bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation and Evaluation of Animal Models of Cardiotoxicity in Antineoplastic Therapy
Authors: Meng Chenchen , Fan Lu , Wang Xiaoming , Wang Yunjiao , Li Yanyang , Pang Shuchao , Lv Shichao , Zhang Junping
Published: July 2022

The continuous development of antineoplastic therapy has significantly reduced the mortality of patients with malignant tumors, but its induced cardiotoxicity has become the primary cause of long-term death in patients with malignant tumors. However, the pathogenesis of cardiotoxicity of antineoplastic therapy is currently unknown, and practical means of prevention and treatment are lacking in clinical practice. Therefore, how to effectively prevent and treat cardiotoxicity while treating tumors is a major challenge. Animal models are important tools for studying cardiotoxicity in antitumor therapy and are of great importance in elucidating pathophysiological mechanisms and developing and evaluating modality drugs. In this paper, we summarize the existing animal models in antitumor therapeutic cardiotoxicity studies and evaluate the models by observing the macroscopic signs, echocardiography, and pathological morphology of the animals, aiming to provide a reference for subsequent experimental development and clinical application.
Visual Question Answering for Intelligent Interaction
Authors: Gao Panpan , Sun Hanxu , Chen Gang , Wang Ruiquan , Li Minggang
Published: July 2022

With the application of deep learning method in the field of image processing, the image-related intelligent interaction technology has also been rapidly developed. Visual question answering (VQA) collects the image information by asking questions related to the image and ultimately achieves the purpose for enriching the image understanding. Vision and language are the two core parts of human intelligence to understand the real world, and also the basic components to realize artificial intelligence, and a lot of research has been carried out in their respective fields. With the continuous promotion and application of deep learning in the fields of computer vision and natural language processing, visual question answering technology across the visual field and natural language disciplines has become a research hotspot in recent years. Visual question answering (VQA) for intelligent interaction collects image information by asking relevant questions to the content of the image and finally achieves the purpose of enriching image understanding. At the same time, as an emerging research direction, the challenges faced by the visual question answering system are huge, and we need to learn and excavate. Through the comprehensive comparison and analysis of the existing models and methods of visual question answering, this paper summarizes the shortcomings and development directions of the current research work and analyzes several models of visual question answering technology for the processing of image input and question input of the visual question answering model. The working principle of the model and the common public data set of the model: it is concluded that extending the structured knowledge base and applying mature technologies such as text question answering and natural language processing to deal with VQA problems are the future development directions of the VQA model.
Evaluation of College English Textbooks Based on Computer-Aided Analysis Corpus
Authors: Gu Yufang , Wu Wang , White Marvin , Aziz Haider , Liew Kwen
Published: July 2022

In order to improve college students’ perception and acceptance of college English textbooks and improve their professional English communication ability in their future careers, the application of corpus plays a guiding role in college English teaching reform and provides reliable resources for college English language research and learning. This study analyzes the college English textbooks in the corpus based on the comparison of conventional technology assistance and computer technology assistance. Through the comparative analysis of the coupling degree, corpus vocabulary, and students’ perception of teaching materials between conventional technology and computer technology, it can be seen that the evaluation of college English textbooks based on computer-aided analysis corpus is more in line with the needs of college students. College students’ learning ability and their English application ability are improved. The establishment of a corpus of college English teaching materials is of great significance to the research of college English teaching and also has a positive impact on college students’ learning English. With the help of computer technology, college English teaching materials can be closer to the diversified concept of university scholarship. Its content is more in line with the current social demand for talents, provides a better scheme for the cultivation of talents, and is conducive to the development of the country and society.
Classification Algorithms for Brain Magnetic Resonance Imaging Images of Patients with End‐Stage Renal Disease and Depression
Authors: Cheng Yan , Liao Tengwei , Jia Nailong
Published: July 2022

This study was aimed to explore the relationship between depression and brain function in patients with end‐stage renal disease (ESRD) complicated with depression based on brain magnetic resonance imaging (MRI) image classification algorithms. 30 people in the healthy control group and 70 people in the observation group were selected as the research objects. First, the preprocessing algorithms were applied on MRI images. With the depression classification algorithm based on deep learning, the features were extracted from the capsule network to construct a classification network, and the network structure was compared to obtain the difference in the distribution of brain lesions. Different classifiers and degree centrality, functional connection, low‐frequency amplitude ratio, and low‐frequency amplitude were selected to analyze the effectiveness of features. In the deep learning method, the neural network model was constructed, and feature extraction and classification network were carried out. The classification layer was based on the capsule network. The results showed that the correct rate of the deep learning feature extraction network structure combined with the capsule network classification was 82.47%, the recall rate was 83.69%, and the accuracy was 88.79%, showing that the capsule network can improve the heterogeneity of depression. The combination of fractional amplitude of low‐frequency fluctuation (fALFF), DC, and amplitude of low‐frequency fluctuation (ALFF) can achieve the accuracy of 100%. In summary, MRI images showed that patients with depression may have neurological abnormalities in the white matter area. In this study, the classification algorithm based on brain MRI images can effectively improve the classification performance.
The Global Transmission of Stock Market: A Spatial Analysis
Authors: Zhang Hong , Gao Xiaojie , Dong Keqiang
Published: July 2022

The stock markets, exhibiting complex self-correlation or cross-correlation over a broad range of time scales, are correlated not only in time but also in space. The conventional spatial weight matrix in the econometric analysis is short of economic relation between nonadjacent economic entities. Therefore, this paper applies the detrended cross-correlation analysis coefficient and partial correlation coefficient to analyze the global spatial interaction. This study computes the spatial Moran’s I value by the two types of weight matrix for the 15 typical stock indices around the world, to explore the spatial agglomeration phenomenon. Then, the Spatial Durbin Model is applied to investigate the transmission of the stock market. The result from the Moran’s I value indicates that the 15 typical stock indices are spatially correlated. The result of the Spatial Durbin Model gives the relationship among the closing price, the opening price, the highest price, and the lowest price.
Isolation and Characterization of Plant Growth-Promoting Rhizobacteria from Coffee Plantation Soils and Its Influence on Maize Growth
Authors: Waday Yasin Ahmed , Girma Aklilu Ermias , Bultum Mohammed Seid , Ramayya Ancha Venkata , Beyene Dejene
Published: July 2022

Plant growth-promoting rhizobacteria (PGPR) are an important bacterial resource as biofertilizers, which can promote plant growth and increase crop yields. In this study, isolation, characterization, and its effect on plant promotion were assessed by isolating PGPR using soil samples collected from Jimma, Ethiopia. Out of 10 isolates, three of them (JEC3, JEC4, and JEC7) exhibited PSB traits in Pikovskaya media by solubilizing phosphate and producing IAA. Of the three isolates, JEC4 recorded the maximum phosphate solubilization index (4.98), soluble phosphate (283 μg/ml), and IAA production (10.21 μg/ml). The findings of the isolates' morphological and biochemical tests showed that JEC3, JEC4, and JEC7 as Bacillus sp., Pseudomonas sp., and Enterobacter sp., respectively. The optimization of phosphate solubilization was done using different incubation times and sources of carbon and nitrogen. Furthermore, the isolate (JEC4) was tested for plant growth-promoting (PGP) activities and indicated the production of ammonia, hydrogen cyanide, and siderophore. JEC4 isolate showed a significant increase in sideways (%) seed germination, root and shoot length, fresh and dry weight of root, and shoot of maize in field experiments than the untreated ones. The results indicate that the JEC4 isolate can be developed as a biological fertilizer for promoting crop productivity and ecosystem dynamics.
Coleman Automorphisms of Some Metabelian Groups
Authors: Hai Jingjing , Li Yanxia , Ling Xian
Published: July 2022

In this study, the approach is through the projective limits, and we obtain some characterizations of the Coleman automorphism groups of a split metabelian group and a generalized dicyclic group. An application of our results is a generalization of the result of Z. Li and Y. Li.
Asymmetric Dimethylarginine Protects Neurons from Oxygen Glucose Deprivation Insult by Modulating Connexin-36 Expression
Authors: Fang Kun , Chen Shufen , Wang Yi , Chen Fangzhe , Cui Mei , Dong Qiang
Published: July 2022

Background. Asymmetric dimethylarginine (ADMA) is a nonselective nitric oxide synthase inhibitor. ADMA is thought to inhibit the production of nitric oxide (NO) by neurons after oxygen-glucose deprivation (OGD). The gap junction protein Connexin-36 (cx-36) is involved in the pathophysiology of stroke. We investigated whether ADMA could protect neurons from OGD insults by regulating the expression of cx-36. Methods. Cultured rat cortical neuronal cells were used. Neurons were treated with OGD with or without ADMA pretreatment. The lactate dehydrogenase (LDH) release rate was used to assess neuronal injury. Intracellular NO levels were determined using 4-amino-5-methylamino-2

′

,7

′

-difluorofluorescein diacetate. Western blotting was performed to detect cx-36 expression. Results. The LDH release rate increased in the supernatant of neurons after the OGD insult, whereas ADMA treatment reduced the LDH release rate. Intracellular NO levels increased following OGD treatment, and this increase was not inhibited by ADMA treatment. Expression of cx-36 was upregulated in neurons under OGD conditions, and treatment with ADMA downregulated the expression of cx-36. Conclusions. ADMA protects neurons from OGD insult, and cx-36 downregulation may be a possible pathway involved in ADMA-mediated neuronal protection.
Metabolic Effects of Recombinant Human Growth Hormone Replacement Therapy on Juvenile Patients after Craniopharyngioma Resection
Authors: Li Shuying , Wang Xi , Zhao Yaling , Nie Min , Ji Wen , Mao Jiangfeng , Wu Xueyan
Published: July 2022

Objective: To investigate the effect of short-term recombinant human growth hormone (rhGH) replacement therapy on metabolic parameters in juvenile patients following craniopharyngioma (CP) resection. Methods. This retrospective study included 42 cases of juvenile patients that had undergone CP resection in the Department of Endocrinology at the Peking Union Medical College Hospital, from April 2013 to August 2020. According to whether they received growth hormone replacement therapy, the patients were divided into either the growth hormone replacement therapy (GHRT) group (30 cases) or the control group (12 cases). Changes in body mass index (BMI), BMI z-score, transaminase activity, fasting blood glucose (FBG) levels, blood lipid profile, and high-sensitivity C-reactive protein (hsCRP) levels were evaluated after one year of GHRT treatment. Results. The average age of the GHRT group was 13.00 (8.00–14.00) years old and these patients had undergone a CP operation an average of 2.00 (1.62–3.15) years earlier. Prior to receiving GHRT treatment, they received appropriate doses of adrenocortical hormone and thyroid hormone replacement therapy. After one year of GHRT treatment, the average BMI z-score decreased from 1.60 ± 1.76 to 1.13 ± 1.73 (

P
=
0.005

). Alanine aminotransferase (ALT) activity decreased from 26.50 (17.00∼98.00) U/L to 18.00 (13.00∼26.48) U/L (

P
≤
0.001

), and similar changes were observed with regard to aspartate aminotransferase (AST) and glutamyl transferase (GGT) activity in the GHRT treatment group. The average total cholesterol (TC) decreased from 4.67 (4.10–6.14) mmol/L to 4.32 ± 0.85 mmol/L (

P
=
0.002

), and low-density lipoprotein (LDL) levels decreased from 3.05 ± 0.95 mmol/L to 2.56 ± 0.65 mmol/L (

P
=
0.001

) in the GHRT treatment group. The average blood urea nitrogen level decreased from 4.53 ± 1.09 mmol/L to 3.92 ± 0.82 mmol/L (

P
=
0.016

) and the average serum creatinine (SCr) level decreased from 55.59 ± 12.54 µmol/L to 51.15 ± 10.51 µmol/L (

P
=
0.005

) in the GHRT treatment group. The average hsCRP level decreased from 3.23 (1.79∼4.34) mg/L to 0.92 (0.42∼1.21) mg/L in the GHRT treatment group. In the control group, the average ALT activity increased from 26.58 ± 8.75 U/L to 42.58 ± 24.59 U/L (

P
=
0.039

), GGT activity increased from 19.0 (13.25–29.25) U/L to 25.00 (14.75–34.75) U/L (

P
=
0.026

), and LDL levels increased from 2.27 ± 0.76 mmol/L to 3.43 ± 1.28 mmol/L (

P
=
0.04

). Conclusion. GHRT treatment improves the metabolic parameters of juvenile patients that have undergone craniopharyngioma resection by reducing BMI z-scores, low-density lipoprotein, and hsCRP levels and improving liver function.
Identification of a Prognostic Transcriptome Signature for Hepatocellular Carcinoma with Lymph Node Metastasis
Authors: Ma Jie , Chen Xue-Qin , Xiang Zuo-Lin
Published: July 2022

Hepatocellular carcinoma (HCC) is one of the most aggressive malignant tumors, and the prognosis of HCC patients with lymph node metastasis (LNM) is poor. However, robust biomarkers for predicting the prognosis of HCC LNM are still lacking. This study used weighted gene coexpression network analysis of GSE28248 (

N
=
80

) microarray data to identify gene modules associated with HCC LNM and validated in GSE40367 dataset (

N
=
18

). The prognosis-related genes in the HCC LNM module were further screened based on the prognostic curves of 371 HCC samples from TCGA. We finally developed a prognostic signature, PSG-30, as a prognostic-related biomarker in HCC LNM. The HCC subtypes identified by PSG-30-based consensus clustering analysis showed significant differences in prognosis, clinicopathological stage, m6A modification, ferroptosis activation, and immune characteristics. In addition, RAD54B was selected by regression model as an independent risk factor affecting the prognosis of HCC patients with LNM, and its expression was significantly positively correlated with tumor mutational burden and microsatellite instability in high-risk subtypes. Patients with high RAD54B expression had a better prognosis in the immune checkpoint inhibitor-treated cohorts but had a poor prognosis in the HCC sorafenib-treated group. The association of high RAD54B expression with LNM in breast cancer (BRCA) and cholangiocarcinoma and its prognostic effect in BRCA LNM cases suggest the value of RAD54B at the pancancer level. In conclusion, PSG-30 can effectively identify HCC LNM population with poor prognosis, and high-risk patients with high RAD54B expression may be more suitable for immunotherapy.
Design and Implementation of Intelligent Control Garbage Bin
Authors: Tu Li-Fen , Peng Qi , Deng Rongpan
Published: July 2022

Aiming at the problem that it was difficult to popularize accurate garbage sorting and delivery, a kind of intelligent garbage bin that is more intelligent, efficient, and functional than the traditional garbage bin was designed and manufactured. The design was based on the STM32 minimum system implementation. The speech recognition module was used to receive the key words and identify which type of garbage the item belongs to. At the same time, a speech reminder was given, and the steering gear was driven to automatically open the corresponding type of garbage bin lid, and the sorting collection was realized. In addition, the ultrasonic distance measuring module was used to detect the residual capacity of the garbage bin in real time. When it was about to be full, the data would be sent to the background management system through the WIFI module to remind the staff to clean it up. The experimental results show that the intelligent garbage bin can effectively help people sort and put domestic garbage and prevent garbage overflow from affecting the living environment, so as to realize the service of science and technology for human beings.
CASC1 Expression in Bladder Cancer Is Regulated by Exosomal miRNA-150: A Comprehensive Pan-Cancer and Bioinformatics Study
Authors: Luo Huarong , Xu Chengdang , Ge Bujun , Wang Tianru
Published: July 2022

This study explored the role of cancer susceptibility 1 (CASC1) in tumorigenesis and development as well as the key pathways affecting bladder cancer progression. CASC1 was examined in various normal tissues in humans using the HPA database to quantify its expression level and subcellular localization. CASC1 is abundantly expressed in tumor tissues, primarily in cytoplasmic vesicles and stroma. TIMER2 was used to analyze the correlation between CASC1 expression levels and the types of infiltrates associated with immune cells and immunosuppressive cells. MDSC, Treg, M2, and CAF were significantly correlated with CASC1 expression in various tumors. Comparing patients with and without CASC1 mutation, those with CASC1 mutation had worse overall survival, progression-free survival, and disease-free survival. The correlation between has-miR-150 and CASC1 (for the case of bladder cancer) was then analyzed, and the related ceRNA network was mapped. A negative relationship between CASC1 expression and has-miR-150 expression was found in cases of bladder cancer. And the presence of miR-150-targeted CASC1 may be associated with bladder cancer progression. CASC1 is expressed at elevated levels in various tumor tissues, and it is associated with tumorigenesis and development. Exosomes containing miR-150-targeted CASC1 may affect the progression of bladder cancer.
ICEEMDAN-Based Transfer Entropy between Global Commodity Classes and African Equities
Authors: Bossman Ahmed , Agyei Samuel Kwaku
Published: July 2022

We examine the information transfer dynamics between global commodity and African equity markets to test their efficiency levels in a denoised transfer entropy approach. Our findings in the short- and medium-term scales lend support to the alternative hypothesis of market efficiency, whereas the transfer entropies at the long-term scale lend support to the efficient market hypothesis and the long-term market efficiency. Investing in a single commodity results in high uncertainty when the return pattern (history) of African equities is acknowledged. Similarly, investing in any single African equity results in high return uncertainty whilst accounting for the history of commodity markets’ returns. Short-term traders could monitor the loopholes in the market efficiency levels between global commodities and African equities to take advantage of arbitrage when needed, whilst long-term investors are assured of efficient market dynamics between global commodity markets and African equities. Regulation of markets may need to strategically incorporate news items as they fall due to either market.
Activation of the P62-Keap1-NRF2 Pathway Protects against Ferroptosis in Radiation-Induced Lung Injury
Authors: Li Xuan , Chen Jingyao , Yuan Sujuan , Zhuang Xibing , Qiao Tiankui
Published: July 2022

Radiation-induced lung injury (RILI) is one of the most common, serious, and dose-limiting toxicities of thoracic radiotherapy. A primary cause for this is the radiation-induced cell death. Ferroptosis is a recently recognized form of regulated cell death, characterized by the accumulation of lipid peroxidation products and lethal reactive oxygen species (ROS). The ROS generated by irradiation might be the original trigger of ferroptosis in RILI. In addition, activation of the P62-Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (NRF2) pathway has been shown to blunt ferroptosis and thus acts as a protective factor. Therefore, this study aimed to explore the protective effect of the P62-Keap1-NRF2 pathway against radiation-induced ferroptosis in alveolar epithelial cells. First, we found that radiation induced ferroptosis in vitro using a RILI cell model, which could be significantly reduced by ferrostatin-1 (Fer-1), a specific ferroptosis inhibitor. Additionally, overexpression of P62 interacted with Keap1 to facilitate the translocation of NRF2 into the nucleus and promote the expression of its target proteins, including quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO1), and ferritin heavy chain 1 (FTH1). In summary, our results demonstrated that the activation of the P62-Keap1-NRF2 pathway prevents radiation-induced ferroptosis in RILI cells, providing a theoretical basis of finding a potential therapeutic approach for RILI.
Stochastic Evolutionary Game in Food Takeaway Management with Improved Replication Dynamic Equations in Postepidemic Era
Authors: Zhang Ying , Zhu Haojie
Published: July 2022

The rapid growth of the food takeaway industry during COVID-19 raises a claim to its quality improvement, especially the hygiene condition. In the takeaway chain, the food takeaway platforms, the restaurants, and the distributors are responsible for food hygiene. Accordingly, this study employs an evolutionary game to study the takeaway management among them. It constructs their traditional replication dynamic equations after parameter design. Then, it improves the equations by introducing the incentive relationships and interference factors. Through the equations, it analyzes and simulates the stochastic evolution process of the three parties, exploring the influence of some parameters’ numerical changes. After that, it concludes that the proportional expenditure coefficient for illegal rectification, the incentive coefficient, the interference intensity coefficient, and the step size can impact the efficiency, the results, or the fluctuations in the evolution, obtaining methods to theoretically control the evolution. Based on that, it puts forward targeted suggestions for constructing the contract mechanism of the takeaway, which provides a reference for the management of food takeaways practically in the postepidemic era.
On Pseudo‐contractibility and Ultra Central Approximate Identity of Some Semigroup Algebras
Authors: Sahami Amir , Shariati Seyedeh Fatemeh
Published: July 2022

In this paper, we investigate the existence of an ultra central approximate identity for a Banach algebra A and its second dual A∗∗. Also, we prove that for a left cancellative regular semigroup S, ℓ1(S)∗∗ has an ultra central approximate identity if and only if S is a group. As an application, we show that for a left cancellative semigroup S, ℓ1(S)∗∗ is pseudo‐contractible if and only if S is a finite group. We also study this property for φ‐Lau product Banach algebras and the module extension Banach algebras.
[Retracted] Effects of Acupuncture Combined with Biofeedback Therapy on Limb Motor Rehabilitation in Patients with Acute Stroke: Systematic Review and Meta‐Analysis
Authors: Song Xinrong , Zhang Xiaoge , Weng Yan , Liu Yu , Shan Qi , Chen Wenna , Ma Wanwan , Dong Qi , Qu Dandan , Guo Yibo , Xiong Jie , Deng Fuhua , Fu Qizhi , Xin Yufu
Published: July 2022

Objective. The purpose of the systematic review is to verify the effect of biofeedback therapy on limb motor rehabilitation in patients with acute stroke and to provide evidence‐based medicine for the promotion and use of biofeedback therapy. Methods. The randomized controlled trials (RCT) of biofeedback therapy in the treatment of cerebral palsy were searched in PubMed, EMBASE, ScienceDirect, Cochrane Library, China National Knowledge Infrastructure (CNKI), China VIP Database, Wanfang Database, and Chinese Biomedical Literature Database (CBM). The starting time and ending time of this study are from the time of building the database of the number of pieces to October 31, 2018. The data included in this study were extracted by two independent researchers and evaluated the bias risk of all the literature included in the study according to the Cochrane manual 5.1.0 criteria. RevMan5.4 statistical software was used to analyze the collected data by meta. Results. This systematic review included 9 RCT studies with a total of 1410 patients. The results of meta‐analysis showed that there were significant differences in the improvement of lower limb muscle tension, comprehensive spasm scale score, EMG score, and passive range of motion of ankle joint between biofeedback therapy and routine rehabilitation therapy. Conclusion. Biofeedback therapy can improve lower limb muscle tension, spasticity, EMG integral value, and passive range of motion of ankle joint in children with cerebral palsy and provide better conditions for improving the motor ability of lower extremities in children with cerebral palsy. However, more studies and follow‐up with higher methodological quality and longer intervention time are needed to further verify.
Topological Descriptors for the Metal Organic Network and Its Structural Properties
Authors: Ahmad Ali , Elahi Kashif , Azeem Muhammad , Swaray Senesie , Asim Muhammad Ahsan
Published: July 2022

Metal organic structures and networks are extensively studied in modern chemistry. These networks are extremely adaptable and useful in a variety of fields. Metal organic networks are thought to be the home of gases, and this structure is also engaged in gas purification and separation. The fact that they have so much utility and applicability stems from that they have so many distinct properties, such as exchanging ions and altering organic ligands. This structure’s chemical and physical properties are considered. There are extensive, time‐consuming, and costly experiments available to investigate these physical and chemical properties. To avoid these complex experiments and tests, a mathematical study provides approximate details of these chemical and physical behaviors of a structure, which is known as topological descriptors. In this work, we discussed the metal organic network’s line graph and studied the structural properties of the resulted network with the help of topological descriptors.
Sustained Oncogenic Signaling in the Cytostatic State Enables Targeting of Nonproliferating Persistent Cancer Cells
Authors: Kim Lisa M. , Kim Paul Y. , Gebreyohannes Yemarshet K. , Leung Cheuk T.
Published: July 2022

Many advanced therapeutics possess cytostatic properties that suppress cancer cell growth without directly inducing death. Treatment-induced cytostatic cancer cells can persist and constitute a reservoir from which recurrent growth and resistant clones can develop. Current management approaches primarily comprise maintenance and monitoring because strategies for targeting nonproliferating cancer cells have been elusive. Here, we used targeted therapy paradigms and engineered cytostatic states to explore therapeutic opportunities for depleting treatment-mediated cytostatic cancer cells. Sustained oncogenic AKT signaling was common, while nonessential, in treatment-mediated cytostatic cancer cells harboring PI3K-pathway mutations, which are associated with cancer recurrence. Engineering oncogenic signals in quiescent mammary organotypic models showed that sustained, aberrant activation of AKT sensitized cytostatic epithelial cells to proteasome inhibition. Mechanistically, sustained AKT signaling altered cytostatic state homeostasis and promoted an oxidative and proteotoxic environment, which imposed an increased proteasome dependency for maintaining cell viability. Under cytostatic conditions, inhibition of the proteasome selectively induced apoptosis in the population with aberrant AKT activation compared with normal cells. Therapeutically exploiting this AKT-driven proteasome vulnerability was effective in depleting treatment-mediated cytostatic cancer cells independent of breast cancer subtype, epithelial origin, and cytostatic agent. Moreover, transient targeting during cytostatic treatment conditions was sufficient to reduce recurrent tumor growth in spheroid and mouse models. This work identified an AKT-driven proteasome-vulnerability that enables depletion of persistent cytostatic cancer cells harboring PTEN–PI3K pathway mutations, revealing a viable strategy for targeting nonproliferating persistent cancer cell populations before drug resistance emerges.

Significance:

This study finds that sustained oncogenic signaling in therapy-induced cytostatic cancer cells confers targetable vulnerabilities to deplete persistent cancer cell populations and reduce cancer recurrence.
CDK4/6 Inhibition Enhances Oncolytic Virus Efficacy by Potentiating Tumor-Selective Cell Killing and T-cell Activation in Refractory Glioblastoma
Authors: Xiao Jingshu , Liang Jiaming , Fan Junjie , Hou Panpan , Li Xiaodong , Zhang Haipeng , Li Kai , Bu Lang , Li Ping , He Miao , Zhong Yongheng , Guo Liping , Jia Penghui , Xiao Qiaoqiao , Wu Junyu , Peng Hong , Li Chunmei , Xing Fan , Guo Deyin
Published: July 2022

Glioblastoma (GBM) is among the most aggressive human cancers. Although oncolytic virus (OV) therapy has been proposed as a potential approach to treat GBM, it frequently fails because GBM cells are usually nonpermissive to OV. Here, we describe a dual-step drug screen for identifying chemical enhancers of OV in GBM. From a high-throughput screen of 1416 FDA-approved drugs, an inhibitor of CDK4/6 was identified as the top enhancer, selectively increasing potency of two OV strains, VSVΔ51 and Zika virus. Mechanistically, CDK4/6 inhibition promoted autophagic degradation of MAVS, resulting in impaired antiviral responses and enhanced tumor-selective replication of VSVΔ51 in vitro and in vivo. CDK4/6 inhibition cooperated with VSVΔ51 to induce severe DNA damage stress and amplify oncolysis. In GBM xenograft models, combined treatment with CDK4/6 inhibitor and VSVΔ51 significantly inhibited tumor growth and prolonged the survival of tumor-bearing mice. Further investigation revealed that CDK4/6 inhibitor and VSVΔ51 synergistically induced immunogenic cell death and boosted antitumor immunity. Together, this study features a promising approach of treating aggressive GBM through the combination of CDK4/6 inhibitor with OV.

Significance:

This study proposes inhibition of cyclin-dependent kinases as a clinically translatable combinatorial strategy to enhance the efficacy of oncolytic virotherapy in GBM.
Association between Body Mass Index and Risk of Gastric Cancer by Anatomic and Histologic Subtypes in Over 500,000 East and Southeast Asian Cohort Participants
Authors: Jang Jieun , Lee Sangjun , Ko Kwang-Pil , Abe Sarah K. , Rahman Md. Shafiur , Saito Eiko , Islam Md. Rashedul , Sawada Norie , Shu Xiao-Ou , Koh Woon-Puay , Sadakane Atsuko , Tsuji Ichiro , Kim Jeongseon , Oze Isao , Nagata Chisato , Tsugane Shoichiro , Cai Hui , Yuan Jian-Min , Gao Yu-Tang , Ozasa Kotaro , Matsuyama Sanae , Kanemura Seiki , Shin Aesun , Ito Hidemi , Wada Keiko , Sugawara Yumi , Chen Yu , Ahsan Habibul , Boffetta Paolo , Chia Kee Seng , Matsuo Keitaro , Qiao You-Lin , Rothman Nathaniel , Zheng Wei , Inoue Manami , Kang Daehee , Park Sue K.
Published: July 2022

Background:

This study was performed to investigate the association between body mass index (BMI) and gastric cancer in East and Southeast Asia where most of gastric cancer is non-cardia gastric cancer.

Methods:

On the basis of 8,997 gastric cancer cases among the Asia Cohort Consortium participants from China, Japan, Korea, and Singapore (N = 538,835), we assessed gastric cancer risk according to BMI by calculating hazard ratios (HR) and 95% confidence intervals (CI) using the Cox proportional hazard regression model.

Results:

A U-shaped associations between BMI and gastric cancer risk were observed. Gastric cancer risks in underweight group (<18.5 kg/m2) and in obesity group (≥27.5 kg/m2) were higher than reference BMI group (23–24.9 kg/m2; HR, 1.15; 95% CI, 1.05–1.25 for underweight; HR, 1.12; 95% CI, 1.03–1.22 for obesity, respectively). The associations of underweight and obesity with gastric cancer risk were consistent in the analyses for non-cardia gastric cancer, intestinal-type gastric cancer, and late-onset gastric cancer. No significant association of underweight and obesity with the risk of cardia gastric cancer, diffuse-type gastric cancer, and early-onset gastric cancer was observed. In addition, we found that the U-shaped association between BMI and gastric cancer risk remained in nonsmokers, while only underweight was related to increased gastric cancer risk in smokers.

Conclusions:

BMI has a U-shaped association with gastric cancer risk in East and Southeast Asian population, especially for the non-cardia gastric cancer, intestinal-type gastric cancer, and late-onset gastric cancer.

Impact:

Future studies with consideration of anatomic location and histology of gastric cancer are needed to establish the association of underweight as well as obesity with gastric cancer risk.
Targeting Ferroptosis Vulnerability in Synovial Sarcoma: Is It All About ME1?
Authors: Subbiah Vivek , Gan Boyi
Published: July 2022

Understanding metabolic dependencies and their therapeutic vulnerabilities is key to precision oncology. Malic enzyme 1 (ME1) is frequently overexpressed in cancers with protumorigenic effects. In contrast, consistent loss of ME1 expression in synovial sarcoma compared with other sarcomas indicates a unique ferroptosis liability for precision therapy in this form of cancer.

See related article by Brashears et al., p. 3573
The Combination of Radiotherapy and Complement C3a Inhibition Potentiates Natural Killer cell Functions Against Pancreatic Cancer
Authors: Sodji Quaovi H. , Nambiar Dhanya K. , Viswanathan Vignesh , von Eyben Rie , Colburg Deana , Binkley Michael S. , Li Caiyun G. , Olcina Monica M. , Chang Daniel T. , Le Quynh-Thu , Giaccia Amato J.
Published: July 2022

Pancreatic cancer is one of the deadliest cancers, against which current immunotherapy strategies are not effective. Herein, we analyzed the immune cell composition of the tumor microenvironment of pancreatic cancer samples in The Cancer Genome Atlas and found that the presence of intratumoral natural killer (NK) cells correlates with survival. Subsequent analysis also indicated that NK cell exclusion from the microenvironment is found in a high percentage of clinical pancreatic cancers and in preclinical models of pancreatic cancer. Mechanistically, NK cell exclusion is regulated in part by complement C3a and its receptor signaling. Inhibition of the C3a receptor enhances NK cell infiltration in syngeneic mouse models of pancreatic cancer resulting in tumor growth delay. However, tumor growth inhibition mediated by NK cells is not sufficient alone for complete tumor regression, but is potentiated when combined with radiotherapy. Our findings indicate that although C3a inhibition is a promising approach to enhance NK cell–based immunotherapy against pancreatic cancer, its combination with radiotherapy holds greater therapeutic benefit.

Significance:

Immunotherapeutic agents are not effective against pancreatic cancer. We show that the inhibition of complement C3a enhances NK cell infiltration in preclinical models of pancreatic cancer, resulting in tumor growth delay. This effect is further potentiated by radiotherapy, thereby leading to significant antitumor activity compared with either therapy alone.
The Molecular Basis of 5α-Reductase Type 2 Deficiency
Authors: Batista Rafael L. , Mendonca Berenice B.
Published: July 2022

The 5α-reductase type 2 enzyme catalyzes the conversion of testosterone into dihydrotestosterone, playing a crucial role in male development. This enzyme is encoded by the SRD5A2 gene, which maps to chromosome 2 (2p23), consists of 5 exons and 4 introns, and encodes a 254 amino acid protein. Disruptions in this gene are the molecular etiology of a subgroup of differences of sex development (DSD) in 46,XY patients. Affected individuals present a large range of external genitalia undervirilization, ranging from almost typically female external genitalia to predominantly typically male external genitalia with minimal undervirilization, including isolated micropenis. This is an updated review of the implication of the SRD5A2 gene in 5α-reductase type 2 enzyme deficiency. For that, we identified 451 cases from 48 countries of this particular 46,XY DSD from the literature with reported variants in the SRD5A2 gene. Herein, we present the SRD5A2 mutational profile, the SRD5A2 polymorphisms, and the functional studies related to SRD5A2 variants to detail the molecular etiology of this condition.
Lung Ultrasound Scores Progress Differently in Extreme and Very Preterm Infants after Birth: A Multicentre Prospective Study
Authors: Alonso-Ojembarrena Almudena , Montero-Gato Jon , Gregorio-Hernández Rebeca , Aldecoa-Bilbao Victoria , Alonso-Quintela Paula , Rodriguez-Fanjul Javier , Concheiro-Guisán Ana , Trujillo-Fagundo Alberto , García-Ojanguren Ana María , de las Heras-Martín Mónica , Pérez-Pérez Alba , Teresa-Palacio Marta , Durán-Fernández-Feijóo Cristina , Morales-Arandojo Patricia , Pumarada-Prieto Marcelino , Oulego-Erroz Ignacio
Published: July 2022

Introduction: The lung ultrasound score (LUS) has been suggested to predict moderate-severe bronchopulmonary dysplasia (msBPD) in preterm infants. We aimed to assess LUS evolution after birth in preterm infants and the effect of gestational age. Methods: This multicentre prospective observational study was performed with newborns born before 33 weeks of gestation. We created two groups: group 1 (23–27 weeks) and group 2 (28–32 weeks). We compared LUSs between the groups from birth until 36 weeks of postmenstrual age, and we estimated the LUS evolution in each group with a linear multilevel mixed-effects regression model. The effects of the need for surfactant or an msBPD diagnosis were also studied. Results: We included 339 patients: 122 (36%) in group 1 and 217 (64%) in group 2. The infants in group 1 showed a steady progression in the LUS from birth until 4 weeks of age and a subsequent decrease; the infants in group 2 showed a progressive decrease in the LUS throughout the study. This progression varied significantly in the first weeks of life in infants who required surfactant at birth and after the first week of life in the patients diagnosed with msBPD. Discussion/Conclusions: Extremely preterm infants showed persistently high LUSs during the first weeks of life, regardless of the progression to msBPD. In this group, the infants who did not require surfactant at birth exhibited an increase in their LUSs after the first week until their values were equal to the remaining infants in their group.
A New Procedure for Guidewire Exchange of Tunneled Hemodialysis Catheters in Chronic Hemodialysis Patients: A Pilot Study
Authors: Leclaire Chanael , Lobbedez Thierry , Henri Patrick , Lanot Antoine , Gautier Nicolas , Béchade Clémence , Ficheux Maxence
Published: July 2022

Introduction: Different techniques of guidewire exchange of tunneled catheters for hemodialysis (HD) have been reported. This study was carried out to assess the feasibility of a new procedure in chronic HD patients who needed catheter exchange because of mechanical dysfunction. Methods: The guidewire exchange method was based on the creation of a new exit site and a new subcutaneous tunnel while using the same venous insertion site. This was a retrospective study of exchanged tunneled catheters because of mechanical complications in patients on chronic HD between June 1, 2015, and December 31, 2019. The feasibility of the procedure was defined by successful exchange and catheter patency at 6 months. Catheter survival and immediate complications were reported. Results: A total of 49 procedures were performed in 34 HD patients. There was no catheter insertion failure. At 6 months, 6 catheters have lost their patency because of a mechanical complication. Thus, the success rate of the procedure was 43/49 (87.8%). Catheter survival censored on death, transplantation, or vascular access creation was 97.8% at 90 days, 86.2% at 180 days, and 74.5% at 1 year. The median catheter survival was 10.2 months. Among the 49 procedures, there were 9 hematomas at the insertion site that did not require surgical intervention. Discussion/Conlusion: Our study shows that guidewire exchange of a tunneled HD catheter by creating a new exit site and a new subcutaneous tunnel by using the same venous access is a newer method in chronic HD patients. This procedure should not be used in patients with coagulation issues. Additional studies are needed to compare the different methods of HD catheter exchange.
Nintedanib bei SSc-ILD
Authors: Xanthouli Panagiota
Published: July 2022

Systemic sclerosis-associated interstitial lung disease (SSc-ILD) is a rare disease with a progressive nature, eventually leading to lung fibrosis. Nintedanib, a tyrosine kinase inhibitor, is a widely accepted drug for treating idiopathic pulmonary fibrosis (IPF), a disease that shares some similarities with SSc-ILD regarding pathological disease processes. In this review, we aim to discuss the pathogenesis of SSc-ILD and the overall role of nintedanib in the management of SSc-ILD. SSc-ILD involves multiple pathological mediators contributing to various pathways that ultimately cause lung fibrosis. The pathogenesis of SSc-ILD is a complex phenomenon and still needs further study. Nintedanib has demonstrated its efficacy in the treatment of SSc-ILD by reducing the progression of the pathological process. It has also proven its clinical significance in the management of SSc-ILD. However, the currently available literature does not have any evidence to compare the effectiveness of nintedanib with the already available treatment modalities such as cyclophosphamide (CYC), mycophenolate mofetil (MMF), and azathioprine (AZT). The current literature also lacks information about nintedanib's long-term consequences on patients with SSc-ILD. Therefore, to create better evidence-based treatment guidelines, we recommend that researchers conduct randomized clinical trials comparing nintedanib to MMF, CYC, AZT, etc., and continue surveillance to explore the long-term consequences of nintedanib.
Quercetin and Osteoarthritis: A Mechanistic Review on the Present Documents
Authors: Samadi Faezeh , Kahrizi Mohammad Saeed , Heydari Fateme , Arefnezhad Reza , Roghani-Shahraki Hossein , Mokhtari Ardekani Abnoos , Rezaei-Tazangi Fatemeh
Published: July 2022

Background: Osteoarthritis (OA), as one of the chronic debilitating conditions, affects 15% of people globally and is linked with serious problems, such as cardiovascular diseases, metabolic syndrome, and autoimmune inflammatory disorders. The current therapeutic options for this disease include nonsteroidal anti-inflammatory drugs, surgery, gene therapy, intrasynovial gel injection, and warm needle penetration. However, these approaches may be accompanied by considerable side effects, high costs, and some limitations for patients. Thus, using an alternative way is needed. Summary: Presently, natural compounds based-therapies, like flavonoids, have acquired much attention in the current era. One of the compounds belonging to the flavonoid family is quercetin, and its therapeutic effects on disorders related to joints and cartilage have been addressed in vivo and in vitro studies. Key Messages: In this review, we summarized evidence indicating its curative capacity against OA with a mechanistic insight.
Distribution of the Clinical Manifestations of Alpha 1 Antitrypsin Deficiency in Respiratory Outpatients from an Area of Northern Italy
Authors: Aiello Marina , Marchi Laura , Ferrarotti Ilaria , Frizzelli Annalisa , Pisi Roberta , Calzetta Luigino , Manari Gaia , Pelà Giovanna , Russo Annalisa , Minerba Roberta , Aloe Rosalia , Ranzieri Silvia , Corradi Massimo , Chetta Alfredo
Published: July 2022

Background: Alpha 1 antitrypsin deficiency (AATD) is an autosomal codominant genetic condition that affects Caucasians of the European population due to the presence of a deficient allele of the SERPINA1 gene. A frequency of about 1/5,000 individuals has been estimated in Italy. Objectives: The aim of the study was to evaluate the distribution of the clinical manifestations of severe and intermediate genetic AATD in the geographic area around Parma in Northern Italy. Method: 238 subjects were submitted to molecular analysis of the SERPINA1 gene, and data on anthropometric variables, smoking habits, number of packs per year, AAT serum concentration, and clinical manifestations were recorded and presented as mean ± SD or median values (1st quartile; 3rd quartile). Results: The results show a distribution of genetic AATD of 4.1% of the screened population in the area encompassing the city of Parma. PI*MS and PI*MZ were the most common genotypes at 40.9% and 28.2% of the population with genetic AATD, and asthma and emphysema were the most represented clinical manifestations. Conclusion: Our study allowed to increase the knowledge of the distribution of genetic AATD in Northern Italy providing information regarding frequencies of genotypes and clinical manifestations of the disorder.
Fetal Echocardiographic Predictors of Postnatal Surgical Strategies in Critical Pulmonary Stenosis or Atresia with Intact Ventricular Septum: A Meta-Analysis
Authors: Shivaram Pushpa , Van den Eynde Jef , Barnes Benjamin T. , Danford David A. , Cedars Ari , Kutty Shelby
Published: July 2022

Background: Critical pulmonary stenosis or atresia with intact ventricular septum (PSAIVS) may be managed either by biventricular repair or univentricular palliation. This systematic review and meta-analysis aimed to synthesize the evidence for the role of fetal echocardiography in predicting the postnatal treatment pathway. Methods: PubMed/MEDLINE, CINHAL, Cochrane Library, Academic Search Complete, Web of Science, and Trip Pro were searched for observational studies published before July 2021. Random-effects meta-analysis was performed to identify factors associated with biventricular repair. Results: Eleven individual studies published between 2006 and 2021, including a total of 285 participants (159 biventricular repair; 126 univentricular palliation), met our eligibility criteria. The pooled estimated prevalence of biventricular repair among patients with PSAIVS was 55.6% (95% confidence interval 48.5–62.5%). Those who underwent biventricular repair had greater right to left ventricle and tricuspid to mitral valve dimension ratios, greater TV z score, and longer TV inflow duration/cardiac cycle length by fetal echocardiography. They were also more likely to have significant tricuspid regurgitation and less likely to have ventriculo-coronary connections (VCCs). Conclusions: Commonly obtained fetal echocardiographic measurements have strong associations with treatment pathway choice for patients with PSAIVS. Greater RV growth appears to favor biventricular repair, whereas patients with VCC almost invariably undergo univentricular palliation. Future studies should aim to establish how these fetal echocardiographic parameters might predict outcomes for the two treatment pathways.