bluuebunny/crossref_metadata_2025 huggingface dataset:
[Retracted] ROS Signaling‐Mediated Novel Biological Targets: Brf1 and RNA Pol III Genes
Authors: Zheng Liling , Lin Yongluan , Zhong Shuping
Published: October 2021

Biomolecule metabolism produces ROS (reactive oxygen species) under physiological and pathophysiological conditions. Dietary factors (alcohol) and carcinogens (EGF, DEN, and MNNG) also induce the release of ROS. ROS often causes cell stress and tissue injury, eventually resulting in disorders or diseases of the body through different signaling pathways. Normal metabolism of protein is critically important to maintain cellular function and body health. Brf1 (transcript factor II B‐related factor 1) and its target genes, RNA Pol III genes (RNA polymerase III‐dependent genes), control the process of protein synthesis. Studies have demonstrated that the deregulation of Brf1 and its target genes is tightly linked to cell proliferation, cell transformation, tumor development, and human cancers, while alcohol, EGF, DEN, and MNNG are able to induce the deregulation of these genes through different signaling pathways. Therefore, it is very important to emphasize the roles of these signaling events mediating the processes of Brf1 and RNA Pol III gene transcription. In the present paper, we mainly summarize our studies on signaling events which mediate the deregulation of these genes in the past dozen years. These studies indicate that Brf1 and RNA Pol III genes are novel biological targets of ROS.
Products of Toeplitz Operators on the 2-Analytic Bergman Space
Authors: Zhang Bo , Yang Yixin , Lu Yufeng
Published: October 2021

Let

f

and

g

be bounded functions, and let

T

f

and

T

g

be Toeplitz operators on

A

2

2

D

. We show that if the product

T

f

T

g

equals zero and one of

f

and

g

is a radial function satisfying a Mellin transform condition, then the other function must be zero.
Multiattribute Decision-Making Problems in terms of the Weighted Mean Operation of Two Aggregation Operators of Orthopair Z-Numbers
Authors: Zhao Mailing , Ye Jun
Published: October 2021

The Z number defined by Zadeh can depict the fuzzy restriction/value and reliability measure by an ordered pair of fuzzy values to strengthen the reliability of the fuzzy restriction/value. However, there exist truth and falsehood Z-numbers in real life. Thus, the Z number cannot reflect both. To indicate both, this study presents an orthopair Z-number (OZN) set to depict truth and falsehood values (intuitionistic fuzzy values) and their reliability levels in uncertain and incomplete cases. Next, we define the operations, score and accuracy functions, and sorting rules of OZNs. Further, the OZN weighted arithmetic mean (OZNWAM) and OZN weighted geometric mean (OZNWGM) operators are proposed based on the operations of OZNs. According to the weighted mean operation of the OZNWAM and OZNWGM operators, a multiattribute decision-making (MADM) model is established in the case of OZNs. Lastly, a numerical example is presented to reflect the flexibility and rationality of the presented MADM model. Comparative analysis indicates that the presented MADM model can indicate its superiority in the reliability and flexibility of decision results. Meanwhile, the resulting advantage of this study is that the presented MADM model can strengthen the reliability level of orthopair fuzzy values and make the decision results more reliable and flexible.
Effect of Acupuncture on Simple Obesity and Serum Levels of Prostaglandin E and Leptin in Sprague-Dawley Rats
Authors: Li Xiaomin , Wu Zijian , Chen Yenong , Cai Ronglin , Wang Zhizhen
Published: October 2021

Aim. The study is aimed at investigating the curative effect of acupuncture on simple obesity and its influence on serum levels of prostaglandin E and leptin in Sprague-Dawley (SD) rats. Methods. In the study, there are 50 male SD rats. We took 10 as healthy controls and fed 40 with a diet of high fat for 8 weeks. After the 40 rat model was established successfully, we fed 10 rats in the model group with a normal diet and treated 10 rats in the acupuncture group by acupuncture. During the experiment, the body fat and body length of rats were measured weekly, and Lee’s index was calculated. After the treatment, the levels of leptin, prostaglandin E, C-reactive protein (CRP), triacylglycerol (TG), cholesterol (CHO), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were detected, and the liver fat morphology was observed by electron microscope. Results. Acupuncture significantly downregulated the serum levels of CRP, TG, CHO, LDL, leptin, and prostaglandin E and upregulated the serum levels of HDL in rats with simple obesity. Conclusion. On basis of these results, it was found that acupuncture could boost fat metabolism and weight loss by inhibiting the production of leptin and prostaglandin E.
SCMAG: A Semisupervised Single-Cell Clustering Method Based on Matrix Aggregation Graph Convolutional Neural Network
Authors: Peng Haonan , Fan Wei , Fang Chujie , Gao Wenliang , Li Yuanyuan
Published: October 2021

Clustering analysis is one of the most important technologies for single-cell data mining. It is widely used in the division of different gene sequences, the identification of functional genes, and the detection of new cell types. Although the traditional unsupervised clustering method does not require label data, the distribution of the original data, the setting of hyperparameters, and other factors all affect the effectiveness of the clustering algorithm. While in some cases the type of some cells is known, it is hoped to achieve high accuracy if the prior information about those cells is utilized sufficiently. In this study, we propose SCMAG (a semisupervised single-cell clustering method based on a matrix aggregation graph convolutional neural network) that takes into full consideration the prior information for single-cell data. To evaluate the performance of the proposed semisupervised clustering method, we test on different single-cell datasets and compare with the current semisupervised clustering algorithm in recognizing cell types on various real scRNA-seq data; the results show that it is a more accurate and significant model.
Fracture Analysis and Fatigue Strength Calculation of Anchor Bolt Used in Circulating Water Pump in Nuclear Power Plant
Authors: Chen Qiang , Zu Shuai , Che Yinhui , Feng Dongxiong , Li Yang
Published: October 2021

A circulating water pump is a key equipment of cooling systems in nuclear power plants. Several anchor bolts were broken at the inlet rings of the same type of pumps. The bolts were turned by a special material for seawater corrosion protection. There were obvious turning tool marks at the root of the thread, which was considered as the source of the crack. The fatigue crack extended to the depth of the bolt, causing obvious radiation stripes on the fracture surface, which was a typical fatigue fracture. Obvious overtightening characteristics were found at the head of the broken bolt. Fracture and energy spectrum analysis showed that the bolt was not corroded. The axial vibration of the pump was measured. The static tensile stress along the bolt axis caused by the preload, the axial tensile stress caused by the axial vibration, and the torsional stress were calculated, respectively. According to the fatigue strength theory, the composite safety factor of the bolt fatigue strength was 1.37 when overtightening at 1.2 times the design torque, which was less than the allowable safety factor of 1.5-1.8, so the bolt was not safe, which further verified the conclusion of fracture analysis. The reason for the low safety factor was caused by the overtightening force. The improvement method was to control the bolt preload or increasing the bolt diameter.
Identification of the Molecular Subgroups in Idiopathic Pulmonary Fibrosis by Gene Expression Profiles
Authors: Zhang Ning , Guo Yali , Wu Cong , Jiang Bohan , Wang Yuguang
Published: October 2021

Background. Idiopathic Pulmonary Fibrosis (IPF) is one of the most common idiopathic interstitial pneumonia, which can occur all over the world. The median survival time of patients is about 3-5 years, and the mortality is relatively high. Objective. To reveal the potential molecular characteristics of IPF and deepen the understanding of the molecular mechanism of IPF. In order to provide some guidance for the clinical treatment, new drug development, and prognosis judgment of IPF. Although the preliminary conclusion of this study has certain guiding significance for the treatment of IPF and so on, it needs more accurate analytical approaches and large sample clinical trials to verify. Methods. 220 patients with IPF were divided into different subgroups according to the gene expression profiles, which were obtained from the Gene Expression Omnibus (GEO) database. In addition, these subgroups present different expression forms and clinical features. Therefore, weighted gene coexpression analysis (WGCNA) was used to seek the differences between subtypes. And six subgroup-specific WGCNA modules were identified. Results. Combined with the characteristics of WGCNA and KEGG enrichment modules, the autophagic pathway was only upregulated in subgroup I and enriched significantly. The differentiation pathways of Th1 and Th2 cells were only upregulated and enriched in subgroup II. At the same time, combined with clinical information, IPF patients in subgroup II were older and more serious, which may be closely related to the differentiation of Th1 and Th2 cells. In contrast, the neuroactive ligand-receptor interaction pathway and Ca+ signaling pathway were significantly upregulated and enriched in subgroup III. Although there was no significant difference in prognosis between subgroup I and subgroup III, their intrinsic biological characteristics were very different. These results suggest that the subtypes may represent risk factors of age and intrinsic biological characteristics and may also partly reflect the severity of the disease. Conclusion. In conclusion, current studies have improved our understanding of IPF-related molecular mechanisms. At the same time, because the results show that patients from different subgroups may have their own unique gene expression patterns, it reminds us that patients in each subgroup should receive more personalized treatment.
Observer‐Based Sliding Mode Load Frequency Control of Power Systems under Deception Attack
Authors: Qiao Siwei , Liu Xinghua , Xiao Gaoxi , Ge Shuzhi Sam
Published: October 2021

This study investigates the observer‐based sliding mode load frequency control for multiarea interconnected power systems under deception attack. By introducing the observer and combining it with the system state equation, the expression of the system error is obtained. A sliding mode surface is proposed to make sure the state of the systems to be stable. Then, the state equation of the system under sliding mode control is derived. The asymptotic stability of the whole system is proved by using the linear matrix inequality (LMI) technique and Lyapunov stability theory. Furthermore, a sliding mode control law is proposed to ensure that the attacked power system can reach a stable position. Numerical simulation results are presented to support the correctness of the results.
Numerical Simulation of Dynamic Characteristics of Dam Concrete Based on Fuzzy Set
Authors: Jianyin Fang , Ke Liu , Faning Dang , Shutian Li
Published: October 2021

The dynamic characteristics of concrete are the key point of the dam seismic safety design. In order to study the dynamic characteristics of concrete, a CT scan test of concrete under dynamic load was carried out; CT scan images of the concrete loading process were obtained. Based on the definition of integrity, integrity area, and intercepted sections in the quantitative zoning theory, the concrete CT images were divided into the hole or crack area (

P

0
−

λ

1

), hardened cement stone area (

P

λ

1

−

λ

2

), and aggregate area (

P

λ

2

−
1

). And the determination method of partition threshold is studied. Then, based on the CT resolution unit, a concrete numerical calculation model of structural random is established, and the numerical simulation experiment of concrete under uniaxial dynamic load is carried out. The results show that the concrete numerical calculation model of structural random is very close to the actual mesostructure of concrete, and the interface thickness between aggregate and hardened cement is very close to the actual interface thickness (which is 40~50 μm). Under the action of dynamic load, the damage of the sample is mainly concentrated in the upper part of the sample, and the damage is easy to occur at the initial defect place, and the damage occurs at multiple points at the same time. The damage crack is relatively straight, the phenomenon of the crack passing through the aggregate is obvious, and the crack expands along the fastest path of energy release.
N-Doped Carbon Dots Derived from Melamine and Triethanolamine for Selective Sensing of Fe3+ Ions
Authors: Munusamy Sathishkumar , Sawminathan Sathish , Arumugham Thanigaivelan , Casales Díaz Maura , Godavarthi Srinivas , Kesarla Mohan Kumar
Published: October 2021

This work reports nitrogen-doped carbon dots (NCDs) as a selective sensing probe to detect Fe3+ in water samples. NCD probes were synthesized via solvothermal method using nitrogen-rich melamine and triethanolamine as precursors. Properties of the resulting NCDs were studied using different characterization techniques, through which N-doping was confirmed. The quantum yield of obtained NCDs was measured to be 21%. When excited at 370 nm, the excellent blue emission property makes this probe adoptable for selectively sensing Fe3+ in practical water samples. The limit of detection (LOD) was identified as 216 nM with a good linear range between the concentrations of 0.2-2 μM. The obtained LOD is far less than the World Health Organization (WHO) permissible limits of Fe3+ in water. Interference studies reveal that the presence of other competing ions did not alter the sensing of Fe3+, even at the presence of 10 equivalents which indicates the high selectivity of NCDs towards Fe3+. The reversibility studies showed that adding a cheap and readily available EDTA ligand to the NCD results in fluorescence regeneration, leading to exceptional reusability for the detection of Fe3+. So, the synthesized NCDs can be used as a suitable probe for the selective determination of Fe3+ in real water samples.
Feasibility and Effectiveness of the Web‐Based WeActive and WeMindful Interventions on Physical Activity and Psychological Well‐Being
Authors: Marenus Michele W. , Murray Andy , Friedman Kathryn , Sanowski Julia , Ottensoser Haley , Cahuas Ana , Kumaravel Varun , Chen Weiyun
Published: October 2021

This study is aimed at examining the feasibility and effectiveness of aerobic and resistance training (WeActive) and mindful exercise (WeMindful) interventions in improving physical activity (PA), psychological well‐being (PWB), and subjective vitality among college students. Participants in this study were 77 college students who were randomly assigned to either the WeActive group (n = 43) or the WeMindful group (n = 28). The WeActive group attended two 30‐minute aerobic and resistance training sessions per week, and the WeMindful group attended two 30‐minute yoga and mindful exercise sessions per week for eight weeks. All participants completed the International Physical Activity Questionnaire, the World Health Organization-Five Well-Being Index, and the Subjective Vitality Scale before and after the intervention, as well as the Assessing Feasibility and Acceptability Questionnaire at the end of the intervention. The primary study outcome measures were PA, PWB, and subjective vitality. A repeated‐measures ANCOVA indicated a significant main effect of time for total PA (F = 7.89, p = 0.006, η2 = 0.049), vigorous PA (F = 5.36, p = 0.024, η2 = 0.022), and walking (F = 7.34, p = 0.009, η2 = 0.042) in both intervention groups. There was a significant interaction effect of time and group for PWB (F = 11.26, p = 0.001, η2 = 0.022), where the WeActive group experienced a decrease in PWB scores while participants in the WeMindful group experienced an increase in PWB scores over time. There was a main effect of group for subjective vitality (F = 8.91, p = 0.007, η2 = 0.088), indicating that the WeMindful group experienced a greater increase in subjective vitality than the WeActive group. Further, the participants in both groups indicated that the synchronized and asynchronized Zoom‐based WeActive and WeMindful interventions were acceptable, appropriate, and feasible for participants. This study demonstrated that mindful exercise is effective in increasing PA, PWB, and subjective vitality while aerobic and resistance training may only be effective in increasing PA.
Exploring the Molecular Mechanism of Astragali Radix-Curcumae Rhizoma against Gastric Intraepithelial Neoplasia by Network Pharmacology and Molecular Docking
Authors: Ji Yuejin , Liu Yajun , Hu Jingyi , Cheng Cheng , Xing Jing , Zhu Lei , Shen Hong
Published: October 2021

Background. Astragali Radix-Curcumae Rhizoma (ARCR), a classic drug pair, has been widely used for the treatment of gastric intraepithelial neoplasia (GIN) in China. However, the underlying mechanisms of this drug pair are still unknown. Thus, elucidating the molecular mechanism of ARCR for treating GIN is imperative. Methods. The active components and targets of ARCR were determined from the TCMSP database, and the differentially expressed genes related to GIN were identified from the GSE130823 dataset. The protein-protein interaction (PPI) network and ARCR-active component-target-pathway network were constructed by STRING 11.0 and Cytoscape 3.7.2, respectively. In addition, a receiver operating characteristic curve (ROC) was conducted to verify the key targets, and enrichment analyses were performed using R software. Molecular docking was carried out to test the binding capacity between core active components and key targets. Results. 31 active components were obtained from ARCR, among which 22 were hit by the 51 targets associated with GIN. Gene Ontology (GO) functional enrichment analysis showed that biological process (BP), molecular function (MF), and cellular component (CC) were most significantly enriched in response to a drug, catecholamine binding, and apical part of the cell, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated ARCR against GIN through regulation of neuroactive ligand-receptor interaction, nitrogen metabolism, calcium signaling pathway, chemical carcinogenesis-receptor activation, drug metabolism, gap junction, and cancers. In the PPI network, 15 potential targets were identified, of which nine key targets were proven to have higher diagnostic values in ROC. Molecular docking revealed a good binding affinity of active components (quercetin, bisdemethoxycurcumin, and kaempferol) with the corresponding targets (CYP3A4, CYP1A1, HMOX1, DRD2, DPP4, ADRA2A, ADRA2C, NR1I2, and LGALS4). Conclusion. This study revealed the active components and molecular mechanism by which ARCR treatment is effective against GIN through regulating multipathway, such as neuroactive ligand-receptor interaction, nitrogen metabolism, and calcium signaling pathway.
An Efficient Method for Choosing Digital Cluster Size in Ultralow Latency Networks
Authors: Paramonov Alexander , Khayyat Mashael , Chistova Natalia , Muthanna Ammar , Elgendy Ibrahim A. , Koucheryavy Andrey , Abd El-Latif Ahmed A.
Published: October 2021

The paper proposes a solution to the problem of choosing the size of a cluster in an ultralow latency network. This work is aimed at designing a method for choosing the size of the digital cluster in an ultralow latency network taking into account the lengths of connecting lines. If the linear dimension calculation is based only on the latency requirements without specifics of building the communication line, it negatively affects timing characteristics. This paper shows the method taking into account the communication line features and basing on the fractal dimension estimation of the road network. The proposed method could be used in planning and designing networks with ultralow latencies. Finally, a numerical experiment was carried out, based on the data of electronic maps, which showed that the assessment of the fractal dimension of roads in the network’s service area makes it possible to increase the accuracy of the size of the formed cluster. Moreover, the proposed method can allow you to reduce the error in estimating the length of connecting lines, which without using it can be on average about 30%.
Qing-Kai-Ling Injection Acts Better Than Shen-Fu Injection in Enhancing the Antitumor Effect of Gefitinib in Resistant Non-Small Cell Lung Cancer Models
Authors: Yu Ya-Ya , Zhu Yan-Juan , Zou Ying , Xiao Zhen-Zhen , Shi Shuai , Liu Yi-Hong , Chang Xue-Song , Chen Ya-Dong , Zhang Hai-Bo
Published: October 2021

Patients with EGFR gene mutation often obtain de novo resistance to epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) or develop secondary resistance to EGFR-TKIs after taking EGFR-TKI therapy. Traditional Chinese medicine (TCM) with different treatment principles, in combination with EGFR-TKIs, plays an important role in the treatment of cancers including resistant non-small cell lung cancer (NSCLC). However, inappropriate use of TCM herbs may induce resistance to gefitinib. Therefore, it is of a great value to evaluate which TCM treatment principle should be combined with EGFR-TKIs, and which one should be avoided, and find out the potential mechanisms. The lentiviral transfection assay was used for overexpression of PIK3CA mutation gene in PC-9 cells to construct PC-9-PIK3CA-mutation (PC-9-PIK3CA-M) cells. Cell proliferation, apoptosis, and the expression of EGFR/PI3K/AKT and EGFR/RAS/RAF/ERK in PC-9-PIK3CA-M and H1975 cells treated by the typical cooling-heat drug, Qing-kai-ling (QKL) and Tan-re-qing (TRQ), or the typical warming-yang drug, Shen-fu (SF) and gefitinib treatment, were detected by MTT, Annexin V/PI double labeling, and Western blot assays, respectively. Tumor xenograft and immunohistochemistry experiments were carried out to confirm the in vitro findings. PC-9-PIK3CA-M cells were less sensitive to gefitinib, when compared with PC-9 cells. QKL injection and TRQ injection, not SF injection, combined with gefitinib induced significantly increased cell growth inhibition and apoptosis in PC-9-PIK3CA-M and H1975 cells. SF injection antagonized the effect of gefitinib in promoting cancer cell apoptosis. QKL injection and TRQ injection increased the sensitivity of gefitinib by inhibiting the phosphorylation of AKT or ERK in H1975 and PC-9-PIK3CA-M cells. Similar findings were observed in vivo in H1975 xenograft mouse model. QKL and TRQ, with cooling-heat TCM treatment principle, should be combined with gefitinib in the treatment of NSCLC. Furthermore, warming-yang drug SF should be avoided to be used together with EGFR-TKIs.
An Efficient Fingertip Photoplethysmographic Signal Artifact Detection Method: A Machine Learning Approach
Authors: Athaya Tasbiraha , Choi Sunwoong
Published: October 2021

A photoplethysmography method has recently been widely used to noninvasively measure blood volume changes during a cardiac cycle. Photoplethysmogram (PPG) signals are sensitive to artifacts that negatively impact the accuracy of many important measurements. In this paper, we propose an efficient system for detecting PPG signal artifacts acquired from a fingertip in the public healthcare database named Multiparameter Intelligent Monitoring in Intensive Care (MIMIC) by using 11 features as the input of the random forest algorithm and classified the signals into two classes: acceptable and anomalous. A real‐time algorithm is proposed to identify artifacts by using the method. The efficient Fisher score feature selection algorithm was used to order and select 11 relevant features from 19 available features that represented the PPG signal very effectively. Six machine learning algorithms (random forest, decision tree, Gaussian naïve Bayes, linear support vector machine, artificial neural network, and probabilistic neural network) were applied with the extracted features, and their classification accuracy was measured. Among them, the random forest had the best performance using only 11 out of 19 features with an accuracy of 85.68%. Our proposed method also achieved good sensitivity and specificity value of 86.57% and 85.09%, respectively. The proposed real‐time algorithm can be an easy and convenient way for real‐time PPG signal artifact detection using smartphones and wearable devices.
Lightning Protection Improvement and Economic Evaluation of Thailand’s 24 kV Distribution Line Based on Difference in Grounding Distance of Overhead Ground Wire
Authors: Sestasombut Pornchai , Ngaopitakkul Atthapol
Published: October 2021

This study determines the voltage across insulators after a direct lightning strike to an overhead ground wire on a 24 kV pole structure for different grounding distances of overhead ground wire, to calculate the maximum ground resistance required to avoid disruption of the distribution line system using ATP-EMTP software. The results show that when a 40 kA lightning current, the average lightning current in Thailand, strikes a 24 kV pole structure, the maximum ground resistance should not exceed 4 Ω for a 40 m grounding distance of overhead ground wire, based on an existing critical insulator flashover of 205 kV. However, because the average ground resistance in Thailand is approximately 10 Ω, this study proposes increasing the insulation level from 205 kV to 300 kV to reduce the likelihood of power outage. The cost-effectiveness of such an investment is assessed in terms of net present value (NPV), internal rate of return (IRR), profitability index (PI), and discounted payback period (DPP) using existing economic tools. Results show that when the critical insulator flashover is increased from 205 kV to 300 kV for a 40 m grounding distance of overhead ground wire, the project is likely to have a DPP of 15.12 years, NPV of 143,321.87 USD, IRR of 12%, and PI of 1.15. On the other hand, grounding distances greater than 40 m for overhead ground wire result in negative NPV, although the back flashover rate can be reduced by 1.51–5.71% with grounding distances of 80–200 m compared to the situation in the absence of grounding.
Characterization of Peptides Targeting Metastatic Tumor Cells as Probes for Cancer Detection and Vehicles for Therapy Delivery
Authors: Subramanian Shraddha , Daquinag Alexes C. , AghaAmiri Solmaz , Ghosh Sukhen C. , Azhdarinia Ali , Kolonin Mikhail G.
Published: October 2021

Metastasis is the leading cause of cancer-related deaths, and metastatic cancers remain largely incurable due to chemoresistance. Biomarkers of metastatic cells are lacking, and probes that could be used to detect and target metastases would be highly valuable. Here we hypothesize that metastatic cancer cells express cell-surface receptors that can be harnessed for identification of molecules homing to metastases. Screening a combinatorial library in a mouse mammary tumor model of spontaneous metastasis identified cyclic peptides with tropism for cancer cells disseminated to the lungs. Two lead peptides, CLRHSSKIC and CRAGVGRGC, bound murine and human cells derived from breast carcinoma and melanoma in culture and were selective for metastatic cells in vivo. In mice, peptide CRAGVGRGC radiolabeled with 67Ga for biodistribution analysis demonstrated selective probe homing to lung metastases. Moreover, systemic administration of 68Ga-labeled CRAGVGRGC enabled noninvasive imaging of lung metastases in mice by PET. A CRAGVGRGC-derived peptide induced apoptosis upon cell internalization in vitro and suppressed metastatic burden in vivo. Colocalization of CLRHSSKIC and CRAGVGRGC with N-cadherin+/E-cadherin− cells indicated that both peptides are selective for cancer cells that have undergone the epithelial-to-mesenchymal transition. We conclude that CRAGVGRGC is useful as a probe to facilitate the development of imaging modalities and therapies targeting metastases.

Significance:

This study identifies new molecules that bind metastatic cells and demonstrates their application as noninvasive imaging probes and vehicles for cytotoxic therapy delivery in preclinical cancer models.
CstF64-Induced Shortening of the BID 3′UTR Promotes Esophageal Squamous Cell Carcinoma Progression by Disrupting ceRNA Cross-talk with ZFP36L2
Authors: Lin Ai , Ji Ping , Niu Xiangjie , Zhao Xuan , Chen Yamei , Liu Weiling , Liu Yachen , Fan Wenyi , Sun Yanxia , Miao Chuanwang , Zhang Shaosen , Tan Wen , Lin Dongxin , Wagner Eric J. , Wu Chen
Published: October 2021

The majority of human genes have multiple polyadenylation sites, which are differentially used through the process of alternative polyadenylation (APA). Dysregulation of APA contributes to numerous diseases, including cancer. However, specific genes subject to APA that impact oncogenesis have not been well characterized, and many cancer APA landscapes remain underexplored. Here, we used dynamic analyses of APA from RNA-seq (DaPars) to define both the 3′UTR APA profile in esophageal squamous cell carcinoma (ESCC) and to identify 3′UTR shortening events that may drive tumor progression. In four distinct squamous cell carcinoma datasets, BID 3′UTRs were recurrently shortened and BID mRNA levels were significantly upregulated. Moreover, system correlation analysis revealed that CstF64 is a candidate upstream regulator of BID 3′UTR length. Mechanistically, a shortened BID 3′UTR promoted proliferation of ESCC cells by disrupting competing endogenous RNA (ceRNA) cross-talk, resulting in downregulation of the tumor suppressor gene ZFP36L2. These in vitro and in vivo results were supported by human patient data whereby 3′UTR shortening of BID and low expression of ZFP36L2 are prognostic factors of survival in ESCC. Collectively, these findings demonstrate that a key ceRNA network is disrupted through APA and promotes ESCC tumor progression.

Significance: High-throughput analysis of alternative polyadenylation in esophageal squamous cell carcinoma identifies recurrent shortening of the BID 3′UTR as a driver of disease progression.
Functional Outcomes and Social Attainment in Asian/Pacific Islander Childhood Cancer Survivors in the United States: A Report from the Childhood Cancer Survivor Study
Authors: Sato Satomi , Li Nan , Dixon Stephanie B. , Kato Miho , Zhang Hui , Li Chi Kong , Howell Rebecca M. , Leisenring Wendy M. , Bhatia Smita , Oeffinger Kevin C. , Armstrong Gregory T. , Yasui Yutaka , Krull Kevin R. , Cheung Yin Ting
Published: October 2021

Background:

Given the relatively small population of Asians or Pacific Islanders (API) in the United States, studies describing long-term outcomes in API survivors of childhood cancer are limited. This study compared functional outcomes between API versus non-Hispanic White (NHW) survivors.

Methods:

This study included 203 API 5-year survivors [age at follow-up: 29.2 (SD = 6.3) years] and 12,186 NHW survivors [age at follow-up 31.5 (SD = 7.3) years] from the Childhood Cancer Survivor Study. Self-reported functional outcomes of neurocognitive function, emotional distress, quality of life, and social attainment were compared between the two groups using multivariable regression, adjusted for sex, age at diagnosis and evaluation, cancer diagnosis, and neurotoxic treatment.

Results:

No statistically significant race/ethnicity-based differences were identified in neurocognitive and emotional measures. API survivors reported, on average, less bodily pain than NHW survivors [mean 54.11 (SD = 8.98) vs. 51.32 (SD = 10.12); P < 0.001]. NHW survivors were less likely to have attained at least a college degree than API survivors [OR = 0.50; 95% confidence interval (CI) = 0.34–0.73]. API survivors were more likely than NHW survivors to be never-married (OR = 2.83; 95% CI = 1.93–4.13) and to live dependently (OR = 3.10; 95% CI = 2.02–4.74). Older age (>45 years), brain tumor diagnosis, and higher cranial radiation dose were associated with poorer functional outcomes in API survivors (all, P < 0.05).

Conclusions:

We observed differences in social attainment between API and NHW survivors, although statistically significant differences in neurocognitive and emotional outcomes were not identified.

Impact:

Future studies should evaluate whether racial/ethnic differences in environmental and sociocultural factors may have differential effects on health and functional outcomes.
Disease-Associated Risk Variants in ANRIL Are Associated with Tumor-Infiltrating Lymphocyte Presence in Primary Melanomas in the Population-Based GEM Study
Authors: Davari Danielle R. , Orlow Irene , Kanetsky Peter A. , Luo Li , Edmiston Sharon N. , Conway Kathleen , Parrish Eloise A. , Hao Honglin , Busam Klaus J. , Sharma Ajay , Kricker Anne , Cust Anne E. , Anton-Culver Hoda , Gruber Stephen B. , Gallagher Richard P. , Zanetti Roberto , Rosso Stefano , Sacchetto Lidia , Dwyer Terence , Ollila David W. , Begg Colin B. , Berwick Marianne , Thomas Nancy E.
Published: October 2021

Background:

Genome-wide association studies have reported that genetic variation at ANRIL (CDKN2B-AS1) is associated with risk of several chronic diseases including coronary artery disease, coronary artery calcification, myocardial infarction, and type 2 diabetes mellitus. ANRIL is located at the CDKN2A/B locus, which encodes multiple melanoma tumor suppressors. We investigated the association of these variants with melanoma prognostic characteristics.

Methods:

The Genes, Environment, and Melanoma Study enrolled 3,285 European origin participants with incident invasive primary melanoma. For each of ten disease-associated SNPs at or near ANRIL, we used linear and logistic regression modeling to estimate, respectively, the per allele mean changes in log of Breslow thickness and ORs for presence of ulceration and tumor-infiltrating lymphocytes (TIL). We also assessed effect modification by tumor NRAS/BRAF mutational status.

Results:

Rs518394, rs10965215, and rs564398 passed false discovery and were each associated (P ≤ 0.005) with TILs, although only rs564398 was independently associated (P = 0.0005) with TILs. Stratified by NRAS/BRAF mutational status, rs564398*A was significantly positively associated with TILs among NRAS/BRAF mutant, but not wild-type, cases. We did not find SNP associations with Breslow thickness or ulceration.

Conclusions:

ANRIL rs564398 was associated with TIL presence in primary melanomas, and this association may be limited to NRAS/BRAF-mutant cases.

Impact:

Pathways related to ANRIL variants warrant exploration in relationship to TILs in melanoma, especially given the impact of TILs on immunotherapy and survival.
Alcohol Intake and Endogenous Hormones in Pre- and Postmenopausal Women: Findings from the UK Biobank
Authors: Tin Tin Sandar , Key Timothy J. , Reeves Gillian K.
Published: October 2021

Background:

Alcohol intake may influence breast cancer risk in women through hormonal changes, but the evidence to date is inconclusive. We investigated cross-sectional associations between habitual alcohol intake and serum concentrations of testosterone, sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), and estradiol (premenopausal women only) in UK Biobank.

Methods:

We included 30,557 premenopausal and 134,029 postmenopausal women aged between 40 and 69 years when recruited between 2006 and 2010. At their initial assessment visit, habitual alcohol intake was assessed using a touchscreen questionnaire, and serum hormone concentrations were assayed. Multivariable linear regression analysis was performed.

Results:

Per 10 g/day increment in alcohol intake, testosterone concentration was 3.9% [95% confidence intervals (CI): 3.3%–4.5%] higher in premenopausal women and 2.3% (1.8%–2.7%) higher in postmenopausal women (Pheterogeneity < 0.0001); SHBG concentration was 0.7% (0.2%–1.1%) higher in premenopausal women and 2.4% (2.2%–2.6%) lower in postmenopausal women (Pheterogeneity < 0.0001); and IGF-1 concentration was 1.9% (1.7%–2.1%) lower in premenopausal women and 0.8% (0.6%–0.9%) lower in postmenopausal women (Pheterogeneity < 0.0001). In premenopausal women, there was no significant overall association of alcohol with estradiol but a positive association was observed in the early and mid-luteal phases: 1.9% (95% CI: 0.2%–3.6%) and 2.4% (95% CI: 0.7%–4.2%) higher, respectively.

Conclusions:

This study confirms significant but modest associations between alcohol intake and hormones, with evidence of heterogeneity by menopausal status.

Impact:

The findings facilitate better understanding of whether alcohol intake influences hormone concentrations, but further work is necessary to fully understand the mechanisms linking alcohol with cancer risk.
Efficacy of Rac and Cdc42 Inhibitor MBQ-167 in Triple-negative Breast Cancer
Authors: Cruz-Collazo Ailed , Ruiz-Calderon Jean F. , Picon Hector , Borrero-Garcia Luis D. , Lopez Irmaris , Castillo-Pichardo Linette , del Mar Maldonado Maria , Duconge Jorge , Medina Julia I. , Bayro Marvin J. , Hernández-O'Farrill Eliud , Vlaar Cornelis P. , Dharmawardhane Suranganie
Published: October 2021

Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer, with a high predisposition for locally invasive and metastatic cancer. With the objective to reduce cancer metastasis, we developed small molecule inhibitors to target the drivers of metastasis, the Rho GTPases Rac and Cdc42. Of these, MBQ-167 inhibits both Rac and Cdc42 with IC50s of 103 and 78 nmol/L, respectively; and consequently, inhibits p21-activated kinase (PAK) signaling, metastatic cancer cell proliferation, migration, and mammosphere growth; induces cell-cycle arrest and apoptosis; and decreases HER2-type mammary fatpad tumor growth and metastasis (Humphries-Bickley and colleagues, 2017). Herein, we used nuclear magnetic resonance to show that MBQ-167 directly interacts with Rac1 to displace specific amino acids, and consequently inhibits Rac.GTP loading and viability in TNBC cell lines. Phosphokinome arrays in the MDA-MB-231 human TNBC cells show that phosphorylation status of kinases independent of the Rac/Cdc42/PAK pathway are not significantly changed following 200 nmol/L MBQ-167 treatment. Western blotting shows that initial increases in phospho-c-Jun and phospho-CREB in response to MBQ-167 are not sustained with prolonged exposure, as also confirmed by a decrease in their transcriptional targets. MBQ-167 inhibits tumor growth, and spontaneous and experimental metastasis in immunocompromised (human TNBC) and immunocompetent (mouse TNBC) models. Moreover, per oral administration of MBQ-167 at 100 mg/kg body weight is not toxic to immunocompetent BALB/c mice and has a half-life of 4.6 hours in plasma. These results highlight the specificity, potency, and bioavailability of MBQ-167, and support its clinical potential as a TNBC therapeutic.
NAP1051, a Lipoxin A4 Biomimetic Analogue, Demonstrates Antitumor Activity Against the Tumor Microenvironment
Authors: Dong Tiange , Dave Priyal , Yoo EunJeong , Ebright Brandon , Ahluwalia Kabir , Zhou Eugene , Asante Isaac , Salimova Malika , Pei Hua , Lin Tracey , Mead Andrew , Li Zeyang , Humayun Mark , Petasis Nicos A. , Epstein Alan L. , Louie Stan G.
Published: October 2021

Resolving tumor-associated inflammation in the tumor microenvironment (TME) may promote antitumor effects. Lipoxin A4 (LXA4) is a short-lived endogenous bioactive lipid with potent anti-inflammatory and pro-resolving properties. Here, a biomimetic of LXA4, NAP1051, was shown to have LXA4-like in vitro properties and antitumor activity in colorectal cancer xenograft models. NAP1051 inhibited neutrophil chemotaxis toward fMLP and dose-dependently promoted dTHP-1 efferocytosis which was equipotent to aspirin-triggered lipoxin A4 (ATLA). In dTHP-1 cells, NAP1051 induced strong phosphorylation on ERK1/2 and AKT similar to formyl peptide receptor 2 (FPR2/ALX) agonists. In two mouse xenograft colorectal cancer models, NAP1051 significantly inhibited tumor growth when given orally at 4.8 to 5 mg/kg/day. Flow cytometric analyses showed that NAP1051 reduced splenic and intratumoral neutrophil and myeloid-derived suppressor cell populations, which correlated to the antitumor effect. In addition, NAP1051 reduced NETosis in the TME while stimulating T-cell recruitment. Overall, these results show that NAP1051 possesses key lipoxin-like properties and has antitumor activity against colorectal cancer via modulation of neutrophils and NETosis in the TME.
Rethinking Cervical Cancer Screening in Brazil Post COVID-19: A Global Opportunity to Adopt Higher Impact Strategies
Authors: Ribeiro Ana , Corrêa Flávia , Migowski Arn , Leal Aline , Martins Sandro , Raiol Tainá , Marques Carla P. , Torres Katia L. , Novetsky Akiva P. , Marcus Jenna Z. , Wentzensen Nicolas , Schiffman Mark , Rodriguez Ana Cecilia , Gage Julia C.
Published: October 2021

The World Health Organization global call to eliminate cervical cancer encourages countries to consider introducing or improving cervical cancer screening programs. Brazil's Unified Health System (SUS) is among the world's largest public health systems offering free cytology testing, follow-up colposcopy, and treatment. Yet, health care networks across the country have unequal infrastructure, human resources, equipment, and supplies resulting in uneven program performance and large disparities in cervical cancer incidence and mortality. An effective screening program needs multiple strategies feasible for each community's reality, facilitating coverage and follow-up adherence. Prioritizing those at highest risk with tests that better stratify risk will limit inefficiencies, improving program impact across different resource settings. Highly sensitive human papillomavirus (HPV)-DNA testing performs better than cytology and, with self-collection closer to homes and workplaces, improves access, even in remote regions. Molecular triage strategies like HPV genotyping can identify from the same self-collected sample, those at highest risk requiring follow-up. If proven acceptable, affordable, cost-effective, and efficient in the Brazilian context, these strategies would increase coverage while removing the need for speculum exams for routine screening and reducing follow-up visits. SUS could implement a nationwide organized program that accommodates heterogenous settings across Brazil, informing a variety of screening programs worldwide.
Disbalance of the Duodenal Epithelial Cell Turnover and Apoptosis Accompanies Insensitivity of Intestinal Redox Homeostasis to Inhibition of the Brain Glucose-Dependent Insulinotropic Polypeptide Receptors in a Rat Model of Sporadic Alzheimer’s Disease
Authors: Homolak Jan , Babic Perhoc Ana , Knezovic Ana , Osmanovic Barilar Jelena , Koc Fatma , Stanton Catherine , Ross R. Paul , Salkovic-Petrisic Melita
Published: October 2021

Introduction: Gastrointestinal dyshomeostasis is investigated in the context of metabolic dysfunction, systemic, and neuroinflammation in Alzheimer’s disease. Dysfunctional gastrointestinal redox homeostasis and the brain-gut incretin axis have been reported in the rat model of insulin-resistant brain state-driven neurodegeneration induced by intracerebroventricular streptozotocin (STZ-icv). We aimed to assess whether (i) the structural epithelial changes accompany duodenal oxidative stress; (ii) the brain glucose-dependent insulinotropic polypeptide receptor (GIP-R) regulates redox homeostasis of the duodenum; and (iii) the STZ-icv brain-gut axis is resistant to pharmacological inhibition of the brain GIP-R. Methods: GIP-R inhibitor [Pro3]-GIP (85 μg/kg) was administered intracerebroventricularly to the control and the STZ-icv rats 1 month after model induction. Thiobarbituric acid reactive substances (TBARSs) were measured in the plasma and duodenum, and the sections were analyzed morphometrically. Caspase-3 expression and activation were assessed by Western blot and multiplex fluorescent signal amplification. Results: Intracerebroventricular [Pro3]-GIP decreased plasma TBARSs in the control and STZ-icv animals and increased duodenal TBARSs in the controls. In the controls, inhibition of brain GIP-R affected duodenal epithelial cells, but not villus structure, while all morphometric parameters were altered in the STZ-icv-treated animals. Morphometric changes in the STZ-icv animals were accompanied by reduced levels of caspase-3. Suppression of brain GIP-R inhibited duodenal caspase-3 activation. Conclusion: Brain GIP-R seems to be involved in the regulation of duodenal redox homeostasis and epithelial cell turnover. Resistance of the brain-gut GIP axis and morphological changes indicative of abnormal epithelial cell turnover accompany duodenal oxidative stress in the STZ-icv rats.
Espaços físicos e afetivos do funk: o musicar local das festas lésbicas de São Paulo
Authors: Martins Raquel Mendonça
Published: October 2021

O artigo apresenta análise sobre etnografia realizada na cena de festas lésbicas que ocorrem no centro da cidade de São Paulo, por onde circula o funk com teor erotizado, como também sobre entrevistas realizadas com participantes da cena durante a pandemia de Covid-19. O campo abrange duas festas: a “Sarrada no Brejo” e a “Fancha”. A partir da noção de musicar local, como também de localidade, deslocamentos e interseccionalidades, analiso os modos como o funk propicia um engajamento entre as participantes, auxiliando nos processos de transformação e identificação que configuram o corpo lésbico e, também, gordo e negro. Observando o funk, a performance e as localidades envolvidas, identifico nessa forma de musicar um conjunto de ações que ressignificam estereótipos e o corpo considerado abjeto, transformando-o num corpo político por meio da diversão, ocupação e criação de espaços.
Revolução através da palavra: reflexões acerca do uso da literatura e da oralidade como expressão social e atuação política no Slam das Minas - RJ
Authors: Sá Tayná Corrêa de
Published: October 2021

A resistência e a luta política dão-se de diversas formas, e uma delas é a através da arte. O presente artigo é resultado de uma pesquisa em desenvolvimento que busca entender os sentidos e os efeitos políticos da participação feminina no slam poetry brasileiro e de como essa forma de manifestação artística se relaciona com o território da cidade. Através de uma abordagem etnográfica, o artigo pretende demonstrar como mulheres e pessoas trans estão atuando politicamente através da poesia falada e de como a união de seus corpos vem incidindo no espaço público nos eventos do Slam das Minas na cidade do Rio de Janeiro.
Ensaio esquizo-analítico com textos e imagens sobre corpos, fantasias e retratos ou O que o espelho nos reflete?
Authors: Grunvald Vitor
Published: October 2021

Este ensaio tem como horizonte algumas projeções e colagens (de trechos anteriores, publicados ou não), conceitos, inspirações, alucinações textuais e imagéticas sobre BDSM (Bondage, Dominação, Disciplina, Sadismo, Submissão, Masoquismo) e práticas de travestimento.