bluuebunny/crossref_metadata_2025 huggingface dataset:
Gene Expression of CD70 and CD27 Is Increased in Alopecia Areata Lesions and Associated with Disease Severity and Activity
Authors: Sayed Mahmoud Marie Radwa El- , Abd El-Fadeel Noha M. , El-Sayed Marei Yara , Atef Lina M.
Published: March 2022

Background. Alopecia areata (AA) is an acquired hair loss disorder induced by a cell‐mediated autoimmune attack against anagen hair follicles. CD27‐CD70 is a receptor‐ligand complex which enhances T helper and cytotoxic T cell activation, survival, and proliferation. The overstimulation of this complex can lead to a lack of tolerance and the development of autoimmunity. Objectives. This study aimed to assess the gene expression of CD27 and CD70 in patients with AA. Methods. CD70 and CD27 mRNA expressions were evaluated by a quantitative real‐time polymerase chain reaction in scalp biopsies from 40 AA patients (both AA lesions and non‐lesional areas) and 40 healthy controls (HCs). The Severity of Alopecia Tool (SALT) score was used to assess AA severity. Patients were evaluated for signs of AA activity, including a positive hair pull test and dermoscopic features of black dots, broken hairs, and tapering hairs. Results. The gene expression of CD70 and CD27 was significantly higher in AA lesions than in non‐lesional areas (p < 0.001 for both) and HCs (p = 0.004, p = 0.014, respectively). There were significant positive correlations between AA severity and gene expression of CD70 (p < 0.001) and CD27 (p = 0.030) in AA lesions. Significant associations were detected between signs of AA activity and lesional gene expression of CD70 and CD27. Additionally, CD70 and CD27 gene expression was significantly lower in non‐lesional biopsies compared to HCs (p < 0.001). Conclusion. Gene expression of CD70 and CD27 was increased in AA lesions and was associated with disease severity and activity. Thus, both molecules can be a predictor of AA severity and activity. Furthermore, the expression was reduced in non‐lesional scalp areas. Thus, a lack of CD27 and CD70 expression may initially predispose to immunological dysregulation and the development of AA.
Determination of T Cell Responses in Thai Systemic Sclerosis Patients
Authors: Likhit Oranit , Louthrenoo Worawit , Pattanakitsakul Sa-nga , Suttitheptumrong Aroonroong , Hannongbua Supot , Rungrotmongkol Thanyada , Noguchi Hiroshi , Takeuchi Fujio , Boonnak Kobporn
Published: March 2022

Objectives. This study is aimed at determining the role of T cells by assessing the numbers of IFN-γ- and IL-2-secreting T cells following stimulation with peptides derived from DNA topoisomerase-I protein in Thai SSc patients. Methods. Fifty Thai SSc patients and 50 healthy controls (HC) joined this study. IFN-γ and IL-2 levels upon stimulation of T cells with 6 peptides derived from DNA topoisomerase-I protein were determined. Anti-nuclear antibodies (ANA) and anti-Scl-70 antibodies were determined by using the ELISA method. Results. In SSc patients, we detected a significantly higher number of IFN-γ- and IL-2-secreting CD8+ T cells than IFN-γ- and IL-2-secreting CD4+ T cells after stimulation with pooled peptides derived from DNA topoisomerase-I protein. A similar percentage of CD4+IL-2+, CD4+IFN-γ+, and CD8+IL-2+ were detected following stimulation with DNA topoisomerase-I protein -in SSc patients with anti-Scl-70 antibody (SSc/anti-Scl-70+) and those without. In contrast, the amount of CD8+IFN-γ+ cells was significantly higher in SSc/anti-Scl-70+ than those without. Stimulation with individual peptides showed that CSLRVEHINLHPELD (sPep3; 15 amino acids; position 505-519 of DNA topoisomerase-I protein) was the optimal epitope that induced T cells secreting the highest levels of IFN-γ and IL-2. A higher percentage of IFN-γ+CD4+ T cells was detected in SSc/anti-Scl-70+ than those without the following stimulation with peptides 2 (amino acid position 475-486 [RAVALYFIDKLA] of protein DNA topoisomerase). Conclusion. The results from this study emphasize the critical role of DNA topoisomerase-I peptides on the activation of T cells in SSc patients. The findings provide a better understanding of SSc’s immunopathogenesis and may lead to the development of diagnostic tools and specific treatments for SSc in the future.
Downregulation of Circular RNA circPSD3 Promotes Metastasis by Modulating FBXW7 Expression in Clear Cell Renal Cell Carcinoma
Authors: Xie Xuexia , Li Haomin , Gao Chongqing , Lai Yiqi , Liang Junjie , Chen Zhiwei , Chen Zheng , Heng Baoli , Yao Nan , Lai Caiyong
Published: March 2022

Circular RNAs (circRNAs), a novel class of noncoding RNAs, have been shown to play critical regulatory roles in clear cell renal cell carcinoma (ccRCC). Metastasis is the main contributor to the poor prognosis of patients with ccRCC. However, the role of circRNAs in ccRCC metastasis has not been fully elucidated. In this study, microarray and RNA-seq analyses revealed that circPSD3 (hsa_circ_0002111) was dramatically downregulated in ccRCC tissues compared to adjacent nontumor tissues. A qRT-PCR analysis performed on our ccRCC cohorts confirmed the downregulation of circPSD3 in ccRCC tissues and further suggested that a low level of circPSD3 expression was associated with tumor metastasis in patients with ccRCC. Based on the results of functional studies, circPSD3 significantly inhibited cell migration, invasion, and the epithelial-mesenchymal transition (EMT) in vitro and blocked pulmonary metastasis in vivo. Mechanistically, circPSD3 functioned as a competing endogenous RNA for microRNA 25-3p (miR-25-3p) to regulate F-box and WD repeat domain-containing 7 (FBXW7) expression. Further verification indicated that circPSD3 overexpression restrained an EMT-like phenotype in cells, while miR-25-3p partially rescued these effects. In summary, circPSD3 inhibits tumor metastasis by repressing the miR-25-3p/FBXW7-EMT axis and might be developed as a potential diagnostic and therapeutic target for ccRCC.
An Optimized Modal Balancing Approach for a Flexible Rotor Using a Vibration Response While the Rotor Is Speeding Up
Authors: Li Liqing , Hou Yuanhang , Cao Shuqian
Published: March 2022

The modal balancing method (MBM) is an effective method for reducing the vibration caused by the unbalancing of a rotor. A rotor’s modal parameters, especially its modal shapes, need to be accurately calculated in this method. This paper proposes an optimized modal balancing approach for flexible rotors. The vibration modes of the rotor are first obtained with experimental modal analysis based on the rotor’s response signals while the rotor is speeding up. The rotor balancing strategy is subsequently optimized by the sensitivity analysis of the mode shapes. Orthogonal trial masses are obtained based on the orthogonality of each vibration mode, and the correction masses are finally calculated by using the influence coefficients of the trial masses. An experimental result is shown to demonstrate and validate that the proposed approach is able to achieve superior accuracy compared to the conventional MBM.
Possible Paternal Hepatitis B Virus Infection with Different Clinical Courses between Siblings: A Report of Two Cases
Authors: Sasaki Yoshiaki , Kajino Hiroki
Published: March 2022

The incidence of hepatitis B virus (HBV) infection is expected to decrease in the future owing to the preventive measures adopted against mother-to-child transmission of HBV and implementation of universal HBV vaccination for children. However, no countermeasure has been established against horizontal infection in nonvaccinated children. We report the case of two siblings who had different clinical courses of possible paternal HBV infection. The younger sibling developed acute hepatitis, whereas the older sibling was an asymptomatic HBV carrier. To eradicate HBV, HBV vaccination of all children and HBV infection screening of fathers and other family members should be encouraged.
Computation Offloading in Multi-UAV-Enhanced Mobile Edge Networks: A Deep Reinforcement Learning Approach
Authors: Li Bin , Yu Shiming , Su Jian , Ou Jianghong , Fan Dahua
Published: March 2022

In this paper, we investigate an unmanned aerial vehicle- (UAV-) enhanced mobile edge computing network (MUEMN), where multiple UAVs are deployed as aerial edge servers to provide computing services for ground moving equipment (GME). Each GME is trained to simulate movement by a Gauss-Markov random model in this MUEMN. Under the condition of limited energy cost, UAV dynamically plans its flight position according to the movement trend of GME. Our objective is to minimize the total energy consumption of GME by jointly optimizing the offloading decisions of GME and the flight positions of UAVs. More explicitly, we model the optimization problem as a Markov decision process and achieve real-time offloading decisions via deep reinforcement learning algorithm according to the dynamic system state, where the asynchronous advantage actor-critic (A3C) framework with asynchronous characteristics is leveraged to accelerate the learning process. Finally, numerical results confirm that our proposed A3C-based offloading strategy can effectively reduce the total of energy consumption of GME and ensure the continuous operation of the GME.
Securing E-Healthcare Images Using an Efficient Image Encryption Model
Authors: Jain Jaishree , Jain Arpit
Published: March 2022

With the advancements in e-healthcare services, it is possible to provide remote medical services to patients and swifter first aid. Medical images play an essential role in e-healthcare applications for providing quick and better remote diagnosis and treatment to patients. Medical images generally comprise secret details about the patients and are therefore prone to various security threats during their transmission over public networks. Thus, it is required to secure these images prior to their communication over public networks. But due to distinctive properties of medical images, like higher correlation and redundancy among the pixels, and larger size, it is required to design an efficient encryption model to resist against various security threats. In this paper, an efficient encryption model for medical images is proposed. To obtain the secret keys, six-dimensional hyperchaotic map (SDHM) is proposed. Firstly, plain medical image is divided into three channels such as red, green, and blue. Secret keys are used to diffuse these channels. Lastly, encrypted channels are concatenated and final encrypted medical image is obtained. Extensive experiments are drawn by considering the benchmark medical images. Also, comparisons are performed among the proposed SDHM and competitive techniques by considering various performance metrics. Comparative analysis reveals that the proposed SDHM achieves remarkably good performance than the existing encryption models.
Self‐Excited and Hidden Chaotic Attractors in Matouk’s Hyperchaotic Systems
Authors: Almatroud A. Othman , Matouk A. E. , Mohammed Wael W. , Iqbal Naveed , Alshammari Saleh
Published: March 2022

Self-excited and hidden chaotic attractors are interesting complex dynamical phenomena. Here, Matouk’s hyperchaotic systems are shown to have self-excited and hidden chaotic attractors, respectively. Two case studies of hidden chaotic attractors are provided which are examined with orders 3.08 and 3.992, respectively. Moreover, self‐excited chaotic attractors are found in the fractional‐order system and its integer‐order counterpart. The existence of one‐eyed face self‐excited chaotic attractors is also reported in this work. Our results show that the fractional derivative affects the appearances of hidden chaotic attractors in this system.
Process Optimization for Biosingeing of 100% Cotton Terry Towel Fabric Using Box–Behnken Design
Authors: Azanaw Aklilu , Ketema Asnake
Published: March 2022

In the present day, numerous researchers have paid more attention to the dyeing and finishing quality of environmentally friendly textile products in the world because the lack of outstanding products is an alarming problem. Therefore, the purpose of the present study is to treat the fabric with cellulase enzymes to improve the dyeing and finishing quality. The effects of varying chemical concentrations, temperatures, and processing times were examined in the model and different process parameters were optimized in the preparation biosingeing process. The results of the Box–Behnken design were obtained as R2 = 0.7243, 0.9027, and 0.9966 for optimum absorbency, weight loss, and tensile strength, respectively. The treated fabric was analyzed using FTIR to know the unknown functional group and the chemical bonds on the fabric molecule. Testing of physical properties of the treated fabric was done and the result was comparable with other untreated fabrics. The treated fabric performance was studied at 40, 50, and 60 minutes and at temperatures of 30, 55, and 80°C. The experimental investigation has been carried out to determine the effect of biosingeing on different physical parameters, such as the tensile strength of treated cotton fabric (437 N), which was almost similar to that of the untreated fabric (443 N), with almost no significant differences. K/S value for the biosingeing fabric of treated fabric was 17.58, but the that of the untreated fabric was 15.6, which was significantly different. Thus, the enzymatically treated fabric is of good quality because the protruding fiber was removed in biosingeing process. This ecofriendly singeing preparatory process is an alternative process for terry towel fabrics.
Tobacco Use among School‐Going Adolescents in Comoros: A Secondary Analysis of the 2015 Comoros Global Youth Tobacco Survey
Authors: James Peter Bai , Kassim Said Abasse , Kabba John Alimamy , Kitchen Chenai
Published: March 2022

Background. Tobacco use among adolescents has long‐term adverse health consequences, especially during adulthood. Currently, little is known about tobacco use behaviour among adolescents in Comoros. Our study aims at estimating the prevalence and identifying key factors associated with tobacco use among adolescents in Comoros using the 2015 Comoros Global Youth Tobacco Survey data. Methods. A national cross‐sectional survey secondary data of 2,810 eligible school‐going adolescents aged between 11 and 17 years was analysed. Complex sample logistic regression analyses were used to determine the correlates of current cigarette smoking and current use of noncigarette tobacco products. Results. The overall prevalence of current cigarette smoking was 14.3% [males (18.5%) and females (9.9%)]. The prevalence of current use of noncigarette tobacco products was 5.8% [males (6.7%) and females (4.9%)]. Being male (AOR = 2.24; 95% CI:1.39‐3.63), exposure to secondhand smoke inside (AOR =3.88; 95% CI:2.84‐5.31) and outside (AOR =1.49; 95% CI: 1.08‐2.03) their home, and exposure to tobacco industry promotion (AOR =2.90; 95% CI:2.21‐3.80) were associated with current cigarette use among school‐going adolescents. However, parental smoke (AOR = 1.20; 95% CI:0.78‐1.87) and not exposed to antismoking education in schools (AOR = 0.97; 95% CI:0.76‐1.22) were not associated with current cigarette use. On the other hand, being male (AOR = 1.24; 95% CI:0.82‐1.86) was not associated with the current use of noncigarette tobacco products. Adolescents who were exposed to tobacco industry promotion (AOR = .2.58; 95% CI:1.54‐4.32) and not exposed to antismoking education in school (AOR = 0.52; 95% CI:0.32‐0.85) were more and less likely associated with noncigarette tobacco use. Conclusion. One in seven school‐going adolescents smokes cigarettes, and approximately one in 20 school‐going adolescents uses noncigarette tobacco products in Comoros. Exposure to secondhand smoke within and outside the home and exposure to tobacco industry promotion were associated with tobacco use in school‐going adolescents in Comoros. Our findings suggest the need for adolescent‐friendly gender‐sensitive tobacco interventions, including strengthening existing tobacco control laws to prevent and reduce tobacco use among school‐going adolescents in Comoros.
Influence of Misalignment on Beveloid Gear Tooth Contact and Dynamic Characteristics in Transfer Case Transmission of AWD Vehicle
Authors: Bai Bo , Kuang Yuhua , Guo Wenchao , Mao Shimin
Published: March 2022

Beveloid gears are usually employed to transfer motion of small shaft angle, but the assembly errors or misalignment can affect the gear tooth contact and dynamic performance. A dynamic model and tooth contact analysis model of the intersecting beveloid gear pair are established, the defects of the theoretical tooth surface in the meshing are analyzed, and a microgeometry modification method to improve the meshing performance is proposed. At the same time, the effects of system misalignment and manufacturing errors on its meshing characteristics are considered. By studying the sensitivity of the static and dynamic characteristics of beveloid gear on different misalignment components, the influence laws of misalignment on the contact pattern, transmission error, mesh stiffness, and dynamic excitation force are obtained, which give suggestions for tooth surface modification and support structural stiffness design of beveloid gear with a good NVH performance.
Complex Spherical Fuzzy Decision Support System Based on Entropy Measure and Power Operator
Authors: Naeem Muhammad , Qiyas Muhammad , Botmart Thongchi , Abdullah Saleem , Khan Neelam
Published: March 2022

The objectives of this paper are to define novel aggregation operators (AOs) for aggregating different complex spherical fuzzy numbers (CSFNs) under the influence of their membership grades. The uncertainties included in the information are dealt with in contemporary studies of the fuzzy set and its extensions by membership grades, which are a subset of real numbers that lose some relevant information and hence alter the decision results. The conversion to these complex spherical fuzzy sets addresses the classes’ uncertainty, whose ranges differ from the specific subset of the complex subset of the unit disk. For this purpose, we defined new CSF power AOs. Some of the desirable properties of these operators have also been investigated. A multiattribute group decision-making (MAGDM) approach is implemented in the structure developed by the CSFNs on the basis of these operators. A numerical example concerning the selection of the best alternatives is given to demonstrate the effectiveness of the defined method and is tested by comparing its results with the various methods.
Semicentralized Power Sharing Scheme for Islanded Parallel-Connected Inverters
Authors: Azrik Roslan Mohd , Ahmed Khaled , Adam Grain , Elkhateb Ahmad , Issa Walid , Williams Barry
Published: March 2022

This paper presents a new control scheme that permits flexible power sharing between parallel inverters connected to microgrid operating in an island mode. The presented scheme processes the information of active and reactive output powers from all inverters in a central controller that calculates the set points for each inverter, based on the desired ratios of their output powers. These necessitate adjustment of the inverters’ terminal voltages (phase and magnitude) relative to the voltage at the common AC bus. The proposed power-sharing scheme uses a robust low bandwidth-based sharing communication to achieve precision and fast dynamic response, minimum circulating current between parallel inverters, and adapting to changes in line impedance, even under information transfer delays. The presented power-sharing scheme has been validated using MATLAB/Simulink simulation and experimental results obtained from a prototype of three three-phase parallel inverters connected to a number of loads. The results emphasize the superiority of the proposed topology performance under different loads (25% to 100%), line impedances, grid conditions, and communication delay.
Mechanistic Insight into Diosmin-Induced Neuroprotection and Memory Improvement in Intracerebroventricular-Quinolinic Acid Rat Model: Resurrection of Mitochondrial Functions and Antioxidants
Authors: Huang Mian , Singh Navpreet , Kainth Ritu , Khalid Mohammad , Kushwah Ajay Singh , Kumar Manish
Published: March 2022

Neurodegeneration is the final event after a cascade of pathogenic mechanisms in several brain disorders that lead to cognitive and neurological loss. Quinolinic acid (QA) is an excitotoxin derived from the tryptophan metabolism pathway and is implicated in several ailments, such as Alzheimer’s, Parkinson’s, Huntington’s, and psychosis disease. Diosmin (DSM) is a natural flavonoid possessing such properties that may halt the course of neurodegenerative progression. In past studies, free radical scavenging, along with properties, such as antihyperglycemic, anti-inflammatory, and vasoactive properties, of DSM were pragmatic. Hence, in the current experimentations, the neuroprotective activity of DSM was investigated in the QA rat prototype. QA was administered through the intracerebroventricular route (QA-ICV) in rats on day one, and DSM (50 and 100 mg/kg, intraperitoneal route) was given from day 1 to 21. Memory, gait, sensorimotor functions, and biomarkers of oxidative mutilation and mitochondrial functions were evaluated in the whole brain. Results showed significant deterioration of sensorimotor performance, gait, and working- and long-term memory in rats by QA-ICV. These behavioral anomalies were significantly attenuated by DSM (50 and 100 mg/kg) and donepezil (standard drug). QA-ICV-induced decrease in body mass (g), diet, and water ingestion were also attenuated by DSM or donepezil treatments. QA-ICV inhibited mitochondrial complex I and II activities that caused an increase in oxidative and nitrosative stress along with a reduction in endogenous antioxidants in the brain. DSM dose-dependently ameliorated mitochondrial functions and decreased oxidative stress in QA-ICV-treated rats. DSM can be a possible alternative in treating neurodegenerative disorders with underlying mitochondrial dysfunction pathology.
Ultrasound Image under Artificial Intelligence Algorithm to Evaluate the Intervention Effect of Accelerated Rehabilitation Surgery Nursing on Laparoscopic Hysterectomy
Authors: Yu Haiwei , Zhao Ziming , Duan Xiuping , Zhou Jian , Su Dechun
Published: March 2022

To explore the application value of accelerated rehabilitation surgery (ERAS) nursing in laparoscopic total hysterectomy, 120 patients who underwent laparoscopic total hysterectomy for benign uterine diseases in the hospital were selected as the research object. According to different nursing schemes, they were divided into 60 cases in the experimental group (ERAS nursing program) and 60 cases in the control group (traditional perioperative nursing). All patients underwent postoperative ultrasonography, and the intraoperative and postoperative rehabilitation indexes of the two groups were analyzed. Moreover, an improved standard Capon beamforming (ISCB) algorithm is proposed, which is compared with SCB algorithm, sequential regression algorithm (SER), and recursive least square (RLS) algorithm. The results showed that the center average power and background average power (−46.92, −33.85) of the ISCB algorithm were significantly lower than those of SCB algorithm (−36.18, −23.64), SER algorithm (−39.02, −27.31), and RLS algorithm (−34.88, −24.66), while the contrast and resolution (19.11, 15.57) were significantly higher than those of SCB algorithm (12.74, 9.01), SER algorithm (13.86, 7.89), and RLS algorithm (13.26, 8.26)

P
<
0.05

. The anal exhaust time (11.84 ± 2.15 hours), analgesic effect score (3.37 ± 1.03 points), hospitalization days (3.72 ± 0.74 days), and hospitalization expenses (11859.03 ± 735.24 ¥) in the experimental group were significantly lower than those in the control group (20.95 ± 3.44 hours, 6.12 ± 1.46 points, 5.48 ± 0.91 days, 16135.22 ± 680.55 ¥)

P
<
0.05

. The score of NRS evaluation scale in the experimental group (2.28 ± 0.37) was significantly better than that in the control group (4.09 ± 0.65)

P
<
0.05

. The proportion of patients in the experimental group (very satisfied + satisfied + generally satisfied) (100%) was significantly better than that in the control group (71%), and the difference was statistically significant

P
<
0.05

. In the experimental group, there were 2 cases of postoperative fever, 1 case of nausea and vomiting, and 2 cases of lower extremity venous thrombosis. In the control group, there were 4 cases of postoperative fever, 4 cases of nausea and vomiting, and 2 cases of lower extremity venous thrombosis. In summary, ultrasound imaging based on the ISCB algorithm can display the pelvic floor structure of patients undergoing laparoscopic total hysterectomy with high quality and improve the diagnostic rate of doctors. ERAS nursing can accelerate patients’ postoperative rehabilitation, reduce postoperative pain, and improve patients’ satisfaction. It was worthy to be popularized and applied in the clinic.
Identification of IL20RB as a Novel Prognostic and Therapeutic Biomarker in Clear Cell Renal Cell Carcinoma
Authors: Guo Hongda , Jiang Songlin , Sun Haoyu , Shi Benkang , Li Yan , Zhou Nan , Zhang Dongqing , Guo Hu
Published: March 2022

Background. Clear cell renal cell carcinoma (ccRCC) is a type of life-threatening malignant tumor of the urinary system. IL20RB, interleukin 20 receptor subunit beta, is a cytokine receptor subunit coding gene and was initially found to play a vital role in human cancers, while its role in ccRCC still remains unclear. Methods. In this work, we explored the prognostic value and therapeutic potential of IL20RB in ccRCC mainly by online tools. Firstly, we used UALCAN and GEPIA to explore the expression profile and prognostic value of IL20RB in various cancers; the expression profile in tumor cell lines was also analysed with CCLE and Expression Atlas. Then, we decided to focus on ccRCC for further analysis; we further demonstrated the significant correlation between expression and clinical features by GEPIA and UALCAN. In order to reveal the potential intrinsic mechanism responsible for the upregulation of IL20RB in ccRCC, we made genetic alternation analysis and methylation analysis. cBioPortal was used for genetic alternation analysis. UALCAN, MethSurv, and Xena were used for methylation analysis. To learn details of how IL20RB might function in ccRCC, we further conducted functional analysis and immune infiltration analysis. STRING and GSEA were used to do functional analysis. TIMER was used for immune infiltration analysis; KM plotter was used for survival analysis. Results. Results show that IL20RB is upregulated in ccRCC, and low methylation may be responsible for its upregulation. Both high expression and low methylation of IL20RB predict worse survival, and both have a strong positive correlation with clinical characteristics. In addition, results indicate that there exists a crosstalk between IL20RB and neutrophils. Furthermore, the immune microenvironment could influence the prognosis predicting ability of IL20RB. Conclusions. In conclusion, IL20RB plays an important role in ccRCC and is identified as a novel prognostic and potential therapeutic biomarker in ccRCC.
The Nervous System Contributes to the Tumorigenesis and Progression of Human Digestive Tract Cancer
Authors: Dai Dayou , Liu Hao
Published: March 2022

Tumors of the gastrointestinal tract are one of the highest incidences of morbidity and mortality in humans. Recently, a growing number of researchers have indicated that nerve fibers and nerve signals participate in tumorigenesis. The current overarching view based on the responses to therapy revealed that tumors are partly promoted by the tumor microenvironment (TME), endogenous oncogenic factors, and complex systemic processes. Homeostasis of the neuroendocrine-immune axis (NEI axis) maintains a healthy in vivo environment in humans, and dysfunction of the axis contributes to various cancers, including the digestive tract. Interestingly, nerves might promote tumor development via multiple mechanisms, including perineural invasion (PNI), central level regulation, NEI axis effect, and neurotransmitter induction. This review focuses on the association between digestive tumors and nerve regulation, including PNI, the NEI axis, stress, and neurotransmitters, as well as on the potential clinical application of neurotherapy, aiming to provide a new perspective on the management of digestive cancers.
ZrMOX Particles for Enhanced Removal of Methyl Orange from Wastewater: Preparation, Characterization, and Adsorption Study
Authors: Yang Hao , Sun Yulong , Zhang Qi , Pu Yanfeng , Wang Jianhong , Cao Leichang , Zhou Shuaishuai , Li Qian , Qiao Congzhen
Published: March 2022

The wide application of organic dyes in many industries has brought challenges to the effective treatment of organic wastewater. In this study, a series of ZrMOX (M: Fe, Co, Ni, Cu) particles were prepared by the coprecipitation method to adsorb methyl orange (MO) in aqueous solution. The adsorbents were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and N2 adsorption-desorption. The selected adsorbent with the best adsorption performance was ZrFeOX with a molar ratio of 1 : 1 and calcination temperature of 573 K; the maximum adsorption capacity was 138.95 mg·g-1. The adsorption behavior of MO onto the adsorbent was studied as a function of contact time, initial concentrations, adsorption temperature, and pH conditions. The analysis results showed that pseudo-second-order, Elovich, and Langmuir models were suitable to describe the adsorption behavior of MO on the adsorbent. In addition, regeneration experiments presented that the MO removal rate reached over 96% after repeated recycling for 5 times. The adsorbent developed in this work is not only simple to prepare and low cost but also green and energy-saving, which can make some contributions to environmental governance.
Abstract BS1-1: PR
Authors: Hagan C
Published: March 2022

Much debate exists surrounding how progesterone receptor (PR) expression and activation by native progesterone affects hormone receptor (HR)-positive breast cancer cells. While its expression is conserved in the majority of HR+ breast cancers, studies have failed to identify a clear link between progesterone signaling and breast cancer proliferation, in contrast to what has been shown for ER signaling. Clinically, many studies have utilized PR expression as an indicator of ER signaling, with associations between PR expression demonstrating greater responsiveness to anti-estrogen therapies and outcomes. However, convincing clinical trial data have shown that women taking progestin (synthetic progesterone)-containing hormone replacement therapy (HRT) have a significantly increased risk of developing breast cancer. Likewise, other clinical studies have demonstrated that progestins contribute to the development of more invasive breast cancers and increase mortality. These clinical findings are supported by a variety of pre-clinical studies using animal models, which collectively suggest that PR signaling enhances the development of invasive breast cancer. Finally, our studies and those of others suggest that PR has a specific transcriptional impact that is distinct from ER signaling. Collectively, these studies have demonstrated a key role for PR in the progression and outcome of HR+ breast cancer, which is distinct from estrogen-mediated proliferation signaling. We believe the lack of clinically available PR-targeted therapies in breast cancer is due to a lack of knowledge about exactly how PR contributes to breast cancer progression, as studies have failed to define a conclusive role for PR signaling in tumor growth. However, our recent studies have unexpectedly revealed a significant immune modulatory role for PR. Specifically, our results have demonstrated a clear role for PR in suppressing local anti-tumor immunity, which may explain reduced T-cell infiltrates and responsiveness to immune checkpoint inhibition observed in HR+ breast cancer. This presentation will discuss the current controversial data regarding PR and progesterone in promoting breast cancer proliferation, as well as highlight new data suggesting that PR/progesterone promote immune shielding for developing breast cancers.

Citation Format: C Hagan. PR [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr BS1-1.
Abstract ES1-3: The ideal partner to HER2 directed therapies
Authors: Hurvitz S
Published: March 2022

Approximately ten percent of breast cancers are characterized by amplification/overexpression of HER2 with expression of one or both hormone receptors, deemed “double positive” or “triple positive” breast cancer. Though this cancer subtype has a lower chance of pathologic complete response with neoadjuvant therapy, it benefits as much from HER2-targeted therapies and has a long-term outcome that is as good or better than outcomes associated with the hormone receptor negative, HER2-positive subtype. Importantly, hormone receptor expression provides another opportunity to target additional signaling pathways implicated in tumor cell growth and survival, thus potentially expanding the armamentarium of effective therapeutics for this cancer subtype. In this presentation, clinical trial evidence evaluating the use of HER2-targeted agents plus endocrine therapy in the curative and advanced stage settings will be considered, including recent data directly comparing an endocrine-based versus chemotherapy-based approach. Results from studies evaluating whether the addition of endocrine therapy to chemotherapy plus HER2-directed treatment leads to antagonistic, null, or additive effects will be presented. The benefit of HER1/HER2-directed tyrosine kinase inhibitors such as lapatinib and neratinib based on tumor hormone receptor expression will be assessed. Finally, data from preclinical and clinical studies evaluating novel therapeutic strategies including the use of CDK4/6- or PI3K-pathway inhibitors will be considered and ongoing clinical trials addressing the optimal management of this disease subtype will be reviewed.

Citation Format: S Hurvitz. The ideal partner to HER2 directed therapies [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES1-3.
Abstract ES4-1: Acupuncture
Authors: Bao T
Published: March 2022

Acupuncture is a Traditional Chinese Medicine technique that involves inserting and manipulating filiform needles into specific points on the body to alleviate symptoms. Although its mechanisms are not fully established, acupuncture appears to interact with and modulate the functioning of nerves, neurotransmitters, and neurohormones. Acupuncture has been used as a complementary therapy to treat a wide range of conditions experienced by breast cancer survivors. In this education session, I will discuss the use of acupuncture to reduce breast cancer treatment-related toxicities such as chemotherapy-induced nausea, vomiting, peripheral neuropathy, and cognitive-impairment; insomnia; hot flashes; and aromatase inhibitor-associated arthralgias. I will start by discussing the definition and mechanisms of acupuncture. I will then share clinical evidence and ongoing trials supporting and investigating the use of acupuncture for these toxicities, and end with a summary of my recommendations.

Citation Format: T Bao. Acupuncture [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES4-1.
Abstract ES4-4: Dietary modification to impact both tumor progression and treatment response
Authors: Simone NL
Published: March 2022

As the landscape of medicine changes to a precision approach to treating patients based on novel therapeutic interventions, the metabolic landscape of our country's population has also been changing at a rapid pace. As rates of metabolic disorders such as obesity and diabetes continues to increase in this country, so will the incidence of cancer. It is well established that patients who present with metabolic disorders such as obesity or diabetes often have increased recurrence rates, poor survival and increase toxicity despite standard treatments of chemotherapy and radiation. Unfortunately, this has created a new type of health disparity. To date, there has been no emphasis on creating novel therapeutics to address the metabolic profile created by an interplay of the patient, or the host, and the tumor. To begin to evaluate if metabolic processes can be altered to enhance radiation and chemotherapy, we began to employ caloric restriction as a concurrent treatment with cytotoxic therapy. Preclinical models demonstrated that caloric restriction could increase local control and overall survival and decrease distant metastases. We have now completed clinical trials to determine that caloric restriction could be used as a therapeutic option in patients undergoing radiation or chemotherapy and noted this treatment to be tolerated well by patients while decreasing typical toxicities of treatment. The preclinical and clinical effects of modulating the metabolic landscape of the patient and the tumor will be discussed as well as future directions.

Citation Format: NL Simone. Dietary modification to impact both tumor progression and treatment response [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES4-4.
Abstract ES5-1: Genomic and transcriptomic landscape of TNBC
Authors: Shao Z
Published: March 2022

Triple-negative breast cancer (TNBC) is highly heterogeneous. Due to the limited number of TNBCs that have been analyzed, molecular events driving subtypes and prognosis are not firmly established, and little is known regarding TNBC in non-Caucasian patients. Our findings advance the understanding of TNBC subtypes, subdivide the established transcriptome-based subtypes in search of more targeted therapeutic strategies, and offer potential insights to guide subtype-specific therapy. We further conducted a phase Ib/II subtyping-based and genomic biomarker guided umbrella trial to evaluate the efficacy of these targets. Objective response rate (ORR) of these 69 refractory metastatic TNBC patients was 29.0%, while the ORR of arm C (immunotherapy) was 52.6%. Still, genomic and transcriptomic-based target mining do not solve all the problems in TNBC treatment, for example the poor treatment efficacy in luminal androgen receptor (LAR) and basal-like immune-suppressed (BLIS) subtypes. Increasing the dimensions of omics to look for potential therapeutic targets would hopefully solve this problem.

Citation Format: Z Shao. Genomic and transcriptomic landscape of TNBC [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES5-1.
Abstract ES6-1: Approving New Therapies for Early Breast Cancer
Authors: Wedam S
Published: March 2022

The approval of a therapy by the US Food and Drug Administration (FDA) for the treatment of early breast cancer (EBC) requires substantial evidence of efficacy and an acceptable benefit-to risk evaluation from adequate and well-controlled investigations. There are two different regulatory pathways by which the FDA may approve drugs and biologics for the treatment of cancer. Regular or traditional approvals are based on the demonstration of direct clinical benefit, such as an improvement in survival or disease-related symptoms, or an improvement in an established surrogate. Examples of endpoints used for regular approval in EBC include invasive disease-free survival (IDFS) and event free survival (EFS). In 1992, new regulations were implemented, allowing for the accelerated approval (AA) of drugs for serious or life-threatening diseases in which the drugs seem to provide benefit over available therapy. AA is based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit. A post marketing requirement to confirm the effect on a direct clinical benefit is required. An example of an endpoint used for AA in EBC is pathologic complete response (pCR). Pertuzumab, neratinib, ado-trastuzumab emtansine and pembrolizumab have all received approvals for treatment of breast cancer in the neo/adjuvant setting over the last decade. Some of these approvals will be discussed to highlight various efficacy endpoints and clinical trial design features that may be used in the early breast cancer setting.

Citation Format: S Wedam. Approving New Therapies for Early Breast Cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES6-1.
Abstract ES7-1: Harnessing Lifestyle Interventions via Diet and Exercise for Cancer Risk Reduction
Authors: Iyengar NM
Published: March 2022

A growing body of evidence indicates the importance of maintaining optimal metabolic health to reduce the risk of developing cancer and to improve outcomes after cancer diagnosis. Classical and normal weight obesity are states of metabolic dysfunction, and highly prevalent risk factors for the development and growth of several cancers. Classical obesity (defined as a body mass index (BMI) ≥ 30) is a risk factor for at least 13 different types of cancer. Recent data indicate that up to one third of normal weight individuals have metabolic obesity and, subsequently, increased risk for several cancers including breast and colon. Methods to risk-stratify metabolic health and subsequent cancer risk beyond traditional anthropometric metrics such as BMI could improve the efficacy of lifestyle interventions aimed at reducing cancer risk and improving cancer outcomes. In this educational session, the molecular mechanisms linking classical and normal weight obesity to cancer growth will be presented. Obesity-related dysfunction can contribute to cancer pathogenesis and treatment resistance through various mechanisms, including those mediated by insulin, leptin, adiponectin, pro-inflammatory mediators, and hormone signaling pathways, particularly in women. Furthermore, adiposity-related changes can influence tumor vascularity and inflammation in the tumor microenvironment, which can support tumor development and growth. Building upon these mechanistic findings, several clinical trials testing “precision lifestyle” interventions targeted at specific biologic pathways are ongoing. Several randomized control trials testing diet, exercise, and weight loss interventions in cancer populations have demonstrated the feasibility of such interventions. Here, the next generation of lifestyle interventions, such as digital interventions, that target specific pathway dysregulation will be presented. Additionally, pharmacologic interventions that target host metabolism are under study as adjuncts to standard cancer therapy. As rates of classical and normal weight obesity continue to increase, the development of individualized and biologically rational lifestyle interventions could represent an impactful strategy to reduce the worldwide cancer burden.

Citation Format: NM Iyengar. Harnessing Lifestyle Interventions via Diet and Exercise for Cancer Risk Reduction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES7-1.
Abstract ES8-1: Options for reducing risk for lymphedema when ALND/regional nodal XRT are needed
Authors: Sbitany H
Published: March 2022

Upper extremity lymphedema following axillary lymph node harvest or radiation therapy, can be extremely debilitating and symptomatic in breast cancer patients, and significantly reduces quality of life. In recent years, surgical procedures to reduce the development and progression of lymphedema have become more prevalent. These surgical procedures carry the aim of restoring lymphatic flow in the extremity following disruption of native channels. The most common procedures include vascularized lymph node transfer (VLNT) to the axilla, and lymphaticovenous bypass (LV bypass). The goal of both procedures is to restore flow, and reduce symptoms (infections, cellulitis, and reduced range of motion). VLNT involves harvest and transfer of autologous lymph node packets from a separate area of the body (most frequently the groin or supraclavicular region), and placement into the involved axilla, followed by microsurgical revascularization of the lymph nodes. Through cell signaling, this allows development of new lymphatic channel pathways, and resumption of drainage. LV bypass involves localized microsurgical anastomosis of lymphatic channels in the downstream affected extremity, directly to superficial veins in their vicinity. This allows lymphatic channels, proximal to the site of obstruction, to still drain their collected lymphatic fluid, directly into the systemic venous circulation in the extremity. In most cases, multiple LV bypass anastomoses are performed, to enhance lymphatic outflow. Due to the safety and efficacy of both procedures, they continue to be incorporated more frequently and routinely as part of breast reconstruction treatment plans.

Citation Format: H Sbitany. Options for reducing risk for lymphedema when ALND/regional nodal XRT are needed [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr ES8-1.