bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Modified Sparrow Search Algorithm with Application in Side Lobe Level Reduction of Linear Antenna Array
Authors: Liang Qiankun , Chen Bin , Wu Huaning , Ma Chaoyi , Li Senyou
Published: June 2021

Antenna arrays play an increasingly important role in modern wireless communication systems. However, how to effectively suppress and optimize the side lobe level (SLL) of antenna arrays is critical for communication performance and communication capabilities. To solve the antenna array optimization problem, a new intelligent optimization algorithm called sparrow search algorithm (SSA) and its modification are applied to the electromagnetics and antenna community for the first time in this paper. Firstly, aimed at the shortcomings of SSA, such as being easy to fall into local optimum and limited convergence speed, a novel modified algorithm combining a homogeneous chaotic system, adaptive inertia weight, and improved boundary constraint is proposed. Secondly, three types of benchmark test functions are calculated to verify the effectiveness of the modified algorithm. Then, the element positions and excitation amplitudes of three different design examples of the linear antenna array (LAA) are optimized. The numerical results indicate that, compared with the other six algorithms, the modified algorithm has more advantages in terms of convergence accuracy, convergence speed, and stability, whether it is calculating the benchmark test functions or reducing the maximum SLL of the LAA. Finally, the electromagnetic (EM) simulation results obtained by FEKO also show that it can achieve a satisfactory beam pattern performance in practical arrays.
The Association between the rs312457 Genotype of the SLC16a13 Gene and Diabetes Mellitus in a Chinese Population
Authors: Zheng Hui , Pu Suying , Zhang Yu , Fan Yujuan , Yang Jialin
Published: June 2021

Objective. SLC16a genes encode H + -coupled monocarboxylate transporters (MCTs). MCTs are involved in maintaining interstitial fluids’ pH and regulating insulin’s binding affinity to its receptor, which is a potential mechanism for the onset of diabetes. In this research, we make explorations of the association between the rs312457 genotype of the SLC16a13 gene and diabetes in the Chinese population. Methods. It included 384 type 2 diabetes patients and 1,468 healthy control subjects in total. We measured the anthropometric parameters, glycaemic index, homeostasis model assessment-B cell (HOMA-%B), lipid profile, and homeostasis model assessment-insulin resistance (HOMA-IR). The associations between the rs312457 genotype and type 2 diabetes were analyzed. Results. The rs312457 genotype was markedly in relation to type 2 diabetes (

P
=
0.002

). The frequency of the rs312457 risk allele (G) was 4.8%, higher than that of the wild-type allele (A) in patients of type 2 diabetes, indicating that allele (G)’s presence seemed to make the risk of type 2 diabetes go up. Compared to the GA and AA genotypes, the GG genotype of rs312457 significantly increased the risk of contracting diabetes mellitus (

P
≤
0.001

). Moreover, the rs312457 genotype was associated with HOMA-%B. Subjects harbored the GG genotype of rs312457, whose HOMA-%B level went down in comparison with that in subjects harboring the AA genotype (

P
=
0.023

). Conclusion. Our results revealed that the rs312457 genotype of the SLC16a13 gene was correlated with the development of diabetes mellitus in the Chinese population.
Chemical Gastroenterocolitis after Dental Root Canal Therapy with Camphorated and Mentholated Chlorophenol
Authors: Kalandarishvili Mikheil , Kolbe Ernst-Wolfgang , Winde Günther , Kaspari Michael
Published: June 2021

A 78-year-old man with a history of pancolitis, after the treatment of dental abscess with oral antibiotics and local application of camphorated and mentholated chlorophenol (CMCP), presented with abdominal pain of 4-day duration, as well as hair loss in the area of moustache and finger nail lifting. He was already treated with rectal application of budesonide because of pancolitis, diagnosed 6 weeks ago and interpreted as an allergic reaction to clindamycin. For further investigation, we performed gastroscopy and colonoscopy, which showed the edematous mucosa with polypus-like changes of the whole mucosa of the stomach, duodenum, first part of the jejunum, distal ileum, complete colon, and rectum. The diagnosis was complicated and was achieved in synopsis with anamnestic details, such as endodontic application of camphorated chlorophenol. The patient symptoms abated after he commenced on mesalazine therapy.
Activity Screening of the Herb Caesalpinia sappan and an Analysis of Its Antitumor Effects
Authors: Li Yuan , Dong Minghong , Wu Zijun , Huang Yongqi , Qian Haibing , Huang Cong
Published: June 2021

Aim. Traditionally, C. sappan medicine was the heartwood, which needs to be cut down as a whole. In this research, the antitumor activity and mechanisms of the leaves and stems were compared with the roots of Caesalpinia sappan; it was in order to investigate whether stems and leaves of C. sappan could be used to replace heartwood for antitumor treatment, thereby reducing resource destruction. Methods. MTT assays were used to identify the active sites of C. sappan based on the application of human liver cancer (HuH-7) cells. High-performance liquid chromatography (HPLC) was used to analyze polar extracts. We also established a H22 hepatoma-bearing mouse model by administering intraperitoneal injections of petroleum ether extracts from the leaves and stems (SY②) at doses of 20 and 65 mg/kg. Mice in the i.g. group were administered intragastrically with the same extracts (at doses of 100 and 325 mg/kg) at the same time (12 days). Results. The antitumor site of C. sappan was the petroleum ether extract. The IC50 for the petroleum ether extract of roots (SG②) was 56.10 μg/ml, while that for the leaves and stems (SY②) was 77.20 μg/ml. Grey relational analysis indicated 11 active fraction peaks that were closely related to antitumor activity. The size of tumors in H22 hepatoma-bearing mice was reduced significantly in mice administered with petroleum ether extracts from the leaves and stems (inhibition rates of high doses were 55.31% and 60.56%). Fibrous tissue proliferation, inflammatory cell infiltration, tumor cell necrosis, and the expression of proliferating cell nuclear antigen (PCNA) and vascular endothelial growth factor (VEGF) were all lower than in the control group (VEGF

P

 < 0.001 and PCNA

P

 < 0.05). Conclusion. Petroleum ether extracts of the roots, leaves, and stems of C. sappan exhibit certain antitumor effects. Our data indicate that the mechanisms underlying these effects may relate to a reduction in the expression of PCNA and VEGF and the inhibition of angiogenesis. Our findings indicate that we can expand the medicinal use of C. sappan to the leaves and stems, thus improving resource utilization and reducing resource damage.
Outage Analysis in SWIPT-Based Decode-and-Forward Relay Networks with Partial Relay Selection
Authors: Tin Phu Tran , Phan Van-Duc , Nguyen Phu X. , Nguyen Thanh-Long , Chau Dong-Si Thien , Nguyen Tan N.
Published: June 2021

This work studies the SWIPT-based half-duplex (HD) decode-and-forward (DF) relay network, wherein the relay user can scavenge power from the source’s radio-frequency (RF) signals and then utilize it to convey the information to the destination. Specifically, two SWIPT-based relaying schemes, termed static power splitting- (SPS-) based relaying (SPSR) and optimal dynamic power splitting- (DPS-) based relaying (ODPSR), are proposed to investigate the benefits of each one fully. Based on the above discussions, the relaying system’s performance for outage probability (OP) is studied. Concretely, we derive the analytical expressions for both SPSR and DPSR methods. Finally, the numerical simulations are executed to corroborate the analysis and simulation results.
GNFCVulFinder: NDEF Vulnerability Discovering for NFC-Enabled Smart Mobile Devices Based on Fuzzing
Authors: Wang Zhiqiang , Lin Yuheng , Zhuo Zihan , Gu Jieming , Yang Tao
Published: June 2021

Near-field communication (NFC) is a set of communication protocols that enable two electronic devices. Its security and reliability are welcomed by mobile terminal manufactures, banks, telecom operators, and third-party payment platforms. Simultaneously, it has also drawn more and more attention from hackers and attackers, and NFC-enabled devices are facing increasing threats. To improve the security of the NFC technology, the paper studied the technology of discovering security vulnerabilities of NFC Data Exchange Format (NDEF), the most important data transmission protocol. In the paper, we proposed an algorithm, GTCT (General Test Case Construction and Test), based on fuzzing to construct test cases and test the NDEF protocol. GTCT adopts four strategies to construct test cases, manual, generation, mutation, and “reverse analysis,” which can detect logic vulnerabilities that fuzzing cannot find and improve the detection rate. Based on GTCT, we designed an NDEF vulnerability discovering framework and developed a tool named “GNFCVulFinder” (General NFC Vulnerability Finder). By testing 33 NFC system services and applications on Android and Windows Phones, we found eight vulnerabilities, including DoS vulnerabilities of NFC service, logic vulnerabilities about opening Bluetooth/Wi-Fi/torch, design flaws about the black screen, and DoS of NFC applications. Finally, we give some security suggestions for the developer to enhance the security of NFC.
Uranium Decontamination from Waste Soils by Chlorination with ZrCl4 in LiCl-KCl Eutectic Salt
Authors: Jang Junhyuk , Kim Tack-Jin , Park Sungbin
Published: June 2021

The dissolution behavior of U, contained in the soils, was examined through chlorination with ZrCl4 to reduce the U concentration to clearance levels. Natural soils, composed of Si, Al, and approximately 2 ppm U, acted as surrogates for the contaminated soils. A salt mixture of LiCl-KCl-ZrCl4 was prepared in an Al2O3 crucible at 500°C, and SiO2 or natural soils were loaded for the chemical reactions. The reaction of SiO2 and Al2O3 with ZrCl4 was monitored by cyclic voltammetry, and no obvious change was observed. The results showed that SiO2 and Al2O3 were stable against ZrCl4. The reaction of natural soils with ZrCl4 indicated that the U content decreased from 2 to 1.2 ppm, while ∼0.4 ppm U appeared in the salt. Thus, the U, in the soils, dissolved into the salt by chlorination with ZrCl4. Therefore, based on these results, a new method to remediate U-contaminated soil wastes by chlorination with ZrCl4, followed by electrorefining of U, is suggested.
Towards Effective Classification of aMCI Based on Resting‐State Multiscale Brain Features and Machine Learning Approaches
Authors: Cai Chunting , Yan Jiqiang , Zhou Yu , Zheng Wuyang , Yang Chenhui , Zhang Zhemin , Chen Bokui , Hong Dan
Published: June 2021

Smart healthcare has undergone new opportunities and challenges with the arrival of the Industry 4.0 era. The intelligent imaging diagnosis system is a staple part of smart healthcare, helping doctors make clinical decisions. Nevertheless, intelligent diagnosis analysis is still confronted with the issue that it is challenging to extract effective features from the limited and high‐dimensional data, particularly in resting‐state data of amnesic mild cognitive impairment (aMCI). Furthermore, the intelligent imaging diagnosis system for aMCI is conductive to make timely predicting groups that may convert to Alzheimer’s disease (AD). To improve the system’s detection performance and reduce its data redundancy, we first develop an adaptive structure feature generation strategy (ASFGS) based on the Laplacian matrix and sparse autoencoder to obtain the structural features of brain functional network (BFN). Concurrently, we present a multiscale local feature detection strategy (MLFDS) to overcome the low utilization of local features of BFN. And finally, multiscale features, including structural features and multiscale local features, are fused by concatenation method to further improve the detection performance of aMCI system. Support vector machine based on radial basis function (RBF‐SVM) for small data learning is adopted to evaluate the effectiveness of the proposed features. Besides, we employ leave‐one‐out cross‐validation strategy to avoid the overfitting problem of classifier training process. The experiment results elucidate that the accuracy (ACC) and the area under the curve (AUC) in this work provide 86.57% and 86.36%, respectively, which outperforms the traditional methods and offers new insights for accuracy requirements of the aMCI system.
Impact of Adenosine Analogue, Adenosine‐5 ′‐N‐Ethyluronamide (NECA), on Insulin Signaling in Skeletal Muscle Cells
Authors: Haddad Mansour
Published: June 2021

Background and Objectives. To investigate whether there are molecular interactions between adenosine analogue (NECA) and insulin signaling pathways at multiple nuclear receptors and at the metabolic and inflammatory levels. Materials and Methods. Rat L6 skeletal muscle cells were cultured in 25 cm2 flasks. These differentiated cells were treated, and then, quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) (probe‐based) was used to measure the relative mRNA expression level for metabolic, inflammatory, and nuclear receptor genes including peroxisome proliferator‐activated receptor gamma (PGC‐1α), carnitine palmitoyl transferase 1 beta (CPT1B), long‐chain acyl‐CoA de hydrogenase (LCAD), acetyl‐CoA carboxylase beta (ACCβ), pyruvate dehydrogenase kinase 4 (PDK4), hexokinase II (HKII), phosphofructokinase (PFK), interleukin‐6 (IL‐6), and nuclear receptor subfamily 4, group A (NR4A) at different treatment conditions. Results. Adenosine‐5 ′‐N‐ethyluronamide (NECA), a stable adenosine analogue, significantly stimulate inflammatory mediator (IL‐6) (p < 0.001) and nuclear receptors (NR4A) (p < 0.05) and significantly modulate metabolic (PFK, LCAD, PGC‐1α, and CPT1B) gene expressions in skeletal muscle cells (p < 0.05, p < 0.05, p < 0.001, and p < 0.01, respectively). This present study shows that there is a noteworthy crosstalk between NECA and insulin at various metabolic levels including glycolysis (HKII), fatty acid oxidation (ACCβ), and insulin sensitivity (PDK4). Conclusions. A novel crosstalk between adenosine analogue and insulin has been demonstrated for the first time; evidence has been gathered in vitro for the effects of NECA and insulin treatment on intracellular signaling pathways, in particular glycolysis and insulin sensitivity in skeletal muscle cells.
Construction and Validation of a Lung Cancer Diagnostic Model Based on 6-Gene Methylation Frequency in Blood, Clinical Features, and Serum Tumor Markers
Authors: Kang Chunyan , Wang Dandan , Zhang Xiuzhi , Wang Lingxiao , Wang Fengxiang , Chen Jie
Published: June 2021

Lung cancer has a high mortality rate. Promoting early diagnosis and screening of lung cancer is the most effective way to enhance the survival rate of lung cancer patients. Through computer technology, a comprehensive evaluation of genetic testing results and basic clinical information of lung cancer patients could effectively diagnose early lung cancer and indicate cancer risks. This study retrospectively collected 70 pairs of lung cancer tissue samples and normal human tissue samples. The methylation frequencies of 6 genes (FHIT, p16, MGMT, RASSF1A, APC, DAPK) in lung cancer patients, the basic clinical information, and tumor marker levels of these patients were analyzed. Then, the python package “sklearn” was employed to build a support vector machine (SVM) classifier which performed 10-fold cross-validation to construct diagnostic models that could identify lung cancer risk of suspected cases. Receiver operation characteristic (ROC) curves were drawn, and the performance of the combined diagnostic model based on several factors (clinical information, tumor marker level, and methylation frequency of 6 genes in blood) was shown to be better than that of models with only one pathological feature. The AUC value of the combined model was 0.963, and the sensitivity, specificity, and accuracy were 0.900, 0.971, and 0.936, respectively. The above results revealed that the diagnostic model based on these features was highly reliable, which could screen and diagnose suspected early lung cancer patients, contributing to increasing diagnosis rate and survival rate of lung cancer patients.
The CD200–CD200R Axis Promotes Squamous Cell Carcinoma Metastasis via Regulation of Cathepsin K
Authors: Khan Iasha Z. , Del Guzzo Christina A. , Shao Anqi , Cho Jiyoon , Du Rong , Cohen Adrienne O. , Owens David M.
Published: June 2021

The CD200–CD200R immunoregulatory signaling axis plays an etiologic role in the survival and spread of numerous cancers, primarily through suppression of antitumor immune surveillance. Our previous work outlined a prometastatic role for the CD200–CD200R axis in cutaneous squamous cell carcinoma (cSCC) that is independent of direct T-cell suppression but modulates the function of infiltrating myeloid cells. To identify effectors of the CD200–CD200R axis important for cSCC metastasis, we conducted RNA sequencing profiling of infiltrating CD11B+Cd200R+ cells isolated from CD200+ versus CD200-null cSCCs and identified the cysteine protease cathepsin K (Ctsk) to be highly upregulated in CD200+ cSCCs. CD11B+Cd200R+ cells expressed phenotypic markers associated with myeloid-derived suppressor cell–like cells and tumor-associated macrophages and were the primary source of Ctsk expression in cSCC. A Cd200R+ myeloid cell–cSCC coculture system showed that induction of Ctsk was dependent on engagement of the CD200–CD200R axis, indicating that Ctsk is a target gene of this pathway in the cSCC tumor microenvironment. Inhibition of Ctsk, but not matrix metalloproteinases, significantly blocked cSCC cell migration in vitro. Finally, targeted CD200 disruption in tumor cells and Ctsk pharmacologic inhibition significantly reduced cSCC metastasis in vivo. Collectively, these findings support the conclusion that CD200 stimulates cSCC invasion and metastasis via induction of Ctsk in CD200R+ infiltrating myeloid cells.

Significance:

These findings highlight the relationship between CD200–CD200R and cathepsin K in cutaneous squamous cell carcinoma metastasis and suggest that either of these components may serve as a viable therapeutic target in this disease.
IQGAP3, a YAP Target, Is Required for Proper Cell-Cycle Progression and Genome Stability
Authors: Leone Marina , Cazorla-Vázquez Salvador , Ferrazzi Fulvia , Wiederstein Janica L. , Gründl Marco , Weinstock Grit , Vergarajauregui Silvia , Eckstein Markus , Krüger Marcus , Gaubatz Stefan , Engel Felix B.
Published: June 2021

Controlling cell proliferation is critical for organism development, tissue homeostasis, disease, and regeneration. IQGAP3 has been shown to be required for proper cell proliferation and migration, and is associated to a number of cancers. Moreover, its expression is inversely correlated with the overall survival rate in the majority of cancers. Here, we show that IQGAP3 expression is elevated in cervical cancer and that in these cancers IQGAP3 high expression is correlated with an increased lethality. Furthermore, we demonstrate that IQGAP3 is a target of YAP, a regulator of cell cycle gene expression. IQGAP3 knockdown resulted in an increased percentage of HeLa cells in S phase, delayed progression through mitosis, and caused multipolar spindle formation and consequentially aneuploidy. Protein–protein interaction studies revealed that IQGAP3 interacts with MMS19, which is known in Drosophila to permit, by competitive binding to Xpd, Cdk7 to be fully active as a Cdk-activating kinase (CAK). Notably, IQGAP3 knockdown caused decreased MMS19 protein levels and XPD knockdown partially rescued the reduced proliferation rate upon IQGAP3 knockdown. This suggests that IQGAP3 modulates the cell cycle via the MMS19/XPD/CAK axis. Thus, in addition to governing proliferation and migration, IQGAP3 is a critical regulator of mitotic progression and genome stability.

Implications:

Our data indicate that, while IQGAP3 inhibition might be initially effective in decreasing cancer cell proliferation, this approach harbors the risk to promote aneuploidy and, therefore, the formation of more aggressive cancers.
REX-1 Represses RASSF1a and Activates the MEK/ERK Pathway to Promote Tumorigenesis in Prostate Cancer
Authors: Liu Weijing , Xie An , Tu Chunhua , Liu Weipeng
Published: June 2021

Epigenetics play an important role in the pathogenesis of prostate cancer; it is urgent to investigate vital transcription factors in methylation regulation with the aim to develop novel treatment strategies targeting prostate cancer. As a member of the zinc finger protein family, REX-1 (reduced expression-1) is a transcription factor that has been reported to be closely linked to the development of several cancers. So far, the expression level and precise function of REX-1 in prostate cancer remain largely unknown. Here, we show that REX-1 was overexpressed in prostate cancer clinical tissues, and its expression level was closely correlated with patient prognosis. REX-1 affected prostate tumor growth in vivo by MEK/ERK phosphorylation. Mechanistic studies indicated that REX-1 recruited DNMT3b (DNA methyltransferase 3b), inhibited the transcription of RASSF1a (RAS association domain family 1a), and further modulated methylation of RASSF1a promoter. Intervention of the REX-1/DNMT3b/RASSF1a axis may shed light on the development of novel therapeutic approaches for prostate cancer treatment.

Implications:

REX1 overexpression recruits DNMT3b and downregulates RASSF1a by promoter methylation, suggesting that epigenetic intervention may contribute to prostate cancer treatment.
Membrane-Associated RING-CH 8 Functions as a Novel PD-L1 E3 Ligase to Mediate PD-L1 Degradation Induced by EGFR Inhibitors
Authors: Qian Guoqing , Guo Jianping , Vallega Karin A. , Hu Changjiang , Chen Zhen , Deng Yunfu , Wang Qiming , Fan Songqing , Ramalingam Suresh S. , Owonikoko Taofeek K. , Wei Wenyi , Sun Shi-Yong
Published: June 2021

Expression of programmed death-ligand 1 (PD-L1) on cancer cells is a critical mechanism contributing to immunosuppression and immune escape. PD-L1 expression may also affect therapeutic outcomes of epidermal growth factor receptor (EGFR)-targeted therapy (e.g., with osimertinib/AZD9291) against EGFR-mutant non–small cell lung cancers (NSCLC) and can even be altered during the treatment albeit with largely undefined mechanisms. This study primarily focuses on elucidating the mechanism by which osimertinib induces PD-L1 degradation in addition to validating osimertinib's effect on decreasing PD-L1 expression in EGFR-mutant NSCLC cells and tumors. Osimertinib and other EGFR inhibitors effectively decreased PD-L1 levels primarily in EGFR-mutant NSCLCs and xenografted tumors. Osimertinib not only decreased PD-L1 mRNA expression, but also prompted proteasomal degradation of PD-L1 protein, indicating both transcriptional and posttranslational mechanisms accounting for osimertinib-induced reduction of PD-L1. Knockdown of β-TrCP or inhibition of GSK3 failed to prevent PD-L1 reduction induced by osimertinib. Rather, knockdown of membrane-associated RING-CH 8 (MARCH8) that encodes a membrane-bound E3 ubiquitin ligase rescued osimertinib-induced PD-L1 reduction. Furthermore, manipulation of MARCH8 expression accordingly altered PD-L1 degradation rate. Critically, MARCH8 interacted with PD-L1 through its N-terminal region and also ubiquitinated PD-L1 in cells. Collectively, these results strongly suggest that MARCH8 is a previously undiscovered E3 ubiquitin ligase responsible for PD-L1 degradation including osimertinib-induced PD-L1 degradation, establishing a novel connection between MARCH8 and PD-L1 regulation.

Implications:

This study has demonstrated a previously undiscovered function of MARCH8 in mediating PD-L1 degradation induced by EGFR inhibitors in EGFR-mutant NSCLC cells, establishing a novel connection between MARCH8 and PD-L1 regulation.
Genomic and Transcriptomic Analyses of Breast Cancer Primaries and Matched Metastases in AURORA, the Breast International Group (BIG) Molecular Screening Initiative
Authors: Aftimos Philippe , Oliveira Mafalda , Irrthum Alexandre , Fumagalli Debora , Sotiriou Christos , Gal-Yam Einav Nili , Robson Mark E. , Ndozeng Justin , Di Leo Angelo , Ciruelos Eva M. , de Azambuja Evandro , Viale Giuseppe , Scheepers Elsemieke D. , Curigliano Giuseppe , Bliss Judith M. , Reis-Filho Jorge S. , Colleoni Marco , Balic Marija , Cardoso Fatima , Albanell Joan , Duhem Caroline , Marreaud Sandrine , Romagnoli Dario , Rojas Beatriz , Gombos Andrea , Wildiers Hans , Guerrero-Zotano Angel , Hall Peter , Bonetti Andrea , Larsson Karolina Fs , Degiorgis Martina , Khodaverdi Silvia , Greil Richard , Sverrisdóttir Ásgerdur , Paoli Marta , Seyll Ethel , Loibl Sibylle , Linderholm Barbro , Zoppoli Gabriele , Davidson Nancy E. , Johannsson Oskar Th , Bedard Philippe L. , Loi Sherene , Knox Susan , Cameron David A. , Harbeck Nadia , Montoya Maite Lasa , Brandão Mariana , Vingiani Andrea , Caballero Carmela , Hilbers Florentine S. , Yates Lucy R. , Benelli Matteo , Venet David , Piccart Martine J.
Published: June 2021

AURORA aims to study the processes of relapse in metastatic breast cancer (MBC) by performing multi-omics profiling on paired primary tumors and early-course metastases. Among 381 patients (primary tumor and metastasis pairs: 252 targeted gene sequencing, 152 RNA sequencing, 67 single nucleotide polymorphism arrays), we found a driver role for GATA1 and MEN1 somatic mutations. Metastases were enriched in ESR1, PTEN, CDH1, PIK3CA, and RB1 mutations; MDM4 and MYC amplifications; and ARID1A deletions. An increase in clonality was observed in driver genes such as ERBB2 and RB1. Intrinsic subtype switching occurred in 36% of cases. Luminal A/B to HER2-enriched switching was associated with TP53 and/or PIK3CA mutations. Metastases had lower immune score and increased immune-permissive cells. High tumor mutational burden correlated to shorter time to relapse in HR+/HER2− cancers. ESCAT tier I/II alterations were detected in 51% of patients and matched therapy was used in 7%. Integration of multi-omics analyses in clinical practice could affect treatment strategies in MBC.

Significance:

The AURORA program, through the genomic and transcriptomic analyses of matched primary and metastatic samples from 381 patients with breast cancer, coupled with prospectively collected clinical data, identified genomic alterations enriched in metastases and prognostic biomarkers. ESCAT tier I/II alterations were detected in more than half of the patients.

This article is highlighted in the In This Issue feature, p. 2659
Establishment of a Systemic Inflammatory Response Syndrome Model and Evaluation of the Efficacy of Umbilical Cord Mesenchymal Stem Cell Transplantation
Authors: Ruan Guang-ping , Yao Xiang , Mo Ping , Wang Kai , Yang Zai-ling , Tian Ni-ni , Liu-Gao Mi-yang , Wang Jin-xiang , Cai Xue-min , Li Zi-an , Pang Rong-qing , Pan Xing-hua
Published: June 2021

Based on the characteristics of modern weapon injury, a repetitive model of traumatic systemic inflammatory response syndrome (SIRS) and an evaluation system were established. The models were treated with GFP-labeled tree shrew umbilical cord mesenchymal stem cells (UCMSCs). Forty out of 50 tree shrews were used to make a unilateral femoral comminuted fracture. Lipopolysaccharide was injected intravenously to create a traumatic SIRS model. The other 10 shrews were used as normal controls. After the model was established for 10 days, 20 tree shrews were injected intravenously with GFP-labeled UCMSCs, and 18 tree shrews were not injected as the model control group. The distribution of GFP-labeled cells in vivo was measured at 2 and 10 days after injection. Twenty days after treatment, the model group, the normal control group, and the treatment group were taken to observe the pathological changes in each tissue, and blood samples were taken for the changes in liver, renal, and heart function. Distribution of GFP-positive cells was observed in all tissues at 2 and 10 days after injection. After treatment, the HE staining results of the treatment group were close to those of the normal group, and the model group had a certain degree of lesions. The results of liver, renal, and heart function tests in the treatment group were returned to normal, and the results in the model group were abnormally increased. UCMSCs have a certain effect on the treatment of traumatic SIRS and provide a new technical solution for modern weapon trauma treatment.
Closure of Full-Thickness Macular Holes Associated with Macular Edema with Medical Therapy
Authors: Kokame Gregg T. , Johnson Mark W. , Lim Jennifer , Flynn Harry W. , de Carlo Talisa , Yannuzzi Nicolas , Ryan Edwin H. , Omizo Jase N. , Sridhar Jayanth , Staropoli Patrick , Goldhagen Brian , Lian Rebecca
Published: June 2021

Purpose: The purpose of this study was to report the closure of macular hole without surgery in 7 cases using medical therapies. Methods: The retrospective review of 7 cases of full-thickness macular holes, which closed after medical therapy without surgery. Results: Seven eyes of 7 patients developed full-thickness macular holes, which initially closed on medical therapy without surgery. Six patients were kept on maintenance therapy; 1 recurred and 5 did not develop recurrence. One patient was taken off of maintenance therapy and later developed recurrent macular hole requiring macular hole surgery. Conclusions: Medical therapy to decrease macular edema may facilitate macular hole closure and should be considered, especially for small macular holes with significant edema. Reopening of macular holes may occur after stopping topical maintenance therapy for macular edema, which occurred at 10 weeks and 9 months after maintenance therapy was discontinued or markedly tapered.
Social Network Characteristics Predict Loneliness in Older Adults
Authors: Kim Hairin , Kwak Seyul , Youm Yoosik , Chey Jeanyung
Published: June 2021

Introduction: Social isolation is detrimental to late-life health outcomes. Although objective social isolation is a major source of perceived loneliness, how different layers of social disconnection systematically constitute the subjective experience of loneliness remains unclear. Methods: This study focused on older adults who participated in the Korean Social Life, Health, and Aging Project (KSHAP) (n = 1,724; mean age = 72.91 years) and examined how the proximal and distal characteristics of social networks predict loneliness using a hierarchical linear regression model. The study also investigated whether the major loss of social roles (marital and working status) influences perceived loneliness through the proximal and distal aspects of social networks by cross-sectional mediation analysis. Results: This study found that the proximal (subjective number of connections) and distal (brokerage and embeddedness) aspects of social networks additively explained the frequency of loneliness. Moreover, the loss of late-life social roles (marital and working status) was related to an increase in loneliness, where the distal characteristic of social networks mediated this relationship. Discussion/Conclusion: The results of this study suggest that the proximal and the distal characteristic of social networks is a social determinant predicting loneliness in late life. Besides, the loss of bridging and cohesive position among community networks may be a critical pathway to psychosocial transition after marital and working status changes.
In vitro Inhibition of Biofilm Formation on Silicon Rubber Voice Prosthesis: Α Systematic Review and Meta-Analysis
Authors: Tsikopoulos Alexios , Petinaki Efi , Festas Charalampos , Tsikopoulos Konstantinos , Meroni Gabriele , Drago Lorenzo , Skoulakis Charalampos
Published: June 2021

Introduction: Biofilm formation on voice prostheses is the primary reason for their premature implant dysfunction. Multiple strategies have been proposed over the last decades to achieve inhibition of biofilm formation on these devices. The purpose of this study was to assess the results of the available in vitro biofilm inhibition modalities on silicone rubber voice prostheses. Methods: We conducted a systematic search in PubMed, Embase, and the Cochrane Central Register of Controlled Trials databases up to February 29, 2020. A total of 33 in vitro laboratory studies investigating the efficacy of different coating methods against Candida, Staphylococcus, Streptococcus, Lactobacilli, and Rothia biofilm growth on silicone rubber medical devices were included. Subgroup analysis linked to the type of prevention modality was carried out, and quality assessment was performed with the use of the modified CONSORT tool. Results: Data from 33 studies were included in qualitative analysis, of which 12 qualified for quantitative analysis. For yeast biofilm formation assessment, there was a statistically significant difference in favor of the intervention group (standardized mean difference [SMD] = −1.20; 95% confidence interval [CI] [−1.73, −0.66]; p < 0.0001). Subgroup analysis showed that combined methods (active and passive surface modification) are the most effective for biofilm inhibition in yeast (SMD = −2.53; 95% CI [−4.02, −1.03]; p = 0.00001). No statistically significant differences between intervention and control groups were shown for bacterial biofilm inhibition (SMD = −0.09; 95% CI [−0.68, 0.46]; p = 0.65), and the results from the subgroup analysis found no notable differences between the surface modification methods. After analyzing data on polymicrobial biofilms, a statistically significant difference in favor of prevention methods in comparison with the control group was detected (SMD = −2.59; 95% CI [−7.48, 2.31]; p = 0.30). Conclusions: The meta-analysis on biofilm inhibition demonstrated significant differences in favor of yeast biofilm inhibition compared to bacteria. A stronger inhibition with the application of passive or combined active and passive surface modification techniques was reported.
Isolated Upward Rotation of the Fetal Cerebellar Vermis (Blake’s Pouch Cyst) Is a Normal Variant: An Analysis of 111 Cases
Authors: Salsi Ginevra , Volpe Grazia , Montaguti Elisa , Fanelli Tiziana , Toni Francesco , Maffei Monica , Votino Carmela , Pompilii Eva , Pilu Gianluigi , Volpe Paolo
Published: June 2021

Introduction: The objective of the study was to provide more detailed data about fetal isolated upward rotation of the cerebellar vermis rotation (Blake’s pouch cyst) in particular regarding pregnancy outcome. Methods: This is a retrospective study of all cases of fetal isolated upward rotation of the cerebellar vermis (URCV) diagnosed in 3 referral centers in Italy from January 2009 to November 2019. Whenever possible, prenatal magnetic resonance imaging (MRI) was performed and a fetal karyotype was obtained. A detailed follow-up was obtained by consultation of medical records, interview with the parents, and the pediatricians. Results: Our study population included 111 patients with a prenatal diagnosis of isolated URCV made at a median gestational age of 21 weeks +3 days (interquartile range (IQR) 21 + 0–22 + 2). The median brain stem-vermis (BV) angle was 27° (IQR 24–29°). In 37.9% of the cases, a regression of the finding with restoration of normal anatomy was noted at a follow-up scan or at postnatal checks. A BV angle of 25° or less predicted regression with a probability in excess of 90%. MRI was performed in utero or at birth in 101 patients and always confirmed sonographic diagnosis. Fetal CGH array and/or karyotype was available in 97 cases and was always normal, but in 1 case. A postnatal follow-up was available in 102 infants (mean 7 months, range 0–10 years of age) and documented a normal neurologic development in all the cases. Conclusions: Isolated URCV is most likely a normal variant of fetal anatomy without clinical consequences, at least at an early follow-up. A BV angle of 25° or less predicts intrauterine regression of the finding, but the outcome is good in all the cases. When a confident sonographic diagnosis is made, MRI is not mandatory. The risk of a chromosomal anomaly in these cases is probably low.
Long-Term Results after Suprapubic ARC Procedure for the Treatment of Stress Urinary Incontinence in Women: A Retrospective Data Analysis
Authors: Jasarevic Samra , Jankovic Doroteja , Hutterer Georg C. , Riedl Regina , Pichler Georg P. , Pummer Karl , Primus Günter
Published: June 2021

Introduction: The aim of this study was to evaluate long-term safety and efficacy of the suprapubic arc (SPARC) procedure for the surgical treatment of stress urinary incontinence (SUI). Materials and Methods: 139 female patients treated by SPARC were included in this retrospective analysis, whereby 126 patients were available for follow-up after 1 year, 70 after 6 years, and 41 after 9 years. The cough test, pad test, uroflowmetry, and post-void residual volume measurements were performed. Severity of bother (visual analogous scale [VAS] 0–10), continence, and the satisfaction rate were assessed. Objective cure was defined as a negative cough test and pad weight ≤1 g, subjective cure as no urine loss during daily activities and no usage of pads. The VAS, pad weight, number of pads per day, and maximal flow rate were compared preoperatively and postoperatively. Results: Objective cure rates at 1, 6, and 9 years were 78.6, 71.4, and 70.7% and subjective cure rates were 72.2, 55.7, and 65.8%, respectively. The VAS, pad weight, number of pads, and maximal flow rate decreased significantly. Study limitations include a relatively small sample size and the retrospective fashion of the analysis. Conclusions: In the long-term context, SPARC showed to represent an efficient and safe procedure for treatment of female SUI.
A formação profissional de Biblioteconomia para atuação em bibliotecas escolares: retrato das universidades federais brasileiras
Authors: Santos Andrea Pereira , Resende Vanessa Ferreira de Almeida
Published: June 2021

Trata-se de um estudo cujo objetivo é analisar os projetos pedagógicos dos cursos de Biblioteconomia das universidades federais brasileiras e responder a seguinte problemática: como acontece a formação de bibliotecários nas universidades para atuação em bibliotecas escolares? A justificativa para tal indagação é o crescimento das demandas do mercado de trabalho com o advento da Lei n. 12.244 de junho de 2010, que estabelece a universalização das bibliotecas em instituições de ensino e o prazo máximo de dez anos para que essa lei seja cumprida. A metodologia deste trabalho consistiu em uma pesquisa exploratória, utilizando-se da abordagem quantitativa para seu desenvolvimento, integrando fases básicas da pesquisa, tais como: planejamento, revisão teórica, coleta e análise de dados; e a avaliação. Os resultados obtidos foram confrontados com o embasamento teórico, levando em consideração os conceitos de biblioteca escolar, letramento informacional, competência informacional e pesquisa escolar. Os indícios mostram que, os cursos de Biblioteconomia das instituições analisadas tendem à formação básica para biblioteca em seus moldes tradicionais, mas buscam, mesmo que timidamente, acompanhar as mudanças que ocorreram ao longo dos anos em especial a atuação na biblioteca escolar
Impact of High-Deductible Health Plans on Emergency Department Patients With Nonspecific Chest Pain and Their Subsequent Care
Authors: Chou Shih-Chuan , Hong Arthur S. , Weiner Scott G. , Wharam J. Frank
Published: June 2021

Background:

Timely evaluation of acute chest pain is necessary, although most evaluations will not find significant coronary disease. With employers increasingly adopting high-deductible health plans (HDHP), how HDHPs impact subsequent care after an emergency department (ED) diagnosis of nonspecific chest pain is unclear.

Methods:

Using a commercial and Medicare Advantage claims database, we identified members 19 to 63 years old whose employers exclusively offered low-deductible (≤$500) plans in 1 year, then, at an index date, mandated enrollment in HDHPs (≥$1000) for a subsequent year. We matched them with contemporaneous members whose employers only offered low-deductible plans. Primary outcomes included population rates of index ED visits with a principal diagnosis of nonspecific chest pain, admission during index ED visits, and index ED visits followed by noninvasive cardiac testing within 3 and 30 days, coronary revascularization, and acute myocardial infarction hospitalization within 30 days. We performed a cumulative interrupted time-series analysis, comparing changes in annual outcomes between the HDHP and control groups before and after the index date using aggregate-level segmented regression. Members from higher-poverty neighborhoods were a subgroup of interest.

Results:

After matching, we included 557 501 members in the HDHP group and 5 861 990 in the control group, with mean ages of 42.0 years, 48% to 49% female, and 67% to 68% non-Hispanic White individuals. Employer-mandated HDHP switches were associated with a relative decrease of 4.3% (95% CI, –5.9 to –2.7; absolute change, –4.5 [95% CI, –6.3 to –2.8] per 10 000 person-years) in nonspecific chest pain ED visits and 11.3% (95% CI, –14.0 to –8.6) decrease (absolute change, –1.7 per 10 000 person-years [95% CI, –2.1 to –1.2]) in visits leading to hospitalization. There was no significant decrease in subsequent noninvasive testing or revascularization procedures. An increase in 30-day acute myocardial infarction admissions was not statistically significant (15.9% [95% CI, –1.0 to 32.7]; absolute change, 0.3 per 10 000 person-years [95% CI, –0.01 to 0.5]) but was significant among members from higher-poverty neighborhoods.

Conclusions:

Employer-mandated HDHP switches were associated with decreased nonspecific chest pain ED visits and hospitalization from these ED visits, but no significant change in post-ED cardiac testing. However, HDHP enrollment was associated with increased 30-day acute myocardial infarction admission after ED diagnosis of nonspecific chest pain among members from higher-poverty neighborhoods.
DRD4 (Dopamine D4 Receptor) Mitigate Abdominal Aortic Aneurysm via Decreasing P38 MAPK (mitogen-activated protein kinase)/NOX4 (NADPH Oxidase 4) Axis–Associated Oxidative Stress
Authors: Liu Xuesong , Guo Yansong , Yang Yuxue , Qi Chunlei , Xiong Ting , Chen Yue , Wu Gengze , Zeng Chunyu , Wang Daxin
Published: June 2021

Oxidative stress plays a vital role in the development of abdominal aortic aneurysm (AAA). DRD4 (dopamine D4 receptor) is involved in oxidative stress. Here, we reasoned that DRD4 may mitigate AAA by its antioxidative effect. Currently, in vivo, DRD4 expression was reduced in AAA patients and experimental models determined by quantitative polymerase chain reaction and Western blot. Reactive oxygen species (ROS) was increased in elastase perfused aorta from
Drd4
−/−
mice compared with elastase perfused wild-type (
WT
) aorta determined by dihydroethidium staining and malondialdehyde, accompanying with more apoptotic vascular smooth muscle cells, inflammatory infiltration, and ECM (extracellular matrix) degradation determined by terminal deoxynucleotidyl transferase-mediated nick end labeling assay, immunohistochemistry, Van Gieson staining, and zymography, respectively. However, pharmacological activation of DRD4 reduced the ROS production and mitigated pathological characteristics of AAA. In vitro, activated DRD4 alleviated ROS production and apoptosis determined by 2,7-dichlorodihydrofluorescein diacetate, dihydroethidium, malondialdehyde, and flow cytometry, whereas DRD4 deficiency or inhibited DRD4 exerted the opposite effect in vascular smooth muscle cells. In terms of mechanism, in vivo, DRD4 deficiency upregulated NOX4 (NADPH oxidase 4) expression instead of other subunits, meanwhile, phosphorylated P38 mitogen-activated protein kinase was also augmented instead of other mitogen-activated protein kinase pathways. In vitro, pharmacological activation of DRD4 downregulated phosphorylated P38 and NOX4 in vascular smooth muscle cells, vice versa. Interestingly, DRD4 mediated the expression of NOX4 through a P38 mitogen-activated protein kinase pathway–dependent manner, which regulated ROS production. DRD4 mitigated AAA progression by downregulating P38 mitogen-activated protein kinase/NOX4 axis mediated ROS production in vascular smooth muscle cells. Therefore, DRD4 may serve as a novel therapeutic target for AAA treatment.
Characterization of the Renin-Angiotensin-Aldosterone System in Young Healthy Black Adults: The African Prospective Study on the Early Detection and Identification of Hypertension and Cardiovascular Disease (African-PREDICT Study)
Authors: Gafane-Matemane Lebo F. , Kruger Ruan , Smith Wayne , Mels Catharina M.C. , Van Rooyen Johannes M. , Mokwatsi Gontse G. , Uys Aletta S. , Brits Sanette J. , Schutte Aletta E.
Published: June 2021

This study presents a detailed profile of the renin-angiotensin-aldosterone system (RAAS), electrolytes, volume loading, blood pressure (BP), and total peripheral resistance in healthy young Black and White adults. We also explored longitudinal associations between BP and RAAS. We included normotensive Black (N=543) and White (N=573) adults (20–30 years) and followed N=324 over ≈4.5 years. We measured clinic (central, brachial) and 24-hour BP, total peripheral resistance and left ventricular dimensions. We determined serum NT-proBNP (N-terminal prohormone B-type natriuretic peptide), RAAS, and 24-hour urinary and serum Na
+
and K
+
. RAAS components, left ventricular internal diameter (diastole), end diastolic volume and NT-proBNP were lower (
P
<0.001) in Black than White adults, despite similar clinic SBP. However, central systolic BP and total peripheral resistance were higher in Black adults (
P
<0.001). Plasma renin activity and angiotensin II were comparable between Black and White groups (
P
>0.05) only in quartile 1 of Na
+
/K
+
values. In both groups, RAAS was lower in the higher quartiles of 24-hour Na
+
and NT-proBNP (all
P
-trend≤0.014). Over 4.5 years, all BPs increased in the Black (
P
<0.001) but not White group. The increase in central systolic BP over time was associated with elevated serum aldosterone only in Black adults (β=0.18,
P
=0.038). We found that RAAS concentrations in healthy Black adults were half of those of White participants, which may not be explained by volume expansion. Yet, baseline aldosterone predicted BP elevation over time in Black adults. RAAS was similar in Black and White adults only at low Na
+
/K
+
scenarios, suggesting an essential role of potassium.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03292094.