bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Immunodeficiency Virus Tat Protein Aids V Region Somatic Hypermutation in Human B Cells
Authors: Wang Xiaohua , Duan Zhi , Yu Guojun , Fan Manxia , Scharff Matthew D. 
Published: April 2018

ABSTRACT
Long-term survivors of human immunodeficiency virus (HIV) infection have been shown to have a greatly increased incidence of B cell lymphomas. This increased lymphomagenesis suggests some link between HIV infection and the destabilization of the host B cell genome, a phenomenon also suggested by the extraordinary high frequency of mutation, insertion, and deletion in the broadly neutralizing HIV antibodies. Since HIV does not infect B cells, the molecular mechanisms of this genomic instability remain to be fully defined. Here, we demonstrate that the cell membrane-permeable HIV Tat proteins enhance activation-induced deaminase (AID)-mediated somatic hypermutation (SHM) of antibody V regions through their modulation of the endogenous polymerase II (Pol II) transcriptional process. Extremely small amounts of Tat that could come from bystander HIV-infected cells were sufficient to promote SHM. Our data suggest HIV Tat is one missing link between HIV infection and the overall B cell genomic instability in AIDS patients.

IMPORTANCE
Although the introduction of antiretroviral therapy (ART) has successfully controlled primary effects of human immunodeficiency virus (HIV) infection, such as HIV proliferation and HIV-induced immune deficiency, it did not eliminate the increased susceptibility of HIV-infected patients to B cell lymphomas. We find that a secreted HIV protein, Tat, enhances the intrinsic antibody diversification mechanism by increasing the AID-induced somatic mutations at the heavy-chain variable (VH) regions in human B cells. This could contribute to the high rate of mutation in the variable regions of broadly neutralizing anti-HIV antibodies and the genomewide mutations leading to B cell malignancies in HIV carriers.
Targeting the Leukemia Antigen PR1 with Immunotherapy for the Treatment of Multiple Myeloma
Authors: Alatrash Gheath , Perakis Alexander A. , Kerros Celine , Peters Haley L. , Sukhumalchandra Pariya , Zhang Mao , Jakher Haroon , Zope Madhushree , Patenia Rebecca , Sergeeva Anna , Yi Shuhua , Young Ken H. , Philips Anne V. , Cernosek Amanda M. , Garber Haven R. , Qiao Na , Weng Jinsheng , St John Lisa S. , Lu Sijie , Clise-Dwyer Karen , Mittendorf Elizabeth A. , Ma Qing , Molldrem Jeffrey J. 
Published: April 2018

Abstract
Purpose: PR1 is a human leukocyte antigen (HLA)-A2 nonameric peptide derived from neutrophil elastase (NE) and proteinase 3 (P3). We have previously shown that PR1 is cross-presented by solid tumors, leukemia, and antigen-presenting cells, including B cells. We have also shown that cross-presentation of PR1 by solid tumors renders them susceptible to killing by PR1-targeting immunotherapies. As multiple myeloma is derived from B cells, we investigated whether multiple myeloma is also capable of PR1 cross-presentation and subsequently capable of being targeted by using PR1 immunotherapies.
Experimental Design: We tested whether multiple myeloma is capable of cross-presenting PR1 and subsequently becomes susceptible to PR1-targeting immunotherapies, using multiple myeloma cell lines, a xenograft mouse model, and primary multiple myeloma patient samples.
Results: Here we show that multiple myeloma cells lack endogenous NE and P3, are able to take up exogenous NE and P3, and cross-present PR1 on HLA-A2. Cross-presentation by multiple myeloma utilizes the conventional antigen processing machinery, including the proteasome and Golgi, and is not affected by immunomodulating drugs (IMiD). Following PR1 cross-presentation, we are able to target multiple myeloma with PR1-CTL and anti-PR1/HLA-A2 antibody both in vitro and in vivo.
Conclusions: Collectively, our data demonstrate that PR1 is a novel tumor-associated antigen target in multiple myeloma and that multiple myeloma is susceptible to immunotherapies that target cross-presented antigens. Clin Cancer Res; 24(14); 3386–96. ©2018 AACR.
Towards Prevention of Breast Cancer: What Are the Clinical Challenges?
Authors: Borgquist Signe , Hall Per , Lipkus Isaac , Garber Judy E. 
Published: April 2018

Abstract
The dramatic increase in breast cancer incidence compels a paradigm shift in our preventive efforts. There are several barriers to overcome before prevention becomes an established part of breast cancer management. The objective of this review is to identify the clinical challenges for improved breast cancer prevention and discuss current knowledge on breast cancer risk assessment methods, risk communication, ethics, and interventional efforts with the aim of covering the aspects relevant for a breast cancer prevention trial. Herein, the following five areas are discussed: (i) Adequate tools for identification of women at high risk of breast cancer suggestively entitled Prevent! Online. (ii) Consensus on the definition of high risk, which is regarded as mandatory for all risk communication and potential prophylactic interventions. (iii) Risk perception and communication regarding risk information. (iv) Potential ethical concerns relevant for future breast cancer prevention programs. (v) Risk-reducing programs involving multileveled prevention depending on identified risk. Taken together, devoted efforts from both policy makers and health care providers are warranted to improve risk assessment and risk counseling in women at risk for breast cancer to optimize the prevention of breast cancer. Cancer Prev Res; 11(5); 255–64. ©2018 AACR.
Theory in Distress? On Being ‘Critical’ with Everything
Authors: Roubekas Nickolas P. 
Published: April 2018

Abstract‘Religion’ is often, if not always, deemed a rather problematic category by critical theorists, who urge scholars to be more attentive to the genealogy and history of the category. As part of the review symposium ofTheory in a Time of Excess(2016), this review essay argues that ‘theory’ itself could be deemed problematic if we wish to be consistent in adopting such a critical stance, which can lead to several dead-ends when excluding other theoretical options and possibilities.
Positive Freedom and the Citizen in Athens
Authors: Campa Naomi T. 
Published: April 2018

Abstract
Freedom in democratic Athens is often understood as consisting of positive freedom in the public sphere in the form of political participation and negative freedom in the private sphere in the form of citizens doing ‘whatever they wish’. The original meaning of positive freedom, though, is more akin to self-mastery than political participation. By looking at phrases describing Athenians’ ability to do ‘whatever they wish’ from Herodotus to Aristotle, this article argues that the phrases instead express individual positive freedom in both private and public spheres. The democratic citizen is free because he is the author of his own actions. Individual autonomy stands in contrast to Spartan and Persian definitions of freedom, which focus on the external, negative freedom of the state. In addition to an ideological distinction, positive freedom also gives rise to the principle of voluntarism.
Plato’s Minos and the Euthyphro
Authors: Priou Alex 
Published: April 2018

Abstract
At the start of Plato’s Minos an anonymous comrade argues that the variability of law according to time and place undermines the claim that it conveys moral truth. But by the end he has accepted Minos as the greatest of lawgivers because of his education by Zeus. How does he manage to slide so quickly from the moral laxity of conventionalism to the moral absolutism of divine revelation? Guided by this question, the author considers how the two divergent parts of the Minos form one whole, and so what Plato suggests is the common basis to conventionalism and piety. Plato’s Minos thus ends up having an unexpectedly close relationship to his Euthyphro.
The Dissipation of Kinetic Energy in the Lofoten Basin Eddy
Authors: Fer Ilker , Bosse Anthony , Ferron Bruno , Bouruet-Aubertot Pascale 
Published: April 2018

AbstractOcean microstructure, current, and hydrography observations from June 2016 are used to characterize the turbulence structure of the Lofoten Basin eddy (LBE), a long-lived anticyclone in the Norwegian Sea. The LBE had an azimuthal peak velocity of 0.8 m s−1 at 950-m depth and 22-km radial distance from its center and a core relative vorticity reaching −0.7f (f is the local Coriolis parameter). When contrasted to a reference station in a relatively quiescent part of the basin, the LBE was significantly turbulent between 750 and 2000 m, exceeding the dissipation rates ε in the reference station by up to two orders of magnitude. Dissipation rates were elevated particularly in the core and at the rim below the swirl velocity maximum, reaching 10−8 W kg−1. The sources of energy for the observed turbulence are the background shear (gradient Richardson number less than unity) and the subinertial energy trapped by the negative vorticity of the eddy. Idealized ray-tracing calculations show that the vertical and lateral changes in stratification, shear, and vorticity allow subinertial waves to be trapped within the LBE. Spectral analysis shows increased high-wavenumber clockwise-polarized shear variance in the core and rim regions, consistent with downward-propagating near-inertial waves (vertical wavelengths of order 100 m and energy levels 3 to 10 times the canonical open-ocean level). The energetic packets with a distinct downward energy propagation are typically accompanied with an increase in dissipation levels. Based on these summer observations, the time scale to drain the volume-integrated total energy of the LBE is 14 years.
Benefit of Adjuvant Radiotherapy in Surgically Staged Stage I-II Endometrial Carcinoma
Authors: Köse Mehmet Faruk , Garipagaoglu Melahat , Kayikçioğlu Fulya , Yalvaç Serdar , Adli Mustafa , Koçak Zafer , Boran Nurettin , Haberal AM , Cakmak Ahmet 
Published: April 2018

Aims and background This study was performed to determine the treatment outcomes and patterns of failure following external beam therapy in patients with pathological stage I-II endometrial carcinoma. Study design Eighty-three patients with stage I-II endometrial carcinoma surgically staged who were found to have high risk factors and who received postoperative radiation therapy are the subject of this report. High risk factors were: histologic grade II-III, depth of myometrial invasion (DMI) ≥1/2, stage II, poor prognostic histology (clear cell, papillary serous cell) and lymphovascular invasion. Results Recurrences were observed in six patients. The recurrences were located in the vagina (1), lung (2), liver (1), and paraaortic lymph nodes (1). Five of the six recurrences were stage IC and II. The overall survival (OS), cause-specific survival (CSS) and disease-free survival (DFS) at five years were 82.9%, 85.0% and 81.3%, respectively. DMI, grade, age and cervical stromal invasion had a significant impact on CSS. Conclusion Adjuvant radiotherapy decreases the rate of relapse in pathologically staged high-risk stage I-II endometrial carcinoma patients. After reviewing the other studies on this subject we conclude that vaginal cuff brachytherapy alone could be used in stage IA grade III and stage IB grade I-II patients because the recurrence rate is low; pelvic radiotherapy + vaginal cuff brachytherapy should be used for stage IC-II disease. Distant metastases occurred in five of our patients and represent a significant type of failure.
Evaluation of Quality of Life in Patients with Malignant Dysphagia
Authors: Brunelli Cinzia , Mosconi Paola , Boeri Paolo , Gangeri Laura , Pizzetti Paolo , Cerrai Federico , Schicchi Angelo , Apolone Giovanni , Tamburini Marcello 
Published: April 2018

Background In the last 10 years of clinical research there has been increasing interest in the evaluation of quality of life. Several generic and specific instruments have been developed for this purpose. EORTC QLQ C-30 is a cancer-specific questionnaire translated into various languages and validated in several European countries including Italy, where the impact of malignant disease on different areas of quality of life is poorly documented. Methods The EORTC QLQ C-30 was administered to 109 patients referred to the endoscopy division of the Istituto Nazionale Tumori, Milan, for endoscopic palliative treatment of malignant dysphagia to test its characteristics in terms of acceptability and clinical validity. Results In this group of patients the impact of advanced esophageal cancer was highly evident for Emotional and Physical Functioning, Fatigue and Global QoL scales. Dysphagia is a serious problem for many patients; there is a correlation between grade of dysphagia and four QoL dimensions. Conclusions QoL assessment is an important tool to evaluate the adequate management of patients with esophageal cancer. The EORTC QLQ-C30 questionnaire proved to be valid and reliable also in this population.
Preoperative Endoscopic Ultrasonography in Patients with Gastric Cancer
Authors: Mancino Gennaro , Bozzetti Federico , Schicchi Angelo , Schiavo Marcello , Spinelli Pasquale , Andreola Salvatore 
Published: April 2018

Aims and background There is a need to assess the accuracy of endoscopic ultrasonography (EUS) in the diagnosis and staging of gastric cancer, especially in the early and very advanced stages of the disease when the therapeutic approach is still controversial. Methods A retrospective study was performed on 79 patients with gastric cancer in order to compare the stage defined by preoperative EUS with that assessed histopathologically. All patients underwent laparotomy for final diagnosis, staging, and eventually treatment. The results of EUS were correlated with the histologic findings of the resected specimens. Results In the uT1 group, which corresponds to early gastric cancer, the diagnosis was histologically confirmed in 85.7% of the cases. In patients with advanced tumors defined as uT3-uT4, i.e., tumors infiltrating the serosa or neighboring structures, the diagnostic concordance was 91.1%. In contrast, concordance for less advanced lesions confined to the muscular layer was only 31.2%. As regards the lymph nodes, they were defined metastatic in 31 patients and confirmed to be histologically involved in 77.4%. In contrast, when the lymph nodes were assessed as negative at EUS, they proved to be metastatic in more than half the cases. Conclusions From the data it appears that EUS has proven to be valuable in correctly staging most of the patients. EUS shows not only tumor depth and local spread but also the passage from a pathologic to a normal wall and lymph node metastasis. EUS appears to represent an important advance in the staging and follow-up of patients with gastric cancer. Instruments and techniques will continue to evolve, but the next level of research should be designed to show that the improved staging provided by EUS has clinical utility and can affect patient outcome. It is noteworthy that the highest accuracy of EUS has been shown in those conditions (uT1 and uT3-4) which currently are under consideration for a therapeutic approach that differs from the standard one.
Feasibility of a Cell Kinetic-Based Adjuvant Chemotherapy Trial in Axillary Node-Negative Breast Cancer
Authors: Volpi Annalisa , Nanni Oriana , Vecci Anna Maria , Naldi Stefania , Bernardi Livia , Marri Liliana , Fedeli Stefano Luzi , Serra Patrizia , Amadori Dino 
Published: April 2018

Aims and background Accumulated information on biologic prognostic indicators and predictors of response to different types of treatment in patients with different tumor characteristics has made it possible to design clinical protocols on biologic bases. Among cell proliferation indices, the thymidine labelling index (TLI) has proved to be an independent and consistent prognostic indicator over time. Moreover, experimental and retrospective analyses of clinical studies have revealed a direct relation between TLI and response to chemotherapy. On the basis of the results, a prospective clinical protocol on axillary node-negative breast cancer was activated in Italy in 1989. Methods Patients with low TLI tumors were treated with local-regional therapy alone, whereas patients with high TLI tumors were randomized to receive local-regional therapy followed or not by adjuvant chemotherapy consisting of 6 cycles of CMF. Results and Conclusions The present paper reports on the feasibility of a prospective clinical protocol based on a subgroup of patients with specific pathologic (node negative) and biologic (rapidly proliferating) breast cancers. However, patient eligibility was only 11%.
Hemangiosarcoma of the Breast Followed by Term Pregnancy
Authors: Marana Heitor R.C. , de Andrade Jurandyr M. , Prado-Filho Francisco Cyro Reis de C. , Llorach-Velludo Maria Angeles Sanches , da Cunha Sergio Pereira , Bighetti Sergio 
Published: April 2018

Aims and background Primary angiosarcoma of the breast is an unusual neoplasm which is generally associated with a dismal prognosis. Given the poor prognosis and the predominance in the third and fourth decades of life when fertility tends to decrease, reports of term pregnancies after treatment of this disease are rare. Methods and study design We report a case of angiosarcoma of the breast in a 17-year-old patient with a recurrent breast nodule treated by local surgery only. After three years of follow-up without evidence of disease recurrence she became pregnant. Results A girl weighing 2,430 g was delivered at 38 weeks and two days. The patient has been free of disease for five years now. Conclusions Our experience of the present case shows the lack of full information about this tumor. Pregnancy does not seem to interfere negatively with the course of the disease.
Information and Awareness of Diagnosis and Progression of Cancer in Adult and Elderly Cancer Patients
Authors: Caruso Anita , Di Francesco Bianca , Pugliese Patrizia , Cinanni Vincenzo , Corlito Anna 
Published: April 2018

Aims and background The present study examines the effects of physicians’ attitudes towards providing information about diagnosis and progression of disease to cancer patients. The aims of the study were to: a) establish how many patients (subdivided into an adult and an elderly group) were informed and how many were aware of the diagnosis and progression of disease; b) identify possible significant differences between the two groups as regards information and awareness of disease; c) determine possible significant differences between information about diagnosis and disease progression and between awareness of diagnosis and progression within each group, and d) identify the patients’ real needs. Methods and study design A total of 311 adults and 92 elderly cancer patients were enrolled in the study. A semi-structured clinical interview was employed to assess the “information'’ and “awareness'’ variables and the patients’ needs. Statistical analyses were made with the chi squared test. Results Significant differences were observed between the two groups as regards information and awareness of diagnosis. Within each group, we found significant differences between information about diagnosis and progression and between awareness of diagnosis and progression. The principle needs expressed in both groups were to have clear information and emotional containment. Conclusions The results of the study showed that physicians informed a greater number of adult than elderly patients and more often during the early rather than in the more advanced stages of the disease.
Surgical Therapy of T1 and Selected Cases of T2 Glottic Carcinoma: Cordectomy, Horizontal Glottectomy and CO2 Laser Endoscopic Resection
Authors: Puxeddu Roberto , Argiolas Federico , Bielamowicz Steven , Satta Maddalena , Ledda Gian Peppino , Puxeddu Paolo 
Published: April 2018

Aims and background Among the different laryngeal neoplasms, glottic carcinoma is known to be one of the most suitable for functional management. Nevertheless, the best treatment for T1 and T2 glottic carcinoma, whether an open neck procedure, endoscopy or radiotherapy, with reference to recurrence, survival, and functional results, has long been debated. Study design From February 1983 to September 1997, 83 patients with well to undifferentiated glottic carcinoma (48 pT1a, 14 pT1b, and 21 selected cases of pT2 with impairment of vocal cord mobility) were submitted to surgery at the Otorhinolaryngologic Section of the Department of Surgical Sciences and Organ Transplantations of Cagliari University. Surgical treatment included 30 laryngofissures with simple or enlarged cordectomy, 22 horizontal glottectomies and 31 endoscopic laser resections. A retrospective review of the records of the patients was performed in order to obtain a better understanding of the outcome of the three different surgical procedures in our institution. Results According to the Kaplan-Meier method, the probability of remaining free of local recurrence 3 years after primary surgery was 0.90 for the T1 group and 0.85 for the T2 group. The distribution of recurrences for cordectomy, glottectomy and CO2 laser at 3 years showed a cumulative probability of remaining free of disease after primary surgery of 0.86, 0.85 and 0.88. The probability of remaining free of local recurrence 3 years after salvage surgery was 0.96 for the T1 group and 0.95 for the T2 group. Analyzing the phenomena for type of surgical procedure, local control at 3 years after salvage surgery for cordectomy, glottectomy and exclusive CO2 laser was 0.93, 0.90 and 0.92, respectively. In the endoscopic group, local control rate after any type of salvage therapy modified the percentage at 3 years to 100%. Anterior commissure spread (AC1-AC2) resulted in a difference (not statistically significant) in local control between the group of patients without and with anterior commissure involvement. Laryngeal preservation was achieved in 93.7% (45/48) of patients who survived after salvage surgery following open neck procedures and in 100% of patients originally submitted to the endoscopic approach. Conclusions In our experience, although open laryngeal procedures can be still considered a valid option in the treatment of T1 and selected cases of T2 glottic carcinoma, endoscopic laser excision offered an oncologically adequate alternative to the traditional techniques, with minimum discomfort for the patient and satisfactory preliminary functional results.