bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of 17 Prenatal Cases with the Chromosomal 1q21.1 Copy Number Variation
Authors: Wen Xiaohui , Xing Huanxia , Qi Keyan , Wang Hao , Li Xiaojun , Zhu Jianjiang , Chen Wenqi , Cui Limin , Zhang Jing , Qi Hong
Published: April 2022

Copy number variations (CNVs) at the chromosomal 1q21.1 region represent a group of hot-spot recurrent rearrangements in human genome, which have been detected in hundreds of patients with variable clinical manifestations. Yet, report of such CNVs in prenatal scenario was relatively scattered. In this study, 17 prenatal cases involving the 1q21.1 microdeletion or duplication were recruited. The clinical survey and imaging examination were performed; and genetic detection with karyotyping and CNV analysis using chromosomal microarray (CMA) or CNVseq were subsequently carried out. These cases were all positive with 1q21.1 CNV, yet presented with exceedingly various clinical and utrasonographic indications. Among them, 12 pregnancies carried 1q21.1 deletions, while the other 5 carried 1q21.1 duplications, all of which were within the previously defined breaking point (BP) regions. According to the verification results, 9 CNVs were de novo, 7 were familial, and the other 1 was not certain. We summarized the clinical information of these cases, and the size and distribution of CNVs, and attempted to analyze the association between these two aspects. The findings in our study may provide important basis for the prenatal diagnosis and genetic counseling on such conditions in the future.
Opinion Mining-Based Term Extraction Sentiment Classification Modeling
Authors: Kim Tae Yeun , Kim Hyoung Ju
Published: April 2022

The spread of social media has accelerated the formation and dissemination of user review data, which contain subjective opinions of users on products, in an e-commerce environment. Because these reviews significantly influence other users, opinion mining has garnered substantial attention in analyzing the positive and negative opinions of users and deriving solutions based on these analytical results. Terms that include sentimental information and used in user reviews serve as the most crucial element in sentimental classification. In this regard, it is crucial to distinguish the most influential terms in user reviews. This study proposed a document-level sentiment classification model based on the collection and application of user reviews generated in an e-commerce environment. Here, a term information extraction method was applied to the proposed model to select core terms, classify the selected terms according to parts of speech (POS), determine terms that can increase information power and influence, and adopt these terms in opinion mining research, based on SVM, SVM+, and SVM+MTL techniques. The results obtained from evaluating the proposed model indicate that it exhibited excellent sentiment analysis performance. The proposed model is expected to be effectively utilized in providing enhanced services for users and increasing competitiveness in the e-commerce environment.
Prescribed Performance-Based Adaptive Terminal Sliding Mode Control for Virtual Synchronous Generators
Authors: Dou Zhenlan , Tang Lianqing , Sun Yongbao , Zhang Chunyan , Yang Weilin , Xu Dezhi
Published: April 2022

Due to the lack of inertia and damping in the distributed power system with power electronic devices as interface, the stability of the power system will be adversely affected when the distributed power system is connected to the grid. In order to solve the problem of low inertia and improve stability, an adaptive terminal sliding mode control method based on the electromagnetic transient characteristics of virtual synchronous generators is proposed. During the design process, projection operators and parameter adaptive law control methods are introduced to compensate for parameter errors caused by environmental interference. Furthermore, by utilizing a prescribed performance function, the terminal sliding surface of the system will have the desired dynamic response, and variations of the system tracking error can be restricted. Simulation results show that the proposed controller has improved control accuracy and response speed, frequency stability, and power response.
Ulam–Hyers Stability for a Class of Caputo-Type Fractional Stochastic System with Delays
Authors: Song Meiling , Luo Zhiguo
Published: April 2022

In this study, we explore the Caputo-type fractional stochastic differential equations (FSDEs) with delays. Firstly, the existence and uniqueness of the solutions for the considered system are obtained under the non-Lipschitz condition by using the Carath

e
´

odory approximation method with the aid of Fatous Lemma, It

o
^

isometry, Cauchy–Schwarz inequality, and Gronwall’s inequality. Secondly, we study the Ulam–Hyers (U–H) stability of the addressed equations with the aid of the Cauchy–Schwarz inequality and Gronwall’s inequality. Finally, an example with numerical simulation is presented to support the validity of our theory.
Image Semantic Segmentation Method Based on Deep Learning in UAV Aerial Remote Sensing Image
Authors: Ling Min , Cheng Qun , Peng Jun , Zhao Chenyi , Jiang Ling
Published: April 2022

The existing semantic segmentation methods have some shortcomings in feature extraction of remote sensing images. Therefore, an image semantic segmentation method based on deep learning in UAV aerial remote sensing images is proposed. First, original remote sensing images obtained by S185 multirotor UAV are divided into smaller image blocks through sliding window and normalized to provide high-quality image set for subsequent operations. Then, the symmetric encoding-decoding network structure is improved. Bottleneck layer with 1 × 1 convolution is introduced to build ISegNet network model, and pooling index and convolution are used to fuse semantic information and image features. The improved encoding-decoding network gradually strengthens the extraction of details and reduces the number of parameters. Finally, based on ISegNet network, five-classification problem is transformed into five binary classification problems for network training, so as to obtain high-precision image semantic segmentation results. The experimental analysis of the proposed method based on TensorFlow framework shows that the accuracy value reaches 0.901, and the F1 value is not less than 0.83. The overall segmentation effect is better than those of other comparison methods.
Removal of Micro-Doppler Effects in ISAR Imaging Based on the Joint Processing of Singular Value Decomposition and Complex Variational Mode Extraction
Authors: Wei Xu , Yang Jun , Lv Mingjiu , Chen Wenfeng , Ma Xiaoyan , Xia Saiqiang , Long Ming
Published: April 2022

For inverse synthetic aperture radar (ISAR) imaging of targets with micromotion parts, the removal of micro-Doppler (m-D) effects is the key procedure. However, under the condition of a sparse aperture, the echo pulse is limited or incomplete, giving rise to the difficulty of eliminating m-D effects. Thus, a novel m-D effects removal algorithm is proposed, which can effectively eliminate m-D effects, as well as the interference introduced by noise and sparse aperture in the ISAR image of the main body. The proposed algorithm mainly includes two processing steps. First, combined with the cut-off point determined by the normalized singular value difference spectrum, the rough estimation of the main body is achieved by singular value decomposition (SVD). Then, the variational mode extraction (VME) is extended to complex variational mode extraction (CVME). The constrained variational problem constructed by bandwidth and spectral overlap constraints is solved by the alternating direction method of multipliers (ADMM), and the precise estimation of the main body is obtained. Experimental results based on both simulated and measured data demonstrate that the proposed algorithm can acquire the high-resolution ISAR image of the main body under noisy and sparse conditions.
A Survey on Location Privacy Attacks and Prevention Deployed with IoT in Vehicular Networks
Authors: Ahmed Nadeem , Deng Zhongliang , Memon Imran , Hassan Fayaz , Mohammadani Khalid H. , Iqbal Rizwan
Published: April 2022

Vehicular ad hoc networks (VANETs) connect two or more vehicles wirelessly to enable data exchange in an Internet of Things (IoT) environment. In VANETs, location privacy is the most crucial piece of information, and its protection is the top priority. However, the location privacy threats have not been adequately addressed in positioning for IoT in VANETs. This paper provides an overview of location privacy attacks and their solutions to address the problems caused by attacks in any IoT environment. Secondly, we have analyzed specific solutions based on anonymity (pseudonym) and cryptographic solutions using a digital signature technique. This enables to improve user privacy and security of location-based services for IoT in VANET. Moreover, we have proposed a faster 5G solution for the VANETs as it rapidly disseminates the data in fast-moving vehicles.
Single Nucleotide Polymorphism in the ADIPOQ Gene Modifies Adiponectin Levels and Glycemic Control in Type Two Diabetes Mellitus Patients
Authors: Alfaqih Mahmoud A. , Al-hawamdeh Aisha , Amarin Zouhair O. , Khader Yousef S. , Mhedat Khawla , Allouh Mohammed Z.
Published: April 2022

Diabetes mellitus (DM) is the ninth leading cause of death worldwide. Mortality from DM is largely attributed to disease complications. Glycemic control of DM patients reduces mortality. Studies indicated that the lack of glycemic control in DM patients could be influenced by the genetic background of the patients. Evidence suggests that adiponectin levels are dysregulated in DM patients with poor glycemic control. Serum adiponectin level is a heritable trait influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. It is hypothesized that SNPs in ADIPOQ could modify glycemic control in DM patients. To test this hypothesis, 375 type 2 DM (T2DM) patients were recruited. Patients were classified into good vs. poor glycemic control according to hemoglobin A1c levels. Study subjects were genotyped for variations of four SNPs in ADIPOQ (rs17300539, rs266729, rs2241766, and rs1501299). Adiponectin levels were measured from the serum. Our analysis showed that reduced serum adiponectin, a longer duration of treatment, and increased insulin resistance were all significant predictors of poor glycemic control. Moreover, the T allele and the TT genotype of rs2241766 were significantly more frequent in patients with poor glycemic control (P < 0.05). Individuals with the TT genotype of rs2241766 had significantly lower levels of serum adiponectin (P < 0.05). It was concluded that lower levels of serum adiponectin and the T allele of rs2241766 SNP in ADIPOQ were associated with poor glycemic control in T2DM patients.
Development of a Colloidal Gold Immunochromatographic Strip for the One-Step Evaluation of the Total Content of Rhein and Aloe-Emodin in Rhubarb
Authors: Sun Ping , Li Xin-Peng , Xin Jie , Xue Tao , Zhang Bo , Liu Yan-Juan
Published: April 2022

In this study, a colloidal gold immunochromatographic strip was developed for simultaneous detection of rhein and aloe-emodin in rhubarb. The cutoff value, defined as the lowest concentration for which the test line was invisible on the strip, was 50 ng mL−1 for both rhein and aloe-emodin. By contrast, the cutoff value for emodin was 2,000 ng mL−1. No competitive inhibition was observed up to 5,000 ng mL−1 of physcion, chrysophanol, sennoside A, sennoside B, or rhaponticin. Semiquantitative analyses of the total contents of rhein and aloe-emodin in raw drug materials via our colloidal gold immunochromatographic strips produced results agreeable with those determined by HPLC. Taken together, our findings suggest that the implementation of our colloidal gold immunochromatographic strips provides a rapid one-step method for estimating the total contents of rhein and aloe-emodin, which may represent a powerful tool for quality control of rhubarb.
Necroptosis-Associated lncRNA Prognostic Model and Clustering Analysis: Prognosis Prediction and Tumor-Infiltrating Lymphocytes in Breast Cancer
Authors: Tao Shigui , Tao Kunlin , Cai Xiaoyong
Published: April 2022

Necroptosis plays an important role in tumor genesis and progression. This study aims to identify necroptosis-related lncRNAs (NR-lncRNAs) in breast cancer (BC), and their prognostic value and relationship with the tumor immune environment (TIE) through bioinformatics. Methods. A total of 67 necroptosis-related genes (NRGs) are retrieved, and 13 prognostically relevant NR-lncRNAs are identified by co-expression and Univariate Cox regression analyses. After unsupervised clustering analysis, the patients are classified into three clusters, and their survival and immune infiltration are compared. Lasso regression analysis is conducted to construct a prognostic model using eight lncRNAs (USP30-AS1, AC097662.1, AC007686.3, AL133467.1, AP006284.1, NDUFA6-DT, LINC01871, AL135818.1). The model is validated by Kaplan-Meier survival analysis, Multivariate Cox regression analysis, and receiver-operating characteristic (ROC) curves. Correlation analysis is useful to identify associations between risk scores and clinicopathological features. GSEA, drug prediction, and immune checkpoints analysis are further used to differentiate between the risk groups. Results. The C3 cluster has longer overall survival (OS) and the highest immune score, indicative of an immunologically hot tumor that may be sensitive to immunotherapy. Furthermore, the OS is significantly higher in the low-risk group, even after dividing the patients into subgroups with different clinical characteristics. The area under the ROC curve (AUC) for 1-, 3-, and 5-year survival in the training set are 0.761, 0.734, and 0.664, respectively, which indicate the moderate predictive performance of the model. Conclusion. NR-lncRNAs can predict the prognosis of BC, distinguish between hot and cold tumors, and are potential predictive markers of the immunotherapy response.
Evaluation Model of College English Teaching Effect Based on Particle Swarm Algorithm and Support Vector Machine
Authors: Wei Chunyan , Tsai Sang-Bing
Published: April 2022

Based on the principle of particle swarm algorithm and support vector machine, this article aims to improve the classification performance of college English teaching effect and explores the best support vector machine parameter optimization algorithm to promote college English teaching for the theory and application research of data analysis. First, the advantages and disadvantages of common support vector machine parameter selection methods such as grid search algorithm, gradient descent method, and swarm intelligence algorithm are studied. Secondly, this article has a detailed analysis and comparison of various other algorithms. Finally, the study analyzed the advantages and disadvantages of the quantum particle swarm algorithm, introduced the dual-center idea into the quantum particle swarm algorithm, and proposed an improved quantum particle swarm algorithm. Through simulation experiments, it is proved that the improved quantum particle swarm algorithm is more superior in optimizing the parameters of support vector machine. In general, this paper uses the PSO algorithm to simultaneously solve the SVM feature selection and parameter optimization problems and has achieved good results. Within the scope of the literature that the author has, there is still a lack of work in this area. Compared with the existing algorithms, the algorithm proposed in this paper has stronger feature selection ability and higher efficiency.
Erythrocyte Storage Lesion Improvements Mediated by Naringin Screened from Vegetable/Fruit Juice Using Cell Extract and HPLC-MS
Authors: She Yuqi , Liu Qiong , Xiong Xiyue , Li Ning , Zhang Jian
Published: April 2022

In blood banking, storage at 4°C for weeks is known to cause damages to erythrocytes, called storage lesions that may later cause transfusion-related adverse events. In previous experiments, we found that vegetable/fruit juices can effectively reduce the storage lesion. Currently, we attempt to analyze the potential bioactive components and test whether the compounds can improve the storage lesions of erythrocytes. Equal portions in wet weight of 20 fresh vegetables and fruits were blended with phosphate buffered solution (PBS), and clear solutions were produced as additive to the packed erythrocytes from consented blood donors at 1 : 10 ratio (ml : gram). The blood samples were stored for 35 days at 4°C, and the supernatants were performed high liquid chromatography–mass spectrometry (HPLC-MS) analysis at 0 days, 14 days, and 35 days. The blood bags supplemented with identified bioactive components were stored in a refrigerator for 35 days, and the morphology, complete blood count (CBC), phosphatidylserine (PS) extroversion, hemolysis, and reactive oxygen species (ROS) levels were measured at the end of storage. Five potential bioactive components from vegetable/fruit juices contributed to the improvements of storage lesion. One of the compounds was unequivocally identified as naringin, and two were tentatively assigned as vitexin 6″-O-malonyl 2″-O-xyloside and luteolin 7-(6″-malonyl neohesperidoside). Naringin alleviated the storage lesion of red blood cells (RBCs) by reducing ROS levels and living cell extraction with HPLC-MS is a simple, reliable, and effective method for screening potential bioactive components.
Association of Low Expression of NUMB in Peripheral Blood with Acute Myocardial Infarction
Authors: Meng Heyu , Li Lihong , Ruan Jianjun , Chen Yanqiu , Yan Zhaohan , Liu Jinsha , Li Xiangdong , Mao Cuiying , Yang Ping
Published: April 2022

Objective. Our study’s goal was to find out acute myocardial infarction (AMI) patients’ NUMB gene expression patterns and to evaluate its role as a diagnostic marker for AMI detection. Methods. Peripheral blood was drawn from 124 individuals who had an AMI and 115 patients who had stable coronary artery disease (SCAD). The real-time quantitative polymerase chain reaction was used to measure the mRNA expression level of the NUMB gene in peripheral blood. Results. The AMI group’s NUMB gene expression was 0.906 (0.181–0.954), whereas the SCAD group’s expression was 1.024 (0.207–1.127). However, the AMI group had 0.885 times lower NUMB mRNA expression than the SCAD group

P
<
0.05

. Conclusion. Multivariate logistic regression evaluation found that lower NUMB expression was correlated with an increased risk of coronary artery disease. However, age and fasting plasma glucose levels were not associated with decreased NUMB expression.
Molecular Hydrogen Inhibits Colorectal Cancer Growth via the AKT/SCD1 Signaling Pathway
Authors: Zhang Xiangyan , Tao Geru , Zhao Ya’nan , Xing Sijie , Jiang Jie , Liu Boyan , Qin Shucun
Published: April 2022

Objective. Molecular hydrogen (H2) has been considered a potential therapeutic target in many cancers. Therefore, we sought to assess the potential effect of H2 on colorectal cancer (CRC) in this study. Methods. The effect of H2 on the proliferation and apoptosis of RKO, SW480, and HCT116 CRC cell lines was assayed by CCK‐8, colony formation, and flow cytometry assays. The effect of H2 on tumor growth was observed in xenograft implantation models (inhalation of 67% hydrogen two hours per day). Western blot and immunohistochemistry analyses were performed to examine the expression of p‐PI3K, PI3K, AKT, pAKT, and SCD1 in CRC cell lines and xenograft mouse models. The expression of SCD1 in 491 formalin‐fixed, paraffin‐embedded CRC specimens was investigated with immunochemistry. The relationship between SCD1 status and clinicopathological characteristics and outcomes was determined. Results. Hydrogen treatment suppressed the proliferation of CRC cell lines independent of apoptosis, and the cell lines showed different responses to different doses of H2. Hydrogen also elicited a potent antitumor effect to reduce CRC tumor volume and weight in vivo. Western blot and IHC staining demonstrated that H2 inhibits CRC cell proliferation by decreasing pAKT/SCD1 levels, and the inhibition of cell proliferation induced by H2 was reversed by the AKT activator SC79. IHC showed that SCD1 expression was significantly higher in CRC tissues than in normal epithelial tissues (70.3% vs. 29.7%, p = 0.02) and was correlated with a more advanced TNM stage (III vs. I + II; 75.9% vs. 66.3%, p = 0.02), lymph node metastasis (with vs. without; 75.9% vs. 66.3%, p = 0.02), and patients without a family history of CRC (78.7% vs. 62.1%, p = 0.047). Conclusion. This study demonstrates that high concentrations of H2 exert an inhibitory effect on CRC by inhibiting the pAKT/SCD1 pathway. Further studies are warranted for clinical evaluation of H2 as SCD1 inhibitor to target CRC.
Research on the Method of Digital Media Content Creation Based on the Internet of Things
Authors: Sun Yiming
Published: April 2022

This paper provides an in-depth study and analysis of the approach to digital media content creation using IoT technology. This study first investigates both WSN and NB-IoT technologies separately and then combines them to investigate the networking structure based on NB-IoT and WSN as well as the related technologies based on fusion. Then, the coverage method of the node redeployment of the traditional network of wireless sensors is elaborated. For the traditional method, a series of problems such as poor node connectivity and low coverage caused by not conducting a local search of subgroup nodes are proposed, and the node redeployment method of wireless sensor network based on the frog hopping algorithm is proposed, introducing the frog hopping algorithm, combining local search of subgroup and global information exchange, and proposing that for wireless sensor network nodes. We propose initializing the nodes of the wireless sensor network, combining the global information exchange with the subgroup, determining the range of the detectable area of the wireless sensor, and solving the calculus method for the irregular area to get the optimal network nodes so that the nodes of the wireless sensor network can be redeployed. In terms of system, this design abandons the CIS structure, which is more used in the current IoT and uses B/S structure and Java-web technology to design a web-based system. SSH (Struts + Spring + Hibernate) framework, AJAX asynchronous request technology, and JXLL/JFreechart technology are fully applied to improve the practicality and comfort of the system, reduce development and maintenance costs, and facilitate popularization. After the system design was completed, the modules were tested with the existing experimental conditions. The experimental results show that the system is designed to be reliable and can operate normally with high stability and practical significance.
Biological Effect of Quercetin in Repairing Brain Damage and Cerebral Changes in Rats: Molecular Docking and In Vivo Studies
Authors: Mehany Ahmed B. M. , Belal Amany , Santali Eman Y. , Shaaban Salwa , Abourehab Mohammad A. S. , El-Feky Ola A. , Diab Mahmoud , Abou Galala Fawzy M. A. , Elkaeed Eslam B. , Abdelhamid Ghada
Published: April 2022

This study examined the protective effect of quercetin against high‐altitude‐induced brain damage in rats. A molecular docking study was performed to investigate the potential effect of quercetin in reducing brain damages through its ability to target the oxidative stress enzymes. Biomarker assessment screening assays were also performed then followed by in vivo studies. Three groups of rats were divided into the control group, an untreated animal model group with induced brain damage, and finally, the quercetin treated group that received quercetin dose equal to 20 mg/kg of their body weights. Molecular docking studies and biomarker assessment screening assays proved the potential effect of quercetin to affect the level of representative biomarkers glutathione (GSH), glutathione reductase (GR), glutathione‐S‐transferase (GST), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA). Additionally, the protective effect of quercetin against high altitude, low pressure, and low oxygen was also investigated by exploring the brain histopathology of experimental rats. Brain damage was observed in the untreated animal model group. After treatment with quercetin, the cerebral edema in the brain tissues was improved significantly, confirming the protective effects of quercetin. Therefore, quercetin can be used as a natural food additive to protect from the highaltitude‐induced brain damage.
LncRNA MBNL1-AS1 Represses Proliferation and Cancer Stem-Like Properties of Breast Cancer through MBNL1-AS1/ZFP36/CENPA Axis
Authors: Ding Yu , Li Yingjie , Duan Yunqiang , Wang Wan , Zheng Wei , Cheng Weilun , Qi Yuan , Feng Jianyuan , Chen Ziang , Yu Tianshui , Hu Anbang , Wang Ting , Li Mingcui , Zhang Hanyu , Li Yanling , Ma Fei , Guo Baoliang
Published: April 2022

Background. Emerging studies have revealed long noncoding RNAs (lncRNAs) were key regulators of cancer progression. In this research, the expression and roles of MBNL1-AS1 were explored in breast cancer (BC). Methods. In this study, the MBNL1-AS1 expression in breast cancer tissue, as well as in cell line, was studied by qRT-PCR assays. The effects of MBNL1-AS1 on proliferation and stemness were evaluated by MTT assays, colony formation assays, orthotopic breast tumor mice models, extreme limiting dilution analysis (ELDA), fluorescence in situ hybridization (FISH), flow cytometry assays, and sphere formation assays. Flexmap 3D assays were performed to show that MBNL1-AS1 downregulated the centromere protein A (CENPA) secretion in BC cells. Western blot, RNA pull-down assays, RNA immunoprecipitation (RIP) assays, and FISH were conducted to detect the mechanism. Results. The results showed that the expression levels of MBNL1-AS1 were downregulated in breast cancer tissues and cell lines. In vitro and in vivo studies demonstrated that overexpression of MBNL1-AS1 markedly inhibited BC cells proliferation and stemness. RNA pull-down assay, RIP assay, western blot assay, and qRT-PCR assay showed that MBNL1-AS1 downregulated CENPA mRNA via directly interacting with Zinc Finger Protein 36 (ZFP36) and subsequently decreased the stability of CENPA mRNA. Restoration assays also confirmed that MBNL1-AS1 suppressed the CENPA-mediated proliferation and stemness in breast cancer cells. Conclusions. The new mechanism of how MBNL1-AS1 regulates BC phenotype is elucidated, and the MBNL1-AS1/ZFP36/CENPA axis may be served as a therapeutic target for BC patients.
The Genetic Evolution of Metastasis
Authors: Rogiers Aljosja , Lobon Irene , Spain Lavinia , Turajlic Samra
Published: April 2022

Cancer is an evolutionary process that is characterized by the emergence of multiple genetically distinct populations or clones within the primary tumor. Intratumor heterogeneity provides a substrate for the selection of adaptive clones, such as those that lead to metastasis. Comparative molecular studies of primary tumors and metastases have identified distinct genomic features associated with the development of metastases. In this review, we discuss how these insights could inform clinical decision-making and uncover rational antimetastasis treatment strategies.
Bilateral Oophorectomy and the Risk of Breast Cancer in BRCA1 Mutation Carriers: A Reappraisal
Authors: Kotsopoulos Joanne , Lubinski Jan , Gronwald Jacek , Menkiszak Janusz , McCuaig Jeanna , Metcalfe Kelly , Foulkes William D. , Neuhausen Susan L. , Sun Sophie , Karlan Beth Y. , Eisen Andrea , Tung Nadine , Olopade Olufunmilayo I. , Couch Fergus J. , Huzarski Tomasz , Senter Leigha , Bordeleau Louise , Singer Christian F. , Eng Charis , Fruscio Robert , Pal Tuya , Sun Ping , Narod Steven A.
Published: April 2022

Background:

The lack of consensus on whether bilateral oophorectomy impacts risk of developing breast cancer among BRCA1 mutation carriers might be attributed to various biases, specifically, cancer-induced testing bias due to inclusion of prevalent cases. We conducted two complementary matched case–control analyses to evaluate the association of oophorectomy and BRCA1 breast cancer.

Methods:

A research questionnaire was administered every two years to collect information on exposures and disease. In the first analysis, we limited the study to prevalent breast cancer cases (diagnosed prior to study entry; n = 2,962) who were matched to controls on year of birth and country of residence (n = 4,358). In the second approach, we limited to 330 incident cases (diagnosed in the follow-up period) and 1,548 matched controls. Conditional logistic regression was used to estimate the adjusted odds ratios (OR) and 95% confidence intervals (CI) of invasive breast cancer.

Results:

In the first approach, there was a significant inverse association between oophorectomy and the risk of developing breast cancer [OR = 0.43; 95% confidence interval (CI), 0.34–0.55; P < 00001]. In the second approach, there was no association between oophorectomy and risk (OR = 1.21; 95% CI, 0.87–1.70; P = 0.26).

Conclusions:

The inclusion of women with a personal history of breast cancer prior to ascertainment likely impacts upon the association of oophorectomy and BRCA1 breast cancer risk.

Impact:

Oophorectomy is unlikely a determinant of breast cancer risk in BRCA1 mutation carriers but should be offered at age 35 to reduce the risk of ovarian and fallopian tube cancer.
Associations of Healthcare Affordability, Availability, and Accessibility with Quality Treatment Metrics in Patients with Ovarian Cancer
Authors: Akinyemiju Tomi F. , Wilson Lauren E. , Diaz Nicole , Gupta Anjali , Huang Bin , Pisu Maria , Deveaux April , Liang Margaret , Previs Rebecca A. , Moss Haley A. , Joshi Ashwini , Ward Kevin C. , Schymura Maria J. , Berchuck Andrew , Potosky Arnold L.
Published: April 2022

Background:

Differential access to quality care is associated with racial disparities in ovarian cancer survival. Few studies have examined the association of multiple healthcare access (HCA) dimensions with racial disparities in quality treatment metrics, that is, primary debulking surgery performed by a gynecologic oncologist and initiation of guideline-recommended systemic therapy.

Methods:

We analyzed data for patients with ovarian cancer diagnosed from 2008 to 2015 in the Surveillance, Epidemiology, and End Results–Medicare database. We defined HCA dimensions as affordability, availability, and accessibility. Modified Poisson regressions with sandwich error estimation were used to estimate the relative risk (RR) for quality treatment.

Results:

The study cohort was 7% NH-Black, 6% Hispanic, and 87% NH-White. Overall, 29% of patients received surgery and 68% initiated systemic therapy. After adjusting for clinical variables, NH-Black patients were less likely to receive surgery [RR, 0.83; 95% confidence interval (CI), 0.70–0.98]; the observed association was attenuated after adjusting for healthcare affordability, accessibility, and availability (RR, 0.91; 95% CI, 0.77–1.08). Dual enrollment in Medicaid and Medicare compared with Medicare only was associated with lower likelihood of receiving surgery (RR, 0.86; 95% CI, 0.76–0.97) and systemic therapy (RR, 0.94; 95% CI, 0.92–0.97). Receiving treatment at a facility in the highest quartile of ovarian cancer surgical volume was associated with higher likelihood of surgery (RR, 1.12; 95% CI, 1.04–1.21).

Conclusions:

Racial differences were observed in ovarian cancer treatment quality and were partly explained by multiple HCA dimensions.

Impact:

Strategies to mitigate racial disparities in ovarian cancer treatment quality must focus on multiple HCA dimensions. Additional dimensions, acceptability and accommodation, may also be key to addressing disparities.
Germline Pathogenic Variants Impact Clinicopathology of Advanced Lung Cancer
Authors: Mukherjee Semanti , Bandlamudi Chaitanya , Hellmann Matthew D. , Kemel Yelena , Drill Esther , Rizvi Hira , Tkachuk Kaitlyn , Khurram Aliya , Walsh Michael F. , Zauderer Marjorie G. , Mandelker Diana , Topka Sabine , Zehir Ahmet , Srinivasan Preethi , Esai Selvan Myvizhi , Carlo Maria I. , Cadoo Karen A. , Latham Alicia , Hamilton Jada G. , Liu Ying L. , Lipkin Steven M. , Belhadj Sami , Bond Gareth L. , Gümüş Zeynep H. , Klein Robert J. , Ladanyi Marc , Solit David B. , Robson Mark E. , Jones David R. , Kris Mark G. , Vijai Joseph , Stadler Zsofia K. , Amos Christopher I. , Taylor Barry S. , Berger Michael F. , Rudin Charles M. , Offit Kenneth
Published: April 2022

Background:

The genetic factors that modulate risk for developing lung cancer have not been fully defined. Here, we sought to determine the prevalence and clinical significance of germline pathogenic/likely pathogenic variants (PV) in patients with advanced lung cancer.

Methods:

We studied clinical and tumor characteristics of germline PV in 5,118 patients who underwent prospective genomic profiling using paired tumor–normal tissue samples in 468 cancer genes.

Results:

Germline PV in high/moderate-penetrance genes were observed in 222 (4.3%) patients; of these, 193 patients had PV in DNA damage repair (DDR) pathway genes including BRCA2 (n = 54), CHEK2 (n = 30), and ATM (n = 26) that showed high rate of biallelic inactivation in tumors. BRCA2 heterozygotes with lung adenocarcinoma were more likely to be never smokers and had improved survival compared with noncarriers. Fourteen patients with germline PV in lung cancer predisposing genes (TP53, EGFR, BAP1, and MEN1) were diagnosed at younger age compared with noncarriers, and of tumor suppressors, 75% demonstrated biallelic inactivation in tumors. A significantly higher proportion of germline PV in high/moderate-penetrance genes were detected in high-risk patients who had either a family history of any cancer, multiple primary tumors, or early age at diagnosis compared with unselected patients (10.5% vs. 4.1%; P = 1.7e−04).

Conclusions:

These data underscore the biological and clinical importance of germline mutations in highly penetrant DDR genes as a risk factor for lung cancer.

Impact:

The family members of lung cancer patients harboring PV in cancer predisposing genes should be referred for genetic counseling and may benefit from proactive surveillance.
Interleukin-2 and Interferon-α for Advanced Renal Cell Carcinoma: Patient Outcomes, Sexual Dimorphism of Responses, and Multimodal Treatment Approaches over a 30-Year Period
Authors: Bonetti Eva , Jenzer Maximilian , Nientiedt Cathleen , Kaczorowski Adam , Geisler Christine , Zschäbitz Stefanie , Jäger Dirk , Hohenfellner Markus , Duensing Stefan , Reimold Philipp
Published: April 2022

Introduction: Cytokine-based immunotherapy (IT) has been the mainstay of systemic treatment of advanced renal cell carcinoma (RCC) from the late 1980s until 2007. With the introduction of immune checkpoint inhibitors, a renaissance of immune oncological approaches is rapidly unfolding. Materials and Methods: In the present study, we revisited survival outcomes, sexual dimorphism of treatment responses, and the relevance of multimodal treatment approaches over a 30-year period in 156 patients with advanced RCC treated with subcutaneous (s.c.) interleukin-2 (IL-2) and interferon-α (IFN-α) between 1990 and 2009. Results: The median progression-free survival following the first IT was 5.8 months with a wide range from 0 to 197 months. The median overall survival (OS) was 25.8 months and the median cancer-specific survival after tumor nephrectomy was 24.6 months. A group of 29 patients (18.6%) and 11 patients (7.1%) survived longer than 5 and 10 years after surgery, respectively. A difference in the 5-year OS rate between male and female patients was detected (men, 21.6%; women, 11.1%). However, no sex-specific survival advantage was observed after 10 years. Conclusions: We provide evidence that IT with s.c. IL-2 and IFN-α played a vital role in long-term survivors either by inducing lasting complete remissions or as part of multimodal approaches that allowed patients to survive until novel therapies became available. The implications for current immune oncological treatment approaches are being discussed.
Audiological and Surgical Correlates of Myringoplasty Associated with Ethnography in the Bay of Plenty, New Zealand
Authors: Housley David M. , Irani Dinaz , Housley Gary D. , Ten Cate Wouter-J.F.
Published: April 2022

Introduction: This retrospective cohort study of myringoplasty performed at Tauranga Hospital, Bay of Plenty, New Zealand from 2010 to 2020 sought to identify predictive factors for successful myringoplasty with particular consideration given to the known high prevalence of middle ear conditions in New Zealand Māori. Methods: Outcomes were surgical success (perforation closure at 1 month) and hearing improvement, which were correlated against demographic, pathological, and surgical variables. Results: 174 patients underwent 221 procedures (139 in children under 18 years old), with 66.1% of patients being New Zealand Māori and 24.7% New Zealand European ethnicity. Normalized by population demographics, New Zealand Māori were 2.3 times overrepresented, whereas New Zealand Europeans were underrepresented by 0.34 times (a 6.8 times relative treatment differential). The rate of surgical success was 84.6%, independent of patient age, gender, and ethnicity. A postauricular approach and the use of temporalis fascia grafts were both correlated with optimal success rates, whereas early postoperative infection (<1 month) was correlated with ∼3 times increased failure. Myringoplasty improved hearing in 83.1% of patients (average air-bone gap reduction of 10.7 dB). New Zealand Māori patients had ∼4 times greater preoperative conductive hearing loss compared to New Zealand Europeans, but benefited the most from myringoplasty. Discussion/Conclusion: New Zealand Māori and pediatric populations required greater access to myringoplasty, achieving good surgical and audiological outcomes. Myringoplasty is highly effective and significantly improves hearing, particularly for New Zealand Māori. Pediatric success rates were equivalent to adults, supporting timely myringoplasty to minimize morbidity from untreated perforations.
Hormone Receptor and HER2 Status Switch in Non-pCR Breast Cancer Specimens after Neoadjuvant Therapy
Authors: Dimpfl Moritz , Mayr Doris , Schmoeckel Elisa , Degenhardt Tom , Eggersmann Tanja K. , Harbeck Nadia , Wuerstlein Rachel
Published: April 2022

Introduction: This project aimed to identify the frequency of a switch of hormone receptor (HR) and/or HER2 status after neoadjuvant chemotherapy (NAC) for early breast cancer. Methods: Tumor samples from patients without pathological complete response (non-pCR) were evaluated. Pathological complete response (pCR) was defined as no invasive tumor in breast and lymph nodes (ypT0/is ypN0). HR and HER2 status determined before NAC was compared with the corresponding receptor status determined in the surgical specimen after NAC. Results: 245 consecutive patients with primary invasive breast cancer, treated with NAC with/without targeted therapy between January 1, 2016 and December 31, 2019, at the LMU Breast Center, Munich, Germany, were identified. In 128 patients (52%), surgery revealed non-pCR after completed NAC. In 35 cases (27%), a switch of either HR and/or HER2 status between the initial biopsy and the surgical specimen was detected. Twenty cases had a switch in HR status, while 15 cases had a switch in HER2 status. Conclusion: In a substantial number (27%) of non-pCR cases, a switch in biomarker status after completed neoadjuvant treatment was detected. These results are consistent with prior evidence. Yet, routine reevaluation of HR and HER2 status is not recommended in guidelines so far. Future research needs to address the impact of HR and HER2 status switch on therapy adaptation and on subsequent patient outcome. Particularly, in view of the recent therapy advances, it will be critical to evaluate whether individualization of treatment concepts based on the biology of the non-pCR specimens is preferable to the initial therapy concept based on the pathology at primary diagnosis.
Diretrizes para apresentação de dissertações e teses da USP: parte I (ABNT) 2.ed
Authors:   Universidade de São Paulo. Faculdade de Odontologia, Funaro Vânia Martins Bueno de Oliveira , Pestana Maria Cláudia ,   Universidade de São Paulo. Faculdade de Odontologia, Garcia Eliana Maria ,   Universidade de São Paulo. Escola Superior de Agricultura " Luiz de Queiroz, Rebello Maria Alice de França Rangel ,   Universidade de São Paulo. Hospital Universitário, Ayello Maria Aparecida Bezerra ,   Universidade de São Paulo. Instituto de Geociências, Carvalho Maria José de Jesus ,   Universidade de São Paulo. Instituto de Ciências Biomédicas, Nascimento Maria Marta ,   Universidade de São Paulo. Instituto de Psicologia, Paschoalino Rosana Alvarez ,   Universidade de São Paulo. Escola de Engenharia de São Carlos, Cardoso Suely Campos ,   Universidade de São Paulo. Faculdade de Medicina, Lombardi Valéria de Vilhena ,   Universidade de São Paulo. Faculdade de Medicina
Published: April 2022

O Sistema Integrado de Bibliotecas da Universidade de São Paulo – SIBi/USP, dentre suas propostas voltadas à padronização dos trabalhos científicos, publica trabalhos no sentido de orientar os alunos de pós-graduação na elaboração de suas teses e dissertações geradas na Universidade. Neste sentido, dando sequência a este trabalho, traz a público a atualização das “Diretrizes para apresentação de dissertações e teses da USP: documento eletrônico e impresso”. Para facilitar a consulta às normas o Grupo responsável pela atualização elaborou o trabalho em quatro partes, cada parte enfocando uma norma específica: Parte I (ABNT – Associação Brasileira de Normas Técnicas), Parte II (APA – American Psychological Association), Parte III (ISO – International Organization for Standardization) e Parte IV (Vancouver). Este documento apresenta a 2ª edição revisada das Diretrizes publicada em 2009, de acordo com a norma ABNT atualizada.
Event Rates and Risk Factors for Recurrent Cardiovascular Events and Mortality in a Contemporary Post Acute Coronary Syndrome Population Representing 239 234 Patients During 2005 to 2018 in the United States
Authors: Steen Dylan L. , Khan Irfan , Andrade Katherine , Koumas Alexandra , Giugliano Robert P.
Published: April 2022

Background

Patients with acute coronary syndrome (ACS) are recognized by guidelines as remaining at high risk for adverse outcomes. Evidence from contemporary, representative ACS populations in a clinical practice setting is necessary to identify subgroups and strategies for improving patient outcomes. We aimed to describe event rates and risk factors in an ACS population over prolonged follow‐up for cardiovascular end points.

Methods and Results

We identified 239 234 patients in the Optum Research Database (57.2% men; mean [standard deviation] age, 69.2 [12.2] years) with evidence of an ACS hospitalization (index ACS) during January 1, 2005 through December 30, 2018. Subgroups were based on index ACS event (myocardial infarction/unstable angina and revascularization status) and the Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention. The 5‐year event rate for the primary end point representing nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular death was 33.4% (95% CI, 33.1%–33.7%;
P
<0.001). The risk of experiencing the primary end point was ≈6‐fold higher immediately after discharge (≈40.9% annualized risk) as compared with the period 1+ years after hospitalization (≈6.4% annualized risk). Among subgroups, the 5‐year primary end point event rate was highest for myocardial infarction without revascularization and a Thrombolysis In Myocardial Infarction Risk Score for Secondary Prevention ≥4, at 47.9% (95% CI, 47.3%–48.4%;
P
<0.001) and 56.7% (95% CI, 55.9%–57.4%;
P
<0.001), respectively.

Conclusions

Patients with ACS remain at very high risk of experiencing recurrent cardiovascular events, particularly early after discharge, with identifiable subgroups at multifold higher risk of specific clinical end points.
National Trends in Use of Sodium‐Glucose Cotransporter‐2 Inhibitors and Glucagon‐like Peptide‐1 Receptor Agonists by Cardiologists and Other Specialties, 2015 to 2020
Authors: Adhikari Rishav , Jha Kunal , Dardari Zeina , Heyward James , Blumenthal Roger S. , Eckel Robert H. , Alexander G. Caleb , Blaha Michael J.
Published: April 2022

Background

Sodium‐glucose cotransporter‐2 inhibitors (SGLT2is) and glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) mitigate cardiovascular risk in individuals with type 2 diabetes, but most eligible patients do not receive them. We characterized temporal trends in SGLT2i and GLP‐1RA use by cardiologists compared with other groups of clinicians.

Methods and Results

We conducted a descriptive analysis of serial, cross‐sectional data derived from IQVIA’s National Prescription Audit, a comprehensive audit capturing ≈90% of US retail prescription dispensing and projected to population‐level data, to estimate monthly SGLT2is and GLP‐1RAs dispensed from January 2015 to December 2020, stratified by prescriber specialty and molecule. We also used the American Medical Association’s Physician Masterfile to calculate average annual SGLT2is and GLP‐1RAs dispensed per physician. Between January 2015 and December 2020, a total of 63.2 million SGLT2i and 63.4 million GLP‐1RA prescriptions were dispensed in the United States. Monthly prescriptions from cardiologists increased 12‐fold for SGLT2is (from 2228 to 25 815) and 4‐fold for GLP‐1RAs (from 1927 to 6981). Nonetheless, cardiologists represented only 1.5% of SGLT2i prescriptions and 0.4% of GLP‐1RA prescriptions in 2020, while total use was predominated by primary care physicians/internists (57% of 2020 SGLT2is and 52% of GLP‐1RAs). Endocrinologists led in terms of prescriptions dispensed per physician in 2020 (272 SGLT2is and 405 GLP‐1RAs). Cardiologists, but not noncardiologists, increasingly used SGLT2is over GLP‐1RAs, with accelerated uptake of empagliflozin and dapagliflozin coinciding with their landmark cardiovascular outcomes trials and subsequent US Food and Drug Administration label expansions.

Conclusions

While use of SGLT2is and GLP‐1RAs by cardiologists in the United States increased substantially over a 6‐year period, cardiologists still account for a very small proportion of all use, contributing to marked undertreatment of individuals with type 2 diabetes at high cardiovascular risk.