bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of HSP90AB1&nbsp;and CC&nbsp;Domain Interaction on Bcr-Abl&nbsp;Protein Cytoplasm Localization and Function in Chronic Myeloid Leukemia Cells
Authors: Peng Yuhang , Huang Zhenglan , Zhou Fangzhu , Wang Teng , Mou Ke , feng wenli 
Published: January 2021

Abstract
Background: The fusion oncoprotein Bcr-Abl is mostly located in the cytoplasm, which causes chronic myeloid leukemia (CML). After moving into the nucleus, the fusion protein can induce apoptosis of CML cells. The coiled-coil domain (CC domain) of Bcr-Abl protein plays a central role in the subcellular localization. However, how CC domain affects subcellular localization of Bcr-Abl remains unclear. Methods: Herein, the key proteins interacting with the Bcr-Abl CC domain were screened by immunoprecipitation binding mass spectrometry. The specific site of Bcr-Abl CC domain binding to target protein was predicted by Deep Viewer. Immunoprecipitation assay was used to confirmed the specific sites of protein binding. IF and western blot were used to observe the subcellular localization of target protein. Western blot was used to examine the protein changes. CCK-8, clonal formation test and FCM cycle detection were used to observe the effect of inhibitor on the proliferation ability of CML cells. FCM apoptosis detection was used to observe the level of cells apoptosis.Results: HSP90AB1 interacts with Bcr-Abl CC domain via N-terminal domain (NTD), preventing the transport of Bcr-Abl protein to the nucleus and maintaining the activation of Bcr-Abl tyrosine kinase. The nucleus-entrapped Bcr-Abl markedly inhibits the proliferation and induces apoptosis of CML cells by activating p73 and repressing the expression of cytoplasmic oncogenic signaling pathways mediated by Bcr-Abl. Moreover, the combination of 17AAG (Tanespimycin) with Leptomycin B (LMB) considerably decreased the proliferation of CML cells.Conclusion: Our study provides evidence that it is feasible to transport Bcr-Abl into the nucleus as an alternative strategy for the treatment of CML, and targeting the NTD of HSP90AB1 to inhibit the interaction with Bcr-Abl is more accurate for the development and application of HSP90 inhibitor in the treatment of CML and other Bcr-Abl-addicted malignancies.
Delayed Embolization Associated With Increased Mortality in Patients With Hemodynamically Stable Pelvic Fracture
Authors: Aoki Makoto , Abe Toshikazu , Matsumoto Shokei , Hagiwara Shuichi , Saitoh Daizoh , Oshima Kiyohiro 
Published: January 2021

Abstract
Background: Embolization is widely used for controlling arterial hemorrhage associated with pelvic fracture. However, the effect of a delay in embolization among hemodynamically stable patients with pelvic fracture is unknown. Therefore, our aim was to investigate the association between the time to embolization and mortality in hemodynamically stable patients with a pelvic fracture.Methods: A multicenter, retrospective cohort study was undertaken using data from the Japan Trauma Data Bank from between 2004 and 2018. Hemodynamically stable patients with pelvic fracture who underwent an embolization within 3 h were divided into six groups of 30-min blocks of time until pelvic embolization (0–30, 30–60, 60–90, 90–120, 120–150, and 150–180 min). We compared the adjusted 30-day mortality rate according to time to embolization. Results: We studied 620 hemodynamically stable patients with a pelvic fracture who underwent pelvic embolization within 3 h of hemorrhage. The median age was 68 (48–79) years and 55% were male. The median injury severity score was 26 (18–38). Thirty-day mortality was 8.9% (55/620) and 24-hour mortality was 4.2% (26/619). A Cochran–Armitage test showed that a 30-min delay for embolization was associated with increased 30-day (p = 0.0186) and 24-hour (p = 0.033) mortality. Mortality within 0–30 min to embolization was 0%. The adjusted 30-day mortality rate increased with delayed embolization and was up to 17.0% (10.2–23.9) for the 150–180 min group. Conclusion: Delayed embolization was associated with increased mortality among hemodynamically stable patients with pelvic fracture. Early identification and embolization reduced mortality in such patients.
A Consensus Statement for Trauma Surgery Capacity Building in Latin America
Authors: Dasari Mohini , Johnson Erica D. , Montenegro Jorge H. , Griswold Dylan , Jiménez Maria Fernanda , Puyana Juan Carlos , Rubiano Andres M. 
Published: January 2021

Abstract
Background: Trauma is a significant public health problem in Latin America (L.A.), contributing to substantial death and disability in the region. Several LA countries have implemented trauma registries and injury surveillance systems. However, the region lacks an integrated trauma system. The consensus conference's goal was to integrate existing L.A. trauma data collection efforts into a regional trauma program and encourage the use of the data to inform health policy.Methods: We created a consensus group of 25 experts in trauma and emergency care with previous data collection and injury surveillance experience in the L.A. region. Experts participated in a consensus conference to discuss the state of trauma data collection in L.A. We utilized the Delphi method to build consensus around strategic steps for trauma data management in the region. Consensus was defined as the agreement of ≥ 70% among the expert panel. Results: The consensus conference determined that action was necessary from academic bodies, scientific societies, and ministries of health to encourage a culture of collection and use of health data in trauma. The panel developed a set of recommendations for these groups to encourage the development and use of robust trauma information systems in L.A. Consensus was achieved in one Delphi round.Conclusions: The expert group successfully reached a consensus on recommendations to key stakeholders in trauma information systems in L.A. These recommendations may be used to encourage capacity-building in trauma research and trauma health policy in the region.
Differences in Heart Rate Variability and Body Composition in Breast Cancer Survivors and Women Without Cancer
Authors: Escutia-Reyes Daniel , Garduño-García José , López-Chávez Gerardo , Gómez-Villanueva Ángel , Pliego-Carrillo Adriana , Soto-Piña Alexandra , Reyes-Lagos José Javier 
Published: January 2021

Abstract
Purpose: To explore cardiac autonomic changes assessed by linear and nonlinear indexes of heart rate variability (HRV) and body composition modifications in breast cancer survivors and cancer-free control women. Methods: Women who were breast cancer survivors (BCS, n=27) and cancer-free control participants with similar characteristics (Control, n=31) were enrolled in the Regional General Hospital No. 251 of the Mexican Institute of Social Security (Metepec, Mexico). We processed five minutes of R-R interval time series, and we calculated relevant linear and nonlinear parameters of HRV such as mean RR interval (RRave), the Root Mean Square of the Successive Differences (RMSSD), the Poincaré plot measures SD1, SD2, SD1/SD2, and the sample entropy (SampEn). Additionally, we indirectly assessed body composition measures such as body weight, fat mass, visceral fat rating (VFR), normalized VRF (nVFR), muscle mass, metabolic age, and total body water.Results: We found that diverse HRV indexes and only one body composition measure showed statistical differences (p<0.05) between the BCS and Control groups: RRave: 729 (648–802) vs. 795 (713–852) ms; RMSSD: 16.5 (8.9–27.0) vs. 19.7 (14.2–28.5) ms; SD1: 11.6 (6.3–19.0) vs. 13.9 (10.0–20.1) ms; SD1/SD2: 2.5 (2.1–3.3) vs. 2.2 (1.9–2.7), SampEn: 1.5 (1.3–1.8) vs. 1.7 (1.5–1.8), and nVFR 0.12 (0.11–0.13) vs.0.10 (0.08–0.12) points/kg, respectively. The nVFR was significantly correlated to several indexes of HRV.Conclusions: BCS exhibit a lower parasympathetic cardiac activity and changes in HRV patterns than controls, likely because of the concomitant increase of visceral fat.
Involvement of TLR4 Signaling Regulated-COX2/PGE2 Axis in Liver Fibrosis Induced by Schistosoma japonicum Infection
Authors: Chen Lan , Ji Xiaofang , Wang Manni , Liao Xiaoyan , Liang Cuiying , Tang Juanjuan , Wen Zhencheng , Dominique Ferrandon , Li Zi 
Published: January 2021

Abstract
Background: The hepatic stellate cells (HSCs) activation plays pivotal role in hepatic inflammation and liver fibrosis.TLR4 pathway activation has been reported to be involved in mice liver fibrosis induced by hepatitis virus infection, alcohol abuse, biliary ligation, carbon tetrachloride 4 treatment and Schistosoma japonicum (Sj) infection. The effect and mechanisms of cyclooxygenase 2 (COX2)/prostanoid E2 (PGE2) axis on liver fibrosis induced by Sj are still unclear. Results: This study investigated the link between COX2/PGE2 axis and TLR4 signaling in the induction of liver fibrogenesis in mice during Sj infection and in vitro culturing hepatic stellate cells (HSCs) strain-LX-2. The COX2/PGE2 axis was positively related with Sj-induced liver fibrosis. TLR4 pathway activation stimulated the COX2/PGE2 axis, in Sj-infected mice andin lipopolysaccharide (LPS)-exposed cultured HSCs. Synthetic PGE2 activated culturing HSCs through up-regulating alpha smooth muscle actin (α-SMA) expression. In LPS-triggered HSCs, NS398, a COX2 inhibitor led to suppression of PGE2 synthesis and reduced expression of α-SMA and type I collagen (COL I). Conclusions: These results indicated firstly the positive association of COX2/PGE2 axis with liver fibrosis induced by Sj infection. TLR4 signaling may control COX2/PGE2 axis in Sj-infected mice liver and in vitro culturing HSCs at least partially. COX2/PGE2-EP2/EP4 axis might be good drug targets against liver fibrosis induced by Sj infection.
Identification of Hub Genes Associated With Progression and Prognosis of Bladder Cancer by Integrated Bioinformatics Analysis.
Authors: Liu Daoquan , Ma Jianhong , Wei Sheng , Liu Jianmin , Li Mingzhou , He Weixiang , Qian Qiaofeng , Zhou Yongying , Li Yan , Fu Xun , Liu Huan , Wang Qian , Chen Ping , Xu Deqiang , Wang Xinhuan , DiSanto Michael E , Zhang Xinhua 
Published: January 2021

Abstract
Background: Bladder cancer (BLCA) is the most popular malignant carcinomas in genitourinary system which has a high incidence and is prone to relapse. However, the molecular mechanism of BLCA remains to be unclear. Moreover, there is still a shortage of effective biomarkers that can predict progression and prognosis of BLCA. The objective of current study is to screen significant genes as biomarkers to forecast the progression and prognosis of BLCA patients.Methods: Gene expression profile downloaded from TCGA database and GEO database was used. Differential gene expression analysis and WGCNA were conducted to identify differential co-expression genes. In addition, GO enrichment analysis and KEGG pathway analysis were used to explore the functions of these genes. Moreover, PPI network, OS and DFS were used to identify survival-related hub genes. Finally, the expression levels of these genes were validated by qRT-PCR and HPA database.Results: About 124 differential co-expression genes were identified. And these genes were mainly enriched in muscle system process and muscle contraction (BP), contractile fiber, myofibril, sarcomere, focal adhesion and cell-substrate junction (CC) and actin binding (MF) in GO enrichment analysis, while enriched in vascular smooth muscle contraction, focal adhesion, cardiac muscle contraction, hypertrophic cardiomyopathy, dilated cardiomyopathy and regulation of actin cytoskeleton in KEGG analysis. Furthermore, five survival-related hub genes (MYH11, ACTA2, CALD1, TPM1, MYLK) were identified via overall OS and DFS. In addition, the expression levels of the five survival-related genes were upregulated with the procession of BLCA, such as grade, stage and TNM stage. Finally, all survival-related hub genes were found to be down-regulated in BLCA via qRT-PCR and HPA database.Conclusions: Our current study verified five new key genes in BLCA, which could help us better understand the pathogenesis of BLCA. And these five hub genes may be involved in the development and progression of BLCA and served as potential biomarkers.
Image-Guided Microwave Ablation of Hepatocellular Carcinoma (≤5.0 cm): Is MR Guidance More Effective Than CT Guidance?
Authors: Li Zhaonan , Wang Chaoyan , Si Guangyan , Zhou Xueliang , Li Yahua , Li Jin , Jiao Dechao , Han Xinwei 
Published: January 2021

Abstract
BackgroundPercutaneous tumor ablation is usually performed using computed tomography (CT) or ultrasound (US) guidance, although reliable visualization of the target tumor may be challenging. MRI guidance can provide more reliable visualization of the target tumor and allow for multiplanar capabilities, making it the modality of choice. Due to the lack of comparative studies of microwave ablation(MWA) guided by different images. This study retrospectively compared the effectiveness of computed tomography (CT)-guided versus magnetic resonance (MR)-guided MWA for hepatocellular carcinoma (HCC≤5.0 cm). MethodsIn this retrospective study, 47 patients and 54 patients received MWA under the guidance of CT and MR, respectively. The inclusion criteria were a single HCC≤5.0 cm or a maximum of three. The local tumor progression (LTP), overall survival (OS), prognostic factors for local progression, and safety of this technique were assessed.ResultsAll procedures were technically successful. The complication rates of the two groups were significantly different with respect to liver abscess and pleural effusion (P<0.05). The mean LTP was 44.264 months in the CT-guided group versus 47.745 months in the MR-guided group of HCC (P = 0.629, log-rank test). The mean OS was 56.772 months in the patients who underwent the CBCT-guided procedure versus 58.123 months in those who underwent the MR-guided procedure (P = 0.630, log-rank test). Multivariate Cox regression analysis further illustrated that tumor diameter (<3 cm) and the number of lesions (single) were important factors affecting LTP and OS.ConclusionsCT-guided and MR-guided MWA are safe and effective in the treatment of HCC with a diameter of less than 5 cm. Furthermore, MR-guided MWA could reduce the incidence of complications.
Phosphorylation of an Arabidopsis villin activates host actin remodeling to restrict microbial invasion
Authors: Zou Minxia , Guo Mengmeng , Zhou Zhaoyang , Xiao Bingxiao , Pan Qing , Li Jiajing , Zhou Jian-Min , Li Jiejie 
Published: January 2021

Abstract
Actin cytoskeleton is a dynamic framework of cytoplasmic filaments that rearranges as the needs of the cell change during growth and development. Incessant turnover mechanisms allow these networks to be rapidly redeployed in defense of host cytoplasm against microbial invaders. However, the precise functions of host actin and the molecular mechanisms underlying actin rearrangements in host defense remain largely unknown. Here, we uncover the mechanism by which host actin controls innate immunity gates on plant surface to actively prevent microbial entry into internal tissue. VLN3, a villin protein from Arabidopsis is a key regulator of this process. Our in vitro and in vivo phosphorylation assays show that VLN3 is a physiological substrate of two pathogen-responsive mitogen-activated protein kinases (MAPKs). Quantitative analyses of actin dynamics and genetic studies reveal that phosphorylation of VLN3 by MAPKs govern actin remodeling to activate innate immunity gating on host surface.
Magnaporthe oryzae Systemic Defense Trigger 1 (MoSDT1)-Mediated Metabolites Regulate Defense Response in Rice
Authors: Duan Guihua , Li Chunqin , Liu Yanfang , Ma Xiaoqing , Luo Qiong , Yang Jing 
Published: January 2021

Abstract
Background: Some of the pathogenic effector proteins play an active role in stimulating the plant defense system to strengthen plant resistance. Results: In this study, ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC/Q-TOF-MS) was implemented to identify altered metabolites in transgenic rice containing over-expressed M. oryzae Systemic Defense Trigger 1 (MoSDT1) that was infected at three-time points. The characterized dominating metabolites were organic acids and their derivatives, organic oxygen compounds, lipids, and lipid-like molecules. Among the identified metabolites, shikimate, galactinol, trehalose, D-mannose, linolenic acid, dopamine, tyramine, and L-glutamine are precursors for the synthesis of many secondary defense metabolites Carbohydrate, as well as amino acid metabolic, pathways were revealed to be involved in plant defense responses and resistance strengthening. Conclusion: The increasing salicylic acid (SA) and jasmonic acid (JA) content enhanced interactions between JA synthesis/signaling gene, SA synthesis/receptor gene, raffinose/fructose/sucrose synthase gene, and cell wall-related genes all contribute to defense response in rice. The symptoms of rice after M. oryzae infection were significantly alleviated when treated with six identified metabolites, i.e., galactol, tyramine, L-glutamine, L-tryptophan, α-terpinene, and dopamine for 72 h exogenously. Therefore, these metabolites could be utilized as an optimal metabolic marker for M. oryzae defense.
Participation in disease management programs and major adverse cardiac events in patients after acute myocardial infarction. A longitudinal study based on registry data
Authors: Fischer Christian , Höpner Jens , Hartwig Saskia , Noutsias Michel , Mikolajczyk Rafael 
Published: January 2021

Abstract
Background: Cardiovascular diseases are still the main cause of death in the western world. However, diminishing mortality rates of acute myocardial infarction (AMI) are motivating the need to investigate the process of secondary prevention after AMI. Besides cardiac rehabilitation, disease management programs (DMPs) are an important component of outpatient care after AMI in Germany. This study aims to analyze outcomes after AMI among those who participated in DMPs and cardiac rehabilitation (CR) in a region with overall increased cardiovascular morbidity and mortality. Methods: Based on data from a regional myocardial infarction registry and a 2-year follow-up period, we assessed the occurrence of major adverse cardiac events (MACE) in relation to participation in CR and DMP, risk factors for complications and individual healthas well as lifestyle characteristics. Multivariable Cox regression was performed to compare survival time between participants and non-participants until an adverse event occurred. Results: Of 1,094 observed patients post-AMI, 272 were enrolled in a DMP. An association between DMP participation and lower hazard rates for MACE compared to non-enrollees could not be proven in the crude model (hazard ratio = 0.93; 95% confidence interval = 0.65-1.33). When adjusted for possible confounding variables, these results remained virtually unchanged (1.03; 0.72-1.48). Furthermore, smokers and obese patients showed a distinctly lower chance of DMP enrollment. In contrast, those who participated in CR showed a lower risk for MACE in crude (0.52; 0.41-0.65) and adjusted analysis (0.56; 0.44-0.71). Conclusions: Participation in DMP was not associated with a lower risk of MACE, but participation in CR showed beneficial effects. Adjustment only slightly changed effect estimates in both cases, but it is still important to consider potential effects of confounding variables.
Effects of pre-emptive pregabalin and multimodal anesthesia on postoperative opioid requirements in patients undergoing robot-assisted laparoscopic prostatectomy
Authors: Sisa Katrin , Huoponen Saara , Ettala Otto , Antila Heikki , Saari Teijo I. , Uusalo Panu 
Published: January 2021

Abstract
Background: Previous findings indicate that pre-emptive pregabalin as part of multimodal anesthesia reduces opioid requirements compared to conventional anesthesia in patients undergoing robot-assisted laparoscopic prostatectomy (RALP). However, recent studies show contradictory evidence suggesting that pregabalin does not reduce postoperative pain or opioid consumption after surgeries. We conducted a register-based analysis on RALP patients treated over a five-year period to evaluate postoperative opioid consumption between two multimodal anesthesia protocols.Methods: We retrospectively evaluated patients undergoing RALP between years 2015 and 2019. Patients with American Society of Anesthesiologists status 1-3, age between 30 and 80 years and treated with standard multimodal anesthesia were included in the study. Pregabalin (PG) group received 150 mg of oral pregabalin as premedication before anesthesia induction, while the control (CTRL) group was treated conventionally. Postoperative opioid requirements were calculated as intravenous morphine equivalent doses for both groups. The impact of pregabalin on postoperative nausea and vomiting (PONV), and length of stay (LOS) was evaluated.Results: We included 245 patients in the PG group and 103 in the CTRL group. Median (IQR) opioid consumption over 24 postoperative hours was 15 (8-24) and 17 (8-25) mg in PG and CTRL groups (p = 0.44). We found no difference in postoperative opioid requirement between the two groups in post anesthesia care unit, or within 12 hours postoperatively (p=0.16; p = 0.09). The length of post anesthesia care unit stay was same in each group and there was no difference in PONV Similarly, median postoperative LOS was 31 hours in both groups.Conclusion: Patients undergoing RALP and receiving multimodal analgesia do not need significant amount of opioids postoperatively and can be discharged soon after the procedure. Pre-emptive administration of oral pregabalin does not reduce postoperative opioid consumption, PONV or LOS in these patients.
Modeling Familial Predictors of Proband Outcomes in Neurogenetic Disorders: Initial Application in XYY Syndrome
Authors: Wilson Kathleen E. , Fish Ari M. , Mankiw Catherine , Xenophontos Anastasia , Warling Allysa , Whitman Ethan , Clasen Liv , Torres Erin , Blumenthal Jonathan , Raznahan Armin 
Published: January 2021

Abstract
Background: Disorders of gene dosage can significantly increase risk for psychopathology, but outcomes vary greatly amongst carriers of any given chromosomal aneuploidy or sub-chromosomal copy number variation (CNV). One potential path to advance precision medicine for neurogenetic disorders is modeling penetrance in probands relative to observed phenotypes in their non-carrier relatives. Here, we seek to advance this general analytic framework by developing new methods in application to XYY syndrome – a sex chromosome aneuploidy that is known to increase risk for psychopathology.Methods: We analyzed a range of cognitive and behavioral domains in XYY probands and their non-carrier family members (n = 58 families), including general cognitive ability (FSIQ), as well as continuous measures of traits related to autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD). Proband and relative scores were compared using covariance, regression and cluster analysis. Comparisons were made both within and across traits.Results: Proband scores were shifted away from family scores with effect sizes varying between 0.9 and 2.4 across traits. Only FSIQ and vocabulary scores showed a significant positive correlation between probands and their non-carrier relatives across families (R2 ~ 0.4). Variability in family FSIQ also cross-predicted variability in proband ASD trait severity. Cluster analysis across all trait-relative pairings revealed that variability in parental psychopathology was more weakly coupled to their XYY versus their euploid offspring.Conclusions: We present a suite of generalizable methods for modeling variable penetrance in aneuploidy and CNV carriers using family data. These methods update estimates of phenotypic penetrance for XYY and suggests that the predictive utility of family data is likely to vary for different traits and different gene dosage disorders. Trial registrations: ClinicalTrials.gov NCT00001246, “89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls.” Date of registry: 01/10/1989.