bluuebunny/crossref_metadata_2025_split huggingface dataset:
Iron Overload contributes to General Anesthesia-induced Neurotoxicity and Cognitive Deficits
Authors: Wu Jing , Yang Jian-Jun , Cao Yan , Li Huihui , Zhao Hongting , Yang Shuofei , Li Kuanyu 
Published: March 2020

Abstract
Background: Increasing evidence suggests that multiple or long-time exposure to general anesthesia (GA) could be detrimental to cognitive development in young subjects, and might also contribute to accelerated neurodegeneration in the elderly. Iron is essential for normal neuronal function and excess iron in brain is implicated in several neurodegenerative diseases. However, the role of iron in GA-induced neurotoxicity and cognitive deficits remains elusive. Methods: We used the primary hippocampal neurons and rodents including young rats and aged mice to examine whether GA impacted iron metabolism and whether the impact contributed to neuronal outcomes. In addition, a pharmacological suppression of iron metabolism was performed to explore the molecular mechanism underlying GAs-mediated iron overload in the brain. Results: Our results demonstrated that GA, induced by intravenous ketamine or inhalational sevoflurane, disturbed iron homeostasis and caused iron overload in both in vitro hippocampal neuron culture and in vivo hippocampus. Interestingly, ketamine or sevoflurane-induced cognitive deficits, very likely, resulted from a novel iron-dependent regulated cell death, ferroptosis. Notably, iron chelator deferiprone attenuated the GA-induced mitochondrial dysfunction, ferroptosis, and further cognitive deficits. Moreover, we found that GA-induced iron overload was activated by NMDAR-RASD1 signalling via DMT1 action in the brain. Conclusion: We conclude that disturbed iron metabolism may be involved in the pathogenesis of GA-induced neurotoxicity and cognitive deficits. Our study provides new vision for consideration in GA-associated neurological disorders.
Fecundity disorders in older women: declines in follicular development and endometrial receptivity
Authors: Wang Li , Lv Shulan , Mao Wenjun , Bai E , Yang Xiaofeng 
Published: March 2020

Abstract
Background : Little research is available on follicular development and endometrial receptivity in older women. This study aimed to assess follicular development and endometrial receptivity, and to evaluate ultrasonic parameters in predicting endometrial receptivity during the implantation window in older women. Methods: For this prospective case-control study, 224 older women and 215 young women were recruited. The follicular development and endometrial thickness were monitored by transvaginal ultrasound. During the implantation window, the pulsatility index (PI) and resistance index (RI) of the uterine arteries and subendometrial region, endometrial volume, vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were calculated between the two groups. The ultrasonic parameters were used to assess endometrial receptivity in older women. Results: The serum anti-Mullerian hormone (AMH) concentration and antral follicle count (AFC) were significantly lower in older women than in young women ( p = 0.019, p = 0.022 respectively). The average diameter of the dominant follicle on days 14, 16, and 18 of the menstrual cycle were significantly smaller ( p =0.041, p =0.032, p =0.025 respectively), and the subendometrial region RI on days 12, 14, 16, and 18 of the menstrual cycle were significantly higher in older women than in young women ( p =0.046, p =0.039, p =0.036, p =0.035 respectively). The normal ovulation rate was significantly lower in older women than in young women ( p =0.001). The subendometrial region RI was significantly higher, and the endometrial VI, FI, and VFI were significantly lower in older women compared with young women ( p =0.041, p =0.019, p =0.015, p =0.007 respectively). The biochemical pregnancy rate, clinical pregnancy rate and ongoing pregnancy rate of older women were significantly lower than in young women ( p =0.012, p =0.003, p =0.001 respectively). The best ultrasonic parameter for predicting endometrial receptivity during the implantation window in older women was VI (AUC =0.889, sensitivity 92.6% and specificity 85.4%). Conclusions: Older women present decreased serum AMH concentrations and AFC, defined as indicators of ovarian reserve function. Older women are characterized by decreased follicular development and endometrial receptivity, which may lead to fecundity disorders.
The Desire to Die in Palliative Care: A sequential mixed methods study to develop a semi-structured clinical aproach
Authors: Kremeike Kerstin , Frerich Gerrit , Romotzky Vanessa , Bostroem Kathleen , Dojan Thomas , Galushko Maren , Shah-Hosseini Kija , Juenger Saskia , Rodin Gary , Pfaff Holger , Perrar Klaus Maria , Voltz Raymond 
Published: March 2020

Abstract
Background: Although desire to die of varying intensity and permanence is frequent in patients receiving palliative care, uncertainty exists concerning appropriate therapeutic responses to it. To support health professionals in dealing with patients´ potential desire to die, a training program and a semi-structured clinical interview approach was developed. This study aimed for a revision of and consensus building on the clinical approach to support proactively addressing desire to die and routine exploration of death and dying distress. Methods: Within a sequential mixed methods design, we invited 16 palliative patients to participate in semi-structured interviews and 377 (inter-)national experts to attend a two-round Delphi process. Interviews were analyzed using qualitative content analysis and an agreement consensus for the Delphi was determined according to predefined criteria. Results: 11 (69%) patients from different settings participated in face-to-face interviews. As key issues for conversations on desire to die they pointed out the relationship between professionals and patients, the setting and support from external experts, if required. A set of 149 (40%) experts (132/89% from Germany, 17/11% from 9 other countries) evaluated ten domains of the semi-structured clinical approach. There was immediate consensus on nine domains concerning conversation design, suggestions for (self-)reflection, and further recommended action. The one domain in which consensus was not achieved until the second round was “proactively addressing desire to die”. Conclusions: We have provided the first semi-structured clinical approach to identify and address desire to die and to respond therapeutically – based on evidence, patients’ views and consensus among professional experts. Trial registration: The study is registered in the German Clinical Trials Register (DRKS00012988; registration date: 27.9.2017) and in the Health Services Research Database (VfD_DEDIPOM_17_003889; registration date: 14.9.2017).
Exosomal lncRNA OIP5-AS1 confers cells trastuzumab resistance in breast cancer through miR-381-3p/HMGB3 axis
Authors: Yu Qiang , Peng Shijun , Li Jing , Tan Xianxiong 
Published: March 2020

Abstract
Background Long noncoding RNA OPA-interacting protein 5 antisense transcript 1 (OIP5-AS1) was confirmed to involve in the malignancy of breast cancer. However, whether exosomal OIP5-AS1 implicated in trastuzumab resistance remains unclear. Methods Cell viability, migration and apoptosis were analyzed by cell counting kit-8, colony formation, transwell assay or flow cytometry. The expression of OIP5-AS1 and microRNA (miR)-381-3p was detected using quantitative real-time polymerase chain reaction. Exosomes were isolated by ultracentrifugation and qualified by nanoparticle tracking analysis (NTA) software. Western blot was used to detect the levels of tumor susceptibility gene 101 (TSG101), CD81, CD63 or high-mobility group protein B3 (HMGB3). The interaction between miR-381-3p and OIP5-AS1 or HMGB3 was confirmed by dual-luciferase reporter assay and pull-down assay. In vivo experiments were conducted using murine xenograft models. Results OIP5-AS1 was elevated in trastuzumab-resistant breast cancer cells, and OIP5-AS1 knockdown rescued trastuzumab sensitivity. Extracellular OIP5-AS1 was packaged into exosomes, which were secreted by trastuzumab-resistant cells, and could be absorbed by trastuzumab-sensitive cells in breast cancer. Importantly, intercellular transfer of OIP5-AS1 via exosomes enhanced trastuzumab resistance in vitro. OIP5-AS1 was a sponge of miR-381-3p; besides, miR-381-3p targeted HMGB3. Murine xenograft analysis showed exosomal OIP5-AS1 induced trastuzumab resistance in vivo. Exosomal OIP5-AS1 was dysregulated in the serum of breast cancer patients, and might be a promising diagnostic biomarker in trastuzumab resistance. Conclusion Intercellular transfer of OIP5-AS1 by exosomes enhanced trastuzumab resistance in breast cancer via miR-381-3p/HMGB3 axis, indicating a potential therapeutic strategy to boost the effectiveness of trastuzumab in resistant breast cancer patients.
Perigraft abscess after DeBakey type-1 aortic dissection: a case report
Authors: Xu Lingling , Lin Shan , Yang Yali 
Published: March 2020

Abstract
Background Perigraft abscess is a rare condition which constitutes a small proportion of aortic graft infection (AGI), early diagnosis is very important for timely intervention and improving the survival rate of patients because of its significant morbidity and mortality. Case presentation A 24-year-old young male patient with a history of complicated total arch replacement using the elephant trunk technique for acute DeBakey type-1 aortic dissection 6 months before visited our hospital with the chief complaint of persistent fever. Antibiotic treatment in local hospital was ineffective. Echocardiography showed liquid dark area around the aortic graft, and a computerized tomography angiography (CTA) was done for further evaluation of periaortic fluid collection which showed findings to suggest perigraft abscess. The patient underwent surgical debridement of the abscess and was found to have an abscess around the aortic graft which was drained followed by antibiotic treatment. The patient was discharged to his local hospital and recovered well at 2 month follow-up appointment. Conclusion This is a very rare case of aortic abscess around the graft that could successfully be managed by graft-conserving surgery, and it emphasizes the significance of early diagnosis of perigraft abscess in patients with aortic dissection surgery.
Comparing Acute Aerobic vs. Resistance Exercise (CAARE) in young and older adults: Design and methods of a randomized acute exercise trial on the immune system
Authors: Markofski Melissa M , Graff Rachel M , Jennings Kristofer 
Published: March 2020

Abstract
Background: It is well accepted that exercise has numerous health benefits, including reducing the risk of developing cardiometabolic diseases and supporting a healthy immune system. Although these benefits are widely recognized, variations in the exercise response still exist. The aim of this study is to explore the variations that may be partially explained by participant age, physical activity status, and/or mode of exercise. Methods: The CAARE (Comparing Acute Aerobic vs. Resistance Exercise) study is a randomized cross-over design trial. Participants are young (18-30 years) or older (55-75 years), and within each age group are either physically active or inactive. All participants complete two acute exercise sessions of similar intensity and duration: a resistance training bout and a treadmill exercise bout. Blood is collected before exercise (PRE), immediately after exercise (POST), and after one hour of recovery (RECOV). Fresh blood is used for flow cytometry analyses to phenotype immune cells. Serum is stored for future analyses. The primary outcome variables are monocyte and T-cell phenotype. Discussion: CAARE is the first study to compare the immune cell response to acute exercise when including age, physical activity status, and mode of exercise. Clinical trial registration: This research study was registered at clinicaltrials.gov NCT03794050 in January 4, 2019. https://clinicaltrials.gov/ct2/show/NCT03794050
ATP4B suppresses cell proliferation and migration via mitochondrial/p53/NF-κB pathway in gastric cancer
Authors: Pan Yuanming , He Yuqi , Lin Shuye , Zhu Min , Li Yangjie , Wang Jianxun , Miao Shuo , Wang Jiheng , Ma Xianzong , Xu Junfeng , Yang Lang , Jin Peng , Yang Guibin , Huang Jiaqiang , Lu Youyong , Sheng Jianqiu 
Published: March 2020

Abstract
Background: Hydrogen/Potassium ATPase β (ATP4B) is a key protein in gastric mucosa barrier acting an essential role in gastric acid secretion. However, the exact role and precise mechanism of ATP4B in gastric cancer (GC) remain obscure. This study aimed to investigate the clinical significance of ATP4B in GC and its biological role in tumor progression.Methods: We evaluated ATP4B expression in GC cell lines and patient specimens via qPCR and Immunofluorescence. The correlations between ATP4B expression level and clinicopathologic parameters, as well as the relevance of ATP4B expression with overall survival were assessed. The functional roles of ATP4B in GC were verified by gain- and loss-of-function cell models and xenograft tumor model. The possible downstream effects of ATP4B were analyzed by iTRAQ‑based quantitative proteomics analysis.Results: A dramatic decrease of ATP4B expression in GC cells and tissues compared with the adjacent normal tissues was observed; Downexpression of ATP4B was associated with the malignant transformation in gastric mucosa lesions and correlated with poor prognosis, high grade of TNM stage, and vessel carcinoma embolus in GC patients. Restoration of ATP4B expression in GC cells significantly inhibited cell proliferation, cell viability, migration, invasion, tumorigenicity and induced apoptosis, whereas ATP4B silencing exerted the opposite effects. Mechanistically, we found a constitutive activation of p53 and inactivation of NF-κB signaling correlated with the mitochondrial pathway in ATP4B-overexpressing GC cells.Conclusion: Our data suggest that ATP4B perform the promising tumor suppressor gene by regulating p53/NF-κB/mitochondrial pathway in GC.
Milrinone is associated with lower in hospital mortality in patients with cardiogenic shock: a retrospective analysis of the MIMIC-III database
Authors: Xue Yangjing , Wang Jinsheng , Peng Yangpei , Huang Kaiyu , Qian Lu , Qian Lala , Chu Maoping , Ji Kangting 
Published: March 2020

Abstract
BackgroundAlthough milrinone has been widely used in daily clinical practice, its effect on survival in patients with cardiogenic shock (CS) is not known. The primary purpose of this study was to evaluate the effectiveness of milrinone on in hospital mortality in a large critical care cohort of patients with CS of various etiological causes.MethodsPatients with CS were identified from the Medical Information Mart for Intensive Care III (MIMIC-III) database. Propensity score matching (PSM) was used to account for the baseline differences in the probability to receive milrinone or not. Multivariate Cox regression model was employed to adjust for imbalance by including parameters and potential confounders.ResultsA total of 1068 critically ill patients with CS were enrolled for this analysis, including 161 in the milrinone group and 907 in the non-milrinone group. Multivariate Cox regression model results found milrinone was associated with a significantly decreased in hospital mortality in critically ill patients with CS (HR 0.61, 95% CI 0.45-0.83; P=0.001). The impact of milrinone on survival benefit in CS was remaining in patients with non-ACS, while it was not statistically significant in subgroup with ACS (HR 0.66, 95% CI 0.40-1.07; P=0.093). Similar results were replicated after PSM.ConclusionsOur study observed that milrinone was related with improved survival in patients with CS, but it was not associated with improved outcome in patients complicated with ACS. The results need to be verified in randomized controlled trials.
A focused netnographic study exploring experiences associated with counterfeit and contaminated anabolic androgenic steroids
Authors: Frude Evelyn , McKay Fiona , Dunn Matthew 
Published: March 2020

Abstract
Background: A primary consequence of illicit drug markets and the absence of regulation is the variable quality or purity of the final product. Analysis of anabolic-androgenic steroid seizures shows that these products can contain adulterated products, product not included on the label, or product of unsatisfactory standard. While the potential negative effects of counterfeit AAS use is a recognised risk associated with use, no study has explored personal experiences associated with use. The aim of the present study was to use online discussion forums to investigate and explore the experiences associated with the purchase and consumption of counterfeit AAS among consumers.Methods: An online search was conducted to identify online forums that discussed counterfeit or contaminated AAS; three were deemed suitable for the study. The primary source of data for this study were the ‘threads’ from these online forums, identified using search terms including ‘counterfeit’, ‘tampered’, and ‘fake’. Threads were thematically analysed for overall content, leading to the identification of themes.Results: Data from 134 threads (2743 posts from 881 unique avatars) was included. Two main themes were identified from the analysis: 1) Experiences with counterfeit product; and 2) Harms and benefits associated with counterfeit product.Conclusions: The use of counterfeit or contaminated substances represents a public health concern. Those who report using PIEDs such as AAS for non-medical purposes report consuming these substances, and experiencing harm as a result. Consumers take steps to limit coming into contact with counterfeit or contaminated product, though recognise that many of these have limitations. The implementation of accessible drug safety checking services may provide an opportunity to provide consumers with information to assist them with making healthier choices.
Aloperine prevents hypoxia-induced epithelial-mesenchymal transition in bladder cancer cells through regulating the mTOR/p70S6K/4E-BP1 pathway
Authors: Lv Weiling , Liu Qian , An Jihong , Song Xiaoyong 
Published: March 2020

Abstract
Background: Aloperine (ALO), a novel active alkaloid extracted from S. alopecuroide, has been reported to possess anti-tumor effect. However, its potential effect on bladder cancer remains unknown. Therefore, the objective of this study was to investigate the effect of ALO bladder cancer cells under hypoxia condition.Methods: Human bladder cancer cell line T24 cells were treated with different concentrations of ALO and maintained in hypoxic condition for 12, 24, or 48 h. MTT assay was performed to detect cell viability. Transwell assay was performed to detect cell migration and invasion. Epithelial-mesenchymal transition (EMT) was evaluated by detecting the expression levels of E-cadherin, N-cadherin, and vimentin using western blot. The mRNA and protein levels of HIF-1α, snail, slug, and twist1 were measured using qRT-PCR and western blot. The expression levels of mTOR/p70S6K/4E-BP1 pathway-related proteins were detected using western blot.Results: Our results showed that ALO inhibited the cell viability of T24 cells cultured in hypoxia condition. ALO also attenuated hypoxia-induced migration and invasion of T24 cells. We also found that ALO treatment caused a significant increase in E-cadherin expression and decreases in N-cadherin and vimentin expressions. Besides, ALO dose-dependently inhibited the expressions of EMT inducers including snail, slug, and twist1 both in mRNA and protein levels in T24 cells induced by hypoxia. Furthermore, ALO significantly inhibited HIF-1α protein synthesis and phosphorylation of mTOR, as well 4E-BP1 and p70S6K in hypoxia-induced T24 cells.Conclusion: These results indicated that ALO exerted anti-tumor effect on bladder cancer in vitro via inhibiting the activation of mTOR/p70S6K/4E-BP1 pathway.
LncRNA CTBP1-AS2 regulates miR-216a/ PTEN to suppress ovarian cancer cell proliferationLncRNA CTBP1-AS2 regulates miR-216a/ PTEN to suppress ovarian cancer cell proliferation
Authors: Cui Kaiying , Zhu Genhai 
Published: March 2020

Abstract
Background: We analyzed TCGA dataset and observed the downregulation of CTBP1-AS2 in ovarian cancer (OC), while the function of CTBP1-AS2 has only been investigated in diabetes and cardiomyocyte hypertrophy, but not in cancer biology. We therefore analyzed the involvement of CTBP1-AS2 in OC. Result: We found that CTBP1-AS2 was downregulated in OC and predicted poor survival. CTBP1-AS2 in luciferase activity assay interacted with miR-216a, while overexpression of CTBP1-AS2 and miR-216a had no significant effects on the expression of each other. However, increased expression level of PTEN, a target of miR-216a, was observed after CTBP1-AS2 overexpression. Increased proliferation rate of OC cells was observed after the overexpression of miR-216a. CTBP1-AS2 and PTEN overexpression resulted in the reduced proliferation rate of OC cells and reduced effects of miR-216a overexpression. Conclusion: CTBP1-AS2 regulates miR-216a/PTEN to suppress OC cell proliferation.
CircPDK1 promotes RCC cell migration and invasion through the miR-377-3p/NOTCH1 axis
Authors: Huang Zhenlin , Ding Yinghui , Zhang Lu , He Siyuan , Jia Zhangkui , Gu Chaohui , Wang Tao , Li Hao , Li Xiang , Jin Zhibo , Ding Yafei , Yang Jinjian 
Published: March 2020

Abstract
Circular RNAs (circRNAs) are novel clusters of endogenous noncoding RNAs (ncRNAs) that are widely expressed in various tissue types. Recent studies have indicated that circRNAs involved in multiple tumorigenesis processes, and the potential significance of circRNAs remains to be explored. However, the roles roles and underlying mechanisms of circRNAs in clear cell renal cell carcinoma (RCC) remain unclear. We found that CircPDK1 is highly expressed in RCC by circRNA-seq assay. Moreover, the functional enrichment experiments showed that CircPDK1 is significantly associated with RCC metastasis. Eighty pairs of clinical samples were analyzed, and the results showed a correlation between CircPDK1 and lymph node and distant organ metastases in RCC. RNA-sequencing following knockdown of CircPDK1 revealed significant changes in the expression of many molecules in the metastasis-associated pathway. After bioinformatics prediction, we verified the relationships between CircPDK1 and miR-377-3p and between miR-377-3p and NOTCH1 by a luciferase reporter assay. Furthermore, the effect of CircPDK1 on RCC metastasis can be functionally influenced by miR-377-3p and NOTCH1. Altogether, our study shows that the CircPDK1 - miR-377-3p - NOTCH1 axis plays an important role in RCC metastasis, suggests CircPDK1 might serve as a potential therapeutic target for RCC treatment.