded that the segmentation of the prefrontal lobe based on an improved clustering algorithm before operation may predict the occurrence of POCD in diabetics.
Study on the Reinforcing Effects of the FRP-PCM Method on Tunnel Linings for Dynamic Strengthening
Authors: Wang Xiaoshan , Wei Lin , Wang Zaiquan , Jiang Yujing , Zhang Liming , Meng Fanzhen , Cong Yu
Published: October 2021

In recent years, fiber-reinforced plastic (FRP) has been widely used in the reinforcement of concrete structure fields due to its favorable properties such as high strength, low weight, easy handling and application, and immunity to corrosion, and the reinforcing effects with FRP grids on tunnel linings should be quantitatively evaluated when the tunnels encounter an earthquake. The aim of the present study is to estimate the reinforcing effects of fiber-reinforced plastic (FRP) grids embedded in Polymer Cement Mortar (PCM) shotcrete (FRP-PCM method) on tunnel linings under the dynamic load. A series of numerical simulations were performed to analyze the reinforcing effects of FRP-PCM method quantitatively, taking into account the impacts of tunnel construction method and cavity location. The results showed that the failure region on lining concrete is improved obviously when the type CII ground is encountered, regardless the influences of construction method and cavity location. With the increment of ground class from CII to DII, the axial stress reduction rate

R

σ

increases from 13.18% to 48.60% for tunnels constructed by the NATM, while for those tunnels constructed by the NATM,

R

σ

merely varies from 0.72% to 2.11%.

R

σ

decreases from 43.35% to 34.80% when a cavity exists on the shoulder of lining, while decreasing from 14.7% to 0.12% when a cavity exists on the crown of lining concrete. All those conclusions could provide valuable guidance for the reinforcing of underground structures.
Osteolysis following PE Wear of a Hastings Head on a Monoblock Hip Stem
Authors: Fischer Sarah , Polster Valerie , Ruhr Miriam , Hube Robert , Morlock Michael M.
Published: October 2021

We report a case of extended osteolysis, requiring a third revision of the left hip in an 85-year-old man 46 years after index operation. Major polyethylene (PE) wear occurred due to a missmatched combination of a bipolar Hastings head with a PE liner and head damage of the originally maintained stem. This case demonstrates that bipolar heads should not be used with PE cup liners since the respective bearing diameters cannot be guaranteed to match due to missing specifications. Furthermore, putting a Hastings head on an already damaged head of the stem should be omitted and rather the stem should initially be revised.
The New Design Nanocapsules from Interactions between Atoms and Carbon Nanotubes with End Caps
Authors: Tiangtrong Prangsai , Chaihathep Narong
Published: October 2021

A massive interest has arisen in nanocapsule, and it is used in different fields. Carbon nanotubes and fullerene are the most commonly used nanomaterials due to their remarkable properties, such as optical, mechanical, electrical, and thermal properties. Especially in biomedical science, nanocapsules are highly recommended to be applied as carriers for drugs. From the Magic bullet theory, it is expected that the nanocapsules can deliver drugs to the target cells, which can reduce the side effects on the nontargeted cells. In this research, we design a new nanocapsule consisting of a finite-length single-wall carbon nanotube with two end caps which are hemispheres of C60 fullerene. By using elementary mechanics and mathematical modelling, we can determine the exact formulae and their numerical solutions of nonbonded interactions between the nanocapsules and the atoms Li, Na, K, Rb, Cs, Ca, Ni, Zn, and Pb which are assumed to be located in the middle of the nanocapsules. Therefore, the optimal lengths of the carbon nanotubes for each case of atoms are determined. This research is a guideline for studying the interaction between the drug and the nanocapsule in the drug delivery system.
Inhibition of PIM Kinases in DLBCL Targets MYC Transcriptional Program and Augments the Efficacy of Anti-CD20 Antibodies
Authors: Szydłowski Maciej , Garbicz Filip , Jabłońska Ewa , Górniak Patryk , Komar Dorota , Pyrzyńska Beata , Bojarczuk Kamil , Prochorec-Sobieszek Monika , Szumera-Ciećkiewicz Anna , Rymkiewicz Grzegorz , Cybulska Magdalena , Statkiewicz Małgorzata , Gajewska Marta , Mikula Michał , Gołas Aniela , Domagała Joanna , Winiarska Magdalena , Graczyk-Jarzynka Agnieszka , Białopiotrowicz Emilia , Polak Anna , Barankiewicz Joanna , Puła Bartosz , Pawlak Michał , Nowis Dominika , Golab Jakub , Tomirotti Andrea M. , Brzózka Krzysztof , Pacheco-Blanco Mariana , Kupcova Kristyna , Green Michael R. , Havranek Ondrej , Chapuy Bjoern , Juszczyński Przemysław
Published: October 2021

The family of PIM serine/threonine kinases includes three highly conserved oncogenes, PIM1, PIM2, and PIM3, which regulate multiple prosurvival pathways and cooperate with other oncogenes such as MYC. Recent genomic CRISPR-Cas9 screens further highlighted oncogenic functions of PIMs in diffuse large B-cell lymphoma (DLBCL) cells, justifying the development of small-molecule PIM inhibitors and therapeutic targeting of PIM kinases in lymphomas. However, detailed consequences of PIM inhibition in DLBCL remain undefined. Using chemical and genetic PIM blockade, we comprehensively characterized PIM kinase–associated prosurvival functions in DLBCL and the mechanisms of PIM inhibition–induced toxicity. Treatment of DLBCL cells with SEL24/MEN1703, a pan-PIM inhibitor in clinical development, decreased BAD phosphorylation and cap-dependent protein translation, reduced MCL1 expression, and induced apoptosis. PIM kinases were tightly coexpressed with MYC in diagnostic DLBCL biopsies, and PIM inhibition in cell lines and patient-derived primary lymphoma cells decreased MYC levels as well as expression of multiple MYC-dependent genes, including PLK1. Chemical and genetic PIM inhibition upregulated surface CD20 levels in an MYC-dependent fashion. Consistently, MEN1703 and other clinically available pan-PIM inhibitors synergized with the anti-CD20 monoclonal antibody rituximab in vitro, increasing complement-dependent cytotoxicity and antibody-mediated phagocytosis. Combined treatment with PIM inhibitor and rituximab suppressed tumor growth in lymphoma xenografts more efficiently than either drug alone. Taken together, these results show that targeting PIM in DLBCL exhibits pleiotropic effects that combine direct cytotoxicity with potentiated susceptibility to anti-CD20 antibodies, justifying further clinical development of such combinatorial strategies.

Significance:

These findings demonstrate that inhibition of PIM induces DLBCL cell death via MYC-dependent and -independent mechanisms and enhances the therapeutic response to anti-CD20 antibodies by increasing CD20 expression.
Hyperpolarized Carbon-13 MRI for Early Response Assessment of Neoadjuvant Chemotherapy in Breast Cancer Patients
Authors: Woitek Ramona , McLean Mary A. , Ursprung Stephan , Rueda Oscar M. , Manzano Garcia Raquel , Locke Matthew J. , Beer Lucian , Baxter Gabrielle , Rundo Leonardo , Provenzano Elena , Kaggie Joshua , Patterson Andrew , Frary Amy , Field-Rayner Johanna , Papalouka Vasiliki , Kane Justine , Benjamin Arnold J.V. , Gill Andrew B. , Priest Andrew N. , Lewis David Y. , Russell Roslin , Grimmer Ashley , White Brian , Latimer-Bowman Beth , Patterson Ilse , Schiller Amy , Carmo Bruno , Slough Rhys , Lanz Titus , Wason James , Schulte Rolf F. , Chin Suet-Feung , Graves Martin J. , Gilbert Fiona J. , Abraham Jean E. , Caldas Carlos , Brindle Kevin M. , Sala Evis , Gallagher Ferdia A.
Published: October 2021

Hyperpolarized 13C-MRI is an emerging tool for probing tissue metabolism by measuring 13C-label exchange between intravenously injected hyperpolarized [1–13C]pyruvate and endogenous tissue lactate. Here, we demonstrate that hyperpolarized 13C-MRI can be used to detect early response to neoadjuvant therapy in breast cancer. Seven patients underwent multiparametric 1H-MRI and hyperpolarized 13C-MRI before and 7–11 days after commencing treatment. An increase in the lactate-to-pyruvate ratio of approximately 20% identified three patients who, following 5–6 cycles of treatment, showed pathological complete response. This ratio correlated with gene expression of the pyruvate transporter MCT1 and lactate dehydrogenase A (LDHA), the enzyme catalyzing label exchange between pyruvate and lactate. Analysis of approximately 2,000 breast tumors showed that overexpression of LDHA and the hypoxia marker CAIX was associated with reduced relapse-free and overall survival. Hyperpolarized 13C-MRI represents a promising method for monitoring very early treatment response in breast cancer and has demonstrated prognostic potential.

Significance:

Hyperpolarized carbon-13 MRI allows response assessment in patients with breast cancer after 7–11 days of neoadjuvant chemotherapy and outperformed state-of-the-art and research quantitative proton MRI techniques.
Álvaro Siza e a construção de uma Escola de Tendência
Authors: Pinto Pedro Luz
Published: October 2021

O arquiteto português Álvaro Siza (1933) formou-se na “escola do Porto” entre 1949-1965. Em 1966, inicia carreira de docente na escola. Desempenharia um papel fundamental na reputação da escola e testemunhou, como aluno e como educador, mudanças cruciais no ensino da arquitetura. Formou-se na transição do sistema “beaux-arts” para a forma “moderna” de ensino da arquitetura e, mais tarde, como docente, participou da passagem de escola a faculdade. Como professor e como projetista, foi um exemplo. Envolveu-se ativamente na luta e no debate pela autonomia curricular, pedagógica e disciplinar, da “escola” e da arquitetura. Em momentos-chave, deixou testemunho de posições desassombradas. Com a passagem de escola para faculdade desenharia, já em um período de grande reconhecimento internacional, as novas instalações, da agora Faculdade de Arquitetura, coroando um período de intenso envolvimento com a “escola”. Este artigo refaz o período de maior envolvimento de Siza na “escola do Porto”, entre 1966 e 1990, permitindo entender a sua participação na construção do projeto pedagógico da escola, assim como a sua posição e sua prática perante o ensino da arquitetura.
Long-Term Prognostic Value of Stress Cardiovascular Magnetic Resonance–Related Coronary Revascularization to Predict Death: A Large Registry With >200 000 Patient-Years of Follow-Up
Authors: Pezel Théo , Unterseeh Thierry , Garot Philippe , Hovasse Thomas , Sanguineti Francesca , Toupin Solenn , Morisset Stéphane , Champagne Stéphane , Garot Jérôme
Published: October 2021

Background:

Although the benefit of coronary revascularization in patients with stable coronary disease is debated, data assessing the potential interest of stress cardiovascular magnetic resonance (CMR) to guide coronary revascularization are limited. We aimed to assess the long-term prognostic value of stress CMR-related coronary revascularization in consecutive patients from a large registry.

Methods:

Between 2008 and 2018, a retrospective cohort study with a median follow-up of 6.0 years (interquartile range, 5.0–8.0) included all consecutive patients referred for stress CMR. CMR-related coronary revascularization was defined by any coronary revascularization performed within 90 days after CMR. The primary outcome was all-cause death based on the National Death Registry.

Results:

Among the 31 762 consecutive patients (mean age 63.7±12.1 years and 65.7% males), 2679 (8.4%) died at 206 453 patient-years of follow-up. Inducible ischemia and late gadolinium enhancement by CMR were associated with death (both
P
<0.001). In multivariable Cox regression, inducible ischemia and late gadolinium enhancement were independent predictors of death (hazard ratio, 1.61 [99.5% CI, 1.41–1.84]; hazard ratio, 1.62 [99.5% CI, 1.41–1.86], respectively;
P
<0.001). In the overall population, CMR-related coronary revascularization was an independent predictor of greater survival (hazard ratio, 0.58 [99.5% CI, 0.46–0.74];
P
<0.001). In 1680, 1:1 matched patients using a limited number of variables (840 revascularized, 840 nonrevascularized), CMR-related revascularization was associated with a lower incidence of death in patients with severe inducible ischemia (≥6 segments,
P
<0.001) but showed no benefit in patients with mild or moderate ischemia (<6 segments,
P
=0.109). Using multivariable analysis in the propensity-matched population, CMR-related revascularization remained an independent predictor of a lower incidence of all-cause mortality (hazard ratio, 0.66 [99.5% CI, 0.54–0.80],
P
<0.001).

Conclusions:

In this large observational series of consecutive patients, stress perfusion CMR had important incremental long-term prognostic value to predict death over traditional risk factors. CMR-related revascularization was associated with a lower incidence of death in patients with severe ischemia.
Triglyceride Levels and Residual Risk of Atherosclerotic Cardiovascular Disease Events and Death in Adults Receiving Statin Therapy for Primary or Secondary Prevention: Insights From the KP REACH Study
Authors: Ambrosy Andrew P. , Yang Jingrong , Sung Sue Hee , Allen Amanda R. , Fitzpatrick Jesse K. , Rana Jamal S. , Wagner Jeffrey , Philip Sephy , Abrahamson David , Granowitz Craig , Go Alan S.
Published: October 2021

Background

Patients with risk factors or established atherosclerotic cardiovascular disease remain at high‐risk for ischemic events. Triglyceride levels may play a causal role.

Methods and Results

We performed a retrospective study of adults aged ≥45 years receiving statin therapy, with a low‐density lipoprotein cholesterol of 41 to 100 mg/dL, and ≥1 risk factor or established atherosclerotic cardiovascular disease between 2010 and 2017. Outcomes included death, all‐cause hospitalization, and major adverse cardiovascular events (myocardial infarction, stroke, or peripheral artery disease). The study sample included 373 389 primary prevention patients and 97 832 secondary prevention patients. The primary prevention cohort had a mean age of 65±10 years, with 51% women and 44% people of color, whereas the secondary prevention cohort had a mean age of 71±11 years, with 37% women and 32% people of color. Median triglyceride levels for the primary and secondary prevention cohorts were 122 mg/dL (interquartile range, 88–172 mg/dL) and 116 mg/dL (interquartile range, 84–164 mg/dL), respectively. In multivariable analyses, primary prevention patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (hazard ratio [HR], 0.91; 95% CI, 0.89–0.94) and higher risk of major adverse cardiovascular events (HR, 1.14; 95% CI, 1.05–1.24). In the secondary prevention cohort, patients with triglyceride levels ≥150 mg/dL were at lower adjusted risk of death (HR, 0.95; 95% CI, 0.92–0.97) and higher risk of all‐cause hospitalization (HR, 1.03; 95% CI, 1.01–1.05) and major adverse cardiovascular events (HR, 1.04; 95% CI, 1.05–1.24).

Conclusions

In a contemporary cohort receiving statin therapy, elevated triglyceride levels were associated with a greater risk of atherosclerotic cardiovascular disease events and lower risk of death.
Impact of Peripheral Microvascular Endothelial Dysfunction on White Matter Hyperintensity
Authors: Toya Takumi , Sara Jaskanwal D. , Scharf Eugene L. , Ahmad Ali , Nardi Valentina , Ozcan Ilke , Lerman Lilach O. , Lerman Amir
Published: October 2021

Background

White matter hyperintensity (WMH), characterized by hyperintensities on T2‐weighted fluid‐attenuated inversion recovery brain magnetic resonance imaging, has been linked to an increased risk of ischemic stroke (IS). Endothelial dysfunction is an indicator of vascular dysfunction, predicting the risk of IS. This study aimed to investigate the association between endothelial dysfunction and regional WMH, and its impact on future risk of IS.

Methods and Results

We enrolled 219 patients (mean age, 53.1±14.1 years; 34.7% men) who underwent peripheral endothelial function assessment using reactive hyperemia peripheral arterial tonometry and brain magnetic resonance imaging without any history of IS. Volumetric WMH segmentation was automatically extrapolated using a validated automated digital tool. Total and juxtacortical WMH volume/intracranial volume (%) increased with aging and became more prominent in patients aged >50 years (n=131) than those aged ≤50 years (n=88) (total WMH: ≤50 years, Pearson
r
=0.24,
P
=0.03; >50 years, Pearson
r
=0.62,
P
<0.0001; juxtacortical WMH: ≤50 years, Pearson
r
=0.09,
P
=0.40; >50 years, Pearson
r
=0.55,
P
<0.0001). Reactive hyperemia peripheral arterial tonometry index was negatively associated with total and juxtacortical WMH volume/intracranial volume (%) in patients aged >50 years after adjustment for other covariates (reactive hyperemia peripheral arterial tonometry index, standardized β coefficient −0.17,
P
=0.04). Juxtacortical WMH volume/intracranial volume (%) was associated with an increased risk of IS during median follow‐up of 6.5 years (hazard ratio, 1.47; 95% CI, 1.05–1.92;
P
=0.03).

Conclusions

Peripheral endothelial dysfunction is associated with an increased volume of juxtacortical WMH in patients aged >50 years, which is a potential marker to predict future risk of IS.
Dual Antiplatelet Therapy Using Cilostazol in Patients With Stroke and Intracranial Arterial Stenosis
Authors: Uchiyama Shinichiro , Toyoda Kazunori , Omae Katsuhiro , Saita Ryotaro , Kimura Kazumi , Hoshino Haruhiko , Sakai Nobuyuki , Okada Yasushi , Tanaka Kortaro , Origasa Hideki , Naritomi Hiroaki , Houkin Kiyohiro , Yamaguchi Keiji , Isobe Masanori , Minematsu Kazuo , Matsumoto Masayasu , Tominaga Teiji , Tomimoto Hidekazu , Terayama Yasuo , Yasuda Satoshi , Yamaguchi Takenori
Published: October 2021

Background

Long‐term benefit of dual antiplatelet therapy (DAPT) over single antiplatelet therapy (SAPT) for the prevention of recurrent stroke has not been established in patients with intracranial arterial stenosis. We compared the efficacy and safety of DAPT with cilostazol and clopidogrel or aspirin to those of SAPT with clopidogrel or aspirin in patients with intracranial arterial stenosis, who were recruited to the Cilostazol Stroke Prevention Study for Antiplatelet Combination trial, a randomized controlled trial in high‐risk Japanese patients with ischemic stroke.

Methods and Results

We compared the vascular and hemorrhagic events between DAPT and SAPT in patients with ischemic stroke and symptomatic or asymptomatic intracranial arterial stenosis of at least 50% in a major intracranial artery. Patients were placed in two groups: 275 were assigned to receive DAPT and 272 patients SAPT. The risks of ischemic stroke (hazard ratio [HR], 0.47; 95% CI, 0.23–0.95); and composite of stroke, myocardial infarction, and vascular death (HR, 0.48; 95% CI, 0.26–0.91) were lower in DAPT than SAPT, whereas the risk of severe or life‐threatening bleeding (HR, 0.72; 95% CI, 0.12–4.30) did not differ between the 2 treatment groups.

Conclusions

DAPT using cilostazol was superior to SAPT with clopidogrel or aspirin for the prevention of recurrent stroke and vascular events without increasing bleeding risk among patients with intracranial arterial stenosis after stroke.

Registration

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT01995370.
Association of ApoE Genotypes and Recovery From Intracerebral Hemorrhage in Very Low Birth Weight Infants
Authors: Humberg Alexander , Dzietko Mark , Schulz Sören , Felderhoff-Müser Ursula , Hüning Britta , Stein Anja , Fortmann Mats I. , Marissen Janina , Rausch Tanja K. , Herting Egbert , Härtel Christoph , Göpel Wolfgang ,   German Neonatal Network (GNN)
Published: October 2021

Background and Purpose:

Associations of APOE genotypes with intracerebral hemorrhage (ICH) in preterm infants were previously described. In adults, APOE-ε4 genotype has been proposed as susceptibility factor for impaired recovery after cerebral insult. We here aim to determine APOE genotype-specific neurological consequences of neonatal ICH at school age.

Methods:

In this multicenter observational cohort study, very low birth weight (<1500 g, <32 weeks gestational age) children were studied for cerebral palsy (CP) after ultrasound diagnosed ICH stratified by APOE genotype. Follow-up examination was done at the age of 5 to 6 years. Study personnel were blinded for perinatal information and complications. Participants were born between January 1, 2009 and December 31, 2013 and enrolled in the German Neonatal Network. Of 8022 infants primarily enrolled, 2467 children were invited for follow-up between January 1, 2014 and December 31, 2019. Univariate analyses and multivariate logistic regression models were used to assess the impact of APOE genotype (APOE-ε2, APOE-ε3, APOE-ε4) on CP after ICH.

Results:

Two thousand two hundred fifteen children participated at follow-up, including 363 children with ultrasound diagnosed neonatal ICH. In univariate analyses of children with a history of ICH, APOE-ε3 carriers had lower frequencies of CP (n=33/250; 13.2 [95% CI, 9.4%–17.8%]), as compared to APOE-ε2 (n=15/63; 23.8 [14.6%–35.3%],
P
=0.037) and –ε4 carriers (n=31/107; 29.0 [21.0%–38.0%],
P
<0.001), respectively. Regression models revealed an association of APOE-ε4 genotype and CP development (odds ratio, 2.77 [1.44–5.32],
P
=0.002) after ICH. Notably, at low-grade ICH (grade I) APOE-ε4 expression resulted in an increased rate of CP (n=6/39; 15.4 [6.7–29.0]) in comparison to APOE-ε3 (n=2/105; 1.9 [0.4%–6.0%],
P
=0.002).

Conclusions:

APOE-ε4 carriers have an increased risk for long-term motor deficits after ICH. We assume an effect even after low-grade neonatal ICH, but more data are needed to clarify this issue.
Treatment-Associated Stroke in Patients Undergoing Endovascular Therapy in the ARUBA Trial
Authors: Burks Joshua D. , Luther Evan M. , Govindarajan Vaidya , Chen Stephanie H. , Starke Robert M.
Published: October 2021

Background and Purpose:

Since the publication of ARUBA trial (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), outcomes in treated and untreated patients with unruptured arteriovenous malformation have been thoroughly compared. However, no prior analysis of ARUBA patients has sought to identify risk factors for perioperative stroke. Improved understanding of risks within the ARUBA cohort will help clinicians apply the study’s findings in a broader context.

Methods:

The National Institute of Neurological Disorders and Stroke database was queried for all data relating to ARUBA patients, including demographics, interventions undertaken, and timing of stroke. Retrospective cohort analysis was performed with the primary outcome of perioperative stroke in patients who underwent endovascular intervention, and stroke risk was modeled with multivariate analysis.

Results:

A total of 64 ARUBA patients were included in the analysis. One hundred and fifty-ninth interventions were performed, and 26 (16%) procedures resulted in stroke within 48 hours of treatment. Posterior cerebral artery supply (adjusted odds ratio, 4.42 [95% CI, 1.23–15.9],
P
=0.02) and Spetzler-Martin grades 2 and 3 arteriovenous malformation (adjusted odds ratio, 7.76 [95% CI, 1.20–50.3],
P
=0.03; 9.64 [95% CI, 1.36–68.4],
P
=0.04, respectively) were associated with increased perioperative stroke risk in patients who underwent endovascular intervention. Patients treated in the United States or Germany had a significantly lower stroke risk than patients treated in other countries (adjusted odds ratio, 0.18 [95% CI, 0.04–0.82],
P
=0.02).

Conclusions:

Knowing patient and lesion characteristics that increase risk during endovascular treatment can better guide clinicians managing unruptured brain arteriovenous malformation. Our analysis suggests risk of perioperative stroke is dependent on Spetzler-Martin grade and posterior-circulation arterial supply. Differences in regional treatment paradigms may also affect stroke risk.