bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interferon-Stimulated Genes Are Involved in Cross-resistance to Radiotherapy in Tamoxifen-Resistant Breast Cancer
Authors: Post Annemarie E.M. , Smid Marcel , Nagelkerke Anika , Martens John W.M. , Bussink Johan , Sweep Fred C.G.J. , Span Paul N. 
Published: April 2018

Abstract
Purpose: Treatment resistance is the main cause of adverse disease outcome in breast cancer patients. Here, we aimed to investigate common features in tamoxifen-resistant and radioresistant breast cancer, as tamoxifen-resistant breast cancer cells are cross-resistant to irradiation in vitro.
Experimental Design: RNA sequencing of tamoxifen-resistant and radioresistant breast cancer cells was performed and validated by quantitative PCR. Pathways were further investigated in vitro and in breast cancer patient cohorts to establish their relation with treatment resistance.
Results: Both tamoxifen-resistant and radioresistant breast cancer cells had increased expression levels of genes involved in type I IFN signaling compared with nonresistant cells. IFN-stimulated genes (ISG) were induced in a dose-dependent and time-dependent manner after tamoxifen treatment and irradiation. Tamoxifen treatment also led to ssDNA presence in the cytoplasm, which is known to induce expression of ISGs, a phenomenon that has already been described for irradiation. Moreover, in a breast cancer patient cohort, high expression levels of ISGs were found in the primary tumor in around half of the patients. This was associated with a tumor-infiltrating lymphocyte (TIL) expression signature, although the ISGs were also expressed by the tumor cells themselves. Importantly, the expression of ISGs correlated with outcome in breast cancer patients treated with adjuvant tamoxifen or radiotherapy, but not in systemically untreated patients or chemotherapy-treated patients.
Conclusions: Our data indicate that expression of ISGs by tumor cells is involved in acquired, treatment-induced resistance to tamoxifen and radiotherapy, and might play a role in intrinsic resistance via interaction with TILs. Clin Cancer Res; 24(14); 3397–408. ©2018 AACR.
Report from the SWOG Radiation Oncology Committee: Research Objectives Workshop 2017
Authors: Okunieff Paul , Casey-Sawicki Katherine , Lockney Natalie A. , Hoppe Bradford S. , Enderling Heiko , Pinnix Chelsea , Welsh James , Krishnan Sunil , Yothers Greg , Brown Martin , Knox Susan , Bristow Robert , Spellman Paul , Mitin Timur , Nabavizadeh Nima , Jaboin Jerry , Manning H. Charles , Feng Felix , Galbraith Susan , Solanki Abhishek A. , Harkenrider Matthew M. , Tuli Richard , Decker Roy H. , Finkelstein Steven E. , Hsu Charles C. , Ha Chul S. , Jagsi Reshma , Shumway Dean , Daly Megan , Wang Tony J.C. , Fitzgerald Thomas J. , Laurie Fran , Marshall David T. , Raben David , Constine Louis , Thomas Charles R. , Kachnic Lisa A. 
Published: April 2018

Abstract
The Radiation Therapy Committee of SWOG periodically evaluates its strategic plan in an effort to maintain a current and relevant scientific focus, and to provide a standard platform for future development of protocol concepts. Participants in the 2017 Strategic Planning Workshop included leaders in cancer basic sciences, molecular theragnostics, pharmaceutical and technology industries, clinical trial design, oncology practice, and statistical analysis. The committee discussed high-priority research areas, such as optimization of combined modality therapy, radiation oncology–specific drug design, identification of molecular profiles predictive of radiation-induced local or distant tumor responses, and methods for normal tissue-specific mitigation of radiation toxicity. The following concepts emerged as dominant questions ready for national testing: (i) what is the role of radiotherapy in the treatment of oligometastatic, oligorecurrent, and oligoprogressive disease? (ii) How can combined modality therapy be used to enhance systemic and local response? (iii) Can we validate and optimize liquid biopsy and other biomarkers (such as novel imaging) to supplement current response criteria to guide therapy and clinical trial design endpoints? (iv) How can we overcome deficiencies of randomized survival endpoint trials in an era of increasing molecular stratification factors? And (v) how can we mitigate treatment-related side effects and maximize quality of life in cancer survivors? The committee concluded that many aspects of these questions are ready for clinical evaluation and example protocol concepts are provided that could improve rates of cancer cure and quality of survival. Clin Cancer Res; 24(15); 3500–9. ©2018 AACR.
Accuracy, Safety, and Reliability of Novel Phase I Trial Designs
Authors: Zhou Heng , Yuan Ying , Nie Lei 
Published: April 2018

Abstract
A number of novel model-based and model-assisted designs have been proposed to find the MTD in phase I clinical trials, but their differences and relative pros and cons are not clear to many practitioners. We review three model-based designs, including the continual reassessment method (CRM), dose escalation with overdose control (EWOC), and Bayesian logistic regression model (BLRM), and three model-assisted designs, including the modified toxicity probability interval (mTPI), Bayesian optimal interval (BOIN), and keyboard (equivalently mTPI-2) designs. We conduct numerical studies to assess their accuracy, safety, and reliability and the practical implications of various empirical rules used in some designs, such as skipping a dose and imposing overdose control. Our results show that the CRM outperforms EWOC and BLRM with higher accuracy of identifying the MTD. For the CRM, skipping a dose is not recommended, as it substantially increases the chance of overdosing patients while providing limited gain for identifying the MTD. EWOC and BLRM appear excessively conservative. They are safe but have relatively poor accuracy of finding the MTD. The BOIN and keyboard (equivalently mTPI-2) designs have similar operating characteristics, outperforming the mTPI, but the BOIN is more intuitive and transparent. The BOIN yields competitive performance comparable with the CRM but is simpler to implement and free of the issue of irrational dose assignment caused by model misspecification, thereby providing an attractive approach for designing phase I trials. Clin Cancer Res; 24(18); 4357–64. ©2018 AACR.
Machine Learning Analysis of Left Ventricular Function to Characterize Heart Failure With Preserved Ejection Fraction
Authors: Sanchez-Martinez Sergio , Duchateau Nicolas , Erdei Tamas , Kunszt Gabor , Aakhus Svend , Degiovanni Anna , Marino Paolo , Carluccio Erberto , Piella Gemma , Fraser Alan G. , Bijnens Bart H. 
Published: April 2018

Background:
Current diagnosis of heart failure with preserved ejection fraction (HFpEF) is suboptimal. We tested the hypothesis that comprehensive machine learning (ML) of left ventricular function at rest and exercise objectively captures differences between HFpEF and healthy subjects.

Methods and Results:

One hundred fifty-six subjects aged >60 years (72 HFpEF+33 healthy for the initial analyses; 24 hypertensive+27 breathless for independent evaluation) underwent stress echocardiography, in the MEDIA study (Metabolic Road to Diastolic Heart Failure). Left ventricular long-axis myocardial velocity patterns were analyzed using an unsupervised ML algorithm that orders subjects according to their similarity, allowing exploration of the main trends in velocity patterns. ML identified a continuum from health to disease, including a transition zone associated to an uncertain diagnosis. Clinical validation was performed (1) to characterize the main trends in the patterns for each zone, which corresponded to known characteristics and new features of HFpEF; the ML-diagnostic zones differed for age, body mass index, 6-minute walk distance, B-type natriuretic peptide, and left ventricular mass index (
P
<0.05) and (2) to evaluate the consistency of the proposed groupings against diagnosis by current clinical criteria; correlation with diagnosis was good (κ, 72.6%; 95% confidence interval, 58.1–87.0); ML identified 6% of healthy controls as HFpEF. Blinded reinterpretation of imaging from subjects with discordant clinical and ML diagnoses revealed abnormalities not included in diagnostic criteria. The algorithm was applied independently to another 51 subjects, classifying 33% of hypertensive and 67% of breathless controls as mild-HFpEF.

Conclusions:
The analysis of left ventricular long-axis function on exercise by interpretable ML may improve the diagnosis and understanding of HFpEF.
Political Implications of Ancient Platonism in Rabelais’s Tiers Livre
Authors: Haglund Timothy 
Published: April 2018

Abstract
François Rabelais’s (1483-1553) Tiers Livre (1546) constitutes a turning point in the five books of Gargantua and Pantagruel, as war finally ends and peace reigns over the Utopian kingdom. Peace brings with it the question of whether Panurge, one of Rabelais’s main characters, should marry. Pantagruel, the prince of Utopia, calls a banquet of experts, each representing a strand of Western civilization, to decide this question. The arrangement of this banquet where each expert speaks in turn and at length, uninterrupted by the others, allows Rabelais to portray the arrayed opinions perspectivally or independently. Rondibilis, a medical expert who speaks at the banquet, presents a Platonism that focuses on ‘natural consequences’ and that appears less adulterated by Christianity and later forms of philosophy than the Neoplatonism of most of Rabelais’s contemporaries. Rondibilis’s advice of resignation to nature is reflected as well in the political rule of prince Pantagruel.
Modeling conflict in a social system using diffusion equations
Authors: Yurevich Petukhov Alexander , Olegovich Malkhanov Alexey , Mikhailovich Sandalov Vladimir , Vasilievich Petukhov Yuri 
Published: April 2018

In this paper the problem of modeling social conflicts of various types with the help of diffusion equations is discussed. The main approaches to and methods of mathematical modeling in contemporary humanitarian sciences are outlined. The main concepts of social conflicts, means of their classification and interpretation – including ethnic-social, religious, and other conflicts – are considered. The notion of a conflict in a social system is defined in terms of mathematical modeling. A model based on the Langevin diffusion equation is introduced. The model is based on the idea that all individuals in a society interact by means of a communication field. This field is induced by each individual in the society and forms informational interaction between individuals. An analytical solution of the system of equations is given in the first approximation for a diverging type of diffusion. It is shown that even for a simple case of the interaction of two groups of individuals the developed model makes it possible to discover characteristic laws of a conflict in a social system. It allows determining the effect of social distance in a society on the conditions of generation of such processes, with account of external effects or a random factor. Based on the analysis of the phase portraits for the given system, it has been concluded that there exists a stability region within which the social system is stable and non-conflicting.
Procalcitonin and albumin as prognostic biomarkers in elderly patients with a risk of bacterial infection
Authors: Higashikawa Toshihiro , Okuro Masashi , Ishigami Keiichirou , Mae Kunihiro , Sangen Ryusho , Mizuno Takurou , Usuda Daisuke , Saito Atushi , Kasamaki Yuji , Fukuda Akihiro , Saito Hitoshi , Morimoto Shigeto , Kanda Tsugiyasu 
Published: April 2018

Aim This study was performed to investigate serum procalcitonin (PCT) and albumin (Alb) as prognostic biomarkers in elderly patients at risk of bacterial infection. Methods Serum PCT was measured in 270 hospitalized patients (mean age, 77.4 years) with suspected bacterial infection. The PCT-negative (<0.5 ng/mL) and PCT-positive (≥0.5 ng/mL) groups comprised 155 and 115 patients, respectively. Logistic regression analysis was performed with various clinical laboratory test values as independent variables and PCT positivity/negativity as the dependent variable. Results C-reactive protein (CRP) was the only independent variable significantly associated with PCT positivity/negativity. In the survival analysis, the 30-day in-hospital death rate was significantly higher in the PCT-positive than -negative group. Within the Alb-positive group (>2.5 g/dL), no significant difference in survival was observed between the PCT-positive and -negative groups. However, within the Alb-negative group (≤2.5 g/dL), the survival rate was significantly lower in the PCT-positive than -negative group. PCT was strongly associated with CRP and Alb, and having both PCT positivity and Alb negativity was a prognostic factor for elderly people at risk of bacterial infection. Conclusions Combined measurement of PCT with Alb is expected to be a valuable tool to assess prognosis in elderly people at risk of bacterial infection.
Comparison of endoscopic-assisted and temporary keratoprosthesis-assisted vitrectomy in combat ocular trauma: experience at a tertiary eye center in Turkey
Authors: Ayyildiz Onder , Hakan Durukan Ali 
Published: April 2018

Objective This study was performed to compare the functional and anatomical results of endoscopic-assisted and temporary keratoprosthesis (TKP)-assisted vitrectomy in patients with combat ocular trauma (COT). Methods The medical records of 14 severely injured eyes of 12 patients who underwent endoscopy or TKP implantation in combination with vitreoretinal surgery from 2007 to 2015 were retrospectively evaluated. The patients’ ocular history and functional and anatomic anterior and posterior segment results were analyzed. Results Eight eyes (57%) underwent TKP-assisted vitrectomy and six eyes (43%) underwent endoscopic vitrectomy. The most common cause of COT was detonation of improvised explosive devices (72%), and the most common type of injury was an intraocular foreign body (50%). The median time from trauma to surgery and the median surgical time were significantly shorter in the endoscopy than TKP group. The postoperative functional and anatomical results were not significantly different between the two groups. Conclusions TKP-assisted vitrectomy should be performed in eyes requiring extensive bimanual surgery. In such cases, a corneal graft must be preserved for the TKP at the end of the surgery. Endoscopy shortens the surgical time and can reduce the complication rate.
Validation of the Modified Tnm-Izumi Classification for Hepatocellular Carcinoma
Authors: Staudacher Carlo , Chiappa Antonio , Biella Francesca , Audisio Riccardo A. , Bertani Emilio , Zbar Andrew P. 
Published: April 2018

Aims and background The clinical value of the UICC TNM classification and the Izumi TNM modification regarding prognosis after hepatic resection was evaluated. Methods Between January 1993 and December 1998, survival and disease-free survival were analyzed in 53 cirrhotic patients (40 males, 13 females; mean age, 65 years; range, 43-81) who underwent hepatic resection for HCC. Results The 1-, 3-, and 5-year overall survivals were: 89%, 54%, and 50%, with disease-free survivals of 70%, 38%, and 28%, respectively. The difference between stages 1 and 2 or stages 3 and 4A using the UICC TNM classification was not significant with respect to survival or disease-free survival. Conversely, the Izumi TNM modification showed a significant difference between each stage with respect to survival and disease-free survival. In a multivariate analysis the lack of micro/macro vascular invasion was predictive of long-term outcome. Conclusions Our results show that the UICC TNM classification for hepatocellular carcinoma is inadequate. The Izumi modified TNM staging system is superior in assessing prognosis for surgical HCC patients.
Prognostic Significance of Anemia and Role of Erythropoietin in Radiation Therapy
Authors: Smaniotto Daniela , Luzi Stefano , Morganti Alessio G. , Cellini Numa 
Published: April 2018

Anemia represents a common finding in cancer patients, especially at an advanced stage. Anemia has an impact on the quality of life and at the same time seems to markedly limit the disease control that can be achieved with radiotherapy. The results of a series of clinical studies published in the last decade allow some general observations: 1. the administration of erythropoietin, especially if associated to ferrous sulfate is able to increase hemoglobulin levels in cancer patients undergoing radiation therapy (combined with concomitant chemotherapy); 2. erythropoietin stimulation of hemoglobin in anemia decreases the need for blood transfusion in cancer patients; 3. tumor response to radiation therapy appears to be enhanced by erythropoietin-induced hemoglobulin increase. Further clinical studies are required for assessment of indications, identification of optimal administration modalities, cost-analysis of this promising therapy for patients undergoing radiation therapy.
Hormonal Profiles and Estrogen Receptors in Egyptian Female Breast Cancer Patients
Authors: Abu-Bedair Farid Ahmed , El-Gamal Basiouny Ahmed , Ibrahim Nagi Ali , El-Aaser Abdelbaset Anwer 
Published: April 2018

Aims and background Hormones are considered to be an important factor in the etiology of breast cancer. Serum hormonal profiles of premenopausal and postmenopausal breast cancer patients as well as estrogen receptor (ER) concentrations in breast cancer tissues were examined in an attempt to establish a possible association between hormones and breast cancer risk and to elucidate the biological features of the disease among Egyptian female patients. Methods Levels of estradiol (E2), testosterone (T), progesterone (P), LH, FSH, prolactin, T3, T4 and TSH were measured by highly specific radioimmunoassays in the sera of women with breast cancer and compared to those of control subjects. ER concentrations in breast tumor tissues were measured using 125I-radioreceptor assay. Results Levels of T and prolactin showed a significant increase in both premenopausal and postmenopausal patients. E2 and P levels were significantly increased in follicular premenopausal and postmenopausal patients. Luteal E2 showed non-significant changes, whereas the luteal P level was significantly decreased. No significant alterations were found in the levels of serum LH, FSH, T3, T4 and TSH either in premenopausal or postmenopausal patients. Higher levels of ER were found in the tumors of postmenopausal than in those of premenopausal patients. A positive correlation was found between levels of ER and age of the patients (r = 0.35), whereas a negative correlation was observed between ER and serum E2 (r = −0.26). Conclusions This study provides evidence of an association between high levels of serum E2 and T and increased risk of breast cancer in postmenopausal women. Abnormalities in serum P and prolactin are probably associated with a breast cancer risk and ER may be considered as a biochemical marker for breast cancer development.
Mutual Predictive Value of c-erbB-2 Overexpression and Various Prognostic Factors in Ductal Invasive Breast Carcinoma
Authors: Jakić-Razumović Jasminka , Petrovečki Mladen , Užarević Branka , Gamulin Stjepan 
Published: April 2018

Aims and background Breast carcinoma is a heterogeneous disease, the prognosis of which correlates with various prognostic factors. The aim of this study was to assess the prognostic significance of c-erbB-2 overexpression in breast carcinoma patients in association with other known prognostic factors. Methods & study design The relationship between immunohistochemical expression of the c-erbB-2 oncoprotein and various established prognostic factors such as tumor size, axillary node status, estrogen and progesterone receptor status, DNA ploidy, proliferation index, cathepsin D expression and histological grade in invasive ductal breast carcinoma is presented in this study. Results Of the 93 ductal invasive carcinomas 22 (23.7%) were grade I, 51 (54.8%) grade II, and 20 (21.5%) grade III, and the majority (78: 83.9%) were 2-5 cm in diameter. Tumor metastases were identified in one or more lymph nodes in 55 (59.1%) patients, the remaining 38 (40.9%) patients being lymph node negative. According to the DNA histograms 40 (43.0%) tumors were aneuploid and 53 (57.0%) were diploid, and the majority of tumors had more than 4% of cells in the S phase of the cell cycle (83.9%). Expression of c-erbB-2 as shown by immunohistochemical intense membrane staining was present in 49 (52.7%) tumors. Cathepsin D-positive cytoplasmic granular staining and cathepsin D-positive stromal macrophages were found in 60 (64.5%) and 72 (77.4%) tumors, respectively. Univariate analysis showed that overall survival correlated significantly with axillary lymph node involvement and with estrogen and progesterone receptor status for each of the receptors separately and for their coexpression, and only marginally with c-erbB-2 overexpression. In mulitivariate analysis only axillary lymph node metastases and coexpression of estrogen and progesterone receptors were found to be independent and significant prognostic factors. Conclusions When patients were stratified according, to c-erbB-2 expression it was shown that those with c-erbB-2 overexpression and grade II tumors, tumor size greater than 2 cm, high content of aneuploid cells and cathepsin D-positive stromal macrophages had a shorter long-term survival than c-erbB-2 negative patients.
Continuous Infusion Fluorouracil in the Management of Advanced Breast Cancer: A Phase II Study
Authors: Crivellari Diana , Magri Maria Donatella , Buonadonna Angela , Lombardi Davide , Paolello Concetta , De Cicco Marcello , Fantin Dario , Veronesi Andrea 
Published: April 2018

Aims and background The evaluation of unconventional schedules of well-known drugs represents a promising avenue in the search for new regimens with a better therapeutic index in metastatic breast cancer. In particular, protracted continuous infusion (PCI) of 5-fluorouracil (5-FU) has yielded interesting results in gastrointestinal malignancies and in breast cancer. Methods From March 1996 30 consecutive patients with heavily pretreated breast cancer were treated with PCI 5-FU at a daily dose of 250 mg/m2 by means of disposable elastomeric pumps until progression or toxicity. The median age was 54 years (range, 28-71) and median performance status was 1 (range, 0-3). All patients but four were pretreated with anthracycline-containing regimens or taxanes; the median number of chemotherapy lines was 3 (range, 2-4). Metastatic sites were predominantly visceral in 60% of the patient population. Results All 30 patients were evaluable for response and toxicity. The median duration of PCI was 20 weeks (range, 2-36 weeks). Two complete responses (7%) and eight partial remissions (26%) were observed, giving an overall response rate of 33%. The median duration of response was six months (range, 4-9 months). Stabilization was observed in seven patients (23%) with a median duration of seven months (range, 3-9 months). The main toxic effects were grade I-II mucositis and hematologic toxicity, while grade 3 hand-foot syndrome was observed in eight patients (27%). Conclusions This study confirms the efficacy and safety of 5-FU at this dosage and schedule in heavily pretreated women with advanced breast cancer. In order to improve on these results further studies are needed in a less advanced stage of the disease and together with other active drugs.