bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic Activity of Glucocorticoid Receptor β Is Controlled by Ubiquitination-Dependent Interaction with USP49 in Glioblastoma Cells
Authors: Hu Yaling , Jiang Yingdi , Zhang Zhenhao , Wang Jingjing , Zhang Bo , Gong Lingli , Ji Li , Pu Zhening , Yang Xusheng , Zou Jian , Yin Ying 
Published: October 2021

AbstractPrevious studies have demonstrated that glucocorticoid receptor β (GRβ) functions as an oncoprotein, regulating the malignant phenotypes and stem-like cell maintaining in human glioblastoma (GBM). Of the glucocorticoid receptor (GR) isoforms, GRβ and GRα are highly homologous, though the mechanism underlying the distinct functions of these two isoforms in GBM has not been clarified. Here by establishing a carboxyl-terminal (COOH-terminal) deletion mutant, we determined that GRβ can be ubiquitinated. We also found that its COOH terminal is essential for this ubiquitination. The mutation of a lysine to arginine at residue 733 (K733R) blocked the ubiquitination of GRβ, indicating that K733 is a key site for ubiquitination. Using K733R to establish nonubiquitinated GRβ, we demonstrated that ubiquitination not only regulates the stability and nuclear translocation of GRβ, but is also a vital mechanism for its oncogenic functions in vitro and in vivo. Protein interaction assay further indicated that ubiquitin-specific protease 49 (USP49) is a GRβ-binding protein and the interaction depends on GRβ ubiquitination. USP49 knockdown resulted in a decrease of cell proliferation, invasion, and an increase of cell apoptosis. More importantly, USP49 knockdown increased ubiquitination and amplified the oncogenic effects of GRβ, confirming the decisive role of ubiquitination on GRβ carcinogenicity. Taken together, these findings established that ubiquitination is a vial process for GRβ the execution of oncogenic functions in GBM and that the K733 site is crucial for ubiquitination of GRβ.Implications:This work is the first identify of the activation GRβ by a single lysine point-mediated ubiquitination and proteasome degradation, which determines its oncogenic functions in GBM.
GLI3 Is Stabilized by SPOP Mutations and Promotes Castration Resistance via Functional Cooperation with Androgen Receptor in Prostate Cancer
Authors: Burleson Marieke , Deng Janice J. , Qin Tai , Duong Thu Minh , Yan Yuqian , Gu Xiang , Das Debodipta , Easley Acarizia , Liss Michael A. , Yew P. Renee , Bedolla Roble , Kumar Addanki Pratap , Huang Tim Hui-Ming , Zou Yi , Chen Yidong , Chen Chun-Liang , Huang Haojie , Sun Lu-Zhe , Boyer Thomas G. 
Published: October 2021

Abstract

Although the Sonic hedgehog (SHH) signaling pathway has been implicated in promoting malignant phenotypes of prostate cancer, details on how it is activated and exerts its oncogenic role during prostate cancer development and progression is less clear. Here, we show that GLI3, a key SHH pathway effector, is transcriptionally upregulated during androgen deprivation and posttranslationally stabilized in prostate cancer cells by mutation of speckle-type POZ protein (SPOP). GLI3 is a substrate of SPOP-mediated proteasomal degradation in prostate cancer cells and prostate cancer driver mutations in SPOP abrogate GLI3 degradation. Functionally, GLI3 is necessary and sufficient for the growth and migration of androgen receptor (AR)–positive prostate cancer cells, particularly under androgen-depleted conditions. Importantly, we demonstrate that GLI3 physically interacts and functionally cooperates with AR to enrich an AR-dependent gene expression program leading to castration-resistant growth of xenografted prostate tumors. Finally, we identify an AR/GLI3 coregulated gene signature that is highly correlated with castration-resistant metastatic prostate cancer and predictive of disease recurrence. Together, these findings reveal that hyperactivated GLI3 promotes castration-resistant growth of prostate cancer and provide a rationale for therapeutic targeting of GLI3 in patients with castration-resistant prostate cancer (CRPC).

Implications:
We describe two clinically relevant mechanisms leading to hyperactivated GLI3 signaling and enhanced AR/GLI3 cross-talk, suggesting that GLI3-specific inhibitors might prove effective to block prostate cancer development or delay CRPC.
Worsened Tricuspid Regurgitation Following Pericardiectomy for Constrictive Pericarditis
Authors: Tabucanon Ray S. , Wang Tom Kai Ming , Chetrit Michael , Furqan Muhammad M. , Chan Nicholas , Pande Amol , Jellis Christine L. , Cremer Paul C. , Kwon Deborah H. , Johnston Douglas , Klein Allan L. 
Published: October 2021

Background:
Worsening tricuspid regurgitation (TR) severity may occur after pericardiectomy surgery for constrictive pericarditis patients; however, its mechanisms and predictors are not well established. We evaluated the clinical characteristics, associated factors, and outcomes of worsening TR after pericardiectomy.

Methods:
Consecutive patients undergoing pericardiectomy for constrictive pericarditis without tricuspid valve surgery and with pre- and postoperative echocardiography available during 2000 to 2017 were retrospectively studied. Clinical, imaging, hemodynamic, and mortality characteristics were analyzed by those with and without worsening TR by at least one grade.

Results:

Among 381 patients (age 61 [17] years, 318 [83.5%] male), 193 (50.7%) had worsening TR post-operatively, and 75 died during the 2.5 (5.4) years follow-up. In univariable analysis, worsening TR was associated with a history of congestive heart failure (47.2% versus 31.9%,
P
=0.003), increased left atrial volume indexed (23 versus 20 mL/m
2
,
P
=0.020), reduced right ventricular fractional area change (47% versus 54%,
P
<0.001), and worsening mitral regurgitation (39.7% versus 16.6%,
P
<0.001). Worsened TR had a trend toward reduced survival during follow-up (log-rank
P
=0.080), especially those with worsened TR but no recovery of TR grade on subsequent echocardiography within the first year compared with those without worsened TR (log-rank
P
=0.02). In multivariable analysis, right ventricular fractional area change, left atrial volume indexed, left ventricular mass indexed, pulmonary artery systolic pressure, and right atrial pressure/pulmonary capillary wedge pressure ratio were most associated with worsened TR, while blood urea nitrogen, hematocrit, lateral and medial e’ tissue Doppler and heart rate were most associated with mortality during follow-up.

Conclusions:
Worsening TR severity was prevalent after pericardiectomy and had a trend toward reduced survival, especially if TR severity did not recover on subsequent echocardiography. Presence of parameters associated with worsened TR and reduced survival should alert clinicians to carefully manage these patients during follow-up.
Salivary CGRP can monitor the different migraine phases: CGRP (in)dependent attacks
Authors: Alpuente Alicia , Gallardo Victor J , Asskour Laila , Caronna Edoardo , Torres-Ferrus Marta , Pozo-Rosich Patricia 
Published: October 2021

Background CGRP plays a key role in the transmission and modulation of nociceptive signals and is a critical component in the pathogenesis of migraine. Objective To assess saliva as a substrate to measure CGRP by comparing interictal levels in patients with episodic migraine and controls; and to evaluate CGRP’s temporal profile during migraine attacks. Methods This prospective observational pilot study included young women with episodic migraine and healthy controls. We monitored salivary CGRP-like immunoreactivity (CGRP-LI) during 30 consecutive days and during migraine attacks. We considered six timepoints for the analysis: interictal (72h headache free), preictal (PRE-24h before the attack), ictal (headache onset, after 2h, after 8h), postictal (POST-24h after the attack). CGRP levels were quantified by ELISA. Results 44 women (22 with episodic migraine, 22 healthy controls) were recruited. Differences in interictal salivary levels of CGRP between patients and controls (Me [IQR]: 98.0 [80.3] (95% CI 56.6, 124.0) vs. 54.3 [44.0] (95% CI 42.2, 70.1) pg/mL, p = 0.034) were found. An increase in CGRP levels during migraine attacks was detected (pre:169.0 [95% CI 104.2–234.0]; headache onset: 247.0 [181.9–312.0]; after 2h: 143.0 [77.6–208.0]; after 8h: 169.0 [103.5–234.0], post: 173.0 [107.8–238.0]). Patients were classified as having CGRP-dependent (79.6%) and non-CGRP dependent migraine attacks (20.4%) according to the magnitude of change between preictal and ictal phase. Accompanying symptoms such as photophobia and phonophobia were significantly associated to the first group. Conclusions Salivary CGRP-LI levels, which interictally are elevated in episodic migraine patients, usually increase during a migraine attack in the majority of patients. However, not every attack is CGRP-dependent, which in turn, might explain different underlying pathophysiology and response to treatment.
No structural brain alterations in new daily persistent headache – a cross sectional VBM/SBM study
Authors: Naegel Steffen , Zeller Julia , Hougaard Anders , Weise Christopher Michael ,   Hans-Christoph-Diener, Zuelow Stefan , Kleinschnitz Christoph , Obermann Mark , Solbach Kasja , Holle Dagny 
Published: October 2021

Objective To identify grey matter alterations in patients suffering new daily persistent headache to enrich the pathophysiological concept of this rare headache disorder characterised by a distinct, clearly remembered onset and its instant chronification. Method Magnetic resonance-based voxel-based and surface-based morphometry was used to investigate 23 patients suffering from new daily persistent headache and 23 age- and gender-matched healthy controls with 1.5 Tesla MRI. Independent statistical analysis was performed at three sites using statistical parametric mapping, as well as FSL(FMRIB Software Library)-based approaches. Results No grey matter changes were detected using this sophisticated and cross-checked method. Conclusion The absence of structural brain changes in patients with new daily persistent headache contribute to the recent discussion regarding structural alterations in primary headache disorders in general and does not provide evidence for grey matter changes being associated with the pathophysiology of new daily persistent headache. Future research will have to determine the underlying pathophysiological mechanisms of this disorder.
Effects of radiation dose and nitrogen purge on collagen scaffold properties
Authors: Sant Nicholas J , Proffen Benedikt L , Murray Martha M 
Published: October 2021

Sterilization of medical devices is commonly performed using radiation methods. However, collagen materials can be damaged when using standard radiation doses (25 kGy). Small increases of radiation dose can allow for increases in the acceptable initial bioburden load of aseptically manufactured devices while maintaining required sterility assurance levels, which is often critical in early stage translational settings. In this study, we hypothesized that small increases in radiation dose from 15 to 20 kGy would result in significant changes to several key characteristics of collagen scaffolds. Scaffolds were manufactured by lyophilizing the pepsin digest of dense bovine connective tissue in cylindrical molds and were irradiated at either 0, 15, 17.5, or 20 kGy with an additional group packaged in nitrogen and irradiated at 17.5 kGy. Groups were evaluated for changes to the soluble collagen and glycosaminoglycan mass fractions, protein banding patterns in electrophoresis, a collagen fragmentation assay, and resistance to enzymatic degradation. All parameters were statistically analyzed using one-way analysis of variance with Tukey’s correction for multiple comparisons. The soluble collagen mass fraction was significantly decreased in the 20 kGy group; however, there was no significant effect of radiation dose or a nitrogen-rich environment on the other measured parameters, including protein banding patterns, fragmented collagen content, and resistance to enzymatic degradation. Statement of Clinical Significance: Collagen scaffolds have proven useful in clinical applications but can be damaged by standard radiation doses. Low-dose sterilization may be a viable alternative that minimally impacts key properties of these scaffolds.
Spiritual Motivations to Practice Medicine: A Survey of Cancer Care Providers
Authors: Kelly Elizabeth Palmer , Myers Brian , Kelly-Brown Joseph , Waterman Brittany L. , Stevens Erin , Pawlik Timothy M. 
Published: October 2021

Background: There is increased interest in the role of spirituality in the cancer care context, but how it may inspire individuals to pursue a career as a healthcare provider is unknown. We sought to determine the relationship between intrinsic religiosity, religious identity, provider role, and spiritual motivations to practice medicine. Methods: A cross-sectional survey was administered to healthcare providers at a large, Midwest Comprehensive Cancer Center. The relationship between provider type, intrinsic religiosity, religious identity, and spiritual motivations to practice medicine was assessed with binary logistic regression. Results: Among 340 participants, most were female (82.1%) or Caucasian (82.6%) and identified as being religious (57.5%); median age was 35 years (IQR: 31-48). Providers included nurses (64.7%), physicians (17.9%), and “other” (17.4%). Compared with physicians, nurses were less likely to agree that they felt responsible for reducing pain and suffering in the world (OR: 0.12, p = 0.03). Similarly, “other” providers were less likely than physicians to believe that the practice of medicine was a calling (OR: 0.28, p = 0.02). Providers with a high self-reported intrinsic religiosity demonstrated a much greater likelihood to believe that the practice of medicine is a calling (OR:1.75, p = 0.001), as well as believe that personal R&S beliefs influence the practice of medicine (OR:3.57, p < 0.001). Provider religious identity was not associated with spiritual motivations to practice medicine (all p > 0.05). Conclusion: Intrinsic religiosity had the strongest relationship with spiritual motivations to practice medicine. Understanding these motivations may inform interventions to avoid symptoms of provider burnout in cancer care.
Proactive language control during bilingual sentence production
Authors: Declerck Mathieu , Grainger Jonathan , Hartsuiker Robert J 
Published: October 2021

Aims and objectives/purpose/research questions: While evidence for proactive language control processes has been found during single word production, very little and conflicting evidence has been observed for such control processes during sentence production. So, the main goal of this study was to investigate whether proactive language control can occur during sentence production. Design/methodology/approach: To investigate proactive language control during sentence production, we relied on a description task in single and mixed language blocks. Data and analysis: Mixing costs and the reversed language dominance effect of language intrusions and filled pauses were used to examine proactive language control. Findings/conclusions: Evidence for proactive language control during sentence production came from the mixing cost effect observed with both language intrusions and filled pauses. Whereas no reversed language dominance effect was observed in mixed language blocks, a significant difference in language pattern was observed between single and mixed language blocks, indicating that proactive language control of the first language might be implemented in mixed language blocks during sentence production. Originality: Unlike the vast majority of studies investigating language control, this study relied on sentence production instead of single word production. Moreover, to the best of our knowledge, this is the first study to examine filled pauses to gain insight into language control. Significance/implications: These data indicate that proactive language control can be implemented during bilingual sentence production.
When Agency Turns Into a Risk Factor: A Literature Review of the Negative Consequences of Children’s Agentic Behaviors on Their Physical and Psychological Well-Being
Authors: Cavazzoni Federica , Fiorini Alec , Veronese Guido 
Published: October 2021

Background: Research has widely documented how, even in conditions of extreme poverty, deprivation, or oppression, children are competent and situated actors, capable of actively mobilizing internal, external, or social resources to protect themselves from their environments and safeguard their everyday lives. Yet, the ways in which their agency might support their well-being or instead increase their own vulnerability has remained underexplored. Aims: The present study aims to provide an assessment of all those contributions which, over the past 20 years, have focused on both the positive and negative consequences of children’s actionability, revealing children’s self-destructive acts alongside their self-empowering and protective ones. In the process, it highlights several major theoretical breakthroughs and findings in this area of research. Method: We provide an assessment of peer-reviewed studies that have focused on both positive and negative consequences of children’s actionability, through a qualitative narrative literature review. Results: Of the 168 studies identified from online searches of the literature and the three additional sources gathered through bibliography mining, 76 qualified for full review, with 12 studies included in the final synthesis. Overall, the literature explored the different conditions in which children’s agentic practices expose them to trauma symptoms and to dangerous or self-harmful situations, thereby failing to safeguard their health and overall well-being. Conclusion: The review highlights the need to focus on the dangerous effect of the agentic practices activated by children in terms of their physical and psychological health.
Differentiation of brain metastases originating from lung and breast cancers using apparent diffusion coefficient histogram analysis and the relation of histogram parameters with Ki-67
Authors: Bozdağ Mustafa , Er Ali , Ekmekçi Sümeyye 
Published: October 2021

Purpose A fast, reliable and non-invasive method is required in differentiating brain metastases (BMs) originating from lung cancer (LC) and breast cancer (BC). The aims of this study were to assess the role of histogram analysis of apparent diffusion coefficient (ADC) maps in differentiating BMs originated from LC and BC, and then to investigate further the association of ADC histogram parameters with Ki-67 index in BMs. Methods A total of 55 patients (LC, N = 40; BC, N = 15) with BMs histopathologically confirmed were enrolled in the study. The LC group was divided into small-cell lung cancer (SCLC; N = 15) and non-small-cell lung cancer (NSCLC; N = 25) groups. ADC histogram parameters (ADCmax, ADCmean, ADCmin, ADCmedian, ADC10, ADC25, ADC75 and ADC90, skewness, kurtosis and entropy) were derived from ADC maps. Mann–Whitney U-test, independent samples t-test, receiver operating characteristic (ROC) analysis and Spearman correlation analysis were used for statistical assessment. Results ADC histogram parameters did not show significant differences between LC and BC groups ( p > 0.05). Subgroup analysis showed that various ADC histogram parameters were found to be statistically lower in the SCLC group compared to the NSCLC and BC groups ( p < 0.05). ROC analysis showed that ADCmean and ADC10 for differentiating SCLC BMs from NSCLC, and ADC25 for differentiating SCLC BMs from BC achieved optimal diagnostic performances. Various histogram parameters were found to be significantly correlated with Ki-67 ( p < 0.05). Conclusion Histogram analysis of ADC maps may reflect tumoural proliferation potential in BMs and can be useful in differentiating SCLC BMs from NSCLC and BC BMs.
Initial experience with the Scepter Mini catheter for the embolization of vascular malformations in the pediatric population
Authors: Matsoukas Stavros , Bageac Devin , Yaeger Kurt , Berenstein Alejandro , T Fifi Johanna , Shigematsu Tomoyoshi 
Published: October 2021

Background Achieving distal access and flow control are of significant importance for the treatment of intracerebral arteriovenous shunting lesions. The Scepter Mini catheter is a low-profile, dual-lumen balloon catheter, designed to provide navigability in small-caliber, tortuous intracranial vessels. Objective To describe the initial experience of the Scepter Mini catheter in the treatment of pediatric arteriovenous malformations and fistulas. Methods A single-institution, retrospective chart review identified all consecutive uses of the Scepter Mini catheter for endovascular embolization of vascular malformations in the pediatric population. Results Three different arterial pedicles were embolized with the Scepter Mini catheter in two different patients. One patient was diagnosed with a vein of Galen malformation that had undergone multiple treatments and the other with a torcular dural arteriovenous fistula. All cases encompassed quite challenging tortuosity of small-caliber feeders which prevented the use of another microcatheter. The Scepter Mini catheter navigated into feeding arteries of diameters 0.65, 1.9, and 1.25 mm, and its balloon was inflated to achieve excellent blood flow control. Total obliteration (100%) of the shunting lesion was achieved in both cases. No reflux, pedicle rupture or other untoward effects were observed. Both patients had an uneventful recovery. Conclusion The Scepter Mini catheter afforded fast and safe distal access, flow control, and treatment of arteriovenous malformations in this initial pediatric cohort. The catheter’s low profile and easy navigability should support its use in tortuous and small arterial feeders, especially in the pediatric population.