bluuebunny/crossref_metadata_2025_split huggingface dataset:
HER2 Overexpression Triggers an IL1α Proinflammatory Circuit to Drive Tumorigenesis and Promote Chemotherapy Resistance
Authors: Liu Shou , Lee Ji Shin , Jie Chunfa , Park Min Ho , Iwakura Yoichiro , Patel Yogin , Soni Mithil , Reisman David , Chen Hexin 
Published: January 2018

Abstract
Systemic inflammation in breast cancer correlates with poor prognosis, but the molecular underpinnings of this connection are not well understood. In this study, we explored the relationship between HER2 overexpression, inflammation, and expansion of the mammary stem/progenitor and cancer stem–like cell (CSC) population in breast cancer. HER2-positive epithelial cells initiated and sustained an inflammatory milieu needed to promote tumorigenesis. HER2 induced a feedforward activation loop of IL1α and IL6 that stimulated NFκB and STAT3 pathways for generation and maintenance of breast CSC. In mice, Il1a genetic deficiency delayed MMTV-Her2–induced tumorigenesis and reduced inflammatory cytokine expression as well as CSC in primary tumors. In clinical specimens of human breast tumor tissues, tissue microarray analysis revealed a strong positive correlation between IL1α/IL6 expression and CSC-positive phenotype. Pharmacologic blockade of IL1α signaling reduced the CSC population and improved chemotherapeutic efficacy. Our findings suggest new therapeutic or prevention strategies for HER2-positive breast cancers.
Significance: IL1α signaling driven by HER2 promotes chronic inflammation needed to support cancer stem-like cell maintenance in HER2-positive breast cancers. Cancer Res; 78(8); 2040–51. ©2018 AACR.
Factors Associated with False Positive Results on Screening Mammography in a Population of Predominantly Hispanic Women
Authors: McGuinness Julia E. , Ueng William , Trivedi Meghna S. , Yi Hae Seung , David Raven , Vanegas Alejandro , Vargas Jennifer , Sandoval Rossy , Kukafka Rita , Crew Katherine D. 
Published: January 2018

Abstract
Background: Potential harms of screening mammography include false positive results, such as recall breast imaging or biopsies.
Methods: We recruited women undergoing screening mammography at Columbia University Medical Center in New York, New York. They completed a questionnaire on breast cancer risk factors and permitted access to their medical records. Breast cancer risk status was determined using the Gail model and a family history screener. High risk was defined as a 5-year invasive breast cancer risk of ≥1.67% or eligible for BRCA genetic testing. False positive results were defined as recall breast imaging (BIRADS score of 0, 3, 4, or 5) and/or biopsies that did not yield breast cancer.
Results: From November 2014 to October 2015, 2,361 women were enrolled and 2,019 were evaluable, of whom 76% were Hispanic and 10% non-Hispanic white. Fewer Hispanic women met high-risk criteria for breast cancer than non-Hispanic whites (18.0% vs. 68.1%), but Hispanics more frequently engaged in annual screening (71.9% vs. 60.8%). Higher breast density (heterogeneously/extremely dense vs. mostly fat/scattered fibroglandular densities) and more frequent screening (annual vs. biennial) were significantly associated with false positive results [odds ratio (OR), 1.64; 95% confidence interval (CI), 1.32–2.04 and OR, 2.18; 95% CI, 1.70–2.80, respectively].
Conclusions: We observed that women who screened more frequently or had higher breast density were at greater risk for false positive results. In addition, Hispanic women were screening more frequently despite having a lower risk of breast cancer compared with whites.
Impact: Our results highlight the need for risk-stratified screening to potentially minimize the harms of screening mammography. Cancer Epidemiol Biomarkers Prev; 27(4); 446–53. ©2018 AACR.
Genome-Wide Association Studies in Glioma
Authors: Kinnersley Ben , Houlston Richard S. , Bondy Melissa L. 
Published: January 2018

Abstract
Since the first reports in 2009, genome-wide association studies (GWAS) have been successful in identifying germline variants associated with glioma susceptibility. In this review, we describe a chronological history of glioma GWAS, culminating in the most recent study comprising 12,496 cases and 18,190 controls. We additionally summarize associations at the 27 glioma-risk SNPs that have been reported so far. Future efforts are likely to be principally focused on assessing association of germline-risk SNPs with particular molecular subgroups of glioma, as well as investigating the functional basis of the risk loci in tumor formation. These ongoing studies will be important to maximize the impact of research into glioma susceptibility, both in terms of insight into tumor etiology as well as opportunities for clinical translation. Cancer Epidemiol Biomarkers Prev; 27(4); 418–28. ©2018 AACR.
See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”
Common Genetic Variation and Breast Cancer Risk—Past, Present, and Future
Authors: Lilyquist Jenna , Ruddy Kathryn J. , Vachon Celine M. , Couch Fergus J. 
Published: January 2018

Abstract
Breast cancer is the most common cancer among women in the United States, with up to 30% of those diagnosed displaying a family history of breast cancer. To date, 18% of the familial risk of breast cancer can be explained by SNPs. This review summarizes the discovery of risk-associated SNPs using candidate gene and genome-wide association studies (GWAS), including discovery and replication in large collaborative efforts such as The Collaborative Oncologic Gene-environment Study and OncoArray. We discuss the evolution of GWAS studies, efforts to discover additional SNPs, and methods for identifying causal variants. We summarize findings associated with overall breast cancer, pathologic subtypes, and mutation carriers (BRCA1, BRCA2, and CHEK2). In addition, we summarize the development of polygenic risk scores (PRS) using the risk-associated SNPs and show how PRS can contribute to estimation of individual risks for developing breast cancer. Cancer Epidemiol Biomarkers Prev; 27(4); 380–94. ©2018 AACR.
See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”
Association of USP10 with G3BP2 Inhibits p53 Signaling and Contributes to Poor Outcome in Prostate Cancer
Authors: Takayama Ken-ichi , Suzuki Takashi , Fujimura Tetsuya , Takahashi Satoru , Inoue Satoshi 
Published: January 2018

Abstract
Ubiquitin-specific protease 10 (USP10) is known to deubiquitylate its target proteins, mainly to enhance their stabilities. USP10 maintains p53 protein levels and controls epigenetic changes induced by the androgen receptor (AR). GTPase-activating protein-binding protein 2 (G3BP2), an androgen-responsive gene, is known as the main component of stress granules (SG) that interacts with USP10 in SGs. This study explores the roles of USP10 in prostate cancer progression in p53, G3BP2, and AR signaling. Using chromatin immunoprecipitation (ChIP) and sequence analysis, it was found that USP10 is transcriptionally induced with AR recruitment to an intronic region. Furthermore, USP10 regulates androgen-mediated signaling and cell growth. USP10 maintained G3BP2 protein stability by reducing polyubiquitylation. G3BP2-dependent growth activation and p53 nuclear export that reduced p53 signaling were repressed by USP10 knockdown. Clinically, USP10 was expressed primarily in the cytoplasm of prostate cancer tissues. High levels of USP10 expression were strongly correlated with high levels of AR, G3BP2, and p53 in the cytoplasm. High expression of USP10 was significantly associated with poor prognosis of patients with prostate cancer. Taken together, USP10 has a repressive effect on p53 signaling for cell growth by regulating G3BP2 expression. These findings highlight an important oncogenic aspect of USP10 through its modulation of the p53–G3BP2 complex and AR signaling in prostate cancer.
Implications: These findings elucidate the oncogenic role of USP10 in prostate cancer through an increase in G3BP2 protein that inhibits p53 activity, in addition to the promotion of AR signaling. Mol Cancer Res; 16(5); 846–56. ©2018 AACR.
The Transcription Factor AP4 Promotes Oncogenic Phenotypes and Cisplatin Resistance by Regulating LAPTM4B Expression
Authors: Wang Lu , Meng Yue , Xu Jian-Jun , Zhang Qing-Yun 
Published: January 2018

Abstract
Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) is a novel oncogene, whose overexpression is involved in cancer occurrence and progression. However, the mechanism of LAPTM4B transcriptional regulation remains unclear. In this study, the results of transcription factor (TF) profiling plate arrays indicated that AP4 was a potential transcription factor regulating LAPTM4B expression. LAPTM4B was positively correlated with AP4 and they were both associated with poor overall and disease-free survival. Luciferase and electrophoretic mobility shift assay assays confirmed that AP4 directly bound to the polymorphism region of LAPTM4B promoter and modulated its transcription. Functionally, AP4 promoted cell proliferation, migration, invasion, and assisted drug resistance in part through upregulation of LAPTM4B. Taken together, these findings identify LAPTM4B as a direct AP4 target gene and the interaction of AP4 and LAPTM4B plays an important role in breast cancer progression.
Implications: This study demonstrates that AP4 promotes cell growth, migration, invasion, and cisplatin resistance through upregulation of LAPTM4B expression, thus representing an attractive therapeutic target for breast cancer. Mol Cancer Res; 16(5); 857–68. ©2018 AACR.
Prognostic Significance of PD-L1+ and CD8+ Immune Cells in HPV+ Oropharyngeal Squamous Cell Carcinoma
Authors: Solomon Benjamin , Young Richard J. , Bressel Mathias , Urban Damien , Hendry Shona , Thai Alesha , Angel Christopher , Haddad Afaf , Kowanetz Marcin , Fua Tsien , Corry June , Fox Stephen , Rischin Danny 
Published: January 2018

Abstract
Human papilloma virus–positive oropharyngeal squamous cell carcinoma (HPV+ OPSCC) represents a distinct subgroup of head and neck cancers associated with clinical outcomes that are not accurately categorized by existing tumor–node–metastasis-based staging methods. Given the significant impact of immune parameters, such as tumor-infiltrating lymphocytes (TIL) in many cancers, we sought to determine if immunophenotyping tumors can improve categorization of HPV+ OPSCCs for prognostic purposes. In a cohort of 190 patients with HPV+ OPSCC, we quantified and determined the localization of CD8+ TILs, as well as PD-L1–expressing tumor cells (TC) and immune cells (IC). The prognostic significance of these parameters on overall survival (OS) was evaluated, and their contribution to existing prognostic models was determined. High CD8+ TIL abundance (≥30% on stromal or intratumoral ICs) was seen in 61.3% patients and was associated with improved OS [HR, 0.4; 95% confidence interval (CI), 0.2–0.9; P = 0.017]. Although the expression of PD-L1 on TC was not prognostic, high expression of PD-L1 on ≥5% of intratumoral ICs was found in 38.5% patients and was significantly associated with improved OS (HR, 0.37; 95% CI, 0.15–0.93; P = 0. 023). Both high intratumoral IC PD-L1 expression and abundant CD8+ TILs in HPV+ OPSCCs identify subgroups of patients with excellent outcomes and provide additional prognostic information beyond existing staging systems. Cancer Immunol Res; 6(3); 295–304. ©2018 AACR.
Increased Serum Leptin Levels in New-Onset, Untreated Female Patients with Coronary Artery Disease and Positively Associated with Inflammatory Markers
Authors: Du Ying , Yang Sheng-Hua , Li Sha , Zhao Xi , Zhang Yan , Sun Di , Zhu Cheng-Gang , Wu Na-Qiong , Guo Yuan-Lin , Xu Rui-Xia , Qing Ping , Gao Ying , Sun Jing , Li Jian-Jun 
Published: January 2018

<b><i>Background/Aims:</i></b> Previous studies have suggested that leptin was associated with atherosclerosis and involved in inflammation. Gender differences between leptin and inflammatory markers have been evaluated less in untreated patients with stable coronary artery disease (CAD). <b><i>Methods:</i></b> In this study, a total of 394 consecutive Chinese patients who received coronary artery angiography were enrolled, including 243 patients with CAD and 151 non-CAD controls. The baseline clinical characteristics were collected and serum leptin levels were determined using ELISA. <b><i>Results:</i></b> The relation of serum leptin levels to inflammatory markers was found only in female patients. Leptin and white blood cell count (WBCC) as well as its subsets were significantly higher in female patients than female controls. In female patients, leptin was positively associated with C-reactive protein (CRP; <i>r</i> = 0.28, <i>p</i> = 0.016), WBCC (<i>r =</i> 0.261, <i>p</i> = 0.02), neutrophil, <i>r</i> = 0.268, <i>p</i> = 0.018, and monocyte, <i>r</i> = 0.228, <i>p</i> = 0.044. Multivariable regression analysis revealed that leptin was significantly and independently associated with CRP (β = 0.317, <i>p</i> = 0.004), WBCC (β = 0.278, <i>p</i> = 0.020), neutrophil (β = 0.262, <i>p</i> = 0.032), and monocyte (β = 0.245, <i>p</i> = 0.032). <b><i>Conclusions:</i></b> The serum leptin levels were higher in female patients and independently associated with CRP, WBCC, and its subsets, suggesting a potential interaction between leptin and inflammation in female CAD patients.
Vernacular Marxism: Proletarian Readings in Russian Poland around the 1905 Revolution
Authors: Marzec Wiktor 
Published: January 2018

AbstractThe article seeks to fill a lacuna in Marxist scholarship concerning the actually-existing Marxism of politically-mobilised workers as an organic philosophy in its own right. To shed light on this issue, I investigate the reading-material which stimulated Marxist conversion and the accompanying intellectual invigoration of workers at the turn of the twentieth century in Russian Poland. For proletarian readers Marxism was the main political language, ushering them into the public sphere and allowing them to comprehend the emerging capitalist world. As a particular liaison of scientific knowledge and a practical political weapon, it allowed its adherents to redefine themselves and make political claims. Such a situational Marxism, drawing from but not reducible to the prevailing ‘orthodoxy’, allows one to see the latter as a socially diverse plethora of ideas.
A reflective case review: Relearning handwriting after a traumatic brain injury
Authors: Titchener Alison , Dunford Carolyn , Wales Lorna 
Published: January 2018

Statement of context A retrospective single case study reflecting on a child relearning handwriting following a traumatic brain injury as part of an inpatient neuro-rehabilitation programme. Applying evidence-based handwriting guidelines and comparisons with community experiences are explored. Critical reflection on practice Relearning to write following a traumatic brain injury showed dramatic improvements in 36 sessions over 12 weeks, supporting the evidence. Progress in this timeframe contrasts with clinical experiences of working with children’s community services. Implications for practice Whilst the literature on handwriting interventions does not include children with traumatic brain injury, following the recommendations was an effective intervention for this individual.
Receipt of Vasopressors Is Positively Associated With the Length of the Actively Dying Process in Hospitalization
Authors: Chou Hsiao-Chen , Huang Hsien-Liang , Chen Chiang-Yi , Wang Chuan-Lan , Shu Chin-Chung , Hsu Nin-Chieh , Lin Yu-Feng , Chen Jin-Shing , Sheng Wang-Huei 
Published: January 2018

Background: End-of-life care is important in general hospitalization care. However, the clinical impact of using vasopressors on the length of the actively dying process is still controversial. Methods: We reviewed patients who were hospitalized in general wards and died before discharge. We classified the patients into 2 groups: those who received vasopressors (RVs) and those who did not receive vasopressors (NRV). We analyzed the factors associated with the length of hospital stay (LOS) and the length of the actively dying process. Results: In all, 745 participants, 10.01% of all admitted patients, were analyzed. Of them, 225 patients were RV group, and the remaining 520 were NRV group. Age and gender were comparable in the 2 groups. The use of vasopressors was associated with an admission diagnosis of sepsis and absence of Do-Not-Resuscitate consent and parenteral use of morphine. In multivariable analysis, a high Barthel index score, the absence of cancer and cardiopulmonary resuscitation (CPR), and no receipt of vasopressors were independent factors for LOS. For the length of the actively dying process, a longer duration of inotropic agent, the receipt of vasopressors, and the absence of CPR were independent factors. Conclusion: In-hospital mortality is not uncommon during hospitalization in a general ward. The length of the actively dying process is extended by the use of vasopressors. Further prospective study is required for cautious evaluation of the pros and cons of using vasopressors at the end of life during hospitalization.
The relationship between ACE/AGT gene polymorphisms and the risk of diabetic retinopathy in Chinese patients with type 2 diabetes
Authors: Qiao Yong-chao , Wang Min , Pan Yan-hong , Zhang Xiao-xi , Tian Fang , Chen Yin-ling , Zhao Hai-lu 
Published: January 2018

Aims: This study aims to investigate the association between renin-angiotensin system gene polymorphism and diabetic retinopathy (DR) in Chinese patients with type 2 diabetes. Methods: We consecutively included 1491 patients for the assessment of ACE I/D and AGT M/T gene polymorphisms in 345 DR cases and 1146 patients without retinopathy (DNR). Albuminuria was defined by urine albumin creatinine ratio and albumin excretion rate. Results: Compared with the NDR patients, the DR cases displayed a higher proportion of diabetic nephropathy (32.68% vs. 6.52%, χ2 = 150.713, p < 0.001). The DR cases and DNR individuals did not differ in the frequency of genotypes and alleles of ACE I/D and AGT M/T (all p > 0.05). Intriguingly, DR patients with obesity showed higher frequency of DD (χ2 = 4.181, p = 0.041), but no significant difference exists in the other stratified BMI and hypertension analyses (all p > 0.05). Binary logistic regression displays that the association of the ACE and AGT gene polymorphisms in DR patients is not significant after adjusting for confounding covariates in all the comparisons. Conclusions: The ACE and AGT gene polymorphisms are not associated with the progress of diabetes developing into retinopathy in Chinese patients with type 2 diabetes. However, more investigations are needed to further prove the association.
Glenohumeral Internal Rotation Deficit and Risk of Upper Extremity Injury in Overhead Athletes: A Meta-Analysis and Systematic Review
Authors: Keller Robert A. , De Giacomo Anthony F. , Neumann Julie A. , Limpisvasti Orr , Tibone James E. 
Published: January 2018

Context: Current perception dictates that glenohumeral internal rotation deficit (GIRD) is a chronic adaptation that leads to an increased risk of pathologic conditions in the dominant shoulder or elbow of overhead athletes. Objective: To determine whether adaptations in glenohumeral range of motion in overhead athletes lead to injuries of the upper extremity, specifically in the shoulder or elbow. Data Sources: An electronic database search was performed using Medline, Embase, and SportDiscus from 1950 to 2016. The following keywords were used: GIRD, glenohumeral internal rotation deficit, glenohumeral deficit, shoulder, sport, injury, shoulder joint, baseball, football, racquet sports, volleyball, javelin, cricket, athletic injuries, handball, lacrosse, water polo, hammer throw, and throwing injury. Study Selection: Seventeen studies met the inclusion criteria for this systematic review. Of those 17 studies, 10 included specific range of motion measurements required for inclusion in the meta-analysis. Study Design: Systematic review and meta-analysis. Level of Evidence: Level 4. Data Extraction: Data on demographics and methodology as well as shoulder range of motion in various planes were collected when possible. The primary outcome of interest was upper extremity injury, specifically shoulder or elbow injury. Results: The systematic review included 2195 athletes (1889 males, 306 females) with a mean age of 20.8 years. Shoulders with GIRD favored an upper extremity injury, with a mean difference of 3.11° (95% CI, –0.13° to 6.36°; P = 0.06). Shoulder total range of motion suggested increased motion (mean difference, 2.97°) correlated with no injury ( P = 0.11), and less total motion (mean difference, 1.95°) favored injury ( P = 0.14). External rotational gain also favored injury, with a mean difference of 1.93° ( P = 0.07). Conclusion: The pooled results of this systematic review and meta-analysis did not reach statistical significance for any shoulder motion measurement and its correlation to shoulder or elbow injury. Results, though not reaching significance, favored injury in overhead athletes with GIRD, as well as rotational loss and external rotational gain.
Testicular masses in congenital adrenal hyperplasia: Using 123I-MIBG scintigraphy to support the diagnosis of testicular adrenal rest tumours
Authors: Hempenstall Lucy Elizabeth , Kwok Michael , Siriwardana Amila Rohan , Wang Gary , Desai Devang , Gleeson Jacob 
Published: January 2018

This case demonstrates the use of 123I-MIBG scintigraphy in the diagnosis of testicular adrenal rest tumours (TART) in an adult with classical congenital adrenal hyperplasia (CAH). TART are common in CAH patients, with MIBG scanning offering a new imaging modality to potentially help verify the diagnosis and prevent invasive investigation. Level of evidence: Level 5 case report
Vitrectomy in the Management of Vitreomacular Traction Syndrome
Authors: Michalewska Zofia , Nawrocki Jerzy 
Published: January 2018

Purpose: To estimate long-term results after vitrectomy with internal limiting membrane peeling in vitreomacular traction syndrome (VMTS), as well as to estimate factors influencing final visual outcome. Methods: Medical records of all patients who underwent pars plana vitrectomy for idiopathic VMTS from 2007 through 2015 were assessed. Spectral domain optical coherence tomography was performed preoperatively and at least 6 months after surgery. The mean horizontal and vertical diameters of the vitreomacular traction (VMT) were measured. The area of vitreomacular attachment was calculated. Results: Twenty-four eyes of 22 patients (mean age, 74 years) were included in this study. Mean visual acuity improved significantly from 0.26 Snellen (0.69 logMAR) to 0.39 Snellen (0.43 logMAR) in the mean of 29 months after surgery (7-90 months; median, 25 months; P = .02, paired t test). Visual acuity improved in 18 eyes, remained unchanged in 2 cases, and decreased postoperatively in 4 eyes. Multiple regression analysis did not reveal any factors significant for determining final visual acuity. However, when regrouping the patients according to the International Vitreomacular Traction Study Group, we observed that final visual acuities were statistically significantly better in eyes with focal vitreous detachment compared to broad vitreous detachment ( P = .04). Conclusions: Despite the fact that VMT is a 3-dimensional disease, the calculated area of attachment was not greater than the vertical diameter of attachment. According to the current study, the classification of VMT proposed by the VMT Study Group might be an important tool in predicting the final visual outcome after vitrectomy.