bluuebunny/crossref_metadata_2025 huggingface dataset:
TNFR2 blockade of regulatory T cells unleashes an antitumor immune response after hematopoietic stem-cell transplantation
Authors: Moatti Audrey , Debesset Anais , Pilon Caroline , Beldi-Ferchiou Asma , Leclerc Mathieu , Redjoul Rabah , Charlotte Frederic , To Nhu Hanh , Bak Adeline , Belkacemi Yazid , Salomon Benoît Laurent , Issa Fadi , Michonneau David , Maury Sebastien , Cohen José Laurent , Thiolat Allan
Published: April 2022

Background

Targeting immune checkpoints that inhibit antitumor immune responses has emerged as a powerful new approach to treat cancer. We recently showed that blocking the tumor necrosis factor receptor-type 2 (TNFR2) pathway induces the complete loss of the protective function of regulatory T cells (Tregs) in a model of graft-versus-host disease (GVHD) prevention that relies on Treg-based cell therapy. Here, we tested the possibility of amplifying the antitumor response by targeting TNFR2 in a model of tumor relapse following hematopoietic stem-cell transplantation, a clinical situation for which the need for efficient therapeutic options is still unmet.

Method

We developed appropriate experimental conditions that mimic patients that relapsed from their initial hematological malignancy after hematopoietic stem-cell transplantation. This consisted of defining in allogeneic bone marrow transplantation models developed in mice, the maximum number of required tumor cells and T cells to infuse into recipient mice to develop a model of tumor relapse without inducing GVHD. We next evaluated whether anti-TNFR2 treatment could trigger alloreactivity and consequently antitumor immune response. In parallel, we also studied the differential expression of TNFR2 on T cells including Treg from patients in post-transplant leukemia relapse and in patients developing GVHD.

Results

Using experimental conditions in which neither donor T cells nor TNFR2-blocking antibody per se have any effect on tumor relapse, we observed that the coadministration of a suboptimal number of T cells and an anti-TNFR2 treatment can trigger alloreactivity and subsequently induce a significant antitumor effect. This was associated with a reduced percentage of activated CD4+ and CD8+ Tregs. Importantly, human Tregs over-expressed TNFR2 relative to conventional T cells in healthy donors and in patients experiencing leukemia relapse or cortico-resistant GVHD after hematopoietic stem cell transplantation.

Conclusions

These results highlight TNFR2 as a new target molecule for the development of immunotherapies to treat blood malignancy relapse, used either directly in grafted patients or to enhance donor lymphocyte infusion strategies. More widely, they open the door for new perspectives to amplify antitumor responses against solid cancers by directly targeting Tregs through their TNFR2 expression.
Educational Gradients in Disability among Asia’s Future Elderly: Projections for the Republic of Korea and Singapore
Authors: CHEN CYNTHIA , LIM JUE TAO , CHIA NGEE CHOON , KIM DAEJUNG , PARK HAEMI , WANG LIJIA , TYSINGER BRYAN , ZHAO MICHELLE , COOK ALEX R. , CHONG MING ZHE , YUAN JIAN-MIN , MA STEFAN , TAN KELVIN BRYAN , NG TZE PIN , KOH WOON-PUAY , YOONG JOANNE , BHATTACHARYA JAY , EGGLESTON KAREN
Published: April 2022

Asia is home to the most rapidly aging populations in the world. This study focuses on two countries in Asia that are advanced in terms of their demographic transition: the Republic of Korea and Singapore. We developed a demographic and economic state-transition microsimulation model based on the Korean Longitudinal Study of Aging and the Singapore Chinese Health Study. The model was employed to compare projections of functional status and disability among future cohorts of older adults, including disparities in disability prevalence by educational attainment. The model also projects increasing disparities in the prevalence of activities-of-daily-living disability and other chronic diseases between those with low and high educational attainment. Despite overall increases in educational attainment, all elderly, including those with a college degree, experience an increased burden of functional disability and chronic diseases because of survival to older ages. These increases have significant economic and social implications, including increased medical and long-term care expenditures, and an increased caregiver burden.
The Space-Efficient Core of Vadalog
Authors: Berger Gerald , Gottlob Georg , Pieris Andreas , Sallinger Emanuel
Published: April 2022

Vadalog is a system for performing complex reasoning tasks such as those required in advanced knowledge graphs. The logical core of the underlying Vadalog language is the warded fragment of tuple-generating dependencies (TGDs). This formalism ensures tractable reasoning in data complexity, while a recent analysis focusing on a practical implementation led to the reasoning algorithm around which the Vadalog system is built. A fundamental question that has emerged in the context of Vadalog is whether we can limit the recursion allowed by wardedness in order to obtain a formalism that provides a convenient syntax for expressing useful recursive statements, and at the same time achieves space-efficiency. After analyzing several real-life examples of warded sets of TGDs provided by our industrial partners, as well as recent benchmarks, we observed that recursion is often used in a restricted way: the body of a TGD contains at most one atom whose predicate is mutually recursive with a predicate in the head. We show that this type of recursion, known as
piece-wise linear
in the Datalog literature, is the answer to our main question. We further show that piece-wise linear recursion alone, without the wardedness condition, is not enough as it leads to undecidability. We also study the relative expressiveness of the query languages based on (piece-wise linear) warded sets of TGDs. Finally, we give preliminary experimental evidence for the practical effect of piece-wise linearity on Vadalog.
Mechanical Control of Cell Differentiation: Insights from the Early Embryo
Authors: Nelson Celeste M.
Published: April 2022

Differentiation is the process by which a cell activates the expression of tissue-specific genes, downregulates the expression of potency markers, and acquires the phenotypic characteristics of its mature fate. The signals that regulate differentiation include biochemical and mechanical factors within the surrounding microenvironment. We describe recent breakthroughs in our understanding of the mechanical control mechanisms that regulate differentiation, with a specific emphasis on the differentiation events that build the early mouse embryo. Engineering approaches that reproducibly mimic the mechanical regulation of differentiation will permit new insights into early development and applications in regenerative medicine.
The Past and Future of Economic Growth: A Semi-Endogenous Perspective
Authors: Jones Charles I.
Published: April 2022

The nonrivalry of ideas gives rise to increasing returns, a fact celebrated in Paul Romer's recent Nobel Prize. An implication is that the long-run rate of economic growth is the product of the degree of increasing returns and the growth rate of research effort; this is the essence of semi-endogenous growth theory. This review interprets past and future growth from a semi-endogenous perspective. For 50+ years, US growth has substantially exceeded its long-run rate because of rising educational attainment, declining misallocation, and rising (global) research intensity, implying that frontier growth could slow markedly in the future. Other forces push in the opposite direction. First is the prospect of “finding new Einsteins”: How many talented researchers have we missed historically because of the underdevelopment of China and India and because of barriers that discouraged women inventors? Second is the longer-term prospect that artificial intelligence could augment or even replace people as researchers. Throughout, the review highlights many opportunities for further research.
Criminal Governance and the Crisis of Contemporary Latin American States
Authors: Feldmann Andreas E. , Luna Juan Pablo
Published: April 2022

Across Latin America, societies are confronting the rise of novel orders in which state officials and political authorities share power with criminal organizations. Criminal governance (i.e., the creation of rules regulating behavior by criminal entities often with the collaboration of state actors), as these arrangements have come to be known, poses significant challenges for democracy and the rule of law and often threatens peoples' enjoyment of fundamental rights. This article reviews the literature on state-criminal relations in Latin America by critically discussing conceptual and methodological issues. In so doing, it looks at three extant literatures that have contributed to enhancing our grasp of alternative forms of governance: studies on violence, works on stateness and the rule of law, and the literature on criminal governance. This article posits that those literatures have done a commendable job in describing and conceptualizing emerging forms of governance that deviate from traditional views. However, we also argue that these bodies of work operate in silos with little integration and display methodological biases and theoretical blind spots that weaken their overall analytical power. We also point out that much more work is needed to assess these new orders' consequences for existing political regimes and state institutions. In the conclusion, we propose concrete steps to strengthen research and foster a more integrated agenda and suggest future investigative avenues.
Visibility of Multisensor Digital Fusion Technology in Public Art Design under Complex Environments
Authors: Chen Guang
Published: April 2022

Application of multisensor digital fusion technology in public art design in complex environments is deliberated to make public art design develop better. First, the more advanced sensor fusion technology is introduced into public art design, and the basic principle and system composition of multisensor fusion technology are analysed. The application of multisensor fusion technology in the field of public art is deeply analysed from multiple angles. Second, the visibility algorithm in public art design based on a fuzzy neural network (FNN) is studied, and the corresponding model is proposed. Finally, the proposed model is tested. The test results show that the root mean squared error of the model is 0.0261, the network has a good fitting effect on the output value, the similarity between the model output value and the real value is high, the fitting effect is good, the model is accurate and effective, and the identification accuracy is achieved. Moreover, the corresponding example model is proposed. The visibility development level of public art design in a region in the next 14 years is predicted. The algorithm proposed provides some ideas for the application of multisensor digital fusion technology in public art design.
20-Year Trends in Detection Rates of Cardia Cancer via Endoscopic Surveillance in Tianjin, China: A Hospital-Based Study
Authors: Wang Rui , Wu Xiaowei , Song Yan , Lin Rui , Zheng Zhongqing , Jiang Kui , Liu Wentian
Published: April 2022

Background. To analyze the time trends in cardia cancer detection rates using endoscopic surveillance from 1999 to 2019 in a high-volume Chinese hospital. Methods. In this retrospective, single-center study, data were collected from the Endoscopy Center of the Department of Gastroenterology, Tianjin Medical University General Hospital, from 1999 to 2019. Cases of cardia cancer (

n
=
1567

) were extracted from a database of patients who underwent endoscopy. Clinical and epidemiological characteristics of patients with cardia cancer were analyzed, including sex, age, and proportion of early gastric cancer and degree of tumor differentiation. The joinpoint regression method was used to identify change points in incidence trends. Annual percent change (APC) values, with 95% confidence intervals (CI), were calculated for time periods before and after change points. Results. Of the 343942 patients who underwent endoscopy during 1999–2009, 1567 (4.6%) were identified with cardia cancer. The overall cardia adenocarcinoma detection rate decreased significantly from 1999 to 2004 (

APC
=
−
37.3

, 95% CI: -20.9, -6.4), followed by a relatively slower decline rate from 2004 to 2019 (

APC
=
−
7.7

, 95% CI: -4.4, -7.6). The crude rate of detection of early cardia cancer could not be determined by joinpoint analysis. Rates of detection reduced significantly in patients aged 60–69 and 70-79 years (

APC
=
−
8.3

, 95% CI: -9.8, -6.8 and

APC
=
−
7.3

, 95% CI: -8.8, -5.8, respectively). The detection rate in males decreased rapidly from 1999 to 2004 (

APC
=
−
35.9

, 95% CI: -18.2, 5.6,

P
<
0.05

), while the decline rate was relatively slow from 2005 to 2019 (

APC
=
−
6.9

, 95% CI: -3.4, -6.1,

P
<
0.05

). Among females, the detection rates also decreased from 1999 to 2004 (

APC
=
−
21.2

, 95% CI: -28.1, -13.7), but remained stable from 2007 to 2019 (

APC
=
−
3.8

, 95% CI: -7.9, -0.5). Detection of poorly differentiated cardia cancer also declined from 2009 to 2019 (

APC
=
−
12.8

, 95% CI: -15.3, -10.0). Conclusions. The detection rate of cardia cancer among gastric cancers has been stable from 2008 to 2019. The trend of detection rate of early cardia cancer showed no significant statistical meaning; hence, it remains necessary to carefully observe the cardia area during endoscopy examination.
[Retracted] Identification of Diagnostic Biomarkers, Immune Infiltration Characteristics, and Potential Compounds in Rheumatoid Arthritis
Authors: Chen Huihui , Zhao Jingyi , Hu Junhui , Xiao Xu , Shi Wenda , Yao Yinhui , Wang Ying
Published: April 2022

Aims. This study is aimed at investigating the pathogenesis of rheumatoid arthritis (RA) by identifying key biomarkers, associated immune infiltration, and small‐molecule compounds using bioinformatic analysis. Methods. Six datasets were obtained from the Gene Expression Omnibus database, and the batch effect was adjusted. Functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to analyse differentially expressed genes (DEGs). Furthermore, candidate small‐molecule drugs associated with RA were selected from the Connectivity Map (CMap) database. The least absolute shrinkage and selection operator regression, support vector machine recursive feature elimination, and multivariate logistic regression analyses were performed on DEGs to screen for RA diagnostic markers. The receiver operating characteristic curve, concordance index, and GiViTi calibration band were the metrics used to assess the diagnostic markers of RA identified in this analysis. The single‐sample gene set enrichment analysis was performed to calculate the scores of infiltrating immune cells and evaluate the activities of immune‐related pathways. Finally, the correlation between screening markers and RA diagnosis was determined. Results. A total of 227 DEGs were identified. Functional enrichment analysis and KEGG revealed that DEGs were enriched by the immune response. CMap analysis identified 11 small‐molecule compounds with therapeutic potential for RA. In gene expression, the activities of 13 immune cells and 12 immune‐related pathways significantly differed between patients with RA and healthy controls. DPYSL3 and SPP1 had the potential to diagnose RA. SPP1 expression was positively correlated with DPYSL3 in 11 immune cells and 10 immune‐related pathways. Conclusion. This study comprehensively analysed DEGs and immune infiltration and screened for potential diagnostic markers and small‐molecule compounds of RA.
Empirical Analysis of the Nursing Effect of Intelligent Medical Internet of Things in Postoperative Osteoarthritis
Authors: Gu Yehong , Su Wen , Zhu Hongxia , Ge Junxia , Wu Xiaojuan
Published: April 2022

In order to analyze the effect of postoperative nursing for bones and joints, this paper combines the intelligent medical Internet of Things technology to construct a postoperative nursing system for bones and joints and conducts research on postoperative nursing methods for bones and joints. Moreover, this paper realizes the integration of “voice data + video data + software data” and the integration of “wired network + RFID sensor network + WIFI wireless network.” In this paper, this paper constructs an intelligent medical IoT nursing analysis system, combines actual cases to analyze the effect of postoperative nursing of bones and joints, and selects an intelligent IoT system and statistical software SPSS23.0 to complete statistical processing.
Automated Detection of Infection in Diabetic Foot Ulcer Images Using Convolutional Neural Network
Authors: Yogapriya J. , Chandran Venkatesan , Sumithra M. G. , Elakkiya B. , Shamila Ebenezer A. , Suresh Gnana Dhas C.
Published: April 2022

A bacterial or bone infection in the feet causes diabetic foot infection (DFI), which results in reddish skin in the wound and surrounding area. DFI is the most prevalent and dangerous type of diabetic mellitus. It will mainly occur in people with heart disease, renal illness, or eye disease. The clinical signs and symptoms of local inflammation are used to diagnose diabetic foot infection. In assessing diabetic foot ulcers, the infection has significant clinical implications in predicting the likelihood of amputation. In this work, a diabetic foot infection network (DFINET) is proposed to assess infection and no infection from diabetic foot ulcer images. A DFINET consists of 22 layers with a unique parallel convolution layer with ReLU, a normalization layer, and a fully connected layer with a dropout connection. Experiments have shown that the DFINET, when combined with this technique and improved image augmentation, should yield promising results in infection recognition, with an accuracy of 91.98%, and a Matthews correlation coefficient of 0.84 on binary classification. Such enhancements to existing methods shows that the suggested approach can assist medical experts in automated detection of DFI.
On Amenability‐Like Properties of a Class of Matrix Algebras
Authors: Rostami M. , Shariati S. F. , Sahami A.
Published: April 2022

In this study, we show that a matrix algebra is a dual Banach algebra, where is a dual Banach algebra and 1 ≤ p ≤ 2. We show that is Connes amenable if and only if I is finite, for every nonempty set I. Additionally, we prove that is always pseudo‐Connes amenable, for 1 ≤ p ≤ 2. Also, Connes amenability and approximate Connes biprojectivity are investigated for generalized upper triangular matrix algebras. Finally, we show that is approximately biflat if and only if is approximately biflat and I is a singleton.
Research on the Relationship between Intelligent Analysis and Weight of Keywords in English Test Questions
Authors: Qiu Jiaosheng
Published: April 2022

With the rapid development of educational informationization, Internet of Things, and other technologies, English education has been paid special attention to, and all aspects such as educational model, learning behavior, teaching philosophy, and teaching evaluation have been greatly influenced by educational informationization. Based on the experience of practical education, this paper explores and studies the connotation and characteristics of English test questions and its influence and application on modern English test questions. This paper constructs a systematic method to extract keywords from English test questions. It perfects the fair and reasonable index of English keywords, establishes the weight system, discusses the relationship of keywords, and conducts academic research on vocabulary, word frequency and word position, emphatically adopts BayesNet algorithm to extract keywords, and realizes the evaluation system of English test keywords based on intelligent analysis and weight relationship. The results show that (1) selecting the calculation method and weight relationship suitable for the text system to carry out intelligent analysis, the weight ratio exceeds 65%; that is, the text keyword retrieval is successful. (2) The average accuracy (%), average recall (%) and average

F

-measure (%) in weighted names are almost less than 70%. Only the BayesNet algorithm has 72.3% weight analysis in keyword extraction in reading comprehension. (3) KEA algorithm, PAT TERR algorithm, and BayesNet algorithm take 0-2.8 s, 0-2.6 s, and 0-2.1 s, respectively, and the BayesNet algorithm takes the shortest time. The calculation time of users is greatly saved. (4) According to the calculation results of CPT model, the sum of the weights of the three algorithms is equal to 1, and the BayesNet algorithm is dominant in extracting keywords with a weight analysis of 0.529 in verb translation.
IGFs in Dentin Formation and Regeneration: Progress and Remaining Challenges
Authors: He Pengcheng , Zheng Liwei , Zhou Xin
Published: April 2022

Tertiary dentin results from the interplay between the host defense and dental injury or infection. Modern endodontics aiming vital pulp treatment take the tertiary dentin formation as the interim step, with the final goal of a physiological pulp-dentin like tissue regeneration. Dental pulp stem cells have been nominated for contributing to differentiating into odontoblast-like cells who are responsible for reparative dentin formation. Understanding the original dentin formation mechanism provides us a blueprint while exploring the reparative dentin formation mechanism builds bridge to bonafide pulp-dentin tissue regeneration. Among all the regulators, growth factors have long been revealed under the spotlight. The insulin-like growth factor (IGF) family has been implicated in critical events of inducing dentin formation, which is essential for pulp treatment. The expression of IGF family members including IGF1, IGF1R, IGF2, and IGF2R has been well characterized in dental papilla cells, dental pulp stem cells, and periodontal ligament cells. Recent studies indicated IGF binding to the receptors activated pathways, including MAPK pathway, and AKT pathway, orchestrated proliferation, and differentiation, and finally, contributed to dentin formation. This review summarizes the role of IGF family in dentin formation during tooth development and tertiary dentin formation during dentin-pulp repair and sheds light on key parts of research for future treatment improvements.
Metabolic Profile in a Cohort of Young Sicilian Patients with Klinefelter’s Syndrome: The Role of Irisin
Authors: Radellini Stefano , Guarnotta Valentina , Sciabica Vincenzo , Pizzolanti Giuseppe , Giordano Carla
Published: April 2022

Klinefelter’s syndrome (KS) is the main cause of hypogonadism and infertility in men and is often related to obesity, metabolic syndrome, and diabetes. The purpose of our real-life observational study was to investigate the metabolic and anthropometric parameters in a population of patients with Klinefelter syndrome compared to a group of healthy age-matched subjects. Methods. In our study, 25 consecutive Caucasian adult outpatients (age range 21–52 years, mean age 32.9 ± 12.2) with KS in testosterone replacement therapy and 30 healthy men (age range 25–45 years, mean age 32.4 ± 7.62) were studied. In both groups of subjects, anthropometric indices, lipid profile, glucose metabolic parameters, HbA1c, the homeostasis model assessment estimate of HOMA-insulin resistance (IR), and the insulin sensitivity index (ISI) were evaluated. In addition, we assessed the complete hormonal gonadic status and irisin values in both groups of patients. Results. No significant differences were found in BMI and total blood testosterone levels between KS and control subjects. Patients with KS had significantly higher values of WC (

p
=
0.028

), HbA1c (

p
=
0.018

), HOMA-IR (

p
<
0.001

), FSH (

p
<
0.001

), LH (

p
<
0.001

), estradiol (

p
=
0.001

), and irisin (

p
=
0.029

) and significantly lower HDL-cholesterol (

p
=
0.002

), AMH (

p
<
0.001

), inhibin B (

p
<
0.001

), and ISI-Matsuda (

p
<
0.001

) compared to healthy controls. Univariate analysis revealed an inverse correlation between irisin and ISI-Matsuda (r = −0.128;

p
=
0.010

). These data were then confirmed in multivariate analysis. Conclusions. KS is characterized by early development of metabolic syndrome and in particular by alterations of the glucose metabolism, independently of testosterone levels serum and BMI. Irisin blood levels of Klinefelter’s patients are higher than in healthy subjects and positively correlate with the degree of insulin resistance.
Dynamic Mechanism and Decision Analysis of Urban Exhibition Tourism Development Based on High-Performance Computing
Authors: Wan Hongzhen
Published: April 2022

MICE tourism has received the attention and support from relevant departments and tourism industry with the growth rate of recent years. In this paper, the dynamics mechanism of urban exhibition tourism development is studied by using high-performance computing, and the dynamics mechanism model of exhibition tourism is constructed. To improve the performance, the solution constructed in the adaptive joint algorithm is used as the initial solution, and then the initial solution is improved using the method proposed by the new neighborhood strategy. It promotes the development of MICE tourism and urban MICE tourism by combining research on theoretical aspects related to tourism development, such as the relationship between tourism development and exhibition, and the development dynamics and stages of MICE tourism. The research results show that, in the assessment of the development mechanism of urban MICE tourism, tourism resources, economic, and policy factors have a relatively large weight, among which the weight coefficient of tourism resources factor is 0.2411. It can be seen that the development power of MICE tourism should start from tourism resources, so that the development power mechanism of urban MICE tourism can be optimized and improved, which not only provides new methods and new ideas for the transformation and upgrading of tourism industry but also promotes tourism enterprises and related departments to creatively develop tourism resources and design competitive tourism products, so as to improve the supply quality of MICE tourism, and then continuously promote the process of supply-side reform of MICE tourism.
Application of Animation Control Technology Based on Internet Technology in Digital Media Art
Authors: Li Yuhui , Zhuge Wenjing
Published: April 2022

The advent of the Internet era has endowed artistic creation with new forms and connotations, and more and more digital media technologies have entered the stage of artistic creation and exhibition. At the same time, Internet technology has also provided more abundant artistic resources and art forms for digital media art for reference. With the development of animation control technology, various character animations present three-dimensional visual effects. Digital media art has emerged as a new concept in the field of multimedia applications and the integration and development of various technologies such as intelligent technology, network technology, media technology, and art design. This makes the art present a three-dimensional beauty with the support of modern high-tech technology. This paper mainly discusses the application of animation control technology in digital media art under the support of Internet technology. This paper also studies the artistic effect of digital media art under animation control technology. Through experimental research, this paper shows that the application of animation control technology in digital media art can improve the vividness of animation characters and promote the integration of digital media technology and culture and art. The fidelity to its simulated reality reaches 98.99%, and the actual effect achieved in the process of digital media art design work is completed, thereby realizing a large number of character animation scenes.
Psychological Analysis for Depression Detection from Social Networking Sites
Authors: Gupta Sonam , Goel Lipika , Singh Arjun , Prasad Ajay , Ullah Mohammad Aman
Published: April 2022

Rapid technological advancements are altering people’s communication styles. With the growth of the Internet, social networks (Twitter, Facebook, Telegram, and Instagram) have become popular forums for people to share their thoughts, psychological behavior, and emotions. Psychological analysis analyzes text and extracts facts, features, and important information from the opinions of users. Researchers working on psychological analysis rely on social networks for the detection of depression-related behavior and activity. Social networks provide innumerable data on mindsets of a person’s onset of depression, such as low sociology and activities such as undergoing medical treatment, a primary emphasis on oneself, and a high rate of activity during the day and night. In this paper, we used five machine learning classifiers—decision trees, K-nearest neighbor, support vector machines, logistic regression, and LSTM—for depression detection in tweets. The dataset is collected in two forms—balanced and imbalanced—where the oversampling of techniques is studied technically. The results show that the LSTM classification model outperforms the other baseline models in the depression detection healthcare approach for both balanced and imbalanced data.
Dosimetric Comparison between Volumetric Modulated Arc Therapy (VMAT) and Intensity-Modulated Radiotherapy (IMRT) for Dental Structures of Head and Neck Cancer Patients
Authors: Ma Yan , Zhou Jianfeng , Wang Hongyong
Published: April 2022

Background. This retrospective study aimed to evaluate the radiation dose delivered to dental structures in intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) without dental dose constraints, compare the dosimetry differences of dental structures between the two radiation techniques, and determine whether dental structures should be one of the organs at risk for IMRT and VMAT plans according to the dosimetric analysis. Materials and Methods. A total of 138 head and neck cancer patients (nasopharyngeal, oral cavity, pharyngeal, hypopharynx, and larynx), who underwent IMRT (69 patients) or VMAT (69 patients) from March 2016 to March 2021 in our hospital, were included to assess the dosimetry difference between two radiotherapy techniques for dental structures. Results. The radiation dose delivered by IMRT and the mean maximum doses delivered by VMAT to the maxillary teeth of nasopharyngeal cancer patients were significantly higher than the dose received by the mandibular teeth. In contrast, the mandibular teeth of oral cavity cancer, oropharynx cancer, and laryngeal cancer received higher radiation doses than maxillary teeth. Except for mandibular teeth of oral cancer patients, the molars received significantly high-dose radiation than premolars and/or incisors in both radiotherapy techniques. No significant difference was observed between IMRT and VMAT in the dosimetric comparison of dental structures, except that oral cavity cancer patients treated with VMAT received a significantly higher mean average dose than those treated with IMRT. When PTV included level Ib, the radiation doses of the mandibular teeth delivered by both radiotherapy techniques were significantly higher than that in PTV when level Ib was excluded. Conclusion. Without dental dose constraints, no major difference was observed between IMRT and VMAT plans in tooth dose distribution. We suggest that dental structures should be delineated as part of the organ at risk (OAR) when IMRT and VMAT are planned. Meanwhile, attention should be paid to dental structures that might have a high-dose area according to the specific tumor location.
DNA Methyltransferase 3b Accelerates the Process of Atherosclerosis
Authors: Zhu Ling , Jia Lei , Liu Na , Wu Runmiao , Guan Gongchang , Hui Rutai , Xing Yujie , Zhang Yong , Wang Junkui
Published: April 2022

Background. DNA methylation plays a key role in establishing cell type–specific gene expression profiles and patterns in atherosclerosis. The underlying mechanism remains unclear. Previous studies have shown that DNA methyltransferase 3b (DNMT3b) may play an important role in atherosclerosis. This study aimed to establish the regulatory role of DNMT3b in the development of atherosclerosis. Methods. We constructed a viral vector carrying Dnmt3b shRNA to transduce ApoE−/− mice. Meanwhile, healthy human peripheral blood Treg cells were treated with inhibitor of DNMT3b (AZA and EGCG) or transduced with DNMT3b shRNA. Results. It showed that Dnmt3b silencing attenuated atherosclerosis, including decreased lesion size and macrophage content and increased collagen and smooth muscle cells content in ApoE−/− mice. To further investigate the possible mechanisms, combined with previous studies by our group, we showed that Foxp3-TSDR methylation level was significantly reduced Foxp3 expression and peripheral blood Treg levels were significantly increased by Dnmt3b shRNA vector transduction in animals committed to western diet for 12 and 18 weeks. Consistently, inhibition of DNMT3b (AZA and EGCG) decreased the expression levels of DNMT3b, which can increase the expression levels of FOXP3, and increase the levels of TGF-β and IL-10 and decrease the levels of IL-β and IFN-γ. After transduction with DNMT3b shRNA, the effect was more obvious. Conclusions. DNMT3b accelerated atherosclerosis, and may be associated with FOXP3 hypermethylation status in regulatory T cells.
Selenium Supplementation Improved Cardiac Functions by Suppressing DNMT2-Mediated GPX1 Promoter DNA Methylation in AGE-Induced Heart Failure
Authors: Zhu Huolan , Wang Xiang , Meng Xuyang , Kong Yiya , Li Yi , Yang Chenguang , Guo Ying , Wang Xiqiang , Yang Haini , Liu Zhongwei , Wang Fang
Published: April 2022

Objective. Advanced glycation end products (AGEs) are featured metabolites associated with diabetic cardiomyopathy which is characterized by heart failure caused by myocyte apoptosis. Selenium was proved cardioprotective. This study was aimed at investigating the therapeutic effects and underlying mechanisms of selenium supplementation on AGE-induced heart failure. Methods. Rats and primary myocytes were exposed to AGEs. Selenium supplementation was administrated. Cardiac functions and myocyte apoptosis were evaluated. Oxidative stress was assessed by total antioxidant capacity (TAC), reactive oxygen species (ROS) generation, and GPX activity. Expression levels of DNA methyltransferases (DNMTs) and glutathione peroxidase 1 (GPX1) were evaluated. DNA methylation of the GPX1 promoter was analyzed. Results. AGE exposure elevated intracellular ROS generation, induced myocyte apoptosis, and impaired cardiac functions. AGE exposure increased DNMT1 and DNMT2 expression, leading to the reduction of GPX1 expression and activity in the heart. Selenium supplementation decreased DNMT2 expression, recovered GPX1 expression and activity, and alleviated intracellular ROS generation and myocyte apoptosis, resulting in cardiac function recovery. DNA methylation analysis in primary myocytes indicated that selenium supplementation or DNMT inhibitor AZA treatment reduced DNA methylation of the GPX1 gene promoter. Selenium supplementation and AZA administration showed synergic inhibitory effect on GPX1 gene promoter methylation. Conclusions. Selenium supplementation showed cardioprotective effects on AGE-induced heart failure by suppressing ROS-mediated myocyte apoptosis. Selenium supplementation suppressed ROS generation by increasing GPX1 expression via inhibiting DNMT2-induced GPX1 gene promoter DNA methylation in myocytes exposed to AGEs.
Evaluation of Soil Streptomyces Isolates from North-Western Ethiopia as Potential Inhibitors against Spoilage and Foodborne Bacterial Pathogens
Authors: Girma Abayeneh , Aemiro Aleka
Published: April 2022

The outbreak and spread of foodborne diseases is a serious concern for global healthcare and security. Finding novel antimicrobial agents with diverse mechanisms of action against the current spoilage and foodborne bacterial pathogens is a central strategy to overcome the problems of antibiotic resistance. Soil actinomycetes are the major antimicrobial producers with great biopreservative and medical value. This study was aimed at isolating Streptomyces from soil samples of northwestern Ethiopia against spoilage and foodborne bacterial pathogens. Thirty-six soil samples were collected at a depth of 5–10 cm in the rhizosphere and agricultural soils of soybean. A total of 118 actinomycete strains were isolated and screened primarily using the perpendicular streak plate method against 3 Gram-positive and 3 Gram-negative bacterial strains. Out of 118 isolates, 36/118 (30.50%) were active against at least two of the tested bacteria, of which 8 isolates were selected for their wide-spectrum antibacterial activities. During the disc diffusion assay, the eight in vitro ethyl acetate extract antibacterial activities range from 7 to 24 mm. The minimum inhibitory concentration and minimum bactericidal concentration values range from 0.10 to 0.25 μg/mL and 0.15 to 0.40 μg/mL, respectively. Following the morphological, physiological, biochemical, and molecular characteristics, eight potent isolates were identified as follows: Streptomyces fasciculus, Streptomyces roseochromogenes, Streptomyces ruber, Streptomyces glaucus, Streptomyces griseus, Streptomyces cellulosae, Streptomyces griseoflavus, and Streptomyces xanthophaeus. After the treatment of potent Streptomyces cell-free culture supernatant with proteinase K, papain, α-amylase, and lysozyme enzymes, their antagonistic effects were also observed. Most Streptomyces cell-free culture supernatant antibacterial activity was highly resistant to heat, acidity, organic solvents, and additives. Thus, the results of this investigation revealed that soil actinomycetes could be a valuable source for novel antibacterial agents applicable in food biopreservation and the treatment of spoilage and foodborne bacterial pathogens.
Angiopep-2 as an Exogenous Chemical Exchange Saturation Transfer Contrast Agent in Diagnosis of Alzheimer’s Disease
Authors: Wang Chengguang , Lin Guisen , Shen Zhiwei , Wang Runrun
Published: April 2022

Background. Chemical exchange saturation transfer (CEST) is a novel imaging modality in clinical practice and scientific research. Angiopep-2 is an artificial peptide that can penetrate blood-brain barrier. The aim of this study was to explore the feasibility of Angiopep-2 serving as an exogenous CEST contrast. Methods. Phantoms of Angiopep-2 with different concentrations were prepared and then scanned using the 7.0T small animal MRI scanner. Different parameters including saturation powers and saturation duration were used to achieve the optimal CEST effect, and the optimal parameters were finally selected based on Z-spectra, asymmetric spectra, and phantom CEST imaging. CEST scanning of dimethyl sulfoxide (DMSO), the substance helping Angiopep-2 to be dissolved in water, was performed to exclude its contribution for the CEST effect. Results. A broad dip was observed from 2.5 to 3.5 ppm in the Z-spectra of Angiopep-2 phantoms. The most robust CEST was generated at 3.2 ppm when using formula (M–3.2ppm − M+3.2ppm)/M–3.2ppm. The CEST effect of Angiopep-2 was concentration dependent; the effect increased as the concentration increased. In addition, the CEST effect was more obvious as the saturation power increased and peaked at 5.5 µT, and the CEST effect increased as the saturation duration increased. DMSO showed nearly 0% of the CEST effect at 3.2 ppm. Conclusions. Our results demonstrate that Angiopep-2 can act as an excellent exogenous CEST contrast. As it can penetrate blood-brain barrier and bind amyloid-β protein, amyloid-β targeting CEST, with Angiopep-2 as an exogenous contrast agent, can be potentially used as a novel imaging modality for early diagnosis of Alzheimer’s disease. Collectively, Angiopep-2 may play a critical role in early diagnosis of Alzheimer’s disease.
Mechanical Strengthening of Lightweight Aluminium Alloys through Friction Stir Process
Authors: Yogesh P. , Shinde Santaji Krishna , C Shyamlal. , Suresh kumar R. , Rinawa Moti Lal , Puthilibai G. , Sudhakar M. , Negash Kassu , S Rajesh
Published: April 2022

The aerospace industries are focused on lightweighting with alloys having good tensile strength, fracture toughness, fatigue resistance, and corrosion resistance. The friction stir welding technology is one of the productive techniques in the aerospace industry to join such alloys with little ease. This paper deals with the composition of alloying elements that makes the structure lightweight and the impact of the precipitates evolved out of the selected alloying elements on the mechanical properties such as tensile strength and hardness of the joint in the aerospace alloys such as AA2xxx conventional aluminium alloys, AA2xxx lithium-based aluminium alloys, and AA7xxx aluminium alloys.
COVID-19 Induced Cardiomyopathy Successfully Treated with Tocilizumab
Authors: Schreiber Ariyon , Elango Kalaimani , Sossou Christoph , Fakhra Sadaf , Asad Shabada , Ahsan Chowdhury
Published: April 2022

Background. Currently, the literature regarding the management of COVID-19 induced cardiomyopathy with reduced ejection fraction is limited. In this case report, we present the first documented case of COVID-19 induced myocardial stunning leading to severely reduced LV systolic function that was reversed by the administration of corticosteroids and tocilizumab. Case Summary. A 39-year-old female with well controlled systemic hypertension, tested positive for SARS-CoV-2 RNA and underwent self-isolation for 14 days. Patient presented to our facility a month later with one-week history of progressively worsening generalized body aches, chills, fever, watery diarrhea, nausea with associated mild dry nonproductive cough, shortness of breath and nonspecific chest pain. Initial labs demonstrated that she was COVID-19 positive, elevated troponin (4.295 ng/ml), and elevated BNP (2,291 pg/ml). Her initial Transthoracic echocardiography demonstrated an Left ventricular ejection fraction (LVEF) of 20-25% with apical akinesis. After administration of tocilizumab and corticosteroids, patient demonstrated interval improvement with LVEF improving to 50-55% within days. Her labs confirmed these findings with improved troponin (0.858 ng/ml) and BNP (209 pg/ml). Discussion. This case demonstrates that it can be safe and efficacious to use tocilizumab and corticosteroids in patients with COVID-19 induced cardiomyopathy. These finding suggest that cytokine storm is the predominant mechanism by which COVID-19 induced cardiomyopathy occurs. Additional studies are required to determine the role of corticosteroids and tocilizumab in management of this condition.
Achtsamkeitsbasierte Interventionen für Menschen mit psychotischen Störungen: Ein Überblick über den Forschungsstand zur Wirksamkeit und Implikationen für die klinische Praxis
Authors: Böge Kerem , Catena Daniel , Hahn Eric
Published: April 2022

Achtsamkeitsbasierte Interventionen (AI) stellen mittlerweile eine zentrale Säule der dritten Welle der Kognitiven Verhaltenstherapie dar. In den letzten Jahren wurden AI bei Patient*innen mit psychotischen Störungen implementiert und deren Wirksamkeit im Rahmen von einer kleineren Anzahl von randomisiert-kontrollierten Studien (RCTs) gezeigt. Der vorliegende narrative Übersichtsartikel stellt den aktuellen Stand der Forschung zur Effektivität, sowie zentrale As­pekte der klinischen Anwendungen von AI bei der Behandlung von Patient*innen mit Schizophrenien und primären psychotischen Störungen dar. Aus aktuellen Metaanalysen lässt sich trotz der Heterogenität der Studienergebnisse schlussfolgern, dass AI im Rahmen von RCTs des Vergleichs einer Kontrollgruppe mit einer gewöhnlichen zumeist psychopharmakologischen Behandlung (treatment-as-usual, TAU) und in Prä-Post-Intervention Analysen zu einer Verbesserung der oft schwer zu behandelnden Negativsymptomatik (g = 0,56 und g = 0,75) oder Positivsymptomatik (g = 0,19 und g = 0,32) mit leichten bis großen Effektstärken führen können. Weiterhin wurden auch positive Effekte auf depressive und ängstliche Symptome (g = 0,20 und g = 0,43), sowie eine Reduktion der Rehospitalisierungsraten 12 Monate nach Entlassung und eine Verkürzung der stationä­ren Behandlungsdauer beobachtet. Im Gegensatz zur Therapieforschung aus dem Vereinigten Königreich, Australien oder Hong Kong befinden sich die wissenschaftliche Evaluation und Implementierung von achtsamkeitsbasierten Behandlungsmöglichkeiten im gesamten deutschsprachigen Raum noch in einem frühen Stadium.
Endothelial BACE1 Impairs Cerebral Small Vessels via Tight Junctions and eNOS
Authors: Zhou Haoyue , Gao Feng , Yang Xiaoli , Lin Tingting , Li Zhenxing , Wang Qiong , Yao Yang , Li Lei , Ding Xinxin , Shi Kaibin , Liu Qiang , Bao Hong , Long Zhenyu , Wu Zujun , Vassar Robert , Cheng Xin , Li Rena , Shen Yong
Published: April 2022

Background:

Cerebral small vessel injury, including loss of endothelial tight junctions, endothelial dysfunction, and blood-brain barrier breakdown, is an early and typical pathology for Alzheimer's disease, cerebral amyloid angiopathy, and hypertension-related cerebral small vessel disease. Whether there is a common mechanism contributing to these cerebrovascular alterations remains unclear. Studies have shown an elevation of BACE1 (β-site amyloid precursor protein cleaving enzyme 1) in cerebral vessels from cerebral amyloid angiopathy or Alzheimer's disease patients, suggesting that vascular BACE1 may involve in cerebral small vessel injury.

Methods:

To understand the contribution of vascular BACE1 to cerebrovascular impairments, we combined cellular and molecular techniques, mass spectrometry, immunostaining approaches, and functional testing to elucidate the potential pathological mechanisms.

Results:

We observe a 3.71-fold increase in BACE1 expression in the cerebral microvessels from patients with hypertension. Importantly, we discover that an endothelial tight junction protein, occludin, is a completely new substrate for endothelial BACE1. BACE1 cleaves occludin with full-length occludin reductions and occludin fragment productions. An excessive cleavage by elevated BACE1 induces membranal accumulation of caveolin-1 and subsequent caveolin-1-mediated endocytosis, resulting in lysosomal degradation of other tight junction proteins. Meanwhile, membranal caveolin-1 increases the binding to eNOS (endothelial nitric oxide synthase), together with raised circulating Aβ (β-amyloid peptides) produced by elevated BACE1, leading to an attenuation of eNOS activity and resultant endothelial dysfunction. Furthermore, the initial endothelial damage provokes chronic reduction of cerebral blood flow, blood-brain barrier leakage, microbleeds, tau hyperphosphorylation, synaptic loss, and cognitive impairment in endothelial-specific BACE1 transgenic mice. Conversely, inhibition of aberrant BACE1 activity ameliorates tight junction loss, endothelial dysfunction, and memory deficits.

Conclusions:

Our findings establish a novel and direct relationship between endothelial BACE1 and cerebral small vessel damage, indicating that abnormal elevation of endothelial BACE1 is a new mechanism for cerebral small vessel disease pathogenesis.