bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transformed Follicular Lymphoma (TFL) Predicts Outcome in Advanced Endometrial Cancer
Authors: Wakahashi Senn , Kawakami Fumi , Wakahashi Kanako , Minagawa Kentaro , Matsuo Keitaro , Katayama Yoshio , Yamada Hideto , Matsui Toshimitsu , Sudo Tamotsu 
Published: May 2018

Abstract
Background: Transformed follicular lymphoma (TFL, ZC3H12D) was identified as a candidate tumor suppressor gene that contributes to cell-cycle arrest through regulation of Rb phosphorylation, but the clinical impact of TFL is unknown. The goal of this study was to evaluate the prognostic significance of TFL expression in advanced endometrial cancer.
Methods: Tissue samples were obtained from 103 patients with Federation Internationale des Gynaecologistes et Obstetristes stage III–IV endometrial cancer. Associations between TFL expression and outcomes were evaluated using the Kaplan–Meier method and multivariate Cox proportional hazards regression models.
Results: There were 24 TFL-low cases (23.3%) and the 10-year progression-free survival (PFS) and overall survival (OS) in these cases were lower than those for patients with normal TFL expression in univariate analysis (PFS, P = 0.003; OS, P = 0.106). In multivariate analysis, TFL status was a significant predictor for PFS [HR = 2.76; 95% confidence interval (CI), 1.45–5.28; P = 0.002] and OS (HR = 1.94; 95% CI, 0.91–4.11; P = 0.085), adjusted for covariates. The TFL gene maps to human chromosome 6q25.1, where estrogen receptor alpha (ERα) gene ESR1 is also located. Lack of ERα expression is a poor prognostic factor in early endometrial cancer. Among 41 ERα-low patients, 10-year PFS was significantly lower in 15 TFL-low cases (univariate analysis, P = 0.055; multivariate analysis, HR = 4.70; 95% CI, 1.68–13.20; P = 0.003).
Conclusions: We identified TFL as a strong independent prognostic factor, regardless of ERα status.
Impact: An investigation of the mechanism underlying tumor suppression by TFL may lead to new therapies for patients with advanced endometrial cancer. Cancer Epidemiol Biomarkers Prev; 27(8); 963–9. ©2018 AACR.
Association of Anthropometric Measures with Prostate Cancer among African American Men in the NCI-Maryland Prostate Cancer Case-Control Study
Authors: Pichardo Margaret S. , Smith Cheryl J. , Dorsey Tiffany H. , Loffredo Christopher A. , Ambs Stefan 
Published: May 2018

Abstract
Background: Obesity is a cancer risk factor. Although it does not increase the risk of localized prostate cancer, it raises the risk of the aggressive disease in men of European ancestry. Few studies investigated obesity as a prostate cancer risk factor in men of African ancestry. Findings from those studies were heterogeneous, but some reported an association of excess body fatness with aggressive disease.
Methods: We examined the relationship of body mass index (BMI), waist circumference, and waist–hip ratio with prostate cancer in African American (AA) and European American (EA) men in the NCI-Maryland Prostate Cancer Case-Control Study consisting of 798 men with incident prostate cancer (402 AA and 496 EA) and 1,008 population-based controls (474 AA and 534 EA). BMI was self-reported. Waist circumference and waist–hip ratio were calculated from measurements at enrollment.
Results: A high BMI either at enrollment or years prior to it was associated with a decreased risk of prostate cancer in AA men. In contrast, an elevated BMI tended to increase the disease risk in EA men. Waist circumference was inversely associated with prostate cancer in both AA and EA men, whereas a high waist–hip ratio did not associate with prostate cancer in AA men but tended to be associated with advanced/aggressive disease in EA men.
Conclusions: Our findings reveal an obesity paradox among AA men in this study population, where a high BMI and waist circumference associated with a decreased disease risk.
Impact: Our observations expand the knowledge of how obesity may affect prostate cancer risks in AAs. Cancer Epidemiol Biomarkers Prev; 27(8); 936–44. ©2018 AACR.
Clinically Relevant Cytotoxic Immune Cell Signatures and Clonal Expansion of T-Cell Receptors in High-Risk MYCN-Not-Amplified Human Neuroblastoma
Authors: Wei Jun S. , Kuznetsov Igor B. , Zhang Shile , Song Young K. , Asgharzadeh Shahab , Sindiri Sivasish , Wen Xinyu , Patidar Rajesh , Najaraj Sushma , Walton Ashley , Guidry Auvil Jaime M. , Gerhard Daniela S. , Yuksel Aysen , Catchpoole Daniel , Hewitt Stephen M. , Sondel Paul M. , Seeger Robert , Maris John M. , Khan Javed 
Published: May 2018

Abstract
Purpose: High-risk neuroblastoma is an aggressive disease. DNA sequencing studies have revealed a paucity of actionable genomic alterations and a low mutation burden, posing challenges to develop effective novel therapies. We used RNA sequencing (RNA-seq) to investigate the biology of this disease, including a focus on tumor-infiltrating lymphocytes (TIL).
Experimental Design: We performed deep RNA-seq on pretreatment diagnostic tumors from 129 high-risk and 21 low- or intermediate-risk patients with neuroblastomas. We used single-sample gene set enrichment analysis to detect gene expression signatures of TILs in tumors and examined their association with clinical and molecular parameters, including patient outcome. The expression profiles of 190 additional pretreatment diagnostic neuroblastomas, a neuroblastoma tissue microarray, and T-cell receptor (TCR) sequencing were used to validate our findings.
Results: We found that MYCN-not-amplified (MYCN-NA) tumors had significantly higher cytotoxic TIL signatures compared with MYCN-amplified (MYCN-A) tumors. A reported MYCN activation signature was significantly associated with poor outcome for high-risk patients with MYCN-NA tumors; however, a subgroup of these patients who had elevated activated natural killer (NK) cells, CD8+ T cells, and cytolytic signatures showed improved outcome and expansion of infiltrating TCR clones. Furthermore, we observed upregulation of immune exhaustion marker genes, indicating an immune-suppressive microenvironment in these neuroblastomas.
Conclusions: This study provides evidence that RNA signatures of cytotoxic TIL are associated with the presence of activated NK/T cells and improved outcomes in high-risk neuroblastoma patients harboring MYCN-NA tumors. Our findings suggest that these high-risk patients with MYCN-NA neuroblastoma may benefit from additional immunotherapies incorporated into the current therapeutic strategies. Clin Cancer Res; 24(22); 5673–84. ©2018 AACR.
Autophagy, Cell Viability, and Chemoresistance Are Regulated By miR-489 in Breast Cancer
Authors: Soni Mithil , Patel Yogin , Markoutsa Eleni , Jie Chunfa , Liu Shou , Xu Peisheng , Chen Hexin 
Published: May 2018

Abstract
It is postulated that the complexity and heterogeneity in cancer may hinder most efforts that target a single pathway. Thus, discovery of novel therapeutic agents targeting multiple pathways, such as miRNAs, holds promise for future cancer therapy. One such miRNA, miR-489, is downregulated in a majority of breast cancer cells and several drug-resistant breast cancer cell lines, but its role and underlying mechanism for tumor suppression and drug resistance needs further investigation. The current study identifies autophagy as a novel pathway targeted by miR-489 and reports Unc-51 like autophagy activating kinase 1 (ULK1) and lysosomal protein transmembrane 4 beta (LAPTM4B) to be direct targets of miR-489. Furthermore, the data demonstrate autophagy inhibition and LAPTM4B downregulation as a major mechanism responsible for miR-489–mediated doxorubicin sensitization. Finally, miR-489 and LAPTM4B levels were inversely correlated in human tumor clinical specimens, and more importantly, miR-489 expression levels predict overall survival in patients with 8q22 amplification (the region in which LAPTM4B resides).
Implications: These findings expand the understanding of miR-489–mediated tumor suppression and chemosensitization in and suggest a strategy for using miR-489 as a therapeutic sensitizer in a defined subgroup of resistant breast cancer patients. Mol Cancer Res; 16(9); 1348–60. ©2018 AACR.
Low-Frequency Sensorineural Hearing Loss in Familial Hemophagocytic Lymphohistiocytosis Type 5
Authors: Bezdjian Aren , Bruijnzeel Hanneke , Pagel Julia , Daniel Sam J. , Thomeer Hans G.X.M. 
Published: May 2018

Introduction: Familial hemophagocytic lymphohistiocytosis (FHL) is an autosomal recessive disease affecting the cytotoxic pathway. Due to the recent advances in molecular diagnosis, immuno-chemo therapy, and hematopoietic stem cell transplantation treatment, FHL survival rates have drastically increased. Case Presentation: Herein, we describe a case of FHL type 5 presenting with low-frequency sensorineural hearing loss. Alongside our reported case, 6 additional patients were identified in the literature. Management and Outcome: The progressive nature of FHL disorder may cause bilateral, low-frequency, irreversible sensorineural hearing loss. This type of hearing loss should be considered among the long-term sequelea presenting with FHL5. Discussion: We recommend audiological evaluation at initial FHL5 diagnosis to assess for hearing functions. Follow-up in audiology should be part of the long-term monitoring of patients with FHL5 as hearing loss could develop long after diagnosis.
Validity of the Hum Test, a Simple and Reliable Alternative to the Weber Test
Authors: Ahmed Omar H. , Gallant Sara C. , Ruiz Ryan , Wang Binhuan , Shapiro William H. , Voigt Erich P. 
Published: May 2018

Objectives: To compare the diagnostic performance of the Hum Test against the Weber Test using pure tone audiometry (PTA) as the “gold standard” comparator. Methods: 29 participants with normal hearing of ages 18 to 35 without any history of hearing abnormalities or otologic conditions were enrolled. Subjects underwent three tests (Hum Test, Weber Test, and PTA) across two conditions: with an ear plug in one ear (side randomized) and without ear plugs. Results: When examining the ability of the Hum Test to detect simulated conductive hearing loss (CHL), the test had a sensitivity of 89.7% and specificity of 100% with high pitched humming and 93.1% and 100%, respectively, with low pitched humming. The Weber Test had a sensitivity and specificity of 96.6% and 100%, respectively. McNemar’s test demonstrated agreement between the Hum Test, performed with either high pitched ( P = .32) or low pitched ( P = .56) humming, and the Weber Test. Receiver operating characteristic (ROC) curves for the Hum Test (both high and low pitched) and Weber test were compared and demonstrated no statistically significant difference. Conclusion: The Hum Test is comparable to the Weber Test with regards to its sensitivity, specificity, and diagnostic accuracy in assessing new onset unilateral CHL in previously normal hearing subjects.
Continuous cytokine haemoadsorption incorporated into a venoarterial ECMO circuit for the management of postcardiotomy cardiogenic and septic shock – a case report
Authors: Nemeth Endre , Szigeti Szabolcs , Varga Tamas , Daroczi Laszlo , Barati Zoltan , Merkely Bela , Gal Janos 
Published: May 2018

Introduction: The acute surgical treatment of infective endocarditis (IE) carries a high risk of postoperative mortality. Most complications are linked to uncontrolled sepsis and inflammatory processes. Cytokine haemoadsorption is an extracorporeal technique which has benefits reported in haemodynamic stability and inflammatory response. Case Report: A 46-year-old male patient underwent emergency cardiac surgery due to progressive IE. Postcardiotomy cardiogenic shock associated with cardiac surgery required the implantation of venoarterial (VA)-ECMO. Three days later, the patient developed secondary septic shock. The novel application of continuous CytoSorbTM treatment installed in the VA-ECMO circuit is demonstrated in this case during the management of simultaneous shocks. Advanced intensive care led to an improvement in the patient’s condition, which facilitated successful weaning from mechanical ventilation. However, the patient died from a new onset fulminant septic shock two months after his initial cardiac surgery. Discussion: VA-ECMO is suitable for installation of the CytoSorbTM cartridge. This modality could be an option for high-volume, continuous cytokine haemoadsorption when VA-ECMO is employed without renal replacement therapy. Conclusion: This specific application of CytoSorbTM was safe, feasible and contributed to the optimal management of simultaneous shocks.
Distribution characteristics of cells in splenomegaly due to hepatitis B-related cirrhotic portal hypertension and their clinical importance
Authors: Han Xiaoyu , Lv Yunfu , Li Yejuan , Deng Jie , Qiu Qingan , Liu Ning , Zhao Shuya , Liao Caixian 
Published: May 2018

Objectives To investigate peripheral cytopenia in patients with splenomegaly due to hepatitis B-related cirrhotic portal hypertension (HBRCPH) by comparing blood cell counts from enlarged spleens with peripheral blood. Methods This prospective study involved patients undergoing splenectomy at the Nangfang Hospital from June 2013 to December 2015. Blood cell counts from peripheral blood were compared with those from splenic blood taken during splenectomies. Results Clinical data were available from 30 patients. White blood cell (WBC), red blood cell (RBC) and platelet counts were statistically significantly lower in peripheral blood compared with splenic blood. After splenectomy, peripheral blood cell counts increased significantly compared with pre-operative levels. Platelet and WBC counts in the lower spleen were significantly higher than those in the porta lienis (middle segment) and upper spleen. Conclusions In patients with splenomegaly due to HBRCPH, the counts of three blood cell lineages were significantly higher in the spleen than in peripheral blood. Splenectomy can aid the return of peripheral blood cell counts to normal levels. The most significant retention of platelets and WBCs occurred in the lower spleen which may be useful information for surgeons performing partial splenectomies.
Does continuing family-based treatment for adolescent anorexia nervosa improve outcomes in those not remitted after 20 sessions?
Authors: Wallis Andrew , Miskovic-Wheatley Jane , Madden Sloane , Alford Colleen , Rhodes Paul , Touyz Stephen 
Published: May 2018

Objective:Our aim was to investigate the benefit of ongoing family-based treatment (FBT) sessions for adolescent anorexia nervosa if remission criteria were not met at session 20.Method:Participants were 69 medically unstable adolescents with Diagnostic and Statistical Manual of Mental Disorders (4th ed; DSM-IV) anorexia nervosa from a randomized controlled trial investigating length of hospital admission prior to outpatient FBT. Participants were divided post hoc into those meeting remission criteria at session 20 ( n = 16), those that had not remitted but continued with FBT ( n = 39) and those who ceased FBT undertaking alternative treatments ( n = 14). Outcome was assessed as remission and hospital readmission days at 12 months after FBT session 20.Results:There were no differences between groups at baseline. There was a significant difference in the use of hospital admission days with those in the Alternate Treatment Group who did not continue with FBT using 71.93 days compared to those in Additional FBT Group with only 12.51 days ( F(2, 66) = 13.239, p < .01). At 12 months after FBT session 20, the Additional FBT Group had a 28.2% increase in remission rate, significantly higher than those in the Alternate Treatment Group (χ2(2) = 17.68, p  < .001).Discussion:Continuing FBT after session 20 if remission is not achieved can significantly reduce hospital readmission days and improve remission rates.
A Feasibility Study Comparing Platelet-Rich Plasma Injection With Saline for the Treatment of Plantar Fasciitis Using a Prospective, Randomized Trial Design
Authors: Johnson-Lynn Sarah , Cooney Alan , Ferguson Diarmaid , Bunn Deborah , Gray William , Coorsh Jonathan , Kakwani Rajesh , Townshend David 
Published: May 2018

Platelet-rich plasma (PRP) has been advocated for treatment of plantar fasciitis but there are few good-quality clinical trials to support its use. We conducted a feasibility study of PRP versus saline for treatment of plantar fasciitis. Patients with 6 months or more of magnetic resonance imaging–proven plantar fasciitis, who had failed conservative treatment were invited to participate in the study. Patients were block randomized to either PRP or an equivalent volume of saline. The techniques used for injection and rehabilitation were standardized for both groups. The patient and assessor were blinded. Visual analogue scale (VAS) for pain and painDETECT score were recorded preoperatively and at 6 months follow-up. From 35 patients approached, 28 (19 female, mean age 50 years) were recruited, with 14 randomized to each arm. At 6 months, 8 patients (28.6%) were lost to follow-up. There was a significant change in VAS score from baseline to follow-up in both intervention (mean change 37.2, P = .008) and control (mean change 42.2, P = .003) groups. There was no correlation between preoperative painDETECT score and change in VAS. Recruitment and loss to follow-up rates were relatively high. Both treatments resulted in a similar, significant, improvement in symptoms. Levels of Evidence: Level II
Validity of electronic hospital discharge prescription records as a source of medication data for pharmacoepidemiological research
Authors: Fanning Laura , Vo Lilian , Ilomäki Jenni , Bell J. Simon , Elliott Rohan A. , Dārziņš Pēteris 
Published: May 2018

Background: The advent of hospital electronic medical records (EMRs) with electronic prescribing provides considerable opportunity for pharmacoepidemiological research. However, validity of EMR prescribing data for research purposes is not well established. Validity concerns the percentage of cases in which medications and characteristics (name, type, formulation, dose) are true when verified with an independent data source. This study evaluated the validity of EMR discharge prescription data within the Eastern Health hospital network in Melbourne, Australia. Methods: A random sample of patients were selected who had a diagnosis of atrial fibrillation (AF) and were prescribed at least five medications. Prescription records from 2012 to 2015 were compared with pharmacy dispensing and hospital medical records (reference standards). Medication name, dose, directions and route of administration were compared. Discrepancies between data sources were categorized as omissions, additions, discrepancies in dose, medication form or route of administration or discrepancies in reordering. Sensitivities and 95% confidence intervals (CIs) for intended medication exposure were estimated for therapeutic classes. Results: A total of 5724 prescription orders for 479 patients for whom reference standards were available were included. There were 163 discrepancies (2.8%) between prescription records and reference standards. Additions were the most common data discrepancy ( n = 65; ~1.1% of total prescriptions evaluated), followed by discrepancies in reordering ( n = 34; 0.59%). Sensitivities for intended patient exposure to a medication for each therapeutic class at the first level of the Anatomical Therapeutic Chemical (ATC) classification system were between 97% and 100%. The genitourinary system and sex hormone level of the ATC system demonstrated the lowest sensitivity, (97.3%; 95% CI 92.0%–100%) and the cardiovascular system level demonstrated the highest sensitivity (99.9%; 95% CI 99.7%–100%). Conclusion: EMR discharge prescription records for patients with AF are a valid information source for conducting pharmacoepidemiological research within Eastern Health in Melbourne, Australia. Further studies in different regions, countries and patient cohorts are required to establish validity of hospital EMR prescription records for pharmacoepidemiological research.
ART Attrition across Health Facilities Implementing Option B+ in Haiti
Authors: Myrtil Martine Pamphile , Puttkammer Nancy , Gloyd Stephen , Robinson Julia , Yuhas Krista , Domercant Jean Wysler , Honoré Jean Guy , Francois Kesner 
Published: May 2018

Background: Describing factors related to high attrition is important in order to improve the implementation of the Option B+ strategy in Haiti. Methods: We conducted a retrospective cohort study to describe the variability of antiretroviral therapy (ART) retention across health facilities among pregnant and lactating women and assess for differences in ART retention between Option B+ clients and other ART patients. Results: There were 1989 Option B+ clients who initiated ART in 45 health facilities. The percentage of attrition varied from 9% to 81% across the facilities. The largest health facilities had 38% higher risk of attrition (relative risk [RR]: 1.38, 95% confidence interval [CI]: 1.08-1.77, P = .009). Private institutions had 18% less risk of attrition (RR: 0.82, 95% CI: 0.70-0.96, P = .020). Health facilities located in the West department and the South region had lower risk of attrition. Conclusion: Being on treatment in a large or public health facility or a facility located in the North region was a significant risk factor associated with high attrition among Option B+ clients. The implementation of the Option B+ strategy must be reevaluated in order to effectively eliminate mother-to-child HIV transmission.
Protein‐coding genes combined with long noncoding RNA as a novel transcriptome molecular staging model to predict the survival of patients with esophageal squamous cell carcinoma
Authors: Guo Jin‐Cheng , Wu Yang , Chen Yang , Pan Feng , Wu Zhi‐Yong , Zhang Jia‐Sheng , Wu Jian‐Yi , Xu Xiu‐E , Zhao Jian‐Mei , Li En‐Min , Zhao Yi , Xu Li‐Yan 
Published: May 2018

AbstractBackgroundEsophageal squamous cell carcinoma (ESCC) is the predominant subtype of esophageal carcinoma in China. This study was to develop a staging model to predict outcomes of patients with ESCC.MethodsUsing Cox regression analysis, principal component analysis (PCA), partitioning clustering, Kaplan–Meier analysis, receiver operating characteristic (ROC) curve analysis, and classification and regression tree (CART) analysis, we mined the Gene Expression Omnibus database to determine the expression profiles of genes in 179 patients with ESCC from GSE63624 and GSE63622 dataset.ResultsUnivariate cox regression analysis of the GSE63624 dataset revealed that 2404 protein‐coding genes (PCGs) and 635 long non‐coding RNAs (lncRNAs) were associated with the survival of patients with ESCC. PCA categorized these PCGs and lncRNAs into three principal components (PCs), which were used to cluster the patients into three groups. ROC analysis demonstrated that the predictive ability of PCG‐lncRNA PCs when applied to new patients was better than that of the tumor‐node‐metastasis staging (area under ROC curve [AUC]: 0.69 vs. 0.65, P < 0.05). Accordingly, we constructed a molecular disaggregated model comprising one lncRNA and two PCGs, which we designated as the LSB staging model using CART analysis in the GSE63624 dataset. This LSB staging model classified the GSE63622 dataset of patients into three different groups, and its effectiveness was validated by analysis of another cohort of 105 patients.ConclusionsThe LSB staging model has clinical significance for the prognosis prediction of patients with ESCC and may serve as a three‐gene staging microarray.