bluuebunny/crossref_metadata_2025 huggingface dataset:
K-Means Clustering Algorithm-Based Detection of Carotid Atherosclerotic Plaque Using Contrast-Enhanced Ultrasound Images
Authors: Zhou Ruitao , Zhou Ruijie , Zhu Zhibo
Published: September 2021

The aim of this study was to investigate the diagnostic value of contrast-enhanced ultrasound (CEUS) based on the K-means clustering (KMC) algorithm for the vulnerability of carotid atherosclerotic plaque (CAA). In this study, 90 patients with CAA were enrolled into a control group (group A) and an experimental group (group B). The angiography method and KMC-based ultrasound detection were applied to diagnose the CAA patients from the two groups, respectively. The results showed that the sensitivity, specificity, and positive predictive value of patients from group B (92.3%, 90.1%, and 94.8%) for diagnosing CAA were obviously higher than those of patients from group A (81.4%, 88.6%, and 75.3%) (

P
<
0.05

). The detection rate of patients from group B (83%, 85%) was dramatically higher than that of patients from group A (65%, 71%) in terms of artery bifurcation and CAA (

P
<
0.05

). Besides, patients from group B were more satisfied with their diagnostic method than group A (

P
<
0.05

). In conclusion, the ultrasound detection method based on KMC had high sensitivity, specificity, and accuracy in the detection of CAA. In addition, ultrasound detection was better than angiography in the diagnosis of plaque in different parts, and it was worthwhile to apply the ultrasound detection method based on KMC in clinical practice.
[Retracted] Screening and Identification of Antidepressant Active Ingredients from Puerariae Radix Extract and Study on Its Mechanism
Authors: Wang Guoze , Luo Peng , Zhang Shuai , Huang Qun , Zhang Shuling , Zeng Qibing , Mao Jingxin
Published: September 2021

Objective. Depression is a common mental disease with long course and high recurrence rate. Previous studies showed that Puerariae Radix and its extracts have powerful antidepressant effects in recent years. The study proposed an integrated strategy, combining network pharmacology and molecular pharmacology experiment to investigate the mechanisms of the antidepressant active ingredients from Puerariae Radix. Methods. TCMSP database, GeneCards database, Venny 2.1, UniProt database, STRING database, Cytoscape 3.7.2, and Metascape database were used to screen the active chemical components, antidepressant‐related genes, and core targets, convert the abbreviated gene names in batch, search and predict the interaction between proteins, and construct the PPI network of Puerariae Radix. KEGG pathway and GO biological process enrichment and biological annotation were used to select antidepressant core gene targets. The MTT method was used to detect the effect of puerarin on the damage of PC12 cells induced by corticosterone. The DCFH‐DA probe and ROS assay kit were utilized to detect the production of ROS in PC12 cells. PI/Annexin V was used to detect the apoptotic rate of puerarin on PC12 cells. Western blotting was used to verify the regulation of puerarin on the key targets of AKT1, FOS, CASP3, STAT3, and TNF‐α in PC12 cells. Results and Conclusion. Eight main active components, 64 potential antidepressant gene targets, and 15 core antidepressant gene targets were obtained. 35 signaling pathways and 52 biological processes related to antidepressant effect of Puerariae Radix were identified. Puerarin was the active ingredient derived from Puerariae Radix which exhibited the antidepression effect by improving the viability of cell, reducing cell apoptosis, regulating ROS production, increasing protein expressions of AKT1 and FOS, and reducing protein expressions of CASP3, STAT3, and TNF‐α. The study revealed the pharmacodynamic material basis and possible antidepressant mechanism of Puerariae Radix and provided new theoretical basis and ideas for antidepressant research.
Intelligent Algorithms-Based CT Image Segmentation in Patients with Cardiovascular Diseases and Realization of Visualization Algorithms
Authors: Huang Xianhua
Published: September 2021

The study focused on the intelligent algorithms-based segmentation of computed tomography (CT) images of patients with cardiovascular diseases (CVD) and the realization of visualization algorithms. The first step was to design a method for precise segmentation under the cylinder model based on the coronary body data of the coarse segmentation, and then the principles of different visualization algorithms were discussed. The results showed that the precise segmentation method can effectively eliminate most of the branches and calcified lesions; curved planar reformation (CPR) and straightened CPR can display the entire blood vessel on one image; and spherical CPR can display the complete coronary artery tree on an image, so that a problem with a certain blood vessel can be quickly found. In conclusion, the precise segmentation of CT images of CVD and visualization algorithm based on the cylinder model have clinical significance in the diagnosis of CVD.
Research on Network Layer Recursive Reduction Model Compression for Image Recognition
Authors: Ling Hongfei , Zhang Weiwei , Tao Yingjie , Zhou Mi
Published: September 2021

ResNet has been widely used in the field of machine learning since it was proposed. This network model is successful in extracting features from input data by superimposing multiple layers of neural networks and thus achieves high accuracy in many applications. However, the superposition of multilayer neural networks increases their computational cost. For this reason, we propose a network model compression technique that removes multiple neural network layers from ResNet without decreasing the accuracy rate. The key idea is to provide a priority term to identify the importance of each neural network layer, and then select the unimportant layers to be removed during the training process based on the priority of the neural network layers. In addition, this paper also retrains the network model to avoid the accuracy degradation caused by the deletion of network layers. Experiments demonstrate that the network size can be reduced by 24.00%–42.86% of the number of layers without reducing the classification accuracy when classification is performed on CIFAR-10/100 and ImageNet.
A Dual-Band Base Station Antenna with a Split Ring for Sub-6 GHz Communication
Authors: Huang Bei , Cao Jie , Lin Weifeng , Zhang Jun , Zhang Gary , Wu Fugen
Published: September 2021

A dual-band base station antenna is introduced in this paper. The proposed antenna is composed of baluns, bowtie patches, and a split ring. The two pairs of bowtie patches excited by the two orthogonal balun structures can achieve dual polarization. The split ring is used to yield two additional resonances to broaden the impedance bandwidth. In this way, a compact dual-band base station antenna is obtained with the size of 0.41 λc × 0.41 λc × 0.13 λc (λc is the wavelength in the free space at the lowest operating frequency band) and the average gain of 8.2 dBi. Moreover, the operating frequency bands of the proposed antenna cover 2515–2675 MHz, 3400–3600 MHz, and 4800–5000 MHz, which can function as an element for macro- or microcells in sub-6 GHz communications.
Optimized Allocation of Resources for Intelligent Construction of Training Venues for Track and Field Teams
Authors: Qin Yan , Wu Wen
Published: September 2021

Because of the problems of low allocation efficiency and accuracy in the traditional resource allocation model for the intelligent construction of track and field team training venues, this paper proposes a new intelligent construction resource allocation model for track and field team training venues. A distributed data collection method is adopted to select the index data for the intelligent construction of the track and field team training venues to optimize the allocation of resources and the mined resource allocation index through extracting the optimized index characteristics. The goal of the optimization problem is transformed into a single-objective solving problem. The suggested approach is based on the two-level programming concept. The simulation experimental results show higher efficiency and better allocation effect of the proposed scheme compared to other state-of-the-art approaches. Our evaluation and observations suggest that the accuracy of the intelligent construction of track and field team training venues is between 90% and 99% which is higher than two other benchmarked models. Furthermore, the proposed model can quickly reach to an optimal decision.
Additive Manufacturing of Biopolymers for Tissue Engineering and Regenerative Medicine: An Overview, Potential Applications, Advancements, and Trends
Authors: Veeman Dhinakaran , Sai M. Swapna , Sureshkumar P. , Jagadeesha T. , Natrayan L. , Ravichandran M. , Mammo Wubishet Degife
Published: September 2021

As a technique of producing fabric engineering scaffolds, three-dimensional (3D) printing has tremendous possibilities. 3D printing applications are restricted to a wide range of biomaterials in the field of regenerative medicine and tissue engineering. Due to their biocompatibility, bioactiveness, and biodegradability, biopolymers such as collagen, alginate, silk fibroin, chitosan, alginate, cellulose, and starch are used in a variety of fields, including the food, biomedical, regeneration, agriculture, packaging, and pharmaceutical industries. The benefits of producing 3D-printed scaffolds are many, including the capacity to produce complicated geometries, porosity, and multicell coculture and to take growth factors into account. In particular, the additional production of biopolymers offers new options to produce 3D structures and materials with specialised patterns and properties. In the realm of tissue engineering and regenerative medicine (TERM), important progress has been accomplished; now, several state-of-the-art techniques are used to produce porous scaffolds for organ or tissue regeneration to be suited for tissue technology. Natural biopolymeric materials are often better suited for designing and manufacturing healing equipment than temporary implants and tissue regeneration materials owing to its appropriate properties and biocompatibility. The review focuses on the additive manufacturing of biopolymers with significant changes, advancements, trends, and developments in regenerative medicine and tissue engineering with potential applications.
Identification and Simultaneous Determination of the Main Toxical Pyrrolizidine Alkaloids in a Compound Prescription of Traditional Chinese Medicine: Qianbai Biyan Tablet
Authors: Yang Mengting , Tan Daopeng , Lu Anjing , Qin Lin , Wang Changhong , Ling Hua , Lu Yanliu , He Yuqi
Published: September 2021

Qianbai biyan tablet (QT) is a compound prescription of traditional Chinese medicine which is used to treat nasal congestion, rhinitis, and nasosinusitis, with Senecio scandens as its main plant material. Several pyrrolizidine alkaloids (PAs) were reported in Senecio scandens and others of Senecio species. Although Senecio scandens is assigned as the legal plant material of QT, whether replaced use of it by other Senecio plants can bring toxicity is unknown because of the lack of quantitative data about toxic PAs between different Senecio species. In the present study, adonifoline, senkirkine, and another PA presumed as emiline have been identified in QT; however, there was no senecionine detected in all tablets. PA contents in QTs varied in different companies and different batches. Adonifoline existed only in Senecio scandens, and senecionine was detected in all eight Senecio plants investigated in the present study. Data showed that replaced use of Senecio scandens with a low level of senecionine by other Senecio plants such as Senecio vulgaris containing a high level of senecionine is advertised to be forbidden. Data of the present study may be used as a reference to make new drug quality regularity and recommendation guideline for the safety of QT.
Modelling Investment Choice Preference of Government Venture Capital Guiding Funds
Authors: Yang Sijing , Cui Jing
Published: September 2021

The continuous development of the government venture capital guiding funds (hereinafter referred to as the “government guiding funds”) has provided financial support and development opportunities for the development of many small- and medium-sized enterprises (SMEs), and government guiding funds have been paid attention by more and more entrepreneurs and investors of SMEs. This paper takes the SMEs listed on the National Equities Exchange and Quotations (“NEEQ,” known as the New Third Board) as a research sample, systematically examines the factors that influence the selection of investment objects of government guiding funds, and studies the preference of government guiding funds from the aspects of financial characteristics and corporate governance of SMEs. The research results show that on one hand, ownership concentration, date of establishment, and asset size are significantly related to government guiding funds, while the return on equity (ROE), the asset-liability ratio, liquidity of assets, growth rate of main business income, and the operating net profit ratio failed to pass the significance test; on the other hand, operating profit ratio, investment interests, asset size, and the amount of investment of government guiding funds are significantly related, while investment rounds, date of establishment, ownership concentration, ROE, asset-liability ratio, liquidity of assets, and operating net profit ratio failed the significance test.
Influencing Factors of Early Neurological Deterioration and Short-Term Prognosis after Intravenous Thrombolysis in Patients with Acute Ischemic Stroke
Authors: Liu Guangsheng , Dai Jianghua , Ma Yinghao , Chen Yongjun , Liao Xiaohong , Zou Ao , Yin Zhian
Published: September 2021

Objective. To explore the factors affecting the early neurological deterioration (END) and short-term prognosis of patients with acute ischemic stroke (AIS) after intravenous thrombolysis. Methods. The clinical data of 212 patients with AIS who received intravenous thrombolysis in our hospital from July 2017 to November 2020 were selected and divided into the END group (n = 71) and the non-END group (n = 141) according to the National Institute of Health Stroke Scale (NIHSS) score and divided into the poor prognosis group (n = 85) and the good prognosis group (n = 127) according to the modified Rankin scale (mRS) score at discharge. The basic data of patients, vascular risk factors, imaging examinations, and laboratory indicators were collected. A logistic regression model was used to analyze the influencing factors of END and the short-term prognosis of AIS patients after intravenous thrombolysis. Results. Univariate analysis showed that the patient's age, time from onset to treatment (OTT), NIHSS score, diabetes, hypertension, atrial fibrillation, TOAST classification, infarct size, carotid artery stenosis, white blood cell count (WBC), C-reactive protein (CRP), and D-dimer (DD) were associated with END (

P
<
0.05

). Multiple logistic regression analysis found that NIHSS score, diabetes, atrial fibrillation, infarct size, carotid stenosis, and CRP were independent influencing factors of END after intravenous thrombolysis in AIS patients (

P
<
0.05

). Univariate analysis showed that the patient's age, OTT, NIHSS score, diabetes, hypertension, atrial fibrillation, infarct size, carotid stenosis, and the occurrence of END were all related to the short-term prognosis of AIS patients (

P
<
0.05

). Multiple logistic regression analysis showed that age, NIHSS score, infarct size, carotid artery stenosis, and the occurrence of END were all independent factors affecting the short-term prognosis of AIS patients. Conclusion. High NIHSS score, combined with diabetes, atrial fibrillation, moderate to severe carotid stenosis, and elevated CRP are all risk factors for END after intravenous thrombolysis in AIS patients. Moreover, advanced age, high NIHSS score, moderate to severe carotid stenosis, and occurrence of END are risk factors for poor short-term prognosis after intravenous thrombolysis in AIS patients.
Embedded Image and Video Coding Algorithm Based on Adaptive Filtering Equation
Authors: Fu Zhe
Published: September 2021

Based on the improved adaptive filtering method, this paper conducts in-depth discussion and research on embedded graphics and video coding and chooses to improve the adaptive filtering algorithm from three aspects: starting point prediction, search template, and window partitioning. The algorithm is imported into the encoder for video capture and encoding. By capturing videos of different formats, resolutions, and times, the memory size of the video files collected before and after the algorithm optimization is compared, and the optimized algorithm occupies the memory space of the video file in the actual system. The conclusion of less and higher coding rates. The collected video information is stored on a personal computer equipped with a freeness, and external electronic devices only need to download and install the browser, and the collected video information can be accessed in the local area network through the protocol. The improved coding algorithm has higher coding efficiency and can reduce the storage space occupied by the video.
The Clinical Value of High-Frequency Ultrasound in the Diagnosis of Psoriatic Arthritis
Authors: Yang Jing , Peng Hanfei , Yan Guangyan
Published: September 2021

Objective. To investigate the clinical value of high-frequency ultrasound in psoriatic arthritis (PSA). The study subjects were 32 outpatients and inpatients with PSA who were pathologically diagnosed from January 2018 to September 2020, including 11 males and 21 females, aged 25–70 years old, with an average of (49.8 ± 14.0) years old. All patients underwent ultrasound and physical examination, including the small joints of the hands and feet on both sides, nails, and the main attachment points of the lower limbs (quadriceps tendon, patellar ligament, Achilles tendon, and plantar fascia attachment). The involvement of these joints, attachment points, and nails was observed and counted, respectively, and statistically analyzed. Results. Physical examination revealed 406 (406/1792, 22.66%) joint lesions, 79 (79/320, 24.69%) attachment inflammation, and 84 (84/320, 26.25%) nail lesions. Ultrasonography revealed 492 (492/1792, 27.46%) joint lesions, 166 (166/320, 51.88%) attachment inflammation, and 203 (203/320, 63.44%) nail lesions. The positive rate of ultrasound examination was higher than that of physical examination (

P
<
0.001

). Conclusion. Ultrasonography can detect joint, attachment, and nail lesions earlier than physical examination in patients with PSA. Ultrasonography is of great value in the diagnosis of PSA.
Can Monetary Incentive Regulate Boarding Passenger Distribution on the Metro Station Platform?
Authors: Yu Jiajie , Kuai Chenchen , Ji Yanjie , Gao Liangpeng
Published: September 2021

To equilibrate the passenger distribution on the metro platform and carriage, a monetary incentive policy was explored in this paper; a discount on travel fare was provided to motivate metro passengers to queue for boarding in the noncrowded areas on the platform. The congested state is evaluated combined with the passenger distribution in the upcoming metro carriage. The utility of metro passengers and companies caused by the monetary incentive policy was analyzed, and the binary logit model was used to relate the utility to the passenger’s willingness to move from crowded areas to noncrowded ones. With data acquired from the questionnaire survey, a regression analysis was employed to explain the variation in passengers’ willingness to move as a function of discount level as well as personal and trip characteristics. The regression results show that effect of incentive discount is greater on female passengers and elderly passengers. A 10% discount can motivate most passengers aged over 40, and a 30% discount works on most female passengers. According to the different levels of passenger sensitivity, a particular discount can be determined to motivate a specific proportion of passengers to move and achieve the regulation of passenger distribution on the metro station platform and metro carriage.
Osthole Induces Apoptosis and Inhibits Proliferation, Invasion, and Migration of Human Cervical Carcinoma HeLa Cells
Authors: Yin Sugai , Liu Hejuan , Wang Jing , Feng Shuying , Chen Yulong , Shang Yiwan , Su Xiuhong , Si Fuchun
Published: September 2021

Purpose. To study the effect of osthole extract on proliferation, migration, invasion, and apoptosis of human cervical carcinoma HeLa cells and investigate its underlying mechanism. Methods. HeLa cells were exposed to osthole at various concentrations. Cell viability, migration, and invasion were detected by MTT assay, scratch wound-healing assay, and invasion assay, respectively. The proportion of cells undergoing apoptosis was analyzed by flow cytometry. Western blot and RT-qPCR were performed to determine changes in the expression of key factors in the Wnt/β-catenin signaling pathway. Results. The osthole extract effectively inhibited the proliferation, migration, and invasion potential of HeLa cells in a dose-dependent manner. The rate of apoptosis induction in HeLa cells treated with the osthole extract for 48 h was significantly higher than that of the untreated controls. Outcomes of the western blotting analysis and RT-qPCR showed that the expression of β-catenin, c-Myc, cyclin D1, survivin, and MMP-9 was significantly inhibited. Conclusion. Osthole could significantly inhibit the malignant behavior of HeLa cells and induce cellular apoptosis. Inactivation of the Wnt/β-catenin signaling pathway by osthole may be a mechanism to control cancer metastasis.
Design of English Interactive Teaching System Based on Association Rules Algorithm
Authors: Nie Aiming
Published: September 2021

The Internet has become a new medium, and educational activities have also undergone changes due to the development of new technologies. In the past, teaching activities that required students to teach in a specific time and space have changed to less time and space constraints, which have also made the educational process pay more attention to the university teaching mode under the Internet situation, which makes the teaching process more comfortable and intelligent. In this paper, we propose an English interactive teaching system based on the association rules algorithm. This method can make full use of the relevance between data to improve the efficiency of English teaching. According to the division of UNESCO, education informatization is divided into four stages: start, application, integration, and innovation. With the initial development of network hardware technology construction in recent years, it has gradually entered the integration and innovation stage of education and information technology. The important task at this stage is to carry out innovations that are different from traditional teaching concepts, innovations that are different from traditional talent training methods, and innovations that are different from traditional education methods and evaluation methods. From the perspective of dialectical materialism, different angles of a certain issue can be expressed differently. Educational activities are based on Huluo’s technology to a certain extent, and the closedness of traditional education methods has been changed. In order to verify the performance of the method proposed in this paper, we test the proposed algorithm as well as compare it with the other two strategies. The experimental results show that the proposed has a better performance.
Effects of GV14 Acupuncture on Cerebral Blood Flow Velocity in the Basilar and Middle Cerebral Arteries and CO2 Reactivity during Hypercapnia in Normal Individuals
Authors: Lee Hyun Ku , Moon Sang-Kwan , Jin Chul , Cho Seung-Yeon , Park Seong-Uk , Jung Woo-Sang , Park Jung-Mi , Ko Chang-Nam , Cho Ki-Ho , Kwon Seungwon
Published: September 2021

The Governing Vessel 14 (GV14) (Dazhui) is one of the acupuncture points referred to as “seven acupoints for stroke.” Nevertheless, there is a scarcity of research on the effects of acupuncture treatment at GV14. This study investigated the effects of acupuncture at GV14 on cerebral blood flow (CBF), especially that in the basilar artery (BA) and the middle cerebral arteries (MCA). Sixteen healthy men aged 20 to 29 years were enrolled in this study. CBF velocity and cerebrovascular reactivity (CVR) were measured using transcranial Doppler sonography (TCD). The following were assessed: closed circuit rebreathing- (CCR-) induced carbon dioxide (CO2) reactivity, modified blood flow velocity at 40 mmHg (CV40) on BA and MCAs, blood pressure (BP), and heart rate (HR). Observed results were obtained after comparison with the baseline evaluation. Statistically significant elevations in CO2 reactivity were recorded in the BA (3.28 to 4.70,

p
<
0.001

) and MCAs (right: 3.81 to 5.25,

p
=
0.001

; left: 3.84 to 5.12,

p
=
0.005

) after acupuncture at GV14. The CV40 increased statistically significantly only in the BA (45.49 to 50.41,

p
=
0.003

). No change was observed in BP (106.83 to 107.08 (mmHg),

p
=
0.335

) and HR (77 to 75 (bpm),

p
=
0.431

). Acupuncture at GV14 improved CBF velocity. These results could be explained by the regulation of endothelium-dependent vessel dilation effected by acupuncture. This trial is registered with Korean Clinical Trial Registry (http://cris.nih.go.kr; registration number: KCT0004787).
Pyridoxal Isonicotinoyl Hydrazone Improves Neurological Recovery by Attenuating Ferroptosis and Inflammation in Cerebral Hemorrhagic Mice
Authors: Zhang Hengli , Wen Min , Chen Jiayu , Yao Chaojie , Lin Xiao , Lin Zhongxiao , Ru Junnan , Zhuge Qichuan , Yang Su
Published: September 2021

Ferroptosis and inflammation induced by cerebral hemorrhage result in an excessive inflammatory response and irreversible neuronal injury. Alleviating ferroptosis might be an effective way to prevent neuroinflammatory injury and promote neural functional recovery. Pyridoxal isonicotinoyl hydrazine (PIH), a lipophilic iron‐chelating agent, has been reported to reduce excess iron‐induced cytotoxicity. However, whether PIH could ameliorate the effects of hemorrhagic stroke is not completely understood. In the present study, the preventive effects of PIH in an intracerebral hemorrhage (ICH) mouse model were investigated. Neurological score, rotarod test, and immunofluorescence around the hematoma were assessed to evaluate the effects of PIH on hemorrhagic injury. The involvement of ferroptosis and inflammation was also examined in vitro to explore the underlying mechanism. Results showed that administration of PIH prevented neuronal cell death and reduced lipid peroxidation in Erastin‐treated PC‐12 cells. In vivo, mice treated with PIH after ICH attenuated neurological deficit scores. Additionally, we found PIH reduced ROS production, iron accumulation, and lipid peroxidation around the hematoma peripheral tissue. Meanwhile, ICH mice treated with PIH showed an upregulation of the key ferroptosis enzyme, glutathione peroxidase 4, and downregulation of cyclooxygenase‐2. Moreover, PIH administration inhibited proinflammatory polarization and reduced interleukin‐1 beta and tumor necrosis factor alpha in ICH mice. Collectively, these results demonstrated that PIH protects mice against hemorrhage stroke, which was associated with mitigation of inflammation and ferroptosis.
Transient Flow of Jeffrey Fluid over a Permeable Wall
Authors: Bajwa Sana , Ullah Saif , Khan Ilyas , Fayz-Al-Asad Md.
Published: September 2021

Transient incompressible flows of Jeffrey fluids over a permeable, flat, and infinite plate have been investigated. The plate motion is an oscillatory translation along the x-axis. Using the Laplace transform and perturbation method, the analytical solution for the velocity field in the transform domain has been obtained. The velocity field in the real domain has been determined by using the numerical Stehfest’s algorithm for the Laplace transform inversion. To have a validation of the obtained solution, we have determined the analytical solution for the flow without transpiration. It was found that when the transpiration parameter approaches zero, the solution for the flow with transpiration tends to the solution corresponding to the case without perspiration. The influence of the system parameters on fluid motion has been investigated by numerical simulations and graphical illustrations prepared with the software package Mathcad.
Integrative Genomic Analysis of Pediatric Myeloid-Related Acute Leukemias Identifies Novel Subtypes and Prognostic Indicators
Authors: Fornerod Maarten , Ma Jing , Noort Sanne , Liu Yu , Walsh Michael P. , Shi Lei , Nance Stephanie , Liu Yanling , Wang Yuanyuan , Song Guangchun , Lamprecht Tamara , Easton John , Mulder Heather L. , Yergeau Donald , Myers Jacquelyn , Kamens Jennifer L. , Obeng Esther A. , Pigazzi Martina , Jarosova Marie , Kelaidi Charikleia , Polychronopoulou Sophia , Lamba Jatinder K. , Baker Sharyn D. , Rubnitz Jeffrey E. , Reinhardt Dirk , van den Heuvel-Eibrink Marry M. , Locatelli Franco , Hasle Henrik , Klco Jeffery M. , Downing James R. , Zhang Jinghui , Pounds Stanley , Zwaan C. Michel , Gruber Tanja A.
Published: September 2021

Genomic characterization of pediatric patients with acute myeloid leukemia (AML) has led to the discovery of somatic mutations with prognostic implications. Although gene-expression profiling can differentiate subsets of pediatric AML, its clinical utility in risk stratification remains limited. Here, we evaluate gene expression, pathogenic somatic mutations, and outcome in a cohort of 435 pediatric patients with a spectrum of pediatric myeloid-related acute leukemias for biological subtype discovery. This analysis revealed 63 patients with varying immunophenotypes that span a T-lineage and myeloid continuum designated as acute myeloid/T-lymphoblastic leukemia (AMTL). Within AMTL, two patient subgroups distinguished by FLT3-ITD and PRC2 mutations have different outcomes, demonstrating the impact of mutational composition on survival. Across the cohort, variability in outcomes of patients within isomutational subsets is influenced by transcriptional identity and the presence of a stem cell–like gene-expression signature. Integration of gene expression and somatic mutations leads to improved risk stratification.

Significance:

Immunophenotype and somatic mutations play a significant role in treatment approach and risk stratification of acute leukemia. We conducted an integrated genomic analysis of pediatric myeloid malignancies and found that a combination of genetic and transcriptional readouts was superior to immunophenotype and genomic mutations in identifying biological subtypes and predicting outcomes.

This article is highlighted in the In This Issue feature, p. 549
Psychological Distress and Quality of Life in Participants Undergoing Genetic Testing for Arrhythmogenic Right Ventricular Cardiomyopathy Caused by TMEM43 p.S358L: Is It Time to Offer Population-Based Genetic Screening?
Authors: Brothers Cassidy , Etchegary Holly , Curtis Fiona , Simmonds Charlene , Houston Jim , Young Terry-Lynn , Pullman Daryl , Mariathas Hensley H. , Connors Sean , Hodgkinson Kathleen
Published: September 2021

Purpose: We have identified 27 families in Newfoundland and Labrador (NL) with the founder variant TMEM43 p.S358L responsible for 1 form of arrhythmogenic right ventricular cardiomyopathy. Current screening guidelines rely solely on cascade genetic screening, which may result in unrecognized, high-risk carriers who would benefit from preemptive implantable cardioverter-defibrillator therapy. This pilot study explored the acceptability among subjects to TMEM43 p.S358L population-based genetic screening (PBGS) in this Canadian province. Methods: A prospective cohort study assessed attitudes, psychological distress, and health-related quality of life (QOL) in unselected individuals who underwent genetic screening for the TMEM43 p.S358L variant. Participants (n = 73) were recruited via advertisements and completed 2 surveys at baseline, 6 months, and 1 year which measured health-related QOL (SF-36v2) and psychological distress (Impact of Events Scale). Results: No variant-positive carriers were identified. Of those screened through a telephone questionnaire, >95% felt positive about population-genetic screening for TMEM43 p.S358L, though 68% reported some degree of anxiety after seeing the advertisement. There were no significant changes in health-related QOL or psychological distress scores over the study period. Conclusion: Despite some initial anxiety, we show support for PBGS among research subjects who screened negative for the TMEM43 p.S358L variant in NL. These findings have implications for future PBGS programs in the province.
Preimplantation Genetic Testing Prevented Intergenerational Transmission of X-Linked Alport Syndrome
Authors: Hu Xiaoling , Zhang Jiahui , Lv Yuan , Chen Xijing , Feng Guofang , Wang Liya , Ye Yinghui , Jin Fan , Zhu Yimin
Published: September 2021

Background: Alport syndrome (AS) is a hereditary renal basement membrane disease that can lead to end-stage renal disease in young adults. It can be diagnosed by genetic analysis, being mostly caused by mutations in COL4A3, COL­4A4, and COL4A5. To date, there is no radical cure for this disease. Objectives: The aim of this study was to avoid the transmission of AS within an affected family by selecting healthy embryos for uterine transfer. The embryos were identified by preimplantation genetic testing for monogenic disorders (PGT-M). Methods: We used next-generation sequencing (NGS) to identify mutations in the proband and his parents. The results of NGS were confirmed by Sanger sequencing. Targeted NGS combined with targeted single-nucleotide polymorphism haplotyping was used for the in vitro identification of COL4A5 mutations in human embryos to prevent their intergenerational transmission. Results: The c.349_359delGGACCTCAAGG and c.360_361insTGC mutations in COL4A5 were identified in a family affected by X-linked AS. Whole-genome sequencing by NGS with targeted haplotyping was performed on biopsied trophectoderm cells. A healthy baby was born after transfer of a single freeze-thawed blastocyst. Conclusions: The use of targeted NGS for identifying diagnostic markers combined with targeted haplotyping is an easy and efficient PGT-M method for preventing intergenerational transmission of AS.
The Montelukast Therapy in Asthmatic Children with and without Food Allergy: Does It Make Any Difference?
Authors: Sahiner Umit Murat , Arik Yilmaz Ebru , Fontanella Sara , Haider Sadia , Soyer Ozge , Custovic Adnan , Kalayci Omer , Sackesen Cansin
Published: September 2021

Introduction: Children with food allergy are at increased risk for asthma and asthma morbidity. Since leukotrienes are implicated in the pathogenesis of both asthma and probably in food allergies, we hypothesized that asthmatic children with concomitant food allergy may have a favorable response to antileukotriene treatment. Methods: Asthmatic children aged 6–18 years with and without food allergy were treated with montelukast and placebo in a double-blind, placebo-controlled cross-over parallel-group study. The primary outcome of the study was improvement in FEV1%. Asthma control tests, spirometry and methacholine challenges were performed as well as Fractional Exhaled Nitric Oxide (FeNO) levels. PGD2, CystLT, and lipoxin levels were measured in exhaled breath condensate (EBC). Results: A total of 113 children were enrolled and 87 completed the study in accordance with the protocol. At baseline, children with food allergy and asthma (FAA) had higher levels of PGD2 and CysLT levels in the EBC than children with asthma alone (AA) (p < 0.001 for each). In the montelukast arm, although FEV1% was significantly higher in the FAA group compared to AA (p = 0.005), this effect was linked to the baseline difference of FEV1% between both arms. Montelukast treatment failed to improve FEV1% in both groups compared to the placebo. No effect of montelukast was observed in the remaining study parameters. Conclusion: Although children with FAA do not show a more favorable response to montelukast treatment compared to AA, a significant difference between baseline PGD2 and CystLT levels between FAA and AA groups may point to a different endotype of childhood asthma.
Parkinson’s Disease and Gut Microbiota
Authors: Hirayama Masaaki , Ohno Kinji
Published: September 2021

Background: Parkinson’s disease (PD) is caused by abnormal aggregation of α-synuclein fibrils, called the Lewy bodies, in the central nervous system. Accumulating knowledge points to the notion that α-synuclein fibrils start from the dorsal vagal nucleus and ascend to the locus ceruleus and the substantia nigra (SN). Even in healthy elderly subjects without motor or cognitive impairment, α-synuclein fibrils are frequently observed in the brain and sometimes in the intestinal neural plexus. Enteroendocrine cells have a direct synapse to the vagal afferents, and the vagal nucleus has synaptic pathways to the SN and the striatum. Intestinal bacteria are likely to be involved in the formation of intestinal α-synuclein fibrils. Summary: A nonparametric meta-analysis of intestinal microbiota in PD in 5 countries, as well as scrutinization of the other reports from the other countries, indicates that mucin-degrading Akkermansia is increased in PD and that short-chain fatty acid (SCFA)-producing bacteria are decreased in PD. Both dysbiosis should increase the intestinal permeability, which subsequently facilitates exposure of the intestinal neural plexus to toxins like lipopolysaccharide and pesticide, which should lead to abnormal aggregation of α-synuclein fibrils. Decreased SCFA also downregulates regulatory T cells and fails to suppress neuronal inflammation. Key Messages: Therapeutic intervention may be able to be established against these mechanisms. Additional biochemical, cellular, and animal studies are required to further dissect the direct association between intestinal microbiota and PD.
Five-Year Outcomes of Medical Management Alone for Adult Patients with Ischemic Moyamoya Disease without Cerebral Misery Perfusion
Authors: Kitakami Kei , Kubo Yoshitaka , Yabuki Masahiro , Oomori Daisuke , Takahashi Tatsuhiko , Igarashi Suguru , Fujiwara Shunrou , Yoshida Kenji , Kobayashi Masakazu , Terasaki Kazunori , Ogasawara Kuniaki
Published: September 2021

Introduction: No clear guidelines for treating adult patients with ischemic moyamoya disease (MMD) without cerebral hemodynamic compromise such as misery perfusion have been established. Our previous prospective cohort study of adult patients with MMD without misery perfusion who were treated with medical management alone, including an antiplatelet drug, showed a recurrent ischemic event rate of 3% per 2 years. The present prospective study aimed to elucidate the 5-year clinical, cerebral perfusion, and cognitive outcomes of medical management alone for Japanese adult patients with ischemic MMD without cerebral misery perfusion by following the same patients for another 3 years. Methods: In total, 68 patients without recurrent events at a 2-year follow-up were prospectively followed up for another 3 years. Cerebral blood flow (CBF) in the symptomatic cerebral hemisphere was measured using brain perfusion single-photon emission computed tomography at inclusion and at the end of the subsequent 3-year follow-up. Neuropsychological testing was performed at inclusion and at the end of the initial 2- and subsequent 3-year follow-ups. Results: During the subsequent 3-year follow-up, 2 patients (3%) developed further ischemic events. In patients without further ischemic events, CBF was significantly greater at the end of the subsequent 3-year follow-up than at inclusion (p = 0.0037), and all neuropsychological test scores improved or remained unchanged at the end of initial 2- and subsequent 3-year follow-ups compared with that at inclusion. Conclusion: In adult patients receiving medical management alone for ischemic MMD without cerebral misery perfusion, the incidence of further ischemic events was 6% per 5 years and did not change between the initial 2 years after the last is­chemic event and the subsequent 3 years. In patients without further ischemic events, CBF and cognitive function had not deteriorated at 5 years after the last ischemic event.
Vacuum Therapy and Internal Drainage as the First-Line Endoscopic Treatment for Post-Bariatric Leaks: A Systematic Review and Meta-Analysis
Authors: Laopeamthong Issaree , Akethanin Thanita , Kasetsermwiriya Wisit , Techapongsatorn Suphakarn , Tansawet Amarit
Published: September 2021

Introduction: Several endoscopic methods can be employed to manage post-bariatric leaks. However, endoluminal vacuum therapy (EVT) and endoscopic internal drainage (EID) are relatively new methods, and studies regarding these methods are scarce. We performed a systematic review of the literature and a meta-analysis to evaluate the efficacy of EVT and EID. Methods: Databases were searched for eligible studies. The clinical success of leak closure was the primary outcome of interest. A proportional meta-analysis was performed for pooling the primary outcome using a fixed-effects model. A meta-analysis or descriptive analysis of other outcomes was performed based on the data availability. Results: Data from 3 EVT and 10 EID studies (n = 279) were used for evidence synthesis. The leak closure rates (95% confidence interval [CI]) of EVT and EID were 85.2% (75.1%–95.4%) and 91.6% (88.1%–95.2%), respectively. The corresponding mean treatment durations (95% CI) were 28 (2.4–53.6) and 78.4 (50.1–106.7) days, respectively. However, data about other outcomes were extremely limited; thus, a pooled analysis could not be performed. Conclusions: Both EVT and EID were effective when used as the first-line treatment for post-bariatric leaks. However, larger studies must be conducted to compare the efficacy of the 2 interventions.
ІНТЕГРАТИВНИЙ ПОРТРЕТ КОРПОРАТИВНОЇ КУЛЬТУРИ В ЗАКЛАДАХ ОХОРОНИ ЗДОРОВ’Я
Authors: Литвинова О. Н. , Абашник Н. М.
Published: September 2021

У статті наведено інтегративний портрет корпоративної культури у закладах охорони здоров’я в період реформування системи охорони здоров’я. Акцентовано увагу на ключових проблемах корпоративної культури в закладах охорони здоров’я, які потребують вирішення.
ОСОБЛИВОСТІ СПІЛКУВАННЯ МАЙБУТНІХ МЕДИЧНИХ СЕСТЕР У КОНФЛІКТНИХ СИТУАЦІЯХ
Authors: Ширяєва А. С.
Published: September 2021

У статті розглянуто особливості спілкування майбутніх медичних сестер у конфліктних ситуаціях. Ви­значено роль вербального і невербального спілкування. Розглянуто реалістичні та нереалістичні конф­лікти між медпрацівником і пацієнтом.
Long-Term Survival, Causes of Death, and Trends in 5-Year Mortality After Intracerebral Hemorrhage: The Tromsø Study
Authors: Carlsson Maria , Wilsgaard Tom , Johnsen Stein Harald , Johnsen Liv-Hege , Løchen Maja-Lisa , Njølstad Inger , Mathiesen Ellisiv B.
Published: September 2021

Background and Purpose:

Data on long-term survival after intracerebral hemorrhage (ICH) are scarce. In a population-based nested case-control study, we compared long-term survival and causes of death within 5 years in 30-day survivors of first-ever ICH and controls, assessed the impact of cardiovascular risk factors on 5-year mortality, and analyzed time trend in 5-year mortality in ICH patients over 2 decades.

Methods:

We included 219 participants from the population-based Tromsø Study, who after the baseline participation had a first-ever ICH between 1994 to 2013 and 1095 age- and sex-matched participants without ICH. Cumulative survival was presented using the Kaplan-Meier method. Hazard ratios (HRs) for mortality and for the association between cardiovascular risk factors and 5-year mortality in 30-day survivors were estimated by stratified Cox proportional hazards models. Trend in 5-year mortality was assessed by logistic regression.

Results:

Risk of death during follow-up (median time, 4.8 years) was increased in the ICH group compared with controls (HR, 1.62 [95% CI, 1.27–2.06]). Cardiovascular disease was the leading cause of death, with a higher proportion in ICH patients (22.9% versus 9.0%;
P
<0.001). Smoking increased the risk of 5-year mortality in cases and controls (HR, 1.59 [95% CI, 1.15–2.19]), whereas serum cholesterol was associated with 5-year mortality in cases only (HR, 1.39 [95% CI, 1.04–1.86]). Use of anticoagulants at ICH onset increased the risk of death (HR, 2.09 [95% CI, 1.09–4.00]). There was no difference according to ICH location (HR, 1.15 [95% CI, 0.56–2.37]). Five-year mortality did not change during the study period (odds ratio per calendar year, 1.01 [95% CI, 0.93–1.09]).

Conclusions:

Survival rates were significantly lower in cases than in controls, driven by a 2-fold increased risk of cardiovascular death. Smoking, serum cholesterol, and use of anticoagulant drugs were associated with increased risk of death in ICH patients. Five-year mortality rates in ICH patients remained stable over time.
Comparing Warfarin and 4 Direct Oral Anticoagulants for the Risk of Dementia in Patients With Atrial Fibrillation
Authors: Lee So-Ryoung , Choi Eue-Keun , Park Sang-Hyun , Jung Jin-Hyung , Han Kyung-Do , Oh Seil , Lip Gregory Y.H.
Published: September 2021

Background and Purpose:

Atrial fibrillation is a risk factor for dementia, and oral anticoagulant use is associated with a decreased risk of dementia in patients with atrial fibrillation. We aimed to investigate whether the risk of dementia would be different between patients treated with direct oral anticoagulants (DOACs) compared with those with warfarin.

Methods:

Using the Korean nationwide claims database from January 2014 to December 2017, we identified oral anticoagulant–naive nonvalvular atrial fibrillation patients aged ≥40 years. For the comparisons, warfarin and DOAC groups were balanced using the inverse probability of treatment weighting method. The primary outcome was incident dementia.

Results:

Among 72 846 of total study patients, 25 948 were treated with warfarin, and 46 898 were treated with DOAC (17 193 with rivaroxaban, 9882 with dabigatran, 11 992 with apixaban, and 7831 with edoxaban). During mean 1.3±1.1 years of follow-up, crude incidence of dementia was 4.87 per 100 person-years (1.20 per 100 person-years for vascular dementia and 3.30 per 100 person-years for Alzheimer dementia). Compared with warfarin, DOAC showed a comparable risks of dementia, vascular dementia, and Alzheimer dementia. In subgroup analyses, DOAC was associated with a lower risk of dementia than warfarin, particularly in patients aged 65 to 74 years (hazard ratio, 0.815 [95% CI, 0.709–0.936]) and in patients with prior stroke (hazard ratio, 0.891 [95% CI, 0.820–0.968]). When comparing individual DOACs with warfarin, edoxaban was associated with a lower risk of dementia (hazard ratio, 0.830 [95% CI, 0.740–0.931]).

Conclusions:

In this large Asian population with atrial fibrillation, DOAC showed a comparable risk of dementia with warfarin overall. DOACs appeared more beneficial than warfarin, in those aged 65 to 74 years or with a history of stroke. For specific DOACs, only edoxaban was associated with a lower risk of dementia than warfarin.