bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting Cancer Prognosis Using Interactive Online Tools: A Systematic Review and Implications for Cancer Care Providers
Authors: Rabin Borsika A. , Gaglio Bridget , Sanders Tristan , Nekhlyudov Larissa , Dearing James W. , Bull Sheana , Glasgow Russell E. , Marcus Alfred 
Published: August 2013

Abstract
Cancer prognosis is of keen interest for patients with cancer, their caregivers, and providers. Prognostic tools have been developed to guide patient–physician communication and decision-making. Given the proliferation of prognostic tools, it is timely to review existing online cancer prognostic tools and discuss implications for their use in clinical settings. Using a systematic approach, we searched the Internet, Medline, and consulted with experts to identify existing online prognostic tools. Each was reviewed for content and format. Twenty-two prognostic tools addressing 89 different cancers were identified. Tools primarily focused on prostate (n = 11), colorectal (n = 10), breast (n = 8), and melanoma (n = 6), although at least one tool was identified for most malignancies. The input variables for the tools included cancer characteristics (n = 22), patient characteristics (n = 18), and comorbidities (n = 9). Effect of therapy on prognosis was included in 15 tools. The most common predicted outcome was cancer-specific survival/mortality (n = 17). Only a few tools (n = 4) suggested patients as potential target users. A comprehensive repository of online prognostic tools was created to understand the state-of-the-art in prognostic tool availability and characteristics. Use of these tools may support communication and understanding about cancer prognosis. Dissemination, testing, refinement of existing, and development of new tools under different conditions are needed. Cancer Epidemiol Biomarkers Prev; 22(10); 1645–56. ©2013 AACR.
Breast Implants and Anaplastic Large-Cell Lymphoma: A Danish Population-Based Cohort Study
Authors: Vase Maja Ølholm , Friis Søren , Bautz Andrea , Bendix Knud , Sørensen Henrik Toft , d'Amore Francesco 
Published: August 2013

Abstract
Background: A potential link between breast implants and anaplastic large-cell lymphoma (ALCL) has been suggested.
Methods: We examined lymphoma occurrence in a nationwide cohort of 19,885 Danish women who underwent breast implant surgery during 1973–2010. Standardized incidence ratios (SIR), with 95% confidence intervals (CI), for ALCL and lymphoma overall associated with breast implantation were calculated.
Results: During 179,246 person-years of follow-up, we observed 31 cases of lymphoma among cohort members. No cases of ALCL were identified. SIRs for ALCL and lymphoma overall were zero (95% CI, 0–10.3) and 1.20 (95% CI, 0.82–1.70), respectively.
Conclusions: In our nationwide cohort study, we did not find an increased risk of lymphoma in general, or ALCL in particular, among Danish women who underwent breast implantation. However, our evaluation of ALCL risk was limited by the rarity of the disease.
Impact: Our results do not support an association between breast implants and ALCL and are consistent with other studies on cancer risk and breast implants. Cancer Epidemiol Biomarkers Prev; 22(11); 2126–9. ©2013 AACR.
Cumulative Genetic Risk Predicts Platinum/Taxane-Induced Neurotoxicity
Authors: McWhinney-Glass Sarah , Winham Stacey J. , Hertz Daniel L. , Yen Revollo Jane , Paul Jim , He Yijing , Brown Robert , Motsinger-Reif Alison A. , McLeod Howard L. ,   For the Scottish Gynaecological Clinical Trials Group
Published: August 2013

Abstract
Purpose: The combination of a platinum and taxane are standard of care for many cancers, but the utility is often limited due to debilitating neurotoxicity. We examined whether single-nucleotide polymorphisms (SNP) from annotated candidate genes will identify genetic risk for chemotherapy-induced neurotoxicity.
Patients and Methods: A candidate–gene association study was conducted to validate the relevance of 1,261 SNPs within 60 candidate genes in 404 ovarian cancer patients receiving platinum/taxane chemotherapy on the SCOTROC1 trial. Statistically significant variants were then assessed for replication in a separate 404 patient replication cohort from SCOTROC1.
Results: Significant associations with chemotherapy-induced neurotoxicity were identified and replicated for four SNPs in SOX10, BCL2, OPRM1, and TRPV1. The population attributable risk for each of the four SNPs ranged from 5% to 35%, with a cumulative risk of 62%. According to the multiplicative model, the odds of developing neurotoxicity increase by a factor of 1.64 for every risk genotype. Patients possessing three risk variants have an estimated OR of 4.49 (2.36–8.54) compared to individuals with 0 risk variants. Neither the four SNPs nor the risk score were associated with progression-free survival or overall survival.
Conclusions: This study shows that SNPs in four genes have a significant cumulative association with increased risk for the development of chemotherapy-induced neurotoxicity, independent of patient survival. Clin Cancer Res; 19(20); 5769–76. ©2013 AACR.
Overexpression of Asparagine Synthetase and Matrix Metalloproteinase 19 Confers Cisplatin Sensitivity in Nasopharyngeal Carcinoma Cells
Authors: Liu Ran-Yi , Dong Zizheng , Liu Jianguo , Zhou Ling , Huang Wenlin , Khoo Sok Kean , Zhang Zhongfa , Petillo David , Teh Bin Tean , Qian Chao-Nan , Zhang Jian-Ting 
Published: August 2013

Abstract
Platinum-based concurrent chemoradiotherapy is considered a standard treatment approach for locoregionally advanced nasopharyngeal carcinoma. However, only a minority of patients benefit from this treatment regimen compared with radiotherapy alone. Identification of a set of molecular markers predicting sensitivity of platinum-based chemotherapy may contribute to personalized treatment of patients with nasopharyngeal carcinoma for better clinical outcome with less toxicity. Previously, we generated a cisplatin-sensitive nasopharyngeal carcinoma cell line, S16, by clonal selection from CNE-2 cells and found that eIF3a is upregulated and contributes to cisplatin sensitivity by downregulating the synthesis of nucleotide excision repair proteins. In this study, we conducted a gene expression profiling analysis and found three other genes, asparagine synthetase (ASNS), choriogonadotropin α subunit (CGA), and matrix metalloproteinase 19 (MMP19), that are upregulated in the cisplatin-sensitive S16 cells compared with the CNE-2 cells. However, only ASNS and MMP19, but not CGA, contributes to cisplatin sensitivity by potentiating cisplatin-induced DNA damage and apoptosis. Thus, ASNS and MMP19, along with eIF3a, are the sensitivity factors for cisplatin treatment and may serve as potential candidate molecular markers for predicting cisplatin sensitivity of advanced nasopharyngeal carcinoma. Mol Cancer Ther; 12(10); 2157–66. ©2013 AACR.
Contribution of ATM and ATR to the Resistance of Glioblastoma and Malignant Melanoma Cells to the Methylating Anticancer Drug Temozolomide
Authors: Eich Marcus , Roos Wynand Paul , Nikolova Teodora , Kaina Bernd 
Published: August 2013

AbstractThe major cytotoxic DNA adduct induced by temozolomide and other methylating agents used in malignant glioma and metastasized melanoma therapy is O6-methylguanine (O6-MeG). This primary DNA damage is converted by mismatch repair into secondary lesions, which block replication and in turn induce DNA double-strand breaks that trigger the DNA damage response (DDR). Key upstream players in the DDR are the phosphoinositide 3-kinases ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related (ATR). Here, we addressed the question of the importance of ATM and ATR in the cell death response following temozolomide. We show that (i) ATM- and ATR-mutated cells are hypersensitive to temozolomide, (ii) O6-MeG triggers ATM and ATR activation, (iii) knockdown of ATM and ATR enhances cell kill in gliobalstoma and malignant melanoma cells with a stronger and significant effect in ATR knockdown cells, (iv) ATR, but not ATM, knockdown abolished phosphorylation of H2AX, CHK1, and CHK2 in glioma cells, and (v) temozolomide-induced cell death was more prominently enhanced by pharmacologic inhibition of CHK1 compared with CHK2. The data suggest that ATM and, even better, ATR inhibition is a useful strategy in sensitizing cancer cells to temozolomide and presumably also other anticancer drugs. Mol Cancer Ther; 12(11); 2529–40. ©2013 AACR.
Mechanism-Based Epigenetic Chemosensitization Therapy of Diffuse Large B-Cell Lymphoma
Authors: Clozel Thomas , Yang ShaoNing , Elstrom Rebecca L. , Tam Wayne , Martin Peter , Kormaksson Matthias , Banerjee Samprit , Vasanthakumar Aparna , Culjkovic Biljana , Scott David W. , Wyman Sarah , Leser Micheal , Shaknovich Rita , Chadburn Amy , Tabbo Fabrizio , Godley Lucy A. , Gascoyne Randy D. , Borden Katherine L. , Inghirami Giorgio , Leonard John P. , Melnick Ari , Cerchietti Leandro 
Published: August 2013

AbstractAlthough aberrant DNA methylation patterning is a hallmark of cancer, the relevance of targeting DNA methyltransferases (DNMT) remains unclear for most tumors. In diffuse large B-cell lymphoma (DLBCL) we observed that chemoresistance is associated with aberrant DNA methylation programming. Prolonged exposure to low-dose DNMT inhibitors (DNMTI) reprogrammed chemoresistant cells to become doxorubicin sensitive without major toxicity in vivo. Nine genes were recurrently hypermethylated in chemoresistant DLBCL. Of these, SMAD1 was a critical contributor, and reactivation was required for chemosensitization. A phase I clinical study was conducted evaluating azacitidine priming followed by standard chemoimmunotherapy in high-risk patients newly diagnosed with DLBCL. The combination was well tolerated and yielded a high rate of complete remission. Pre- and post-azacitidine treatment biopsies confirmed SMAD1 demethylation and chemosensitization, delineating a personalized strategy for the clinical use of DNMTIs.Significance: The problem of chemoresistant DLBCL remains the most urgent challenge in the clinical management of patients with this disease. We describe a mechanism-based approach toward the rational translation of DNMTIs for the treatment of high-risk DLBCL. Cancer Discov; 3(9); 1002–19. ©2013 AACR.See related commentary by Steinhardt and Gartenhaus, p. 968This article is highlighted in the In This Issue feature, p. 953
Systemic Hypertension in Low-Gradient Severe Aortic Stenosis With Preserved Ejection Fraction
Authors: Eleid Mackram F. , Nishimura Rick A. , Sorajja Paul , Borlaug Barry A. 
Published: August 2013

Background—
Low-gradient severe aortic stenosis with preserved ejection fraction is an increasingly recognized entity, and symptomatic patients may benefit from aortic valve replacement. However, systemic hypertension frequently coexists with low-gradient severe aortic stenosis, which itself may cause elevated left ventricular (LV) filling pressures with resultant symptoms of dyspnea.

Methods and Results—

Symptomatic patients with hypertension (aortic systolic pressure >140 mm Hg) and low-gradient (mean gradient <40 mm Hg) severe aortic stenosis (aortic valve area <1 cm
2
) with preserved ejection fraction (ejection fraction >50%) who underwent invasive hemodynamic catheterization of the left and right sides of the heart received infusion of intravenous sodium nitroprusside to reduce blood pressure and arterial afterload. At baseline, patients had severe hypertension (aortic systolic pressure, 176±26 mm Hg), pulmonary hypertension (mean pressure, 39±12 mm Hg), elevated LV end-diastolic pressure (19±5 mm Hg), and reduced stroke volume (33±8 mL/m
2
). All measures of afterload were reduced with nitroprusside (
P
<0.001 for all). Nitroprusside reduced mean pulmonary artery pressure (25±10 mm Hg) and LV end-diastolic pressure (11±5 mm Hg;
P
<0.001 for both compared with baseline). Aortic valve area (0.86±0.11 to 1.02±0.16 cm
2
;
P
=0.001) and mean gradient (27±5 to 29±6 mm Hg;
P
=0.02) increased with nitroprusside.

Conclusions—
Systemic hypertension in low-gradient severe aortic stenosis with preserved ejection fraction is associated with elevated LV filling pressures and pulmonary hypertension. Treatment of hypertension with vasodilator therapy results in a lowering of the total LV afterload, with a decrease in LV filling pressures and pulmonary artery pressures. These findings have important implications for the management of patients with low-gradient severe aortic stenosis with preserved ejection fraction and hypertension.
Hepatic Extracellular Signal–Regulated Kinase 2 Suppresses Endoplasmic Reticulum Stress and Protects From Oxidative Stress and Endothelial Dysfunction
Authors: Kujiraoka Takehiko , Satoh Yasushi , Ayaori Makoto , Shiraishi Yasunaga , Arai‐Nakaya Yuko , Hakuno Daihiko , Yada Hirotaka , Kuwada Naruo , Endo Shogo , Isoda Kikuo , Adachi Takeshi 
Published: August 2013

Background

Insulin signaling comprises 2 major cascades: the insulin receptor substrate/phosphatidylinositol 3′‐kinase/protein kinase B and Ras/Raf/mitogen‐activated protein kinase/kinase/ERK pathways. While many studies on the tissue‐specific effects of the insulin receptor substrate/phosphatidylinositol 3′ ‐kinase/protein kinase B pathway have been conducted, the role of the other cascade in tissue‐specific insulin resistance has not been investigated. High glucose/fatty acid toxicity, inflammation, and oxidative stress, all of which are associated with insulin resistance, can activate
ERK
. The liver plays a central role in metabolism, and hepatosteatosis is associated with vascular diseases. The aim of study was to elucidate the role of hepatic
ERK
2 in hepatosteatosis, metabolic remodeling, and endothelial dysfunction.

Methods and Results

We created liver‐specific ERK2 knockout mice and fed them with a high‐fat/high‐sucrose diet for 20 weeks. The high‐fat/high‐sucrose diet–fed liver‐specific ERK2 knockout mice exhibited a marked deterioration in hepatosteatosis and metabolic remodeling represented by impairment of glucose tolerance and decreased insulin sensitivity without changes in body weight, blood pressure, and serum cholesterol/triglyceride levels. In the mice, endoplasmic reticulum stress was induced together with decreased
mRNA
and protein expressions of hepatic sarco/endoplasmic reticulum Ca
2+
‐ATPase 2. In a hepatoma cell line, inhibition of ERK activation– induced endoplasmic reticulum stress only in the presence of palmitate. Vascular reactive oxygen species were elevated with upregulation of nicotinamide adenine dinucleotide phosphate oxidase1 (Nox1) and Nox4 and decreased phosphorylation of endothelial nitric oxide synthase, which resulted in the remarkable endothelial dysfunction in high‐fat/high‐sucrose diet–fed liver‐specific ERK2 knockout mice.

Conclusions

Hepatic
ERK
2 suppresses endoplasmic reticulum stress and hepatosteatosis in vivo, which results in protection from vascular oxidative stress and endothelial dysfunction. These findings demonstrate a novel role of hepatic
ERK
2 in obese‐induced insulin resistance in the protection from hepatovascular metabolic remodeling and vascular diseases.
Cognitive remediation as a treatment for major depression: A rationale, review of evidence and recommendations for future research
Authors: Porter Richard J , Bowie Christopher R , Jordan Jennifer , Malhi Gin S 
Published: August 2013

Objective: There is considerable literature regarding the effectiveness of cognitive remediation (CR) in schizophrenia and in conditions such as stroke and traumatic brain injury. Patients with major depressive disorder (MDD) present with significant cognitive impairment which in many cases may not resolve with treatment. Neurobiological data suggest that this may relate to underlying dysfunction of pre-frontal cortical areas of the brain and their connections with limbic structures. There has been limited research into specific CR to activate these areas and target impaired cognitive function in MDD. We therefore review current evidence, examine the theoretical basis for and present a rationale for research into CR in MDD. In addition, we will examine important methodological issues in developing such an approach. Method: Based on preliminary studies using CR-based techniques, data from CR in schizophrenia, data regarding baseline and residual cognitive impairment in depression, and knowledge of the neurobiology of MDD, we examine the possible utility of CR strategies in the treatment of MDD and make recommendations for research in this area. Results: A small number of previous studies have examined specific CR in MDD. The studies are small and inconclusive. However, data on the neuropsychological function and neurobiology of MDD suggest that this is an approach that deserves further attention and research. Conclusions: Further research is required in carefully selected populations, using well-defined CR techniques and some form of comparator treatment.
Instability and Degenerative Arthritis of the Sternoclavicular Joint
Authors: Martetschläger Frank , Warth Ryan J. , Millett Peter J. 
Published: August 2013

Background: Injuries to the sternoclavicular (SC) joint typically occur with high-energy mechanisms such as those obtained in automobile accidents or contact sports. Many disorders of the SC joint can be treated nonoperatively. However, surgical treatment may be indicated for locked posterior dislocations; symptomatic, chronic instability; or persistent, painful osteoarthritis that fails nonoperative therapy. Purpose: To provide an updated review on the current diagnosis and management of instability and degenerative arthritis of the SC joint. Study Design: Current concepts review. Methods: A preliminary PubMed database search using the terms sternoclavicular instability, dislocation, arthritis, resection, and stabilization was performed in August 2012. All anatomic and biomechanical studies, review articles, case reports, case series, and technique papers that were relevant to the topic were included. Results: The search identified 929 articles, 321 of which, after screening of the titles and abstracts, were considered potentially relevant to this study. Of the 321 articles, 30 were anatomic or imaging studies, 2 were biomechanical studies, 69 were review papers, 189 were case series or reports, and 31 were technique papers. The majority of these studies were classified as evidence level 4, with a few scattered level 3 studies. Because the level of evidence obtained from this search was not adequate for systematic review (or meta-analysis), a current concepts review of the diagnosis and management of SC joint instability and degenerative arthritis is presented. Conclusion: Injuries to the SC joint are uncommon. Recognition and classification of these injuries are critical to proper management, thus minimizing potential long-term sequelae such as posttraumatic arthritis and recurrent instability. Although nonoperative therapy is the modality of choice in anterior dislocations, posterior dislocations require special attention because of the presence of vulnerable posterior hilar structures. Surgical management of chronic instability and degenerative arthritis of the SC joint includes resection arthroplasty of the medial clavicle with or without reconstruction of the sternoclavicular ligaments with graft material. Although resection is typically performed open, an arthroscopic technique is described that theoretically decreases operating and recovery times while also decreasing the risk of iatrogenic injury. Currently, when reconstruction is needed for stability, a figure-of-8 graft reconstruction is the recommended method based on biomechanical data and small clinical series.
Arthroscopic Capsular Plication and Labral Preservation in Borderline Hip Dysplasia
Authors: Domb Benjamin G. , Stake Christine E. , Lindner Dror , El-Bitar Youssef , Jackson Timothy J. 
Published: August 2013

Background: The role of hip arthroscopy in the treatment of patients with dysplasia is unclear because of the spectrum of dysplasia that exists. Patients with borderline dysplasia are generally not candidates for periacetabular osteotomy because of the invasive nature of the procedure. However, arthroscopy in dysplasia has had mixed results and has the potential to exacerbate instability. Hypothesis: Patients with borderline dysplasia will demonstrate postoperative improvement, high satisfaction rates, and low reoperation rates after a surgical approach that includes arthroscopic labral repair augmented by capsular plication with inferior shift. Study Design: Case series; Level of evidence, 4. Methods: Between April 2008 and November 2010, patients less than 40 years old who underwent hip arthroscopy for symptomatic intra-articular hip disorders, with a lateral center-edge (CE) angle ≥18° and ≤25°, were included in this study. Patients with Tönnis grade 2 or greater, severe hip dysplasia (CE ≤17°), and Legg-Calve-Perthes disease were excluded. Patient-reported outcome scores, including the modified Harris Hip Score (mHHS), Non-Arthritic Hip Score (NAHS), Hip Outcome Score–Sport-Specific Subscale (HOS-SSS), Hip Outcome Score–Activity of Daily Living (HOS-ADL), and visual analog scale (VAS) for pain were obtained in all patients preoperatively and at 1, 2, and 3 years postoperatively. Revision surgery and complications were recorded for each group. Results: A total of 26 patients met the criteria to be included in the study. Of these, 22 (85%) patients were available for follow-up. The mean (± standard deviation) length of follow-up for this cohort was 27.5 ± 5.5 months (range, 17-39 months) and the average age was 20 years (range, 14-39 years). The mean lateral CE angle was 22.2° (range, 18°-25°) and the mean Tönnis angle was 5.8° (range, 0°-17°). There was significant improvement in all patient-reported outcome scores (mHHS, NAHS, HOS-SSS, and HOS-ADL) ( P < .0001). There was a significant improvement in VAS scores from 5.8 to 2.9 ( P < .0001). Overall patient satisfaction was 8.4 out of 10. Seventeen patients had good/excellent results (77%). Two patients required revision arthroscopy. Conclusion: Patients with borderline dysplasia have often fallen into a gray area between arthroscopy and periacetabular osteotomy, and viable treatment options have remained scarce. The current study demonstrates favorable results at 2-year follow-up for an arthroscopic approach that includes labral repair augmented by capsular plication with inferior shift.