bluuebunny/crossref_metadata_2025 huggingface dataset:
[Retracted] Russian Speech Conversion Algorithm Based on a Parallel Corpus and Machine Translation
Authors: Zhang Yingyi
Published: March 2022

The phonetic conversion technology is crucial in the resource construction of Russian phonetic information processing. This paper explains how to build a corpus and the key algorithms that are used, as well as how to design auxiliary translation software and implement the key algorithms. This paper focuses on the “parallel corpus” method of problem solving and the indispensable role of a parallel corpus in Russian learning. This paper examines the foundations, motivations, and methods for using parallel corpora in translation instruction. The main way of using a parallel corpus in the classroom environment is to present data, so that learners can be exposed to a large amount of easily screened bilingual data, and translation skills and specific language item translation can be taught in a concentrated and focused manner. Among them, the creation of a large‐scale Russian‐Chinese parallel corpus will play an important role not only in improving the translation quality of Russian‐Chinese machine translation systems but also in Chinese and Russian teaching as well as other branches of linguistics and translation studies, all of which should be given sufficient attention. This paper proposes the use of automatic speech analysis technology to assist Russian pronunciation learning and designs a Russian word pronunciation learning assistant system with demonstration, scoring, and feedback functions, in response to the shortcomings of pronunciation teaching in Russian teaching in China. It can provide corpus support for gathering a large number of parallel corpora and, in the future, enabling online translation. This system is used for corpus automatic construction, and future corpus automatic construction systems could be built on top of it. The proper application of parallel corpus data will aid in the development of a high‐quality autonomous learning and translation teaching environment.
[Retracted] Keratoconus Classification with Convolutional Neural Networks Using Segmentation and Index Quantification of Eye Topography Images by Particle Swarm Optimisation
Authors: P. Subramanian , G. P. Ramesh
Published: March 2022

In keratoconus, the cornea assumes a conical shape due to its thinning and protrusion. Early detection of keratoconus is vital in preventing vision loss or costly repairs. In corneal topography maps, curvature and steepness can be distinguished by the colour scales, with warm colours representing curved steep areas and cold colours representing flat areas. With the advent of machine learning algorithms like convolutional neural networks (CNN), the identification and classification of keratoconus from these topography maps have been made faster and more accurate. The classification and grading of keratoconus depend on the colour scales used. Artefacts and minimal variations in the corneal shape, in mild or developing keratoconus, are not represented clearly in the image gradients. Segmentation of the maps needs to be carried out for identifying the severity of the keratoconus as well as for identifying the changes in the severity. In this paper, we are considering the use of particle swarm optimisation and its modifications for segmenting the topography image. Pretrained CNN models are then trained with the dataset and tested. Results show that the performance of the system in terms of accuracy is 95.9% compared to 93%, 95.3%, and 84% available in the literature for a 3‐class classification that involved mild keratoconus or forme fruste keratoconus.
Experimental Study on Mechanical Properties of Integrated Wall Panels of Grain Warehouse with “Thermal Insulation”
Authors: Li Xuesen , Ding Yonggang , Zhao Jinquan , Xu Qikeng
Published: March 2022

The walls of grain cottage silos are still being built by clay brick masonry featured with single‐structure form, poor air tightness, large workload of manual masonry on site, and huge consumption of raw materials and burning materials, which is not conducive to energy saving and environmental protection. In order to study the mechanical function of the new wall under the action of grain side pressure, the static loading test was conducted on the model of scaled‐down wall panel under the action of side pressure. The damage process, the damage pattern, and the bearing capacity of the wall panel were studied through the analysis of the crack development process and distribution law to reveal the force characteristics of the wall panel. The test results show that the span deflection of the “structure‐insulation” integrated wall panel under the lateral pressure meets the requirement of the limit state of normal use; the inner and outer leaf wall panels can work together under the action of the joint; the ratio of the load borne by the inner and outer leaf wall panels is equal to the ratio of their stiffness; the flexural stiffness of the wall panels after cracking is proposed based on the combined effect analysis. Based on the analysis of the combined effect, the degradation factor of the wall panel after cracking is proposed, and the deflection calculation formula of the inner and outer leaf wall panel is established, which provides a theoretical basis for the design and the promotion of the “structure‐insulation” integrated wall panel.
[Retracted] Deleterious Effects of Amoxicillin on Immune System and Haematobiochemical Parameters of a Rabbit
Authors: Hussain Khalid , Lashari Mushtaq Hussain , Farooq Umer , Mehmood Tahir
Published: March 2022

The present study is aimed at evaluating the haematobiochemical and immune system alterations in rabbit’s exposure to amoxicillin. Thirty‐two healthy rabbits were randomly divided into four (n = 8) groups comprising of three experimental groups and one control group. After 7 days of the acclimatization period, the study animals were given different doses of amoxicillin orally (100, 150, and 200 mg/kg body weight) for 21 days. The hematological results revealed that red blood cells, hemoglobin, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration decreased significantly (P < 0.05) whereas white blood cells, neutrophils, and granulocyte exhibited a significantly increasing trend. Serum biochemical analysis showed a significantly increased concentration of HDL, LDL, serum globulin cholesterol, triglyceride, urea, uric acid, creatine, and calcium while plasma fibrinogen, blood sugar, albumin, and total protein were decreased significantly. Furthermore, liver function enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and bilirubin significantly increased. Antioxidant enzymes and oxidative stress parameters such as malondialdehyde concentrations (MDA) increased significantly while catalase, superoxide dismutase, reduced glutathione, and peroxidase reduced significantly in antibiotic amoxicillin‐treated groups as compared to the untreated control group (P < 0.05). Microscopic histopathological examination showed negative structural changes in liver, kidney, and heart tissues due to karyorrhexis; a disorganized hepatic cord in the liver; increased Bowman’s space, necrotic renal tubules, and degenerative glomerulus in the kidney; and necrotic cardiac cells and cytoplasmic vacuolization in the heart, in antibiotic amoxicillin‐treated rabbit groups as compared to the control group. In conclusion, amoxicillin induced stress and physiological and immunological impairments due to the adverse effects on haematobiochemical parameters and histopathological and tissue protein changes in target animals.
Radiomics Profiling Identifies the Incremental Value of MRI Features beyond Key Molecular Biomarkers for the Risk Stratification of High‐Grade Gliomas
Authors: Yang Guoqiang , Sha Yongjian , Wang Xiaochun , Tan Yan , Zhang Hui
Published: March 2022

Objective. To identify the incremental value of magnetic resonance imaging (MRI) features beyond key molecular biomarkers for the risk stratification of high‐grade gliomas (HGGs). Methods. A total of 241 patients with preoperative magnetic resonance (MR) images and clinical and genetic data were retrospectively collected from our institution and The Cancer Genome Atlas/The Cancer Imaging Archive (TCGA/TCIA) dataset. Radiomic features (n = 1702) were extracted from both postcontrast T1‐weighted (CE‐T1) and T2‐weighted fluid attenuation inversion recovery (T2FLAIR) MR images. The least absolute shrinkage and selection operator (LASSO) method was used to select effective features. A multivariate Cox proportional risk regression model was established to explore the prognostic value of clinical features, molecular biomarkers, and radiomic features. Kaplan–Meier survival analysis and the log‐rank test were used to evaluate the prognostic model, and a stratified analysis was conducted to demonstrate the incremental value of the radiomics signature. A nomogram was developed to predict the 1‐year, 2‐year, and 3‐year overall survival (OS) probabilities of the patients with HGGs. Results. The radiomics signature provided significant prognostic value for the risk stratification of patients with HGGs. The combined model integrating the radiomics signature with clinical data (age) and O6‐methylguanine‐DNA methyltransferase (MGMT) promoter methylation status had the best prognostic value, with C‐index values of 0.752 and 0.792 in the training set and external validation set, respectively. Stratified Kaplan–Meier survival analysis showed that the radiomics signature could identify the risk subgroups in different clinical and molecular subgroups. Conclusion. This radiomics signature can be used for the risk stratification of patients with HGGs and has incremental value beyond key molecular biomarkers, providing a preoperative basis for individualized diagnosis and treatment decision‐making.
Technology Topic Identification and Trend Prediction of New Energy Vehicle Using LDA Modeling
Authors: Hu Renjie , Ma Wencong , Lin Weiqiang , Chen Xiude , Zhong Zuchang , Zeng Chuhong
Published: March 2022

As new energy vehicle (NEV) is the future of automobile development, it is of great significance to dig deeper into the technical topics and development trends of new energy vehicles for accurately understanding the technical trends of the new energy vehicle industry, grasping development opportunities, and scientifically formulating strategic plans. This paper takes the patent texts in the field of new energy vehicles from 2000 to 2020 in the patent database of CNKI as the data source, identifies 25 technical topics implied in the patent texts by using the LDA (Latent Dirichlet Allocation) topic model, analyzes the evolution trend of the 25 technical topics in terms of importance and popularity, and predicts the popularity and development trend of each technical topic in new energy vehicles from 2021 to 2025 by constructing the ARIMA model. The popularity and development trend of each technology topic of new energy vehicles in China from 2021 to 2025 are predicted by constructing ARIMA model. Drawing on quantitative evidence, the study found that there are top five technical topics in terms of importance in this field, namely, Topic 8 (Installation and Fixation), Topic 5 (Heat Dissipation), Topic 14 (Vehicle Data Monitoring), Topic 9 (Charging Pile), and Topic 15 (Damping). From 2014 to 2020, the importances of Topic 5 (Heat Dissipation), Topic 8 (Installation and Fixation), Topic 6 (Electric Drive System), Topic 9 (Charging Pile), and Topic 15 (Damping) are gradually rising. In terms of popularity of technical topics, from 2014 to 2020, the first to fifth topics are Topic 20 (Safety), Topic 8 (Installation and Fixation), Topic 3 (Cable Insulation Materials), Topic 15 (Damping), and Topic 10 (Pump Cooling). Based on the prediction of ARIMA model, it is found that the popularity of these five technical topics is steadily increasing from 2021 to 2025, among which the popularity of Topic 20 (Safety) will increase from 63.58 to 113.07, the largest increase in popularity among all technical topics. The paper provides implications for countries dedicated to developing the new energy vehicle industry.
A Review of Railway Track Laboratory Tests with Various Scales for Better Decision‐Making about More Efficient Apparatus Using TOPSIS Analysis
Authors: Najafi Moghaddam Gilani Vahid , Habibzadeh Mohammad , Hosseinian Seyed Mohsen , Salehfard Reza
Published: March 2022

Improving the performance of railways depends on increasing their efficiency and the speed of locomotives, which is provided by improving the infrastructure of railways. Therefore, in various studies, researchers seek to modify ballast materials, sleepers and rails, or to study various geometric and environmental conditions in order to reduce the existing weaknesses of railways. Therefore, in order to evaluate the above conditions, various tests should be performed on railways. Some of the tests take place in the field when the train is passing. However, these tests have various limitations and endanger the safety of researchers and are associated with difficulties. Therefore, many tests are performed using various apparatuses on a laboratory scale. In this study, by reviewing different apparatuses used by researchers to simulate loading on the railway, they were compared and by examining different criteria such as loading type, different loading directions, scale of apparatuses, static and dynamic simulated loads and other environmental and geometric conditions, the best apparatuses on a laboratory scale are recommended for simulating vertical, longitudinal and lateral loads and measuring noise and vibration. By the use of TOPSIS analysis on 16 introduced apparatuses from reviewing different studies, it was found that the scaled railway track model had the first rank among different apparatuses and by modifying the weaknesses of this apparatus, it can be turned into the most comprehensive laboratory apparatus to simulate the loading of railway tracks with a scale of 1 : 5. Among the introduced apparatuses, wheel on roller test rig and roller rig had the second and third ranks, respectively, the apparatuses of which usually have a scale of 1 : 5 and deal with the interaction between the rail and the wheel and the impact of the vehicle on the railway track.
Elderly People Activity Recognition in Smart Grid Monitoring Environment
Authors: Ganesan Anusha , Paul Anand , Seo HyunCheol
Published: March 2022

Elderly people activity recognition has become a vital necessity in many countries, because most of the elderly people live alone and are vulnerable. Thus, more research to advance in the monitoring systems used to recognize the activities of elderly people is required. Many researchers have proposed different monitoring systems for activity recognition using wired and wireless wearable sensing devices. However, the activity classification accuracy achieved so far should be improved to meet the challenges of more precise activity monitoring. Our study proposes a smart Human Activity Recognition system architecture utilizing an open source dataset generated by wireless, batteryless sensors used by 14 healthy aged persons and unsupervised and supervised machine learning algorithms. In this paper, we also propose using a smart grid for checking regularly the wearable sensing device operational status to address the well-known reliability challenges of these devices, such as wireless charging and data trustworthiness. As the data from the sensing device is very noisy, we employ the K-means++ clustering to identify outliers and use advanced ensemble classification techniques, such as the stacking classifier for which a meta model built using the random forest algorithm gave better results than all other base models considered. We also employ a bagging classifier, which is an ensemble meta-estimator fitting the prediction outputs of the base classifiers and aggregating them to produce the ensemble output. The best classification accuracy of 99.81 was achieved by the stacking classifier in training and 99.78% in testing, respectively. Comparisons for finding the best model were conducted using the recall, F1 score, and precision values.
Differential Gain-of-Function Activity of Three p53 Hotspot Mutants In Vivo
Authors: Xiong Shunbin , Chachad Dhruv , Zhang Yun , Gencel-Augusto Jovanka , Sirito Mario , Pant Vinod , Yang Peirong , Sun Chang , Chau Gilda , Qi Yuan , Su Xiaoping , Whitley Elizabeth M. , El-Naggar Adel K. , Lozano Guillermina
Published: March 2022

The majority of TP53 missense mutations identified in cancer patients are in the DNA-binding domain and are characterized as either structural or contact mutations. These missense mutations exhibit inhibitory effects on wild-type p53 activity. More importantly, these mutations also demonstrate gain-of-function (GOF) activities characterized by increased metastasis, poor prognosis, and drug resistance. To better understand the activities by which TP53 mutations, identified in Li–Fraumeni syndrome, contribute to tumorigenesis, we generated mice harboring a novel germline Trp53R245W allele (contact mutation) and compared them with existing models with Trp53R172H (structural mutation) and Trp53R270H (contact mutation) alleles. Thymocytes from heterozygous mice showed that all three hotspot mutations exhibited similar inhibitory effects on wild-type p53 transcription in vivo, and tumors from these mice had similar levels of loss of heterozygosity. However, the overall survival of Trp53R245W/+ and Trp53R270H/+ mice, but not Trp53R172H/+ mice, was significantly shorter than that of Trp53+/− mice, providing strong evidence for p53-mutant–specific GOF contributions to tumor development. Furthermore, Trp53R245W/+ and Trp53R270H/+ mice had more osteosarcoma metastases than Trp53R172H/+ mice, suggesting that these two contact mutants have stronger GOF in driving osteosarcoma metastasis. Transcriptomic analyses using RNA sequencing data from Trp53R172H/+, Trp53R245W/+, and Trp53R270H/+ primary osteosarcomas in comparison with Trp53+/– indicated that GOF of the three mutants was mediated by distinct pathways. Thus, both the inhibitory effect of mutant over wild-type p53 and GOF activities of mutant p53 contributed to tumorigenesis in vivo. Targeting p53 mutant–specific pathways may be important for therapeutic outcomes in osteosarcoma.

Significance:

p53 hotspot mutants inhibit wild-type p53 similarly but differ in their GOF activities, with stronger tumor-promoting activity in contact mutants and distinct protein partners of each mutant driving tumorigenesis and metastasis.
Epigenetic and Transcriptional Regulation of Innate Immunity in Cancer
Authors: Chen Chuan , Man Na , Liu Fan , Martin Gloria Mas , Itonaga Hidehiro , Sun Jun , Nimer Stephen D.
Published: March 2022

Innate immune cells participate in the detection of tumor cells via complex signaling pathways mediated by pattern-recognition receptors, such as Toll-like receptors and nucleotide-binding and oligomerization domain–like receptors. These pathways are finely tuned via multiple mechanisms, including epigenetic regulation. It is well established that hematopoietic progenitors generate innate immune cells that can regulate cancer cell behavior, and the disruption of normal hematopoiesis in pathologic states may lead to altered immunity and the development of cancer. In this review, we discuss the epigenetic and transcriptional mechanisms that underlie the initiation and amplification of innate immune signaling in cancer. We also discuss new targeting possibilities for cancer control that exploit innate immune cells and signaling molecules, potentially heralding the next generation of immunotherapy.
A Paradigm of Cancer Immunotherapy Based on 2-[18F]FDG and Anti–PD-L1 mAb Combination to Enhance the Antitumor Effect
Authors: Wen Xuejun , Shi Changrong , Zeng Xinying , Zhao Liang , Yao Lanlin , Liu Zhida , Feng Lixia , Zhang Deliang , Huang Jinxiong , Li Yesen , Lin Qin , Chen Haojun , Zhuang Rongqiang , Chen Xiaoyuan , Zhang Xianzhong , Guo Zhide
Published: March 2022

Purpose:

Efforts have been devoted to select eligible candidates for PD-1/PD-L1 immune checkpoint blocker (ICB) immunotherapy. Here, we have a serendipitous finding of positron emission tomography (PET) imaging tracer 2-[18F]FDG as a potential immunomodulator. Therefore, we hypothesize that 2-[18F]FDG could induce PD-L1 expression change and create an immune-favorable microenvironment for tumor immunotherapy.

Experimental Design:

We designed a series of assays to verify PD-L1 upregulation, and tested immunotherapy regimens based on 2-[18F]FDG and anti–PD-L1 mAb, as monotherapy and in combination, in fully immunocompetent mice of MC38 and CT26 models. PD-L1 expression and tumor microenvironment (TME) changes were analyzed by Western blot, transcriptomics study, and flow-cytometric analysis.

Results:

PD-L1 was upregulated in a time- and dose-dependent manner after being induced by 2-[18F]FDG. The activation of NF-κB/IRF3 pathway and STAT1/3-IRF1 pathway play crucial parts in modulating PD-L1 expression after DNA damage and repair. Improved αPD-L1 mAb utilization rate and significant tumor growth delay were observed when the personalized therapeutic alliance of 2-[18F]FDG stimulation and ICB was used. In addition, combination of 2-[18F]FDG with αPD-L1 mAb could reprogram a TME from “cold” to “hot,” to make low immunoactivity tumors sensitive to ICB therapy.

Conclusions:

In summary, this promising paradigm has the potential to expand the traditional tumor theranostics. 2-[18F]FDG-based ICB immunotherapy is highly significant in enhancing antitumor effect. A research of 2-[18F]FDG-based ICB immunotherapy has been proposed to enhance the antitumor effect.
Reverse Transcriptase Inhibition Disrupts Repeat Element Life Cycle in Colorectal Cancer
Authors: Rajurkar Mihir , Parikh Aparna R. , Solovyov Alexander , You Eunae , Kulkarni Anupriya S. , Chu Chong , Xu Katherine H. , Jaicks Christopher , Taylor Martin S. , Wu Connie , Alexander Katherine A. , Good Charly R. , Szabolcs Annamaria , Gerstberger Stefanie , Tran Antuan V. , Xu Nova , Ebright Richard Y. , Van Seventer Emily E. , Vo Kevin D. , Tai Eric C. , Lu Chenyue , Joseph-Chazan Jasmin , Raabe Michael J. , Nieman Linda T. , Desai Niyati , Arora Kshitij S. , Ligorio Matteo , Thapar Vishal , Cohen Limor , Garden Padric M. , Senussi Yasmeen , Zheng Hui , Allen Jill N. , Blaszkowsky Lawrence S. , Clark Jeffrey W. , Goyal Lipika , Wo Jennifer Y. , Ryan David P. , Corcoran Ryan B. , Deshpande Vikram , Rivera Miguel N. , Aryee Martin J. , Hong Theodore S. , Berger Shelley L. , Walt David R. , Burns Kathleen H. , Park Peter J. , Greenbaum Benjamin D. , Ting David T.
Published: March 2022

Altered RNA expression of repetitive sequences and retrotransposition are frequently seen in colorectal cancer, implicating a functional importance of repeat activity in cancer progression. We show the nucleoside reverse transcriptase inhibitor 3TC targets activities of these repeat elements in colorectal cancer preclinical models with a preferential effect in p53-mutant cell lines linked with direct binding of p53 to repeat elements. We translate these findings to a human phase II trial of single-agent 3TC treatment in metastatic colorectal cancer with demonstration of clinical benefit in 9 of 32 patients. Analysis of 3TC effects on colorectal cancer tumorspheres demonstrates accumulation of immunogenic RNA:DNA hybrids linked with induction of interferon response genes and DNA damage response. Epigenetic and DNA-damaging agents induce repeat RNAs and have enhanced cytotoxicity with 3TC. These findings identify a vulnerability in colorectal cancer by targeting the viral mimicry of repeat elements.

Significance:

Colorectal cancers express abundant repeat elements that have a viral-like life cycle that can be therapeutically targeted with nucleoside reverse transcriptase inhibitors (NRTI) commonly used for viral diseases. NRTIs induce DNA damage and interferon response that provide a new anticancer therapeutic strategy.

This article is highlighted in the In This Issue feature, p. 1397
Instructing Mouse Germ Cells to Adopt a Female Fate
Authors: Spiller Cassy , Bowles Josephine
Published: March 2022

Background: Germ cells are critical for the survival of our species. They are the only cells that undergo meiosis – the reductive form of cell division that is necessary for genetic reassortment of chromosomes and production of the haploid gametes, the sperm and eggs. Remarkably, the initial female/male fate decision in fetal germ cells does not depend on whether they are chromosomally XX or XY; rather, initial sexual fate is imposed by influences from the surrounding tissue. In mammals, the female germline is particularly precious: despite recent suggestions that germline stem cells exist in the ovary, it is still generally accepted that the ovarian reserve is finite, and its size is dependant on germ cells of the fetal ovary initiating meiosis in a timely manner. Summary: Prior to 2006, evidence suggested that gonadal germ cells initiate meiotic prophase I by default, but more recent data support a key role for the signalling molecule retinoic acid (RA) in instructing female germ cell fate. Newer findings also support a key meiosis-inducing role for another signalling molecule, bone morphogenic protein (BMP). Nonetheless, many questions remain. Key Messages: Here, we review knowledge thus far regarding extrinsic and intrinsic determinants of a female germ cell fate, focusing on the mouse model.
Incidence of Aphasia in Ischemic Stroke
Authors: Grönberg Angelina , Henriksson Ingrid , Stenman Martin , Lindgren Arne G.
Published: March 2022

Introduction: A decrease in ischemic stroke (IS) incidence has been observed in high income countries during the last decades. Whether this has influenced the occurrence of aphasia in IS is uncertain. We therefore examined the incidence rate and potentially related determinants of aphasia in IS. Methods: We prospectively examined consecutive patients admitted to hospital with first-ever acute IS between March 1, 2017, and February 28, 2018, as part of the Lund Stroke Register (LSR) Study, comprising patients from the uptake area of Skåne University Hospital, Lund, Sweden. Patients were assessed with National Institutes of Health Stroke Scale (NIHSS) at stroke onset. Presence of aphasia was evaluated with NIHSS item 9 (language). We registered IS subtypes and risk factors. To investigate possible temporal changes in aphasia incidence, we made comparisons with corresponding LSR data from 2005 to 2006. Incidence rates were calculated and adjusted to the European Standard Population (ESP) and to the Swedish population. Results: Among 308 included IS patients, 30% presented with aphasia (n = 91; 95% CI: 25–35), a proportion of aphasia in IS that was similar to 2005–2006. The incidence rate of aphasia was 31 per 100,000 person-years adjusted to the ESP (95% CI: 25–38 per 100,000 person-years) corresponding to a significant decrease of 30% between 2005–2006 and 2017–2018. The decrease was significantly more pronounced in men. The initial severity of aphasia remained unchanged, with the majority of patients having severe to global aphasia. No significant differences between vascular stroke risk factors were noted among stroke patients with or without aphasia. Conclusion: Even though the overall IS incidence rate has decreased during the first decades of the 21st century, the proportion of IS patients with aphasia at stroke onset remains stable at 30%. Aphasia continues to be an important symptom that needs to be considered in stroke care and rehabilitation.
Ticagrelor With or Without Aspirin in Chinese Patients Undergoing Percutaneous Coronary Intervention: A TWILIGHT China Substudy
Authors: Han Yaling , Claessen Bimmer E. , Chen Shao-Liang , Chunguang Qiu , Zhou Yujie , Xu Yawei , Hailong Lin , Chen Jiyan , Qiang Wu , Zhang Ruiyan , Luo Suxin , Li Yongjun , Zhu Jianhua , Zhao Xianxian , Cheng Xiang , Wang Jian’an , Su Xi , Tao Jianhong , Sun Yingxian , Wang Geng , Li Yi , Bian Liya , Goel Ridhima , Sartori Samantha , Zhang Zhongjie , Angiolillo Dominick J. , Cohen David J. , Gibson C. Michael , Kastrati Adnan , Krucoff Mitchell , Mehta Shamir R. , Ohman E. Magnus , Steg Philippe Gabriel , Liu Yuqi , Dangas George , Sharma Samin , Baber Usman , Mehran Roxana
Published: March 2022

Background:

The risk/benefit tradeoff of dual antiplatelet therapy after percutaneous coronary intervention may vary in East Asian patients as compared with their non-East Asian counterparts.

Methods:

The double-blind, placebo-controlled, randomized TWILIGHT trial (Ticagrelor With Aspirin or Alone in High-Risk Patients After Coronary Intervention) enrolled patients undergoing high-risk percutaneous coronary intervention. After 3 months of treatment with ticagrelor plus aspirin, event-free and adherent patients remained on ticagrelor and were randomly assigned to receive aspirin or placebo for 1 year. The primary end point was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding; the key secondary end point was the first occurrence of death from any cause, nonfatal myocardial infarction, or nonfatal stroke.

Results:

Of 9006 enrolled and 7119 randomized patients in TWILIGHT, 1169 patients (13.0%) were enrolled at 27 Chinese sites in this prespecified substudy, of whom 1028 (14.4%) patients were randomized after 3 months. The incidence of the primary end point was 6.2% in the ticagrelor+aspirin group versus 3.5% in the ticagrelor+placebo group between randomization and 1 year (hazard ratio, 0.56 [95% CI, 0.31–0.99];
P
=0.048). The key secondary end point occurred in 3.4% of patients in the ticagrelor+aspirin group versus 2.4% in the ticagrelor+placebo group (hazard ratio, 0.70 [95% CI, 0.33–1.46];
P
=0.34). There was no interaction between the region of randomization (China versus the rest of the world) and randomized treatment assignment in terms of the primary or key secondary end points.

Conclusions:

Ticagrelor monotherapy significantly reduced clinically relevant bleeding without increasing ischemic events as compared with ticagrelor plus aspirin in Chinese patients undergoing high-risk percutaneous coronary intervention.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT02270242.
Ten-Second Heart Rate Variability, Its Changes Over Time, and the Development of Hypertension
Authors: Kang Jeonggyu , Chang Yoosoo , Kim Yejin , Shin Hocheol , Ryu Seungho
Published: March 2022

Background:

The role of ultrashort-term heart rate variability (HRV) and its temporal changes in incident hypertension are unknown. We aimed to investigate the association between 10-second HRV, its changes, and incident hypertension in adults aged <40 years and older.

Methods:

This cohort study included 232 587 Koreans (mean age 37.6 years) without hypertension. Hypertension was defined according to the 2017 American College of Cardiology and American Heart Association hypertension guidelines. HRV, including the root mean square of successive R-R interval differences and the SD of normal-to-normal R-R intervals, was estimated using standard 12-lead, 10-second electrocardiography.

Results:

During a median follow-up of 3.8 years, 40 268 hypertension cases were identified (incidence rates: 36.1 and 67.9 per 1000 person-years for young and older participants, respectively). An inverse association was observed between HRV and hypertension risk, in a dose-dependent manner. The multivariable-adjusted hazard ratios (95% CIs) for hypertension comparing the first to the fifth quintiles of root mean square of successive R-R interval difference and SD of normal-to-normal R-R interval were 1.58 (1.52–1.63) and 1.35 (1.30–1.39), respectively. These associations were stronger in young adults than in older adults. In a subsample of 150 301 participants, compared with stable HRV, an increase in HRV over time was also inversely associated with incident hypertension.

Conclusions:

A higher HRV and its increase over time on a 10-second electrocardiography were associated with a lower risk of hypertension. Our findings indicate that autonomic function, estimated using 10-second standard electrocardiography, plays a role in predicting hypertension, with a stronger effect in young adults.
Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial
Authors: Zhang Jack Jiaqi , Bai Zhongfei , Fong Kenneth N.K.
Published: March 2022

Background:

Intermittent theta burst stimulation (iTBS) creates a state with increased excitability that permits treatment modalities to induce neuroplasticity and motor learning. Continuous theta burst stimulation before iTBS may induce metaplasticity and boost the facilitatory effect of iTBS. This study investigated the effects of priming iTBS (ie, applying continuous theta burst stimulation before iTBS) on poststroke hemiparetic upper limb recovery.

Methods:

In this randomized controlled trial, 42 patients with chronic stroke were recruited and randomly allocated to 10 sessions of either priming iTBS, nonpriming iTBS, or sham stimulation to the ipsilesional motor cortex, immediately before robot-assisted training. Outcomes included Fugl-Meyer Assessment-Upper Extremity, Action Research Arm Test and mean movement velocity during each robot-assisted training session. Twenty-one patients were enrolled for measuring the sensorimotor beta event-related desynchronization induced by either mirror visual feedback or movement.

Results:

The Fugl-Meyer Assessment-Upper Extremity scores revealed a significant time-by-group interaction (
P
=0.011). Priming and nonpriming iTBS were both superior to sham stimulation in post hoc comparisons; however, the superiority was diminished at follow-up. Among patients with a higher functioning upper limb, priming iTBS yielded a significantly greater improvement in Fugl-Meyer Assessment-Upper Extremity scores than nonpriming iTBS (
P
=0.025) and sham stimulation (
P
=0.029) did. No significant interaction was found when analyzing the Action Research Arm Test and mean movement velocity. Priming iTBS enhanced the patients’ mirror visual feedback–induced high beta sensorimotor event-related desynchronization over their ipsilesional hemisphere.

Conclusions:

Priming and nonpriming iTBS are both superior to sham stimulation in enhancing treatment gains from robot-assisted training, and patients with a higher functioning upper limb may experience more benefits from priming iTBS. Priming iTBS may facilitate poststroke motor learning by enhancing the permissiveness of the ipsilesional sensorimotor area to therapeutic sensory modalities, such as the mirror visual feedback.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT04034069.
Multilingual Autoregressive Entity Linking
Authors: De Cao Nicola , Wu Ledell , Popat Kashyap , Artetxe Mikel , Goyal Naman , Plekhanov Mikhail , Zettlemoyer Luke , Cancedda Nicola , Riedel Sebastian , Petroni Fabio
Published: March 2022

We present mGENRE, a sequence-to- sequence system for the Multilingual Entity Linking (MEL) problem—the task of resolving language-specific mentions to a multilingual Knowledge Base (KB). For a mention in a given language, mGENRE predicts the name of the target entity left-to-right, token-by-token in an autoregressive fashion. The autoregressive formulation allows us to effectively cross-encode mention string and entity names to capture more interactions than the standard dot product between mention and entity vectors. It also enables fast search within a large KB even for mentions that do not appear in mention tables and with no need for large-scale vector indices. While prior MEL works use a single representation for each entity, we match against entity names of as many languages as possible, which allows exploiting language connections between source input and target name. Moreover, in a zero-shot setting on languages with no training data at all, mGENRE treats the target language as a latent variable that is marginalized at prediction time. This leads to over 50% improvements in average accuracy. We show the efficacy of our approach through extensive evaluation including experiments on three popular MEL benchmarks where we establish new state-of-the-art results. Source code available at https://github.com/facebookresearch/GENRE.
ByT5: Towards a Token-Free Future with Pre-trained Byte-to-Byte Models
Authors: Xue Linting , Barua Aditya , Constant Noah , Al-Rfou Rami , Narang Sharan , Kale Mihir , Roberts Adam , Raffel Colin
Published: March 2022

Most widely used pre-trained language models operate on sequences of tokens corresponding to word or subword units. By comparison, token-free models that operate directly on raw text (bytes or characters) have many benefits: They can process text in any language out of the box, they are more robust to noise, and they minimize technical debt by removing complex and error-prone text preprocessing pipelines. Because byte or character sequences are longer than token sequences, past work on token-free models has often introduced new model architectures designed to amortize the cost of operating directly on raw text. In this paper, we show that a standard Transformer architecture can be used with minimal modifications to process byte sequences. We characterize the trade-offs in terms of parameter count, training FLOPs, and inference speed, and show that byte-level models are competitive with their token-level counterparts. We also demonstrate that byte-level models are significantly more robust to noise and perform better on tasks that are sensitive to spelling and pronunciation. As part of our contribution, we release a new set of pre-trained byte-level Transformer models based on the T5 architecture, as well as all code and data used in our experiments.1
What Is Negative Disjunctivism?
Authors: de Bruijn David
Published: March 2022

Negative disjunctivists like Mike Martin and Bill Fish understand hallucinations in purely epistemic terms, and do not attribute phenomenal character to these visual misfires. However, the approaches by Martin and Fish are importantly different, and there has been little systematic work on how negative disjunctivism is motivated. In this paper, I argue for a version of negative disjunctivism that centers on the idea that perception involves the exercise of a fallible self-conscious capacity. I claim that this at once explains hallucinations in purely negative terms that are close to Martin’s approach, while at the same time providing negative disjunctivism with an explanatory basis that Fish attempts to provide and Martin’s view lacks.
La Figura del Sabio Como Modelo Integral de Conocimiento y Conducta en la Filosofía Antigua
Authors: Silva Trinidad
Published: March 2022

From the significance of the sage in ancient philosophy and the emergence of the notion of wisdom in contemporary psychology, I propose to reevaluate the role of the wise man as integral model of knowledge and action in ancient philosophy. I claim that this model is rooted in the Greek tradition from archaic literature, but it is not a central element in the philosophy of the classical period (i.e., Plato and Aristotle) as it is in Hellenistic philosophy, particularly with the Stoics. The analysis includes an assessment of the conditions allowing a theory that offers the figure of the wise man as a guiding model of both knowledge and action. For this, I consider three relevant criteria: the wise man is human (even if similar to god), he proves to be integrally wise (without excluding theory from praxis) and his wisdom is useful (because of his advice or example).
An Update and Errata for the Catalog of the Biting Midges of the World (Diptera: Ceratopogonidae)
Authors: BORKENT ART , DOMINIAK PATRYCJA , DÍAZ FLORENTINA
Published: March 2022

A list of corrections as well as the addition of new taxa described since Borkent & Dominiak (2020) published a catalog of the Ceratopogonidae of the world is provided. We record a further 70 extant and 7 fossil species and 2 new fossil genera. Beyond the summary provided by Borkent & Dominiak (2020, Table 1), the family now includes 6276 extant and 303 fossil species and 23 fossil genera. The number of species names that are nomina dubia is now 181.
Taxonomic revision of the genus Deltepilissus Pereira, 1949 (Coleoptera: Scarabaeidae: Scarabaeinae: Deltochilini)
Authors: SILVA FERNANDO A. B. , FERREIRA ANA B. M. , GÉNIER FRANÇOIS
Published: March 2022

Deltepilissus Pereira, 1949 (Coleoptera: Scarabaeidae: Scarabaeinae: Deltochilini) is revised and consists of two valid species, both endemic to the Brazilian Atlantic Forest. Deltepilissus diabolicus (Harold, 1880), from Bahia, and D. infernalis (Harold, 1880), from Espírito Santo to São Paulo, are redescribed, including characters of the adult female and of the male genitalia, both described and illustrated here for the first time. Lectotypes are designated for D. diabolicus (Harold, 1880) and D. infernalis (Harold, 1880). A detailed literature review, synonymies, diagnoses, key for species identification, illustration of key morphological characters, as well as data of the studied material and geographic distribution are provided for each species. A discussion about their conservation status is also provided.
Annotated checklist of the bat flies (Diptera: Nycteribiidae) of Romania
Authors: PÉTER ÁRON , MIHALCA ANDREI DANIEL , SÁNDOR ATTILA D.
Published: March 2022

Bat flies (Diptera: Hippoboscoidea: Nycteribiidae, Streblidae) are obligate, blood-feeding, highly specialized ectoparasites of bats (Chiroptera). Of the 17 nycteribiid species present in Europe, 11 have been recorded in Romania. Here, we present a checklist with all the previously published data and new records from recent years, for a total of 2218 records of bat-bat fly associations. Host-parasite associations are updated for Basilia italica Theodor, B. nana Theodor, B. nattererii (Kolenati), Nycteribia kolenatii Theodor & Moscona, N. latreillii (Leach), N. pedicularia Latreille, N. schmidlii Schiner, N. vexata Westwood, Penicillidia conspicua Speiser, Pe. dufourii (Westwood) and Phthiridium biarticulatum Hermann.
Four new stink bug mitogenomes corroborate the internal inconsistencies in the classification of Pentatomidae (Hemiptera)
Authors: GONÇALVES LEONARDO TRESOLDI , PEZZI PEDRO HENRIQUE , BIANCHI FILIPE MICHELS
Published: March 2022

Stink bugs (Pentatomidae) are a speciose group of insects that feed mostly on plants. Many species are considered agricultural pests of economically important crops around the globe. Mitochondrial genomes are valuable for evolutionary and phylogenetic studies, but have been little explored for Pentatomidae. Here, we characterized the mitochondrial genomes of four pentatomid species (Diceraeus melacanthus, Euschistus heros, Piezodorus guildinii, and Stiretrus anchorago) and performed a comparative analysis for this family and its subfamilies. Stink bug mitogenomes disclosed a conserved gene order and content, although we detected two uncommon armless tRNAs in E. heros and D. melacanthus. Phylogenetic results indicate that Pentatominae is polyphyletic, showing that internal relationships of Pentatomidae should be further investigated. Stink bug mitochondrial genes are under strong purifying selection, except for ATP8 which showed signs of positive selection.
Bone Marrow Mesenchymal Stem Cells (BMSCs)-Originated miR-1298 Impedes the Aggressiveness of Non-Small Cell Lung Cancer by Hindering the Chemokine Receptor 4 (CXCR4)-Induced Epithelial-Mesenchymal Transition (EMT) Process
Authors: Nie Guangjie , Wei Xiaoqun , Ye Jun
Published: March 2022

Exosomes are a subclass of extracellular vesicles, which are produced and secreted by various cells including bone marrow mesenchymal stem cells (BMSCs). BMSCs-originated exosomes can provide a beneficial microenvironment and manipulate tumor growth. However, whether BMSCs-derived miR-1298
exerts roles in NSCLC remains unclear. miR-1298 level was quantified in NSCLC tumor tissues and para-cancerous tissues and NSCLC cell lines. Cells were transfected with miR-136 mimics/miR-136 inhibitors or treatment with BMSCs-originated exosomes to measure cell biological behaviors. Our results
found a diminished miR-1298 expression in NSCLC tumor specimens and cell lines. Meanwhile, miR-1298 overexpression or miR-1298 derived from BMSC-originated exosomes can restrain the proliferating feature of NSCLC cells, and impedes cell aggressiveness via hindering EMT process. Additionally,
CXCR4 was a target of miR-1298. In conclusion, miR-1298 is served as a tumor suppressor gene in NSCLC and can retard the proliferating and invading behaviors of NSCLC cells by targeting CXCR4 expression, indicating that it might be a novel therapeutic target for treating NSCLC.
Simvastatin Alleviates Vascular Cognitive Impairment Caused by Lacunar Cerebral Infarction Through Protein Kinase B/Nuclear Factor Erythroid 2–Related Factor 2 (AKT/Nrf2) Signaling Pathway
Authors: You Yiping , He Min
Published: March 2022

Lacunar cerebral infarction (LACI) is one of the main causes of vascular cognitive impairment (VCI). Herein, this study explored the potential effect of Simvastatin (Sim) on VCI secondary to LACI and Akt/Nrf2 signaling transduction and apoptosis. We established a rat model of VCI and the animals were administered with Sim (40 mg/kg and 80 mg/kg) every day for 28 days. After that, the cognition and memory abilities of rats were assessed together with analysis of morphological changes of hippocampal neurons by immunohistochemistry staining and level of anti-apoptotic related proteins and Akt and Nrf2 signaling proteins by western blot. Compared with normal saline (control group), Sim administration significantly improved the capacity spatial learning and relieved the memory impairment with an improvement in morphological defects. Importantly, Sim treatment restored the p-Akt, t-Nrf2, n-Nrf2 and HO-1 expression along with up-regulation of Bcl-2 and down-regulation of Bax. In conclusion, Sim improves cognitive and morphological disorders induced by LACI possibly through regulating Akt/Nrf2 signaling pathway. These evidence might promote the development of Sim-based treatment for VCI and LACI.
Effect of Valproic Acid on NLR Family Pyrin Domain Containing 1/3 (NLRP1/3) Inflammasome in Rats with Acute Spinal Cord Injury
Authors: Sun Feng , Huang Tianwen , Shi Jianhui , Wei Tianli , Zhang Haiwei
Published: March 2022

Our study assesses valproic acid’s effect on NLRP1/3 inflammasome in rats with acute spinal cord injury (SCI). SD rats were clamped by aneurysm clips to establish SCI model followed by analysis of functional recovery by BBB score, degree of inflammatory infiltration, by H&E
staining, NLRP1/NLRP3 and P2X7 level by western blot, IL-1β and IL-18 level by ELISA, blood spinal cord barrier by EVANS blue method. After SCI, the lower limb motor function of rats decreased and recovered after valproic acid treatment (P < 0.05). Inflammatory cell infiltration
of SCI group increased and decreased after treatment. After SCI, NLRP1/3 level increased and P2X7 protein level elevated which were reversed after valproic acid treatment (P < 0.05). In rats with SCI, IL-1β level in spinal cord was higher than sham operation and lower
after treatment (P < 0.05) without difference of IL-18 between injury group and treatment group (P > 0.05). In addition, fluorescence was higher in injury group than sham operation group and lower in valproic acid injection group than injury group. In conclusion, Valproic
acid can promote motor function recovery in rats after SCI and inhibit inflammasome 1 and 3 expression, thereby inhibiting the maturation and release of IL-1β, and reducing P2X7 level after SCI.