bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ferroptosis Driver SOCS1 and Suppressor FTH1 Independently Correlate With M1 and M2 Macrophage Infiltration in Head and Neck Squamous Cell Carcinoma
Authors: Hu Zhang-Wei , Wen Yi-Hui , Ma Ren-Qiang , Chen Lin , Zeng Xue-Lan , Wen Wei-Ping , Sun Wei 
Published: September 2021

ObjectiveTo investigate the role of ferroptosis, an iron-dependent form of non-apoptotic cell death, in the head and neck squamous cell carcinoma (HNSCC) immune microenvironment.Materials and MethodsA list of ferroptosis-related genes was obtained from the FerrDb database. Gene expression data were acquired from the cancer genome atlas (TCGA) and analyzed using the R language. Protein–protein interaction analysis was conducted using STRING and GeneMANIA. The correlations between gene expression levels and a patient’s survival were analyzed using GEPIA, the Kaplan–Meier estimate, and a multivariate Cox proportional hazards model. The expression results were verified using Oncomine and Human Protein Atlas data. We used the TIMER, GEPIA2, GEPIA2021, and TIMER2 databases to investigate the relationships between gene expression and infiltrating immune cells.ResultsAnalysis of differentially expressed genes (DEGs) identified nine each ferroptosis drivers and ferroptosis suppressors, among which four genes correlated with survival as follows: two drivers (SOCS1, CDKN2A) associated with better survival and two suppressors (FTH1, CAV1) associated with poorer survival. Multivariate Cox survival analysis identified SOCS1 and FTH1 as independent prognostic factors for HNSCC, and their higher expression levels were verified using Oncomine and HPA data. The results acquired using TIMER, GEPIA2, GEPIA2021, and TIMER2 data revealed that the driver SOCS1 and the suppressor FTH1 independently correlated with M1 and M2 macrophage infiltration.ConclusionsThe ferroptosis driver SOCS1 and suppressor FTH1 are independent prognostic factors and that correlate with M1 and M2 macrophage infiltration in HNSCC. Targeting ferroptosis-immunomodulation may serve as a strategy to enhance the activity of immunotherapy.
The Role of Transthoracic Echocardiography in the Evaluation of Patients With Ischemic Stroke
Authors: Teodoro Robson Sarmento , Sampaio Silva Gisele , Modolo Gabriel Pinheiro , Trivellato Stella De Angelis , Souza Juli Thomaz de , Luvizutto Gustavo José , Nunes Hélio Rubens de Carvalho , Martin Luis Cuadrado , Bazan Rodrigo , Zanati Bazan Silméia Garcia 
Published: September 2021

Background: Ischemic stroke can be classified into five etiological types, according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification, and its adequate investigation and characterization can aid in its clinical management and in preventing new events. Transthoracic echocardiography (TTE) plays a key role in investigating its etiology; approximately one-third of the patients remain without an adequate definition of the etiology or are classified as the undetermined TOAST type.Objectives: To evaluate if the percentage of patients with indeterminate etiology according to the TOAST classification decreased after transthoracic echocardiography, to determine whether or not the prognosis after ischemic stroke is worse among patients classified as the undetermined TOAST type, and to verify the predictive capacity of echocardiography on the prognosis after ischemic stroke.Methods: In this retrospective cohort study, clinical, neurological, and echocardiographic examinations were conducted when the patient was hospitalized for stroke. In-hospital mortality and functional capacity were evaluated at hospital discharge and 90 days thereafter. Multiple linear regression and multiple logistic regression models were adjusted for confounding factors. The level of significance was 5%.Results: A total of 1,100 patients (men = 606; 55.09%), with a mean age of 68.1 ± 13.3 years, were included in this study. Using TTE, 977 patients (88.82%) were evaluated and 448 patients (40.7%) were classified as the undetermined TOAST type. The patients who underwent TTE were 3.1 times less likely to classified as the undetermined TOAST type (OR = 0.32; p &lt; 0.001). Echocardiography during hospitalization was a protective factor against poor prognosis, and reduced the odds of in-hospital death by 11.1 times (OR: 0.090; p &lt; 0.001). However, the presence of the undetermined TOAST classification elevated the chance of mortality during hospitalization by 2.0 times (OR: 2.00; p = 0.013).Conclusions: Echocardiography during hospitalization for ischemic stroke reduces the chances of an undetermined TOAST classification and the risk of in-hospital mortality. However, being classified as the undetermined TOAST type increases the chance of mortality during hospitalization, suggesting that evaluating patients using echocardiography during hospitalization for acute ischemic stroke is important.
Developmental Angiogenesis Requires the Mitochondrial Phenylalanyl-tRNA Synthetase
Authors: Li Bowen , Chen Kun , Liu Fangfang , Zhang Juan , Chen Xihui , Chen Tangdong , Chen Qi , Yao Yan , Hu Weihong , Wang Li , Wu Yuanming 
Published: September 2021

Background: Mitochondrial aminoacyl-tRNA synthetases (mtARSs) catalyze the binding of specific amino acids to their cognate tRNAs and play an essential role in the synthesis of proteins encoded by mitochondrial DNA. Defects in mtARSs have been linked to human diseases, but their tissue-specific pathophysiology remains elusive. Here we examined the role of mitochondrial phenylalanyl-tRNA synthetase (FARS2) in developmental angiogenesis and its potential contribution to the pathogenesis of cardiovascular disease.Methods: Morpholinos were injected into fertilized zebrafish ova to establish an in vivo fars2 knock-down model. A visualization of the vasculature was achieved by using Tg (fli1: EGFP)y1 transgenic zebrafish. In addition, small interference RNAs (siRNAs) were transferred into human umbilical vein endothelial cells (HUVECs) to establish an in vitro FARS2 knock-down model. Cell motility, proliferation, and tubulogenesis were determined using scratch-wound CCK8, transwell-based migration, and tube formation assays. In addition, mitochondria- and non-mitochondria-related respiration were evaluated using a Seahorse XF24 analyzer and flow cytometry assays. Analyses of the expression levels of transcripts and proteins were performed using qRT-PCR and western blotting, respectively.Results: The knock-down of fars2 hampered the embryonic development in zebrafish and delayed the formation of the vasculature in Tg (fli1: EGFP)y1 transgenic zebrafish. In addition, the siRNA-mediated knock-down of FARS2 impaired angiogenesis in HUVECs as indicated by decreased cell motility and tube formation capacity. The knock-down of FARS2 also produced variable decreases in mitochondrial- and non-mitochondrial respiration in HUVECs and disrupted the regulatory pathways of angiogenesis in both HUVECs and zebrafish.Conclusion: Our current work offers novel insights into angiogenesis defects and cardiovascular diseases induced by FARS2 deficiency.
Sedimentary Dynamics of the Central South Yellow Sea Revealing the Relation Between East Asian Summer and Winter Monsoon Over the Past 6000 years
Authors: Lyu Wenzhe , Fu Tengfei , Hu Zhangxi , Tang Ying Zhong , Chen Guangquan , Xu Xingyong , Chen Yanping , Chen Shenliang 
Published: September 2021

The mud areas of East Asian marginal seas record considerable information about regional environmental evolution. However, debate continues regarding the relative importance of the major factors in regional sedimentary dynamics, i.e., the East Asian summer monsoon, East Asian winter monsoon, and oceanic circulation. In this study, we investigated the characteristics of grain size from a gravity core obtained in the South Yellow Sea to reveal changes in sedimentary dynamics since 6,000 years BP, and to elucidate the relationship between the East Asian summer monsoon and the East Asian winter monsoon. We found that the mean grain size was in the range of 6.9–7.8 Φ, the sediment was poorly sorted within a small range (1.2, 1.5), and the M values from 4.7 to 6.7 μm and most of the C values from 24 to 65 μm suggested pelagic suspension transport. Results indicated that the intensity of both the East Asian summer monsoon and the East Asian winter monsoon showed a fluctuating trend of decrease after approximately 6,000 years BP, and that the relationship between them was generally anticorrelated. Based on these results, we suggest that positive correlation between the East Asian summer monsoon and the East Asian winter monsoon usually results in the fall or establishment of ancient dynasties in the Central Plains of China and that negative correlation between them is controlled by strong solar radiation. Weakening of solar radiation diminishes its control of the intensity of (and thus the correlation between) the East Asian summer monsoon and the East Asian winter monsoon, at which time the North Atlantic Oscillation plays a modulating role.
The Application of Principal Component Analysis on Clinical and Biochemical Parameters Exemplified in Children With Congenital Adrenal Hyperplasia
Authors: Ljubicic Marie Lindhardt , Madsen Andre , Juul Anders , Almstrup Kristian , Johannsen Trine Holm 
Published: September 2021

PurposePrincipal component analysis (PCA) is a mathematical model which simplifies data into new, combined variables. Optimal treatment of pediatric congenital adrenal hyperplasia (CAH) remains a challenge and requires evaluation of all biochemical and clinical markers. The aim of this study was to introduce PCA methodology as a tool to optimize management in a cohort of pediatric and adolescent patients with CAH by including adrenal steroid measurements and clinical parameters.MethodsThis retrospective, longitudinal cohort of 33 children and adolescents with CAH due to 21-hydroxylase deficiency included 406 follow-up observations. PCAs were applied to serum hormone concentrations and compared to treatment efficacy evaluated by clinical parameters.ResultsWe provide and describe the first PCA models with hormone parameters denoted in sex- and age-adjusted standard deviation (SD) scores to comprehensibly describe the combined ‘endocrine profiles’ of patients with classical and non-classical CAH, respectively. Endocrine profile scores were predictive markers of treatment efficacy for classical (AUC=92%; accuracy 95%; p=1.8e-06) and non-classical CAH (AUC=80%; accuracy 91%; p=0.004). A combined PCA demonstrated clustering of patients with classical and non-classical CAH by serum 17-hydroxyprogesterone (17-OHP) and dehydroepiandrosterone-sulphate (DHEAS) concentrations.ConclusionAs an example of the possibilities of PCA, endocrine profiles were successfully able to distinguish between patients with CAH according to treatment efficacy and to elucidate biochemical differences between classical and non-classical CAH.
Progestin-Primed Ovarian Stimulation Protocol for Patients in Assisted Reproductive Technology: A Meta-Analysis of Randomized Controlled Trials
Authors: Guan Shaogen , Feng Yuezhi , Huang Yonghan , Huang Jia 
Published: September 2021

ObjectivesProgestin-primed ovarian stimulation (PPOS) is a new ovarian stimulation protocol that can block the luteinizing hormone (LH) surge through progesterone instead of traditional down regulating or gonadotropin-releasing hormone (GnRH) antagonist, and in order to achieve multi-follicle recruitment. This paper aims to investigate the effectiveness of PPOS and its suitability for infertile patients with different ovarian reserve functions.MethodsWe searched published randomized controlled trials (RCTs) about PPOS on Cochrane Library, PubMed, Embase, and Web of Science. The search period spanned from January 1, 2015 to November 16, 2020. The data were extracted, and the meta-analysis was performed on ovarian stimulation as well as embryological and clinical outcomes. The outcomes were pooled by a random effects model, and the risk of heterogeneity was evaluated. Subgroup analysis was performed for different ovarian reserve patients.ResultsThe clinical pregnancy rates and live birth or ongoing pregnancy rates with the PPOS protocol were not different from those with the control group. In the diminished ovarian reserve (DOR) subgroup, the PPOS protocol had a lower rate of premature LH surge [RR = 0.03, 95% CI = 0.01 to 0.13, p &lt; 0.001]. The PPOS protocol had a lower rate of ovarian hyperstimulation syndrome (OHSS) [RR = 0.52, 95% CI = 0.36 to 0.76, p &lt; 0.001, I2 = 0.00%]. The secondary outcomes showed that the number of oocytes retrieved, MII oocytes, and viable embryos was higher than that of the control protocol in DOR patients [(MD = 0.33, 95% CI = 0.30 to 0.36, p &lt; 0.001), (MD = 0.30, 95% CI = 0.27 to 0.33, p &lt; 0.001), (MD = 0.21, 95% CI = 0.18 to 0.24, p &lt; 0.001)] and normal ovarian reserve (NOR) patients [(MD = 1.41, 95% CI = 0.03 to 2.78, p &lt; 0.001), (MD = 1.19, 95% CI = 0.04 to 2.35, p &lt; 0.001), (MD = 1.01, 95% CI = 0.21 to 1.81, p = 0.01)].ConclusionThe findings suggest that PPOS is an effective ovarian stimulation protocol and is beneficial for patients with different ovarian reserve functions, which needs to be validated in more RCTs with larger samples.
Secular Trends in the Epidemiologic Patterns of Thyroid Cancer in China Over Three Decades: An Updated Systematic Analysis of Global Burden of Disease Study 2019 Data
Authors: Li Yongze , Piao Jianming , Li Min 
Published: September 2021

BackgroundThyroid cancer is the most common malignant endocrine disease worldwide. The changing epidemiologic pattern of thyroid cancer at the national level in China has remained unknown over the last three decades.MethodsFollowing the general analytical strategy used in the Global Burden of Disease Study (GBD) 2019, the age- and sex-specific incidence, mortality, and prevalence rates of thyroid cancer in China were analyzed. Trends in the incidence, mortality, prevalence, and disability-adjusted life years (DALYs) due to thyroid cancer from 1990 to 2019 were assessed by joinpoint regression analysis. Age, period, and cohort effects on incidence were estimated by an age-period-cohort model.ResultsFrom 1990 to 2019, the age-standardized prevalence and incidence rates significantly increased in both males and females, and the age-standardized mortality rate decreased in females but increased in males. Moreover, the increments in all the age-standardized measures of thyroid cancer in China were higher in males than in females. The age effect showed that those aged 40–44 years had the highest relative risk (RR) among females, and the RR increased with age among males. The incidence increased with time and began to substantially increase in 2009. The cohort effect showed that the incidence decreased in successive birth cohorts.ConclusionsThe burden of thyroid cancer in China showed unexpected patterns that varied by sex, age, and year. Notably, males had higher average annual percentage changes in thyroid cancer incidence and mortality rates than females. More attention should be given to improving the thyroid cancer burden in males in China.
Case Report: Low Bone and Normal Lean Mass in Adolescents With Complete Androgen Insensitivity Syndrome
Authors: Misakian Aaron , McLoughlin Michelle , Pyle Louisa C. , Kolon Thomas F. , Kelly Andrea , Vogiatzi Maria G. 
Published: September 2021

IntroductionOsteopenia and osteoporosis have been reported in adults with Complete Androgen Insensitivity Syndrome (CAIS). Little is known about changes in bone mineral density (BMD) in adolescents with CAIS and whether it is affected by early gonadectomy. Body composition data have not been reported.MethodsSingle-center, retrospective study of CAIS adolescents who underwent dual-energy x-ray absorptiometry (DXA) (Hologic, Horizon A). Body composition is presented as lean and fat mass indices (LMI, FMI). Z-scores for lumbar spine areal BMD (LBMD), total body less head (TBLH), bone mineral content (BMC), LMI, and FMI were calculated using female normative data. Results are expressed as median and min, max.ResultsSix females with genetically confirmed CAIS were identified—one with intact gonads and five with history of gonadectomy at 2–11 months. In the subject with intact gonads, LBMD-Z and TBLH BMC-Z were −1.56 and −1.26, respectively, at age 16 years. Among those with gonadectomy, LBMD-Z was −1.8 (−3.59 to 0.49) at age 15.6 years (12–16.8) and decreased in all three subjects who had longitudinal follow-up despite hormone replacement therapy (HRT). Adherence to HRT was intermittent. LMI-Z and FMI-Z were 0.1 (−1.39 to 0.7) and 1.0 (0.22 to 1.49), respectively.ConclusionsThese limited data indicate that adolescents with CAIS have bone mass deficit. Further studies are needed to understand the extent of BMD abnormalities and the effect of gonadectomy, especially early in childhood, and to establish the optimal HRT regimen for bone accrual. Data on lean mass are reassuring.
A Novel Scoring System for Predicting the Metastases of Posterior Right Recurrent Laryngeal Nerve Lymph Node Involvement in Patients With Papillary Thyroid Carcinoma by Preoperative Ultrasound
Authors: Lu Kai-Ning , Zhang Yu , Da Jia-Yang , Zhou Tian-han , Zhao Ling-Qian , Peng You , Pan Gang , Shi Jing-Jing , Zhou Li , Ni Ye-Qin , Luo Ding-Cun 
Published: September 2021

ObjectiveOur goal was to investigate the correlation between papillary thyroid carcinoma (PTC) characteristics on ultrasonography and metastases of lymph nodes posterior to the right recurrent laryngeal nerve (LN-prRLN). There is still no good method for clinicians to judge whether a patient needs LN-prRLN resection before surgery, and we also wanted to establish a new scoring system to determine whether patients with papillary thyroid carcinoma require LN-prRLN resection before surgery.Patients and MethodsThere were 482 patients with right or bilateral PTC who underwent thyroid gland resection from December 2015 to December 2017 recruited as study subjects. The relationship between the PTC characteristics on ultrasonography and the metastases of LN-prRLN was analyzed by univariate and logistic regression analyses. Based on the risk factors identified in univariate and logistic regression analysis, a nomogram-based LN-prRLN prediction model was established.ResultLN-prRLN were removed from all patients, of which 79 had LN-prRLN metastasis, with a metastasis rate of 16.39%. Multivariate logistic regression analysis revealed that LN-prRLN metastasis was closely related to sex, age, blood supply, larger tumors (&gt; 1 cm) and capsular invasion. A risk prediction model has been established and fully verified. The calibration curve used to evaluate the nomogram shows that the consistency index was 0.75 ± 0.065.ConclusionPreoperative clinical data, such as sex, age, abundant blood supply, larger tumor (&gt; 1 cm) and capsular invasion, are positively correlated with LN-prRLN metastasis. Our scoring system can help surgeons non-invasively determine which patients should undergo LN-prRLN resection before surgery. We recommend that LN-prRLN resection should be performed when the score is above 103.1.
Effects of Acute and Chronic Exposure to Semicarbazide on the Sea Cucumber Apostichopus japonicus
Authors: Tian Xiuhui , Li Huanjun , Zhang Xiuzhen , Xu Yingjiang , Zhang Huawei , Han Dianfeng , Liu Huan , Wang Bin , Cui Yanmei , Liu Huihui , Zhou Quanli , Gong Xianghong 
Published: September 2021

The effects of acute and chronic exposure to semicarbazide were carried out on the sea cucumber Apostichopus japonicus. A half-maximal lethal concentration of 3.72 g/L of semicarbazide hydrochloride (95% confidence interval 3.43–4.02 g/L) was deduced. At 20, 4, and 2% of the half-maximal lethal concentrations, a 28-days exposure induced morphological alterations, oxidative stress, and acetylcholinesterase (AChE) activity in the respiratory tree, intestinal tract, and longitudinal muscle of A. japonicus. Exposure to 20% of the half-maximal lethal concentration resulted in lesions in the respiratory tree and disintegration in the intestinal tract. Exposure to lower concentration induced a gradual accumulation of lesions in the respiratory tree, intestinal tract, and longitudinal muscle. Levels of markers of oxidative stress and neurotransmission, including superoxide dismutase (SOD), catalase, and AChE, were increased during the initial days of exposure and then decreased. The activity of SOD, catalase, and AChE were highest in A. japonicus exposed to 4%, followed by 20 and 2% of the half-maximal lethal concentration at the same time. At the later stages of the 28-days exposure, marker levels were decreased and close to levels in the control groups. Non-targeted metabolomics indicated that significantly different metabolites were screened out, 28 in the positive ion mode and 38 in the negative ion mode, impairments in neurological function, osmotic pressure regulation, energy metabolism, and protein digestion and absorption following exposure of A. japonicus to semicarbazide. KEGG pathway enrichment showed that the exposure affected pathways related to ABC transporters, central carbon metabolism in cancer, protein digestion and absorption, aminoacyl-tRNA biosynthesis, and biosynthesis of unsaturated fatty acids.
Identification of Key Genes Associated With the Process of Hepatitis B Inflammation and Cancer Transformation by Integrated Bioinformatics Analysis
Authors: Zhang Jingyuan , Liu Xinkui , Zhou Wei , Lu Shan , Wu Chao , Wu Zhishan , Liu Runping , Li Xiaojiaoyang , Wu Jiarui , Liu Yingying , Guo Siyu , Jia Shanshan , Zhang Xiaomeng , Wang Miaomiao 
Published: September 2021

BackgroundHepatocellular carcinoma (HCC) has become the main cause of cancer death worldwide. More than half of hepatocellular carcinoma developed from hepatitis B virus infection (HBV). The purpose of this study is to find the key genes in the transformation process of liver inflammation and cancer and to inhibit the development of chronic inflammation and the transformation from disease to cancer.MethodsTwo groups of GEO data (including normal/HBV and HBV/HBV-HCC) were selected for differential expression analysis. The differential expression genes of HBV-HCC in TCGA were verified to coincide with the above genes to obtain overlapping genes. Then, functional enrichment analysis, modular analysis, and survival analysis were carried out on the key genes.ResultsWe identified nine central genes (CDK1, MAD2L1, CCNA2, PTTG1, NEK2) that may be closely related to the transformation of hepatitis B. The survival and prognosis gene markers composed of PTTG1, MAD2L1, RRM2, TPX2, CDK1, NEK2, DEPDC1, and ZWINT were constructed, which performed well in predicting the overall survival rate.ConclusionThe findings of this study have certain guiding significance for further research on the transformation of hepatitis B inflammatory cancer, inhibition of chronic inflammation, and molecular targeted therapy of cancer.