bluuebunny/crossref_metadata_2025_split huggingface dataset:
The efficacy of etanercept as anti-breast cancer treatment is attenuated by residing macrophages
Authors: Shirmohammadi Elnaz , Ebrahimi Seyed-Esmaeil Sadat , Farshchi Amir , Salimi Mona 
Published: September 2020

Abstract
Background
Interaction between microenvironment and breast cancer cells often is not considered at the early stages of drug development leading to failure of many drugs at later clinical stages. Etanercept is a TNF-alpha inhibitor that has been investigated for potential antitumor effect in breast cancer with conflicting results.

Methods
Secretome data on MDA-MB-231 cancer cell-line were from public repositories and subjected to gene enrichment analyses. Since MDA-MB-231 cells secrete high levels of Granulocyte-Monocyte Colony Stimulating Factor, which activates macrophages to promote tumor growth, the effect of macrophage co-culturing on anticancer efficacy of Etanercept in breast cancer was evaluated using the Boolean network modeling and in vitro experiments including invasion, cell cycle, Annexin PI, and tetrazolium based viability assays and NFKB activity.

Results
The secretome profile of MDA-MB-231 cells was similar to the expression of genes following treatment of breast cancer cells with TNF-α. Accordingly, inhibition of TNF-α by Etanercept decreased MDA-MB-231 cell survival, induced apoptosis and cell cycle arrest in vitro and inhibited NFKB activation. The inhibitory effect of Etanercept on cell viability, cell cycle progression, invasion and induction of apoptosis decreased following co-culturing of the cancer cells with macrophages. The Boolean network modeling of the changes in the dynamics of intracellular signaling pathways revealed NFKB activation by secretome of macrophages, leading to a decreased efficacy of Etanercept, suggesting NFKB inhibition as an alternative approach to inhibit cancer cell growth in the presence of macrophage crosstalk.

Conclusion
This study indicates that the effect of Etanercept may be influenced by residing macrophages in tumor microenvironment, and suggests a method to predict the effect of drugs in the presence of stromal cells to guide experimental designs in drug development.
SNHG17 drives malignant behaviors in astrocytoma by targeting miR-876-5p/ERLIN2 axis
Authors: Du Fengping , Hou Qian 
Published: September 2020

Abstract
Background
Astrocytoma is a common tumor type in primary central nervous system and has a high death rate around the world. Aberrant expression of long non-coding RNAs (lncRNAs) has been introduced by emerging studies to result in the development of diverse cancers.

Methods
RT-qPCR examined the expression of SNHG17, miR-876-5p and ERLIN2, and western blot evaluated ERLIN2 protein level. RNA pull down and luciferase reporter assays illustrated the relationships between SNHG17 and its downstream molecules.

Results
SNHG17 was up-regulated in astrocytoma cells. Moreover, SNHG17 silence could repress the proliferation, migration and invasion of astrocytoma cells. Besides, miR-876-5p was selected out as a downstream molecule of SNHG17 in astrocytoma. ERLIN2 was determined to be targeted by miR-876-5p. ERLIN2 mRNA and protein levels were lessened by miR-876-5p overexpression and SNHG17 silence. Additionally, miR-876-5p overexpression decelerated the biological processes of astrocytoma cells, so did ERLIN2 knockdown. More importantly, the impacts of SNHG17 down-regulation on the malignant behaviors of astrocytoma cells were counteracted by overexpressed ERLIN2 or inhibited miR-876-5p.

Conclusions
SNHG17 could induce the progression of astrocytoma by sponging miR-876-5p to elevate the expression of ERLIN2. This study indicated that SNHG17 has a high potential to be a therapeutic target for astrocytoma.
WDHD1 facilitates G1 checkpoint abrogation in HPV E7 expressing cells by modulating GCN5
Authors: Zhou Yunying , Pei Fengyan , Ji Mingyu , Zhang Fang , Sun Yingshuo , Zhao Qianqian , Wang Xiao , Hong Yatian , Tian Juanjuan , Wang Yunshan , Chen Jason J. 
Published: September 2020

Abstract
Background
Genomic instability is a hallmark of cancer. The G1 checkpoint allows cells to repair damaged DNA that may lead to genomic instability. The high-risk human papillomavirus (HPV) E7 gene can abrogate the G1 checkpoint, yet the mechanism is still not fully understood. Our recent study showed that WDHD1 (WD repeat and high mobility group [HMG]-box DNA-binding protein 1) plays a role in regulating G1 checkpoint of E7 expressing cells. In this study, we explored the mechanism by which WDHD1 regulates G1 checkpoint in HPV E7 expressing cells.

Methods
NIKS and RPE1 derived cell lines were used. Real-time PCR, Rescue experiment, FACS and BrdU labeling experiments were performed to examine role of GCN5 in G1 checkpoint abrogation in HPV-16 E7 expressing cells.

Results
In this study, we observed that WDHD1 facilitates G1 checkpoint abrogation by modulating GCN5 in HPV E7 expressing cells. Notably, depletion of WDHD1 caused G1 arrest while overexpression of GCN5 rescued the inhibitory effects of WDHD1 knockdown on G1/S progression. Furthermore, siWDHD1 significantly decreased cell cycle proliferation and DNA synthesis that was correlated with Akt phosphorylation (p-Akt), which was reversed by GCN5 overexpression in HPV E7 expressing cells.

Conclusions
In summary, our data identified a WDHD1/GCN5/Akt pathway leading to the abrogation of G1 checkpoint in the presence of damaged DNA, which may cause genomic instability and eventually HPV induced tumorigenesis.
LINC00649 underexpression is an adverse prognostic marker in acute myeloid leukemia
Authors: Guo Chao , Gao Ya-yue , Ju Qian-qian , Zhang Chun-xia , Gong Ming , Li Zhen-ling 
Published: September 2020

Abstract
Background
Long noncoding RNAs (lncRNA) play a role in leukemogenesis, maintenance, development, and therapeutic resistance of AML. While few studies have focused on the prognostic significance of LINC00649 in AML, which we aim to investigate in this present study.

Methods
We compared the expression level of LINC00649 between AML patients and healthy controls. The Kaplan-Meier curves of AML patients expressing high versus low level of LINC00649 was performed. The LINC00649 correlated genes/miRNAs/lncRNAs and methylation CpG sites were screened by Pearson correlation analysis with R (version 3.6.0), using TCGA-LAML database. The LINC00649 associated ceRNA network was established using lncBase 2.0 and miRWalk 2.0 online tools, combining results from correlation analysis. Finally, a prediction model was constructed using LASSO-Cox regression.

Results
LINC00649 was underexpressed in bone marrow of AML group than that in healthy control group. The patients of LINC00649-low group have significantly inferior PFS and OS. A total of 154 mRNAs, 31 miRNAs, 28 lncRNAs and 1590 methylated CpG sites were identified to be significantly correlated with LINC00649. Furthermore, the network of ceRNA was established with 6 miRNAs and 122 mRNAs. The Lasso-Cox model fitted OS/PFS to novel prediction models, which integrated clinical factors, ELN risk stratification, mRNA/miRNA expression and methylation profiles. The analysis of time-dependent ROC for our model showed a superior AUC (AUC = 0.916 at 1 year, AUC = 0.916 at 3 years, and AUC = 0.891 at 5 years).

Conclusions
Low expression of LINC00649 is a potential unfavorable prognostic marker for AML patients, which requires the further validation. The analysis by LASSO-COX regression identified a novel comprehensive model with a superior diagnostic utility, which integrated clinical and genetic variables.
Cell-in-cell phenomenon associates with aggressive characteristics and cancer-related mortality in early oral tongue cancer
Authors: Almangush Alhadi , Mäkitie Antti A. , Hagström Jaana , Haglund Caj , Kowalski Luiz Paulo , Nieminen Pentti , Coletta Ricardo D. , Salo Tuula , Leivo Ilmo 
Published: September 2020

Abstract
Background
Cell-in-cell structures (caused by cell cannibalistic activity) have been related to prognosis of many cancers. This is the first multi-institutional study to assess the prognostic impact of cell-in-cell structures in a large cohort of early oral tongue squamous cell carcinomas (OTSCC).

Methods

A total of 308 cases from five Finnish University Hospitals and from the A.C. Camargo Cancer Center, São Paulo, Brazil, were included in this study. Cell-in-cell structures were evaluated on surgical postoperative sections that stained with hematoxylin and eosin staining.

Results

We found that cell-in-cell structures associated with cancer-related mortality in univariable analysis with a hazard ratio (HR) of 2.99 (95%CI 1.52–5.88; P = 0.001). This association was confirmed in multivariable analysis (HR 2.22, 95%CI 1.12–4.44; P = 0.024). In addition, statistically significant associations were observed between the cell-in-cell structures and other adverse histopathologic characteristics including deep invasion (P <  0.001), high index of tumor budding (P = 0.007), worst pattern of invasion (P <  0.001), perineural invasion (P = 0.01), and stroma-rich pattern (P = 0.001).

Conclusions
Our findings demonstrate a significant relationship between cell-in-cell formation and aggressive characteristics of early OTSCC. Cell-in-cell structures have a distinct impact as a novel prognostic indicator in early OTSCC and they can be easily assessed during routine pathology practice.
Patient and physician factors associated with Oncotype DX and adjuvant chemotherapy utilization for breast cancer patients in New Hampshire, 2010–2016
Authors: Schwedhelm Thomas M. , Rees Judy R. , Onega Tracy , Zipkin Ronnie J. , Schaefer Andrew , Celaya Maria O. , Moen Erika L. 
Published: September 2020

Abstract
Background
Oncotype DX® (ODX) is used to assess risk of disease recurrence in hormone receptor positive, HER2-negative breast cancer and to guide decisions regarding adjuvant chemotherapy. Little is known about how physician factors impact treatment decisions. The purpose of this study was to examine patient and physician factors associated with ODX testing and adjuvant chemotherapy for breast cancer patients in New Hampshire.

Methods
We examined New Hampshire State Cancer Registry data on 5630 female breast cancer patients diagnosed from 2010 to 2016. We performed unadjusted and adjusted hierarchical logistic regression to identify factors associated with a patient’s receipt of ODX, being recommended and receiving chemotherapy, and refusing chemotherapy. We calculated intraclass correlation coefficients (ICCs) to examine the proportion of variance in clinical decisions explained by between-physician and between-hospital variation.

Results
Over the study period, 1512 breast cancer patients received ODX. After adjustment for patient and tumor characteristics, we found that patients seen by a male medical oncologist were less likely to be recommended chemotherapy following ODX (OR = 0.50 (95% CI = 0.34–0.74), p < 0.01). Medical oncologists with more clinical experience (reference: less than 10 years) were more likely to recommend chemotherapy (20–29 years: OR = 4.05 (95% CI = 1.57–10.43), p < 0.01; > 29 years: OR = 4.48 (95% CI = 1.68–11.95), p < 0.01). A substantial amount of the variation in receiving chemotherapy was due to variation between physicians, particularly among low risk patients (ICC = 0.33).

Conclusions
In addition to patient clinicopathologic characteristics, physician gender and clinical experience were associated with chemotherapy treatment following ODX testing. The significant variation between physicians indicates the potential for interventions to reduce variation in care.
Survival analysis of patients with stage T2a and T2b perihilar cholangiocarcinoma treated with radical resection
Authors: Zhao Jian , Zhang Wei , Zhang Jun , Zhang Yi , Ma Wen-Jie , Liu Si-Yun , Li Fu-Yu , Song Bin 
Published: September 2020

Abstract
Background
Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging system for perihilar cholangiocarcinoma (pCCA) had the same definition for T2a and T2b. But the value of this classification as prognostic factor remains unclear.

Methods
178 patients with stage T2a or T2b who underwent curative intent resection for pCCA between Jan 2010 and Dec 2018 were enrolled. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate Cox regression analysis. The overall survival (OS) were calculated by Kaplan-Meier method.

Results
There was no significant difference in OS between T2a and T2b groups, and the median OS duration were 37 and 31 months (P = 0.354). Both the 7th and 8th edition of the AJCC TNM staging demonstrated a poor prognostic predictive performance. High level of preoperative AST (≥85.0 IU/L) and CA19–9 (≥1000 U/mL), vascular resection and lower pathological differentiation of the tumor were the independent predictors for poor survival after resection.

Conclusion
The newly released 8th edition of AJCC staging system demonstrated a poor ability to discriminate the prognosis of patients with stage T2a and T2b pCCA after resection.
Caregiver dissatisfaction with their child’s participation in home activities after pediatric critical illness
Authors: Jarvis Jessica M. , Fayed Nora , Fink Ericka L. , Choong Karen , Khetani Mary A. 
Published: September 2020

Abstract
Background
Pediatric critical care is often accompanied by a variety of functional impairments. Preliminary evidence suggests children’s participation in home activities has a slow trajectory post-pediatric intensive care unit (PICU) discharge, however, additional and more granular knowledge on specific problematic activities is needed to inform patient-centric rehabilitative care. The objectives of this study are to identify common home activities in which caregivers’ report dissatisfaction and to determine predictors of caregivers’ dissatisfaction with their child’s participation in home activities post-PICU discharge.

Methods
Secondary analyses of data from a prospective cohort study, the Wee-Cover study, using a subsample of caregivers (N = 170) of children 1–17 years, admitted to a PICU ≥48 h with data on our primary outcome measure from at least one time point. Data were gathered at enrollment and at 3 and 6 months post-PICU discharge. Caregivers reported on their dissatisfaction with their child’s participation in home activities via the Participation and Environment Measure. Common activities were identified by plotting caregiver dissatisfaction for each activity pre-and post-PICU, reporting activities in which ≥50% of caregivers reported dissatisfaction with post-PICU, and assessing for significantly different dissatisfaction levels between time-points for each activity. Predictors of caregiver dissatisfaction were assessed using Poisson generalized estimated equation models.

Results
There was variability in reported dissatisfaction across all activities; ≥50% of caregivers reported dissatisfaction with five activities, including getting clean, personal care management, and mealtime for younger children and household chores and homework for school-aged children and youth. Four activities had significantly higher caregiver dissatisfaction post-PICU: sleep (children < 5 years), homework, indoor play and games, and computer/video games (children ≥5 years). Home environmental support and the interaction of having participation-focused strategies with receiving PICU-based rehabilitation services were negatively associated with caregiver dissatisfaction. Increased caregiver stress and functional performance were associated with increased dissatisfaction.

Conclusions
Individualized PICU-based rehabilitation services to determine family priorities and develop participation-focused strategies, specifically those increasing environmental supports within the home, may ease the family’s transition home post-PICU.

Trial registration
ClinicalTrials.gov Identifier NCT02148081 05/28/2014.
Prevalence of and risk factors for anxiety and depression in Chinese patients with unruptured intracranial aneurysms treated by endovascular intervention
Authors: Zhai Xiao-Dong , Yu Jia-Xing , Ma Yong-Jie , Xiang Si-Shi , Li Gui-Lin , He Chuan , Hu Peng , Zhang Hong-Qi 
Published: September 2020

Abstract
Background
Studies on anxiety and depression in unruptured intracranial aneurysm (UIA) patients after treatment via endovascular intervention are rare and controversial. We aimed to explore the prevalence of anxiety and depression among Chinese patients with UIAs treated by endovascular intervention and to identify which factors contribute to the development of these symptoms.

Methods
We performed a cross-sectional study on anxiety and depression in patients who underwent endovascular treatment for UIAs using the Hospital Anxiety and Depression Scale (HADS). The demographic, clinical and radiological data for all patients were retrospectively collected from the aneurysm database and medical records. Moreover, we utilized data from a large sample of 200 UIA patients and multivariate logistic regression analysis to investigate the risk factors for anxiety and depression in these patients. Candidate variables with P values less than 0.20 in univariate analysis were included in the multivariate logistic regression analysis.

Results
Two hundred patients returned completed questionnaires in this study. Of these 200 patients, 34 (17.0%) suffered from anxiety and 31 (15.5%) suffered from depression 30.67 ± 8.6 months after being discharged. The multivariate analysis results indicated that shorter sleep times were statistically significantly associated with depression (OR = 1.62, 95% CI: 1.14 ~ 2.29, P = 0.007, Adjusted P = 0.02). .

Conclusion
The prevalences of anxiety and depression in UIA patients treated by endovascular intervention were 17.0 and 15.5%, respectively. Shorter sleep times were significantly associated with depression. Our findings provide evidence for the clinical and psychological management of these patients.
Risk factors of hospitalization for any medical condition among patients with prior emergency department visits for mental health conditions
Authors: Penzenstadler Louise , Gentil Lia , Grenier Guy , Khazaal Yasser , Fleury Marie-Josée 
Published: September 2020

Abstract
Background
This longitudinal study identified risk factors for frequency of hospitalization among patients with any medical condition who had previously visited one of six Quebec (Canada) emergency departments (ED) at least once for mental health (MH) conditions as the primary diagnosis.

Methods
Records of n = 11,367 patients were investigated using administrative databanks (2012–13/2014–15). Hospitalization rates in the 12 months after a first ED visit in 2014–15 were categorized as no hospitalizations (0 times), moderate hospitalizations (1–2 times), and frequent hospitalizations (3+ times). Based on the Andersen Behavioral Model, data on risk factors were gathered for the 2 years prior to the first visit in 2014–15, and were identified as predisposing, enabling or needs factors. They were tested using a hierarchical multinomial logistic regression according to the three groups of hospitalization rate.

Results
Enabling factors accounted for the largest percentage of total variance explained in the study model, followed by needs and predisposing factors. Co-occurring mental disorders (MD)/substance-related disorders (SRD), alcohol-related disorders, depressive disorders, frequency of consultations with outpatient psychiatrists, prior ED visits for any medical condition and number of physicians consulted in specialized care, were risk factors for both moderate and frequent hospitalizations. Schizophrenia spectrum and other psychotic disorders, bipolar disorders, and age (except 12–17 years) were risk factors for moderate hospitalizations, while higher numbers (4+) of overall interventions in local community health service centers were a risk factor for frequent hospitalizations only. Patients with personality disorders, drug-related disorders, suicidal behaviors, and those who visited a psychiatric ED integrated with a general ED in a separate site, or who visited a general ED without psychiatric services were also less likely to be hospitalized. Less urgent and non-urgent illness acuity prevented moderate hospitalizations only.

Conclusions
Patients with severe and complex health conditions, and higher numbers of both prior outpatient psychiatrist consultations and ED visits for medical conditions had more moderate and frequent hospitalizations as compared with non-hospitalized patients. Patients at risk for frequent hospitalizations were more vulnerable overall and had important biopsychosocial problems. Improved primary care and integrated outpatient services may prevent post-ED hospitalization.
Strategies for increasing impact, engagement, and accessibility in HIV prevention programs: suggestions from women in urban high HIV burden counties in the Eastern United States (HPTN 064)
Authors: Abrams Jasmine A. , Odlum Michelle , Tillett Emily , Haley Danielle , Justman Jessica , Hodder Sally , Vo Linda , O’Leary Ann , Frew Paula M. ,   the HIV Prevention Trials Network 064 (HTPN) Study Team
Published: September 2020

Abstract
Background
Merely having the tools to end HIV is insufficient. Effectively ending the epidemic necessitates addressing barriers that impede engagement in biomedical and behavioral prevention and wide scale implementation and utilization of existing interventions. This qualitative study identifies suggestions for increasing access to, engagement in, and impact of HIV prevention among women living in cities in high HIV burden counties in the eastern US.

Methods
Data analyzed for the current study were collected via a qualitative sub-study within the HIV Prevention Trials Network Study 064 (HPTN 064), a multisite observational cohort study designed to estimate HIV incidence among women residing in communities with elevated HIV prevalence who also reported personal or partner characteristics associated with increased risk of HIV acquisition. Focus group and interview participants in the qualitative sub-study (N = 288) were from four cities in the eastern US.

Results
Thematic analyses revealed four themes describing women’s most frequently stated ideas for improving prevention efforts: 1) Promote Multilevel Empowerment, 2) Create Engaging Program Content, 3) Build “Market Demand”, and 4) Ensure Accessibility. We conducted additional analyses to identify contradictory patterns in the data, which revealed an additional three themes: 1) Address Structural Risk Factors, 2) Increase Engagement via Pleasure Promotion, 3) Expand Awareness of and Access to Prevention Resources.

Conclusions
Findings may be useful for enhancing women’s engagement in and uptake of behavioral and biomedical HIV prevention resources, improving policy, and addressing multilevel risk factors.

Trial registration
Clinicaltrials.gov: NCT00995176, prospectively registered.