bluuebunny/crossref_metadata_2025 huggingface dataset:
Pyogenic Lumbar Facet Joint Infection with Foot Drop
Authors: Maehara Haruka , Sano Toshihiro , Yanagawa Yuki , Hashimoto Kyuichi , Tadokoro Nobuaki
Published: April 2021

Pyogenic facet joint infection (PFJI) is a relatively rare spinal infection. Clinical suspicion of this condition is a key for diagnosis. We report a case of PFJI which required decompression surgery for severe neurological dysfunction. The patient was a 44-year-old woman who had a previous history of orthotic therapy for idiopathic scoliosis. The patient was admitted to our hospital with a history of two days of high fever and severe low back pain. There was no neurologic deficit, and blood tests revealed high levels of inflammatory markers. There was a slight amount of fluid that had collected at L4/5 facet joint in lumbar MRI. She was admitted for examination and treatment of fever of unknown origin and low back pain. Antibiotic treatment started the day after hospitalization since the first report of the blood culture taken upon admission tested positive to gram-positive cocci. As low back pain and fever persisted, an MRI was taken again on the fifth day of hospitalization. Repeated MRI showed fluid extension from the left facet joint to paravertebral muscles and epidural space. She was diagnosed with PFJI, and facet joint puncture was performed. At this time, it became clear that she had foot drop on the right, the contralateral side of the PFJI. She underwent irrigation, debridement, and partial laminectomy. Methicillin-sensitive Staphylococcus aureus (MSSA) was detected in blood cultures at the time of hospitalization, in the puncture fluid and tissue collected during surgery. The patient recovered completely from foot drop after the operation and a three-month course of antibiotics. As the imaging findings may be inadequate in the early stages of onset and PFJI potentially causes neurologic deficit such as foot drop, neurological findings need to be carefully observed even after hospitalization and one should reexamine the MRI if symptoms or clinical findings did not improve or were aggravated.
Research on Seismic Test and Calculation Model for Improving Factor of Composite Board with Heat Preservation Function
Authors: Ma Shaochun , Fang Hongyuan
Published: April 2021

Since the composition and stress state of thermal‐insulation composite plates are extremely complex, it is difficult to conduct calculation using conventional methods. Further calculation on its composition structure is even more difficult. To settle this difficulty, this paper conducted experimental investigations on thermal‐insulation composite plate and conventional composite plates, and a simplified calculation method with improved factors was deduced based on the experimental results. In this study, the influence of nonstructural thermal insulation system on the composite plate was specially considered. The calculated expressions are deduced, while the stiffness and damping (properties) are determined. Case analysis was carried out to validate the reliability and accuracy of the simplified calculation method of improvement factor. The research results indicate that the modeling difficulty and computational effort are greatly reduced, with relatively small errors. Hence, it is beneficial to the calculation and analysis of composite plates and global structures.
Distributed Blockchain‐Based Authentication and Authorization Protocol for Smart Grid
Authors: Zhong Yuxin , Zhou Mi , Li Jiangnan , Chen Jiahui , Liu Yan , Zhao Yun , Hu Muchuang
Published: April 2021

Authentication and authorization (A & A) mechanisms are critical to the security of Internet of Things (IoT) applications. Smart grid system processing and exchanging data without human intervention, known as smart grids, are well‐known as IoT scenarios. Entities in such smart grid systems need to identify and validate one another and ensure the integrity of data exchange mechanisms. However, at present, most commonly used A & A protocols are centralized, resulting in security risks such as information leaks, illegal access, and identity theft. In this study, we propose a new distributed A & A protocol for smart grid networks based on blockchain technology to address with these risks. The proposed protocol integrates the decentralized authentication and immutable ledger characteristics of blockchain architectures suitable for power systems with a novel blockchain technique to realize both identity authentication and resource authorization for smart grid systems. We discuss the security of and threat models for prior A & A protocols and demonstrate how our protocol protects against these threats. We further demonstrate an approach to a real deployment of our A & A protocol using the FISCO consortium platform, applying algorithms from smart contract systems. Finally, we present the results of experimental simulations showing the efficacy and efficiency of our proposed protocol.
Experimental Investigation on a Novel Particle Polymer for Enhanced Oil Recovery in High Temperature and High Salinity Reservoirs
Authors: Liu Yang , Zhang Jian , Wu Xingcai , Kang Xiaodong , Guan Baoshan , Li Xianjie , Ye Yinzhu , Xiao Peiwen , Wang Xiaocong , Li Shichao
Published: April 2021

Conventional polymer flooding include polymer flooding, surfactant-polymer flooding (SP), alkaline-surfactant-polymer flooding (ASP), and crosslinked polymer gel flooding. However, these technologies in oilfield, especially in high temperature and high salinity, are limited due to the poor ability of temperature and salinity resistance of polymer. In this work, a novel polymer particle (soft microgel, SMG) is used as the research object under the reservoir condition of high salinity (20 × 104 mg/L) to evaluate the physical and chemical properties of submillimeter-scale SMG and the effect of profile control and oil displacement. The investigation of the physical and chemical properties of submillimeter-scale SMG shows that it has the characteristics of low viscosity, easy injection, good plugging property, swelling property, rheological property, and excellent thermal stability. After 6 months of high temperature and high salinity aging, there is no hydration and hydrolysis of submillimeter-scale SMG as the traditional polymers under high temperature and high salinity. The parallel two-core flooding experiments indicate that the submillimeter-scale SMG has a better effect of profile control and oil displacement, which increases the fraction flow rate(

f

w

) of low-permeability core from 5.12% before SMG-flooding to 85.29% and the total increase of recovery as high as 14.07%. The comprehensive analysis demonstrates that the submillimeter-scale SMG has the potential to solve the problem that the polymer flooding cannot be applied to the high temperature and high salinity reservoir, and it is also expected to improve the uneven waterflooding in the reservoir.
Drug Repurposing Approach, Potential Drugs, and Novel Drug Targets for COVID-19 Treatment
Authors: Kifle Zemene Demelash , Ayele Akeberegn Gorems , Enyew Engidaw Fentahun
Published: April 2021

Novel coronavirus first appeared in Wuhan, China, in December 2019, and it speedily expanded globally. Some medications which are used to treat other diseases seem to be effective in treating COVID-19 even without explicit support. The existing drugs that are summarized in this review primarily focused on therapeutic agents that possessed activity against other RNA viruses such as MERS-CoV and SARS-CoV. Drug repurposing or repositioning is a promising field in drug discovery that identifies new therapeutic opportunities for existing drugs such as corticosteroids, RNA-dependent RNA polymerase inhibitors, interferons, protease inhibitors, ivermectin, melatonin, teicoplanin, and some others. A search for new drug/drug targets is underway. Thus, blocking coronavirus structural protein, targeting viral enzyme, dipeptidyl peptidase 4, and membrane fusion blocker (angiotensin-converting enzyme 2 and CD147 inhibitor) are major sites based on molecular targets for the management of COVID-19 infection. The possible impact of biologics for the management of COVID19 is promising and includes a wide variety of options such as cytokines, nucleic acid-based therapies targeting virus gene expression, bioengineered and vectored antibodies, and various types of vaccines. This review demonstrates that the available data are not sufficient to suggest any treatment for the eradication of COVID-19 to be used at the clinical level. This article aims to review the roles of existing drugs and drug targets for COVID-19 treatment.
UWB Base Station Cluster Localization for Unmanned Ground Vehicle Guidance
Authors: Wu Yuzhan , Ding Susheng , Ding Yuanhao , Li Meng
Published: April 2021

In this paper, we seek to provide unmanned ground vehicles with positioning service using ultrawideband (UWB) technology, a high-accuracy positioning approach. UWB is chosen for two distinct reasons. First, it does not rely on global navigation satellite systems like GPS, making it able to be applied indoors or in an environment where GPS signal is unstable. Second, it is immune to interference from other signals and accurate enough to guide unmanned ground vehicles moving precisely in a complex environment within a narrow road. In this paper, three UWB base stations are aggregated as a group in a 2D space for localization. A large number of tests are performed with a UWB base station cluster in order to validate its positioning performance. Based on the experiment results, we further develop a dynamic particle swarm optimization-based algorithm and a genetic algorithm to deploy multiple clusters of UWB base stations to cover an area of interest. The performance of the proposed algorithms has been tested through a series of simulations. Finally, experiments using unmanned ground vehicles are carried out to validate the localization performance. The results confirm that the robots can follow complex paths accurately with the proposed UWB-based positioning system.
Excitation and Propagation of Longitudinal L (0, 2) Mode Ultrasonic Guided Waves for the Detection of Damages in Hexagonal Pipes: Numerical and Experimental Studies
Authors: Wan Xiang , Liu Meiru , Zhang Xuhui , Fan Hongwei , Mao Qinghua , Dong Ming , Wang Xing , Ma Hongwei
Published: April 2021

The hexagonal pipe is a special kind of tube structure. Its inner surface of the cross section is in the shape of circle, while the outer surface is hexagonal. It has functioned as an essential and critical part of a drill stem in a high‐torque drill machine used in various resource exploitation fields. The inspection of a hexagonal pipe to avoid its failure and thus to ensure safe operation of a drilling machine is becoming increasingly urgent and important. In this study, the excitation and propagation of ultrasonic guided waves for the purpose of detecting defects in hexagonal pipes are proposed. Dispersion curves of hexagonal pipes are firstly derived by using semianalytical ﬁnite element method. Based on these dispersion curves, longitudinal L (0, 2) mode at 100 kHz is selected to inspect hexagonal pipes. A ring of piezoelectric transducers (PZTs) with the size of 25 mm × 5 mm ×0.5 mm is able to maximize the amplitude of L (0, 2) mode and successfully suppress the undesired L (0, 1) mode in the experiments. Numerical and experimental studies have shown that the displacement field of L (0, 2) mode at 100 kHz is almost uniformly distributed along the circumferential direction. Furthermore, L (0, 2) mode ultrasonic guided waves at 100 kHz are capable of detecting circular through‐hole damages located in the plane and near the edge in a hexagonal pipe. Our study results have demonstrated that the use of longitudinal L (0, 2) mode ultrasonic guided wave provides a promising and effective alternative for the detection of defects in hexagonal pipe structures.
Unsupervised Structural Damage Detection Technique Based on a Deep Convolutional Autoencoder
Authors: Rastin Zahra , Ghodrati Amiri Gholamreza , Darvishan Ehsan
Published: April 2021

Structural health monitoring (SHM) is a hot research topic with the main purpose of damage detection in a structure and assessing its health state. The major focus of SHM studies in recent years has been on developing vibration‐based damage detection algorithms and using machine learning, especially deep learning‐based approaches. Most of the deep learning‐based methods proposed for damage detection in civil structures are based on supervised algorithms that require data from the healthy state and different damaged states of the structure in the training phase. As it is not usually possible to collect data from damaged states of a large civil structure, using such algorithms for these structures may be impractical. This paper proposes a new unsupervised deep learning‐based method for structural damage detection based on convolutional autoencoders (CAEs). The main objective of the proposed method is to identify and quantify structural damage using a CAE network that employs raw vibration signals from the structure and is trained by the signals solely acquired from the healthy state of the structure. The CAE is chosen to take advantage of high feature extraction capability of convolution layers and at the same time use the advantages of an autoencoder as an unsupervised algorithm that does not need data from damaged states in the training phase. Applications on the two numerical models of IASC‐ASCE benchmark structure and a grid structure located at the University of Central Florida, as well as the full‐scale Tianjin Yonghe Bridge, prove the efficiency of the proposed algorithm in assessing the global health state of the structures and quantifying the damage.
Towards Learner-Oriented Monitoring and Evaluation in Adult Education Program: A Vital Approach to Ensure Adult Learners’ Learning Needs
Authors: Assefa Yalalem
Published: April 2021

Monitoring and evaluation practice of adult education by its flexible nature highly needs effective and continuous professional support based on a bureaucratic system that accomplishes expectations using a hierarchical arrangement. The central essence of adult education monitoring is conceptualized as the continuous comparison of implementation progress against the predetermined principles. As well, another common vital task is evaluation. Such practice can provide formative and summative information about program implementation and outcomes for concerned stakeholders. This study placed on examining learner-oriented monitoring and evaluation practices in integrated functional adult education programs. In doing so, a qualitative research approach and case study design were employed. Purposive and available sampling techniques were used to select 83 respondents. Data were collected through interviews, FGD, and document analysis. The collected data were analyzed using thematic analysis. Results showed that integrated functional adult education monitoring practice was limited to report learners’ enrollment data and mere attendance in literacy class. Narrow emphasis is given to monitoring and evaluation activities that can enhance adult learners’ academic performance and ability in relation to their life skills and practical learning needs have been largely forgotten.
Nursing of Gastrointestinal Peristalsis Function Recovery after Abdominal Mirror Surgery for Rectal Cancer Patients Based on Intelligent Electronic Medicine
Authors: Ding Yanyan , Zhu Sujuan , Pang Jieqiong , Li Zhitao , Ming Congkun , Song Xiaofang
Published: April 2021

In recent years, with the rapid development of colorectal surgery technology and laparoscopic instruments, laparoscopic radical resection of colorectal cancer has been widely used. Although laparoscopic surgery has the characteristics of small trauma, less blood loss, less hospitalization days, and low incidence of adverse reactions such as incision infection, it is still inevitable to have different degrees of gastrointestinal dysfunction after surgery. This paper mainly studies the recovery nursing of gastrointestinal peristalsis after abdominal mirror in rectal cancer patients based on intelligent electronic medicine. In this paper, an intelligent medical monitoring system is designed for the posterior care of rectal cancer patients with abdominal mirror image, which can realize the collection and transmission of wireless sign parameters of postoperative rectal cancer patients and improve the efficiency of postoperative monitoring in medical work. All parameter data are sent to the Lora base station in real time via Lora wireless communication, which is then uploaded to the medical monitoring platform. The experimental results showed that the first postoperative exhaust time of the treatment group using the intelligent medical monitoring system was significantly shortened, and the difference was statistically significant (

P
<
0.05

). The first defecation time was shortened, and the difference was statistically significant (

P
<
0.05

). The recovery time of total fluid diet was shortened, and the difference was statistically significant (

P
<
0.05

). The above results indicate that the intelligent medical monitoring device designed in this paper has positive significance for improving the work efficiency of the hospital, the clinical experience of patients after abdominal mirror surgery for rectal cancer, and the real-time monitoring of signs of patients in intensive care.
Calibration of Discrete Element Simulation Parameters for Powder Screw Conveying
Authors: Shen Changpu , Li Yongxiang , Xu Xuemeng
Published: April 2021

In order to obtain the accurate contact parameters in the simulation process of powder screw conveying, this paper took wheat flour as an example, based on the discrete element JKR (Johnson-Kendall-Roberts) contact model, and directly calibrated the simulation contact parameters in the process of screw conveying in response to the mass flow rate of wheat flour. Firstly, the simulation density of wheat flour particles was calibrated, and the simulation density of wheat flour particles was 1320 kg/m. Then, Plackett-Burman experiment was used to screen out the parameters that had significant influence on the mass flow rate: surface energy JKR, coefficient of static friction between wheat flour and wheat flour, and the coefficient of static friction between wheat flour and stainless steel. The second-order regression model of mass flow rate and significance parameters was established and optimized based on Box-Behnken experiment, and the optimal combination of significance parameters: JKR was obtained to be 0.364; the static friction coefficient of wheat flour to wheat flour was 0.437; and the static friction coefficient of wheat flour to stainless steel was 0.609. Finally, the calibration parameters were used for simulation. By comparing the mass flow rate of simulation and experiment, the relative error of the two was 1.37%. The simulation and experiment flow rate values at different rotating speeds (60 r/min, 80 r/min, 100 r/min, 120 r/min, and 140 r/min) were further compared, and the errors were all within 3%. The method of directly calibrating the simulation contact parameters through the screw conveying process can improve the accuracy of screw conveying simulation, and providing a method and basis for powder contact parameters calibration and screw conveying simulation of wheat flour.
Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy Experience in Peritoneal Carcinomatosis: Single-Center Analysis of 180 Cases
Authors: Karadayi Kursat , Bostanci Meric Emre , Mollaoglu Murat Can , Karabacak Ufuk
Published: April 2021

Background. In peritoneal carcinomatosis (PC), increased life span and disease-free survival times are shown in patients with hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) following cytoreductive surgery (SRC). In this study, our main objective was to present our experience of performing SRC and perioperative intraperitoneal chemotherapy (HIPEC and EPIC) on patients with PC, in light of the literature. Methods. Demographic data, follow-up results, peritoneal carcinomatosis index (PCI), completeness of cytoreduction (CCR) score, and morbidity and mortality rates of 180 patients treated with SRC + HIPEC + EPIC for PC at the Department of Surgical Oncology at Sivas Cumhuriyet University between January 2008 and July 2020 were analyzed retrospectively. Results. Distribution of 180 PC cases according to primary organs included 53 ovarian, 39 colorectal, 33 stomach, 25 primary peritoneum, 10 uterus, 10 tuba, five soft tissue, and five appendix originated carcinoma. The average PCI of the cases detected preoperatively was 21 (5–30). Completeness of cytoreduction scores of CCR-0 in 102 cases, CCR-1 in 67 cases, CCR-2 in eight cases, and CCR-3 in three cases was obtained. Median operation time was 300 (200–540) minutes. Perioperative morbidity rate was 47.0%, and perioperative mortality rate was 13.5%. Conclusion. The peritonectomy procedure is a difficult, long-lasting, troublesome intervention, but it is the most important treatment option with acceptable morbidity and mortality rates in patients selected for PC treatment in experienced centers.
Maxillary First Molars with Two Palatal Root Canals
Authors: Sung Kun-Hwa , Hwang Ho-Keel , Jo Hyoung-Hoon
Published: April 2021

Understanding the anatomical variations in the roots and root canal systems of a tooth is important for the success of root canal treatment. The palatal roots of the maxillary molars have fewer anatomical variations than the other roots, and fewer variations occur in the first molars than in the second molars. This case report describes two distinct cases of maxillary first molars with two palatal canals. For the root canal treatment of teeth with anatomical variations, it is essential to plan specific treatment strategies using cone-beam computed tomography and to execute them using a dental operating microscope. Knowledge of the anatomical variations in the palatal roots of maxillary first molars will help to increase the success rate of root canal treatments.
[Retracted] Complexity Computer Simulation in the Study of the Overall Playing Method of Campus Football
Authors: Dai Zhao
Published: April 2021

With the mutual exchange and integration of world football, modern football is in an increasingly comprehensive direction. This research mainly discusses complexity computer simulation in the study of the overall play of campus football. Complexity computer simulation is used to design the background of the simulated football field, and the area is divided according to the size ratio of the actual football field. Then, it uses drawing software to draw the football and player controls. The construction of the knowledge base of this paper is mainly combined with the functional modules of rapid formation and response tactics. In the fast formation function, the required formation can be quickly given through football experience and knowledge rules. In the applied tactics function, for the responsibilities of forwards, midfielders, defenders, and other roles, the tactics implemented are given, including partially coordinated offensive and defensive tactics, personal offensive and defensive tactics, and set‐ball tactics. The “holistic play” football tactics studied in this paper use XML files as recording and playback data, which not only greatly reduce the amount of file data but also make the operation of XML files intuitive and simple. XML can not only realize the recording and playback of player and football track but also be used in the function of rapid formation. The coach uses the “holistic play” football tactics simulation to demonstrate the movement route through the image, guide the players in each position to perceive the game scene by observing the movement route, and analyze and judge the tactical coordination of their respective positions. The computer simulation tactical analysis of the precision of the passing and running and the path coefficient of the passing factor is 0.606 and 0.59, respectively. This research helps to provide guidance on the overall playing tactics of football.
An Adaptive Immune Ant Colony Optimization for Reducing Energy Consumption of Automatic Inspection Path Planning in Industrial Wireless Sensor Networks
Authors: Li Chaoqun , Xiao Jing , Liu Yang , Qi Guohong , Qin Hu , Zhou Jie
Published: April 2021

Industrial wireless sensor networks (IWSNs) are usually fixedly deployed in industrial environments, and various sensor nodes cooperate with each other to complete industrial production tasks. The efficient work of each sensor node of IWSNs will improve the efficiency of the entire network. Automated robots need to perform timely inspection and maintenance of IWSNs in an industrial environment. Excessive inspection distance will increase inspection costs and increase energy consumption. Therefore, shortening the inspection distance can reduce production energy consumption, which is very important for the efficient operation of the entire system. However, the optimal detection path planning of IWSNs is an N‐P problem, which can usually only be solved by heuristic mathematical methods. This paper proposes a new adaptive immune ant colony optimization (AIACO) for optimizing automated inspection path planning. Moreover, novel adaptive operator and immune operator are designed to prevent the algorithm from falling into the local optimum and increase the optimization ability. In order to verify the performance of the algorithm, the algorithm is compared with genetic algorithm (GA) and immune clone algorithm (ICA). The simulation results show that the inspection distance of IWSNs using AIACO is lower than that of GA and ICA. In addition, the convergence speed of AIACO is faster than that of GA and ICA. Therefore, the AIACO proposed in this paper can effectively reduce the inspection energy consumption of the entire IWSN system.
Plasma miRNA Biomarkers in Limited Volume Samples for Detection of Early-stage Pancreatic Cancer
Authors: Dittmar Rachel L. , Liu Suyu , Tai Mei Chee , Rajapakshe Kimal , Huang Ying , Longton Gary , DeCapite Christine , Hurd Mark W. , Paris Pamela L. , Kirkwood Kimberly S. , Coarfa Cristian , Maitra Anirban , Brand Randall E. , Killary Ann M. , Sen Subrata
Published: April 2021

Early detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes; however, PDAC is usually diagnosed late. Therefore, blood-based minimally invasive biomarker assays for limited volume clinical samples are urgently needed. A novel miRNA profiling platform (Abcam Fireplex-Oncology Panel) was used to investigate the feasibility of developing early detection miRNA biomarkers with 20 μL plasma from a training set (58 stage II PDAC cases and 30 controls) and two validation sets (34 stage II PDAC cases and 25 controls; 44 stage II PDAC cases and 18 controls). miR-34a-5p [AUC = 0.77; 95% confidence interval (CI), 0.66–0.87], miR-130a-3p (AUC = 0.74; 95% CI, 0.63–0.84), and miR-222-3p (AUC = 0.70; 95% CI, 0.58–0.81) were identified as significantly differentially abundant in plasma from stage II PDAC versus controls. Although none of the miRNAs individually outperformed the currently used serologic biomarker for PDAC, carbohydrate antigen 19-9 (CA19-9), combining the miRNAs with CA 19-9 improved AUCs from 0.89 (95% CI, 0.81–0.95) for CA 19-9 alone to 0.92 (95% CI, 0.86–0.97), 0.94 (95% CI, 0.89–0.98), and 0.92 (95% CI, 0.87–0.97), respectively. Gene set enrichment analyses of transcripts correlated with high and low expression of the three miRNAs in The Cancer Genome Atlas PDAC sample set. These miRNA biomarkers, assayed in limited volume plasma together with CA19-9, discriminate stage II PDAC from controls with good sensitivity and specificity. Unbiased profiling of larger cohorts should help develop an informative early detection biomarker assay for diagnostic settings.

Prevention Relevance:

Development of minimally invasive biomarker assays for detection of premalignant disease and early-stage pancreatic cancer is key to improving patient survival. This study describes a limited volume plasma miRNA biomarker assay that can detect early-stage resectable pancreatic cancer in clinical samples necessary for effective prevention and clinical intervention.
Transcriptional Silencing of ALDH2 Confers a Dependency on Fanconi Anemia Proteins in Acute Myeloid Leukemia
Authors: Yang Zhaolin , Wu Xiaoli S. , Wei Yiliang , Polyanskaya Sofya A. , Iyer Shruti V. , Jung Moonjung , Lach Francis P. , Adelman Emmalee R. , Klingbeil Olaf , Milazzo Joseph P. , Kramer Melissa , Demerdash Osama E. , Chang Kenneth , Goodwin Sara , Hodges Emily , McCombie W. Richard , Figueroa Maria E. , Smogorzewska Agata , Vakoc Christopher R.
Published: April 2021

Hundreds of genes become aberrantly silenced in acute myeloid leukemia (AML), with most of these epigenetic changes being of unknown functional consequence. Here, we demonstrate how gene silencing can lead to an acquired dependency on the DNA repair machinery in AML. We make this observation by profiling the essentiality of the ubiquitination machinery in cancer cell lines using domain-focused CRISPR screening, which revealed Fanconi anemia (FA) proteins UBE2T and FANCL as unique dependencies in AML. We demonstrate that these dependencies are due to a synthetic lethal interaction between FA proteins and aldehyde dehydrogenase 2 (ALDH2), which function in parallel pathways to counteract the genotoxicity of endogenous aldehydes. We show DNA hypermethylation and silencing of ALDH2 occur in a recurrent manner in human AML, which is sufficient to confer FA pathway dependency. Our study suggests that targeting of the ubiquitination reaction catalyzed by FA proteins can eliminate ALDH2-deficient AML.

Significance:

Aberrant gene silencing is an epigenetic hallmark of human cancer, but the functional consequences of this process are largely unknown. In this study, we show how an epigenetic alteration leads to an actionable dependency on a DNA repair pathway through the disabling of genetic redundancy.

This article is highlighted in the In This Issue feature, p. 2113
NKX3.1 Localization to Mitochondria Suppresses Prostate Cancer Initiation
Authors: Papachristodoulou Alexandros , Rodriguez-Calero Antonio , Panja Sukanya , Margolskee Elizabeth , Virk Renu K. , Milner Teresa A. , Martina Luis Pina , Kim Jaime Y. , Di Bernardo Matteo , Williams Alanna B. , Maliza Elvis A. , Caputo Joseph M. , Haas Christopher , Wang Vinson , De Castro Guarionex Joel , Wenske Sven , Hibshoosh Hanina , McKiernan James M. , Shen Michael M. , Rubin Mark A. , Mitrofanova Antonina , Dutta Aditya , Abate-Shen Cory
Published: April 2021

Mitochondria provide the first line of defense against the tumor-promoting effects of oxidative stress. Here we show that the prostate-specific homeoprotein NKX3.1 suppresses prostate cancer initiation by protecting mitochondria from oxidative stress. Integrating analyses of genetically engineered mouse models, human prostate cancer cells, and human prostate cancer organotypic cultures, we find that, in response to oxidative stress, NKX3.1 is imported to mitochondria via the chaperone protein HSPA9, where it regulates transcription of mitochondrial-encoded electron transport chain (ETC) genes, thereby restoring oxidative phosphorylation and preventing cancer initiation. Germline polymorphisms of NKX3.1 associated with increased cancer risk fail to protect from oxidative stress or suppress tumorigenicity. Low expression levels of NKX3.1 combined with low expression of mitochondrial ETC genes are associated with adverse clinical outcome, whereas high levels of mitochondrial NKX3.1 protein are associated with favorable outcome. This work reveals an extranuclear role for NKX3.1 in suppression of prostate cancer by protecting mitochondrial function.

Significance:

Our findings uncover a nonnuclear function for NKX3.1 that is a key mechanism for suppression of prostate cancer. Analyses of the expression levels and subcellular localization of NKX3.1 in patients at risk of cancer progression may improve risk assessment in a precision prevention paradigm, particularly for men undergoing active surveillance.

See related commentary by Finch and Baena, p. 2132.

This article is highlighted in the In This Issue feature, p. 2113
Integrated Genomic Analysis Identifies Driver Genes and Cisplatin-Resistant Progenitor Phenotype in Pediatric Liver Cancer
Authors: Hirsch Theo Z. , Pilet Jill , Morcrette Guillaume , Roehrig Amélie , Monteiro Benedict J.E. , Molina Laura , Bayard Quentin , Trépo Eric , Meunier Léa , Caruso Stefano , Renault Victor , Deleuze Jean-François , Fresneau Brice , Chardot Christophe , Gonzales Emmanuel , Jacquemin Emmanuel , Guerin Florent , Fabre Monique , Aerts Isabelle , Taque Sophie , Laithier Véronique , Branchereau Sophie , Guettier Catherine , Brugières Laurence , Rebouissou Sandra , Letouzé Eric , Zucman-Rossi Jessica
Published: April 2021

Pediatric liver cancers (PLC) comprise diverse diseases affecting infants, children, and adolescents. Despite overall good prognosis, PLCs display heterogeneous response to chemotherapy. Integrated genomic analysis of 126 pediatric liver tumors showed a continuum of driver mechanisms associated with patient age, including new targetable oncogenes. In 10% of patients with hepatoblastoma, all before three years old, we identified a mosaic premalignant clonal expansion of cells altered at the 11p15.5 locus. Analysis of spatial and longitudinal heterogeneity revealed an important plasticity between “hepatocytic,” “liver progenitor,” and “mesenchymal” molecular subgroups of hepatoblastoma. We showed that during chemotherapy, “liver progenitor” cells accumulated massive loads of cisplatin-induced mutations with a specific mutational signature, leading to the development of heavily mutated relapses and metastases. Drug screening in PLC cell lines identified promising targets for cisplatin-resistant progenitor cells, validated in mouse xenograft experiments. These data provide new insights into cisplatin resistance mechanisms in PLC and suggest alternative therapies.

Significance:

PLCs are deadly when they resist chemotherapy, with limited alternative treatment options. Using a multiomics approach, we identified PLC driver genes and the cellular phenotype at the origin of cisplatin resistance. We validated new treatments targeting these molecular features in cell lines and xenografts.

This article is highlighted in the In This Issue feature, p. 2355
Association of Pre-ESRD Serum Bicarbonate with Post-ESRD Mortality in Patients with Incident ESRD
Authors: Tantisattamo Ekamol , Murray Victoria , Obi Yoshitsugu , Park Christina , Catabay Christina J. , Lee Yuji , Wenziger Cachet , Hsiung Jui-Ting , Soohoo Melissa , Kleine Carola-Ellen , Rhee Connie M. , Kraut Jeffrey , Kovesdy Csaba P. , Kalantar-Zadeh Kamyar , Streja Elani
Published: April 2021

Background: Serum bicarbonate or total carbon dioxide (CO2) concentrations decline as chronic kidney disease (CKD) progresses and rise after dialysis initiation. While metabolic acidosis accelerates the progression of CKD and is associated with higher mortality among patients with end stage renal disease (ESRD), there are scarce data on the association of CO2 concentrations before ESRD transition with post-ESRD mortality. Methods: A historical cohort from the Transition of Care in CKD (TC-CKD) study includes 85,505 veterans who transitioned to ESRD from October 1, 2007, through March 31, 2014. After 1,958 patients without follow-up data, 3 patients with missing date of birth, and 50,889 patients without CO2 6 months prior to ESRD transition were excluded, the study population includes 32,655 patients. Associations between CO2 concentrations averaged over the last 6 months and its rate of decline during the 12 months prior to ESRD transition and post-ESRD all-cause, cardiovascular (CV), and non-CV mortality were examined by using hierarchical adjustment with Cox regression models. Results: The cohort was on average 68 ± 11 years old and included 29% Black veterans. Baseline concentrations of CO2 were 23 ± 4 mEq/L, and median (interquartile range) change in CO2 were −1.8 [−3.4, −0.2] mEq/L/year. High (≥28 mEq/L) and low (<18 mEq/L) CO2 concentrations showed higher adjusted mortality risk while there was no clear trend in the middle range. Consistent associations were observed irrespective of sodium bicarbonate use. There was also a U-shaped association between the change in CO2 and all-cause, CV, and non-CV mortality with the lowest risk approximately at −2.0 and 0.0 mEq/L/year among sodium bicarbonate nonusers and users, respectively, and the highest mortality was among patients with decline in CO2 >4 mEq/L/year. Conclusion: Both high and low pre-ESRD CO2 levels (≥28 and <18 mEq/L) during 6 months prior to dialysis transition and rate of CO2 decline >4 mEq/L/year during 1 year before dialysis initiation were associated with greater post-ESRD all-cause, CV, and non-CV mortality. Further studies are needed to determine the optimal management of CO2 in patients with advanced CKD stages transitioning to ESRD.
Associations of Sleep Quality with Gait Speed and Falls in Older Adults: The Mediating Effect of Muscle Strength and the Gender Difference
Authors: Zhang Li , Liu Shuqin , Li Yujie , Li Suyun , Wu Yili
Published: April 2021

Introduction: Although previous studies have reported the significant associations of sleep quality with gait speed and falls, the mechanisms underlying these associations are unclear. We aimed to examine the gender-specific associations of sleep quality with gait speed and falls among older adults and to explore the possible mediating effect of muscle strength on these relationships. Methods: Data were taken from wave 6 (2012–2013) of the English Longitudinal Study of Aging (ELSA), including 7,664 participants aged 60 years and older. Sleep quality and falls were assessed by self-report. Gait speed was measured by the “timed walking test” and then adjusted by height. As an indicator of overall muscle strength, grip strength was measured by using the Smedley dynamometer. Baron and Kenny’s causal steps and the Karlson/Holm/Breen method were used to examine the mediating effect. Results: Higher sleep quality was associated with the higher level of gait speed (β = 0.008, p = 0.031 in men; β = 0.008, p = 0.017 in women) and with lower prevalence of falls (OR = 0.878, 95% CI: 0.773, 0.998 in men; OR = 0.874, 95% CI: 0.792, 0.965 in women). Grip strength mediated these associations in men but not in women, and the mediating effects of grip strength can explain 23.74 and 11.01% of the total effect of sleep quality on gait speed and falls, respectively. Conclusion: Our findings help explain the mechanism underlying the associations of sleep quality with gait speed and falls. Effort to maintain the mobility of the older men should focus on improving both sleep quality and muscle strength.
The Primary Ciliary Dyskinesia Computed Tomography Score in Adults with Bronchiectasis: A Derivation und Validation Study
Authors: Rademacher Jessica , Dettmer Sabine , Fuge Jan , Vogel-Claussen Jens , Shin Hoen-oh , Shah Anand , Pedro Paula Inês , Wilson Rob , Welte Tobias , Wacker Frank , Loebinger Michael R. , Ringshausen Felix C.
Published: April 2021

Background: Primary ciliary dyskinesia (PCD) is a rare genetic disorder which requires a complex diagnostic workup. Thus, an easy and widely available screening method would be helpful to identify patients who need a further diagnostic workup for PCD. Objectives: The aim of the study was to develop and validate a computed tomography (CT) score for PCD to facilitate etiological diagnosis in adults with bronchiectasis. Method: Chest CTs from 121 adults with bronchiectasis were scored for bronchiectasis morphology, distribution, and associated findings. Patients with and without the etiological diagnosis of PCD (46 and 75, respectively) were compared. Significantly, different imaging findings (p < 0.05) in univariate analysis were considered for multivariate analysis. Distinct findings were used to build the score. Based on this score, receiver operating characteristic (ROC) curve analysis was performed. The score was validated with 2 independent cohorts, another cohort from the same institution with 56 patients (28 with PCD) and an external cohort from another referral center with 172 patients (86 with PCD). Results: The following parameters predicted PCD in adults with bronchiectasis and were included in the score with weighting according to their regression coefficients: 2 points were given for predominance in the middle/lower lobe, 2 points for tree-in-bud pattern, 2 points for atelectasis or prior resection of a middle/lower lobe, and 3 points for absence of emphysema and fibrosis. Situs inversus was only observed in subjects with PCD (Kartagener syndrome) and, thus, was not used in the primary ciliary dyskinesia computed tomography (PCD-CT) score as group comparisons could not be performed. ROC curve analysis revealed an area under the curve (AUC) of 0.90 (95% CI 0.85–0.96). Youden index was the highest at a threshold of >6 with a sensitivity of 83% and a specificity of 83%. In the validation cohorts, ROC curve analysis confirmed the performance of the score with an AUC of 0.83 (95% CI 0.72–0.94) in the first validation cohort and 0.79 (95% CI 0.73–0.86) in the external validation cohort. Conclusions: The PCD-CT score provides the first validated CT score for PCD and helps physicians in identifying adult bronchiectasis patients who require further diagnostic workup. Key message: The PCD-CT score provides the first validated CT score to assist physicians in identifying adult bronchiectasis patients who require a further diagnostic workup for PCD. It potentially improves earlier recognition of this rare and underdiagnosed disease.
Encapsulating Peritoneal Sclerosis and Mortality Related to Infection in Patients on Combination Once-Weekly Hemodialysis with Peritoneal Dialysis
Authors: Murashima Miho , Hamano Takayuki , Abe Masanori , Masakane Ikuto
Published: April 2021

Introduction: Previous studies showed that the combination of peritoneal dialysis (PD) and once-weekly hemodialysis is associated with lower all-cause and cardiovascular mortality. This study aimed to compare the incidence of encapsulating peritoneal sclerosis (EPS) and infection-related mortality among those on combination therapy and those on PD alone. Methods: This prospective study on the Japanese Renal Data Registry included patients on PD from 2010 to 2014. Subjects were followed up until the end of 2015. Exposure of interest was combination therapy compared with PD alone. Patients who transitioned to combination therapy were matched with those on PD alone by propensity scores. Outcomes were EPS and infection-related mortality. Data were analyzed using Cox regression models. Results: Among the matched cohort, 608 and 869 patients were on combination therapy and on PD alone, respectively. Dialysate-to-plasma creatinine (D/P Cr) ratio decreased over time among those on combination therapy, while the ratio increased among those on PD alone (p = 0.01 by the mixed-effects model). During a median follow-up of 2.5 years, 33 experienced EPS and 55 died of infection. Combination therapy was associated with lower infection-related mortality (HR [95% CI]: 0.52 [0.28–0.95]) but not with EPS (HR: 1.21 [0.61–2.40]). Lower mortality was not limited to intra-abdominal infection but also observed for pulmonary infection. Sensitivity analyses considering the effects of dialysis facilities yielded similar results. Conclusions: Combination therapy was associated with lower infection-related mortality. It was also associated with a decline in the D/P Cr ratio over time but not with lower incidence of EPS during the short observation period.
Nutritional Profiles of US Adults with Suboptimal Dietary Creatine Intake
Authors: Ostojic Sergej M.
Published: April 2021

Introduction: Recent population-based studies reported an inadequate dietary intake of creatine, a conditionally essential nutrient that plays an important role in human metabolism. Methods: We analyzed here the nutritional profiles of US adults with low creatine consumption, using data from the 2017 to 2018 National Health and Nutrition Examination Survey (NHANES). Results: Among 4,004 NHANES adult participants that reported detailed dietary intake information, 2,611 (65.2%) were calculated to have dietary creatine intake below recommended levels of 1.00 g/day. The average daily creatine intake in this subpopulation was 0.52 ± 0.26 g (95% confidence interval, from 0.51 to 0.53). This was accompanied by a significantly lower dietary intake of meat-based protein, as compared to participants whose dietary creatine intake was equal to or above recommended levels (20.1 ± 10.2 g/day vs. 67.1 ± 30.4 g/day; p < 0.001). Conclusion: The large-scale rate of suboptimal dietary creatine intake found in this cross-sectional study warrants additional research, and calls for immediate public health measures fostering creatine-rich foods in human nutrition.
Elevated Expression of DNA Methyltransferases and Enhancer of Zeste Homolog 2 in Helicobacter pylori - Gastritis and Gastric Carcinoma
Authors: Purkait Suvendu , Patra Susama , Mitra Suvradeep , Behera Minakshi M. , Panigrahi Manas Kumar , Kumar Pankaj , Kar Madhabananda , Hallur Vinaykumar , Chandra Samal Subash
Published: April 2021

Aim: The aim of this study was to study the role of key epigenetic regulators pertaining to DNA methylation and histone-modification systems in Helicobacter pylori (HP)-associated gastritis and gastric carcinogenesis. Methods: The expression of DNA methyltransferase (DNMT-1, 3A, and 3B) and the catalytic subunit of polycomb repressive complex-2 (enhancer of zeste homolog 2 [EZH2]) in gastric carcinomas (n = 104), mucosa adjacent to carcinoma (n = 104), HP-associated gastritis (n = 95), and histologically normal mucosa (n = 31) was assessed by immunohistochemistry and qRT-PCR. Results: The expression of all 3 DNMTs and EZH2 was significantly higher in HP-associated gastritis and carcinoma cases than in those with adjacent and normal mucosa. The expression of DNMT-1 and 3B was maximum in HP-associated gastritis. DNMT-3A showed higher expression in carcinoma-adjacent mucosa than in normal mucosa. Interestingly, the expression of EZH2 was higher in cases of HP-associated gastritis with metaplasia than in those without metaplasia and also in cases of intestinal type of adenocarcinoma. Significant positive correlation of EZH2 was identified with DNMT-1, DNMT-3A, and DNMT-3B. However, none of these markers was associated with survival outcome. Conclusion: This study establishes an important role of the key epigenetic regulators in the pathogenesis of both HP-associated gastritis and gastric carcinoma. Higher expression of all the epigenetic markers in the gastritis and their persistence in the carcinoma point toward their implications in HP-driven gastric carcinogenesis. Further, an inter-relation between the 2 arms of epigenetics, namely, DNA methylation and histone-modification in the pathogenesis of gastric carcinoma, is also documented. Given the reversibility of epigenetic phenomenon, these molecules may be of important therapeutic use.