bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reduction of Bladder Cancer Chemosensitivity Induced by the Effect of HOXA-AS3 as a ceRNA for miR-455-5p That Upregulates Notch1
Authors: Chen Dajin , Xie Shangzhi , Wu Ying , Cui Yu , Cai Ying , Lan Lan , Yang Hao , Chen Jianghua , Chen Wei 
Published: February 2021

Chemoresistance is one of the main causes of recurrence in bladder cancer patients and leads to poor prognosis. Recently, long non-coding RNAs, like HOXA-AS3, have been reported to regulate chemoresistance in several types of cancer. In this study, we aimed to determine whether HOXA-AS3 can mediate cisplatin resistance in bladder cancer, and its potential mechanism of action. We determined the viability, proliferation, and apoptosis of bladder cancer cells using a CCK-8 assay, EdU staining, and flow cytometry, respectively. We used western blot analysis to assess the expression of markers of epithelial-mesenchymal transition (EMT) and Notch1. We then confirmed expression of these EMT-related markers by immunofluorescence analysis. We found that hypoxia promoted resistance to cisplatin and upregulated the level of HOXA-AS3 in BC cells. Inhibition of HOXA-AS3 enhanced hypoxia-induced cisplatin sensitivity by regulating EMT and Notch1 in BC cells. A dual-luciferase reporter assay confirmed that HOXA-AS3 directly targets miR-455-5p and that Notch1 was a potential target of miRNA-455-5p. We also found that the positive effect of HOXA-AS3 inhibition on cisplatin resistance and tumorigenesis was alleviated when BC cells were transfected with miR-455-5p. Finally, we showed combining HOXA-AS3 small interfering RNA (siRNA) with cisplatin treatment inhibited tumorigenesis in a BALB/c nu/nu mouse model. Our findings indicate that HOXA-AS3 may function as a competing endogenous RNA (ceRNA) of miR-455-5p to regulate Notch1 and play an important role in regulating chemotherapeutic drug sensitivity in BC cells. Therefore, HOXA-AS3 may be a novel therapeutic target for treating bladder cancer.
P. aeruginosa Mediated Necroptosis in Mouse Tumor Cells Induces Long-Lasting Systemic Antitumor Immunity
Authors: Qi Jia-long , He Jin-rong , Jin Shu-mei , Yang Xu , Bai Hong-mei , Liu Cun-bao , Ma Yan-bing 
Published: February 2021

Necroptosis is a form of programmed cell death (PCD) characterized by RIP3 mediated MLKL activation and increased membrane permeability via MLKL oligomerization. Tumor cell immunogenic cell death (ICD) has been considered to be essential for the anti-tumor response, which is associated with DC recruitment, activation, and maturation. In this study, we found that P. aeruginosa showed its potential to suppress tumor growth and enable long-lasting anti-tumor immunity in vivo. What’s more, phosphorylation- RIP3 and MLKL activation induced by P. aeruginosa infection resulted in tumor cell necrotic cell death and HMGB1 production, indicating that P. aeruginosa can cause immunogenic cell death. The necrotic cell death can further drive a robust anti-tumor response via promoting tumor cell death, inhibiting tumor cell proliferation, and modulating systemic immune responses and local immune microenvironment in tumor. Moreover, dying tumor cells killed by P. aeruginosa can catalyze DC maturation, which enhanced the antigen-presenting ability of DC cells. These findings demonstrate that P. aeruginosa can induce immunogenic cell death and trigger a robust long-lasting anti-tumor response along with reshaping tumor microenvironment.
Clinical Utility of 18F-PSMA-1007 Positron Emission Tomography/Magnetic Resonance Imaging in Prostate Cancer: A Single-Center Experience
Authors: Liu Ao , Zhang Miao , Huang Hai , Zhang Chuanjie , Ruan Xiaohao , Lin Wenhao , Li Biao , Chen Lu , Xu Danfeng 
Published: February 2021

PurposeThis study aimed to evaluate the clinical utility of 18F-PSMA-1007 positron emission tomography (PSMA PET)/magnetic resonance imaging (MRI) imaging in patients with suspected or defined prostate cancer.MethodsIn the pilot study, we retrospectively investigated 62 patients who underwent PSMA-PET/MRI for suspected or defined PCa between June 2019 and June 2020. Patients were grouped into three subgroups: (1) suspected PCa without histological evidence, (2) primary PCa, (3) biochemical recurrent prostate cancer (BRPCa). Two nuclear physicians independently interpreted the results of PSMA-PET/MRI. Management strategies before PSMA-PET/MRI were retrospectively reported, and the management strategy was re-evaluated for each patient considering the PSMA-PET/MRI result. The changes in strategies were recorded. Besides, the correlation between prostate specific antigen (PSA) level and management changes was also accessed by Fisher exact test, and two-side p &lt; 0.05 was assumed as statistical significance.ResultsThere were 28 patients in the suspected PCa group (group 1), 12 in the primary PCa group (group 2), and 22 in the BRPCa group (group 3). Overall, the intended decisions were changed in 26 (41.9%) of 62 patients after PSMA-PET/MRI, including 11/28 (39.3%) in suspected PCa group, 1/12 (8.4%) in primary PCa group, and 14/24 (63.6%) in BCR group. In group 1, the main impact on subsequent management included decreased active surveillance (from 20 to 9) and increased prostate biopsy (from 8 to 19). PSA levels were not significantly associated with management changes in suspected PCa patients (p = 0.865). In group 2, the main impact on subsequent management included decreased radical surgery (from 8 to 7), and multimodal therapy appearance (n = 1). Only in the category of PSA levels of ≥20 ng/ml, the management of primary PCa was changed. In group 3, the main impact on subsequent management included decreased salvage radiotherapy (from 5 to 2), increased systemic therapy (from 6 to 7), and increased multimodal therapy (from 11 to 13). The highest proportion of management changes occurred in BCR patients with 0.5≤PSA&lt;1 ng/ml.ConclusionFrom our preliminary experience, PSMA-PET/MRI may be a valued tool for defining PCa lesions and changing management. The biggest impact of management intent was in patients with BRPCa, especially in patients with 0.5≤PSA&lt;1 ng/ml. However, further studies are needed to confirm our pilot findings.
Which Definition of Upper Rectal Cancer Is Optimal in Selecting Stage II or III Rectal Cancer Patients to Avoid Postoperative Adjuvant Radiation?
Authors: Gao Xian Hua , Zhai Bai Zhi , Li Juan , Kabemba Jean Luc Tshibangu , Gong Hai Feng , Bai Chen Guang , Liu Ming Lu , Zhang Shao Ting , Shen Fu , Liu Lian Jie , Zhang Wei 
Published: February 2021

BackgroundIn most guidelines, upper rectal cancers (URC) are not recommended to take neoadjuvant or adjuvant radiation. However, the definitions of URC vary greatly. Five definitions had been commonly used to define URC: 1) &gt;10 cm from the anal verge by MRI; 2) &gt;12 cm from the anal verge by MRI; 3) &gt;10 cm from the anal verge by colonoscopy; 4) &gt;12 cm from the anal verge by colonoscopy; 5) above the anterior peritoneal reflection (APR). We hypothesized that the fifth definition is optimal to identify patients with rectal cancer to avoid adjuvant radiation.MethodsThe data of stage II/III rectal cancer patients who underwent radical surgery without preoperative chemoradiotherapy were retrospectively reviewed. The height of the APR was measured, and compared with the tumor height measured by digital rectal examination (DRE), MRI and colonoscopy. The five definitions were compared in terms of prediction of local recurrence, survival, and percentages of patients requiring radiation.ResultsA total of 576 patients were included, with the intraoperative location of 222 and 354 tumors being above and straddle/below the APR, respectively. The median distance of the APR from anal verge (height of APR) as measured by MRI was 8.7 (range: 4.5–14.3) cm. The height of APR positively correlated with body height (r=0.862, P&lt;0.001). The accuracy of the MRI in determining the tumor location with respect to the APR was 92.1%. Rectal cancer above the APR had a significantly lower incidence of local recurrence than those straddle/below the APR (P=0.042). For those above the APR, there was no significant difference in local recurrence between the radiation and no-radiation group. Multivariate analyses showed that tumor location regarding APR was an independent risk factor for LRFS. Tumor height as measured by DRE, MRI and colonoscopy were not related with survival outcomes. Fewer rectal cancer patients required adjuvant radiation using the definition by the APR, compared with other four definitions based on a numerical tumor height measured by MRI and colonoscopy.ConclusionsThe definition of URC as rectal tumor above the APR, might be the optimal definition to select patients with stage II/III rectal cancer to avoid postoperative adjuvant radiation.
Endothelin-1 Exhibiting Pro-Nociceptive and Pro-Peristaltic Activities Is Increased in Peritoneal Carcinomatosis
Authors: Greco Céline , Basso Lilian , Désormeaux Cléo , Fournel Audren , Demuynck Benedicte , Lafendi Leila , Chapiro Sylvie , Lemoine Antoinette , Zhu Ying-Ying , Knauf Claude , Cenac Nicolas , Boucheix Claude , Dietrich Gilles 
Published: February 2021

Background: Peritoneal carcinomatosis often results in alterations in intestinal peristalsis and recurrent abdominal pain. Pain management in these patients is often unsatisfactory. This study aimed to investigate whether endothelin-1 (EDN1) was involved in pain mediation in peritoneal carcinomatosis, and thus whether the EDN1 pathway could be a new therapeutic target for peritoneal carcinomatosis-associated pain.Methods: EDN1 plasma levels and abdominal pain severity were assessed in patients with abdominal tumors, with or without peritoneal carcinomatosis, and in healthy donors. The effects of EDN1 on the visceromotor response to colorectal distension, and on colonic contractions were then examined in mice, and the mechanism of action of EDN1 was then investigated by measuring the impact of EDN1 exposure on calcium mobilization in cultured neurons. Inhibition studies were also performed to determine if the effects of EDN1 exposure could be reversed by EDN1-specific receptor antagonists.Results: A positive correlation between EDN1 plasma levels and abdominal pain was identified in patients with peritoneal carcinomatosis. EDN1 exposure increased visceral sensitivity and the amplitude of colonic contractions in mice and induced calcium mobilization by direct binding to its receptors on sensory neurons. The effects of EDN1 were inhibited by antagonists of the EDN1 receptors.Conclusions: This preliminary study, using data from patients with peritoneal carcinomatosis combined with data from experiments performed in mice, suggests that EDN1 may play a key role mediating pain in peritoneal carcinomatosis. Our findings suggest that antagonists of the EDN1 receptors might be beneficial in the management of pain in patients with peritoneal carcinomatosis.
Chemical Characteristics of Platycodon grandiflorum and its Mechanism in Lung Cancer Treatment
Authors: Deng Yaling , Ye Xianwen , Chen Yufan , Ren Hongmin , Xia Lanting , Liu Ying , Liu Minmin , Liu Haiping , Zhang Huangang , Wang Kairui , Zhang Jinlian , Zhang Zhongwei 
Published: February 2021

Objective: The technology, network pharmacology and molecular docking technology of the ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to explore the potential molecular mechanism of Platycodon grandiflorum (PG) in the treatment of lung cancer (LC).Methods: UPLC-Q-TOF-MS/MS technology was used to analyze the ingredients of PG and the potential LC targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database, and the Analysis Platform (TCMSP), GeneCards and other databases. The interaction network of the drug-disease targets was constructed with the additional use of STRING 11.0. The pathway enrichment analysis was carried out using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) in Metascape, and then the “Drug-Ingredients-Targets-Pathways-Disease” (D-I-T-P-D) network was constructed using Cytoscape v3.7.1. Finally, the Discovery Studio 2016 (DS) software was used to evaluate the molecular docking.Results: Forty-seven compounds in PG, including triterpenoid saponins, steroidal saponins and flavonoids, were identified and nine main bioactive components including platycodin D were screened. According to the method of data mining, 545 potential drug targets and 2,664 disease-related targets were collected. The results of topological analysis revealed 20 core targets including caspase 3 (CASP3) and prostaglandin-endoperoxide synthase 2 (PTGS2) suggesting that the potential signaling pathway potentially involved in the treatment of LC included MAPK signaling pathway and P13K-AKT signaling pathway. The results of molecular docking proved that the bound of the ingredients with potential key targets was excellent.Conclusion: The results in this study provided a novel insight in the exploration of the mechanism of action of PG against LC.
Identification and Enzymatic Activity Evaluation of a Novel CYP2C9 Allelic Variant Discovered in a Patient
Authors: Zhou Xiao-Yang , Lu Xiang-Ran , Li Ying-Hui , Ma Ya-Qing , Zhao Shi-Wen , Wang Fang , Xu Ren-Ai , Hu Guo-Xin , Cai Jian-Ping 
Published: February 2021

Warfarin is a widely prescribed anticoagulant but the doses required to attain the optimum therapeutic effect exhibit dramatic inter-individual variability. Pharmacogenomics-guided warfarin dosing has been recommended to improve safety and effectiveness. We analyzed the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) genes among 120 patients taking warfarin. A new coding variant was identified by sequencing CYP2C9. The novel A &gt; G mutation at nucleotide position 14,277 led to an amino acid substitution of isoleucine with valine at position 213 (I213V). The functional consequence of the variant was subsequently evaluated in vitro. cDNA of the novel variant was constructed by site-directed mutagenesis and the recombinant protein was expressed in vitro using a baculovirus–insect cell expression system. The recombinant protein expression was quantified at apoprotein and holoprotein levels. Its enzymatic activities toward tolbutamide, warfarin and losartan were then assessed. It exhibited changed apparent Km values and increases of 148%, 84% and 67% in the intrinsic clearance of tolbutamide, warfarin and losartan, respectively, compared to wild-type CYP2C9*1, indicating dramatically enhanced in vitro enzymatic activity. Our study suggests that the amino acid at position 213 in wild-type CYP2C9*1 may be important for the enzymatic activity of CYP2C9 toward tolbutamide, warfarin and losartan. In summary, a patient taking high-dose warfarin (6.0 mg/day) in order to achieve the target international normalized ratio was found to have a mutation in the CYP2C9 gene.
Network-centric Indicators for Fragility in Global Financial Indices
Authors: Samal Areejit , Kumar Sunil , Yadav Yasharth , Chakraborti Anirban 
Published: February 2021

Over the last 2 decades, financial systems have been studied and analyzed from the perspective of complex networks, where the nodes and edges in the network represent the various financial components and the strengths of correlations between them. Here, we adopt a similar network-based approach to analyze the daily closing prices of 69 global financial market indices across 65 countries over a period of 2000–2014. We study the correlations among the indices by constructing threshold networks superimposed over minimum spanning trees at different time frames. We investigate the effect of critical events in financial markets (crashes and bubbles) on the interactions among the indices by performing both static and dynamic analyses of the correlations. We compare and contrast the structures of these networks during periods of crashes and bubbles, with respect to the normal periods in the market. In addition, we study the temporal evolution of traditional market indicators, various global network measures, and the recently developed edge-based curvature measures. We show that network-centric measures can be extremely useful in monitoring the fragility in the global financial market indices.
Continuous Support Promotes Obstetric Labor Progress and Vaginal Delivery in Primiparous Women – A Randomized Controlled Study
Authors: Stjernholm Ylva Vladic , Charvalho Paula da Silva , Bergdahl Olga , Vladic Tomislav , Petersson Maria 
Published: February 2021

Background: Obstetric labor and childbirth are mostly regarded as a physiological process, whereas social, cultural, psychological and transcendental aspects have received less attention. Labor support has been suggested to promote labor progress. The aim of this study was to investigate whether continuous labor support by a midwife promotes labor progress and vaginal delivery.Material and Methods: A randomized controlled study at a university hospital in Sweden in 2015–17. Primiparous women with singleton pregnancy and spontaneous labor onset were randomized to continuous support (n = 30) or standard care (n = 29) during delivery. The primary outcome was the duration of active labor. Secondary outcomes were delivery mode, women's need of labor analgesia and satisfaction with delivery, maternal cortisol levels, and neonatal morbidity.Results: Continuous support was followed by shorter active labor 11.0 ± 5.7 h compared to 13.7 ± 3.9 h with standard care (p = 0.001). Women in the continuous support group tended to have lower cortisol levels and low cortisol during the first (p = 0.02) and second (p = 0.04) stages of labor were correlated with shorter active labor. Continuous support was followed by spontaneous delivery in 73%, instrumental delivery in 24% and emergency cesarean section in 3% in contrast to standard care which was followed by spontaneous delivery in 62%, instrumental delivery in 24% and cesarean in 14% (p = 0.19). The continuous support group received combined analgesic methods more often (p = 0.04). Women's satisfaction with delivery and neonatal morbidity were comparable.Conclusion: Continuous labor support was followed by shorter active labor compared to standard care. Women with continuous support had a high rate of vaginal delivery and tended to have lower cortisol levels during all stages of active labor reflecting a lower stress level. Low cortisol was correlated to shorter active labor. Based on these results, we recommend continuous labor support for all primiparous women during active labor.
The Causal Influence of Life Meaning on Weight and Shape Concerns in Women at Risk for Developing an Eating Disorder
Authors: van Doornik Sanne F. W. , Glashouwer Klaske A. , Ostafin Brian D. , de Jong Peter J. 
Published: February 2021

Background: Although previous studies have shown an inverse relation between life meaning and eating disorder symptoms, the correlational nature of this evidence precludes causal inferences. Therefore, this study used an experimental approach to test the causal impact of life meaning on individuals' weight and shape concerns.Methods: Female students at risk for developing an eating disorder (N = 128) were randomly assigned to the control or the meaning condition, which involved thinking about and committing to pursue intrinsically valued life goals. A color-naming interference task was used to assess the motivational salience of body-related stimuli, and self-report measures were used to assess participants' overvaluation of weight and shape.Results: The meaning manipulation was effective in activating intrinsically valued life goals. However, it did not result in lower self-reported overvaluation of weight and shape or lower color-naming interference effects of body-related stimuli, compared to the control condition. Post-hoc analyses suggested that baseline meaning in life was related to the impact of the manipulation.Conclusions: This experimental study did not provide evidence for a causal influence of life meaning on the overvaluation of weight and shape in a high-risk group. The current findings suggest that we first need to examine the relationship between life meaning and eating disorder symptoms in more detail, before implementing brief meaning manipulations in clinical practice.
A Randomized Controlled Trial Evaluating the Effectiveness of Face-to-Face and Digital Training in Improving Child Mental Health Literacy Rates in Frontline Pediatric Hospital Staff
Authors: O'Connell Jennifer , Shafran Roz , Pote Helen 
Published: February 2021

Background: Children with chronic physical health conditions are up to six times more likely to develop a mental health condition than their physically well peers. Frontline pediatric hospital staff are in a good position to identify mental health problems and facilitate appropriate support for patients. To date, no evaluation of mental health literacy training has taken place with this professional group to enable early identification of difficulties. It is also not known whether face-to-face or digital training is more effective or preferable in this setting. To improve the skills of frontline hospital staff, a face-to-face and digital mental health literacy training course was delivered using MindEd content and evaluated in a randomized controlled trial.Method: Two-hundred and three frontline staff across different professions from a tertiary pediatric hospital were randomized to a face-to-face (n = 64), digital (n = 71), or waitlist control group (n = 68). Face-to-face training was two and a half hours and digital training took ~1 h. The effects of training were evaluated pre- and post-training and at two-week follow-up. Questionnaires assessed mental health knowledge, stigma, confidence in recognizing concerns and knowing what to do, actual helping behavior, as well as training delivery preference, completion rate, and satisfaction.Results: Both face-to-face and digital training increased mental health knowledge, confidence in recognizing mental health problems and knowing what to do compared to waitlist controls. Digital training increased actual helping behavior relative to the waitlist controls and stigma decreased across all groups. Staff were satisfied with both delivery methods but preferred face-to-face training.Conclusions: The results provide promising findings that digital content is an effective way of improving mental health literacy in frontline pediatric hospital staff. Providing digital training could be a time-efficient way of upskilling non-mental health professionals to identify mental health needs in a pediatric population and facilitate access to appropriate care.