bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prospective Clinical Trial of Ixazomib, Dexamethasone, and Rituximab as Primary Therapy in Waldenström Macroglobulinemia
Authors: Castillo Jorge J. , Meid Kirsten , Gustine Joshua N. , Dubeau Toni , Severns Patricia , Hunter Zachary R. , Yang Guang , Xu Lian , Treon Steven P. 
Published: April 2018

Abstract
Purpose: Proteasome inhibition is of proven efficacy in patients with Waldenström macroglobulinemia (WM). However, WM remains incurable with standard treatments. Novel agents, safe and effective, are needed.
Patients and Methods: We designed a prospective phase II study evaluating the combination of ixazomib, dexamethasone, and rituximab (IDR) as primary therapy in symptomatic patients with WM. Protocol therapy consisted of oral ixazomib, 4 mg, with intravenous or oral dexamethasone, 20 mg, on days 1, 8, and 15 every 4 weeks for induction cycles 1 and 2, and in combination with intravenous rituximab, 375 mg/m2, on day 1, every 4 weeks for cycles 3 to 6. Maintenance therapy followed 8 weeks later with IDR given every 8 weeks for 6 cycles.
Results: Twenty-six patients were enrolled. All patients had the MYD88 L265P mutation, and 15 patients (58%) had a CXCR4 mutation. The median time to response was 8 weeks, which was longer (12 weeks) in WM patients with CXCR4 mutations (P = 0.03). The overall response rate was 96%, and the major response rate was 77%. With a median follow-up of 22 months, the median progression-free survival was not reached. Grade ≥2 adverse events reported in &gt;1 patient included infusion-related reactions (19%), rash (8%), and insomnia (8%).
Conclusions: IDR offers a highly effective and well tolerated, neuropathy-sparing regimen for primary therapy in patients with WM. This trial is registered at www.clinicaltrials.gov under ID NCT02400437. Clin Cancer Res; 24(14); 3247–52. ©2018 AACR.
πέφυκεν πλεονεκτεῖν? Plato and the Sophists on Greed and Savage Humanity
Authors: Balla Chloe 
Published: April 2018

Abstract
Fifth-century authors often invoke the idea that human beings are by nature savage, and that the civilized state of human societies is imposed on them by law and custom. A possible consequence of this idea is a pessimistic anthropological account, according to which pleonexia or greed is a natural characteristic of human beings, and therefore a justified drive of human behaviour. Scholars often attribute this pessimistic account of human nature to the sophists, whose views are considered to be reflected in the speeches of Plato’s characters Glaucon and Callicles. Taking into account the genres and the contexts in which the original sophistic arguments concerning savage humanity appear, as well as the practices for which such arguments were implemented, this paper argues that the pessimistc view of human nature is not a product of sophistic thought, but is rather developed by authors such as Thucydides, who uses it in order to explain the atrocities committed in the course of the Peloponnesian war, and Plato, who uses it as a foil to his arguments concerning the superiority of human nature.
Polybius’ Interpretation of Plato’s Arcadian Tale: Platonic Influences on Polybius’ Histories
Authors: Burghart William Devon 
Published: April 2018

Abstract
In his Histories, Polybius compares the descent of the rule of King Philip v of Macedon to tyranny to Plato’s description from the Republic of a man transforming into a werewolf. Such imagery is unique in classical Greek historiography, and exemplifies Polybius’ reliance on the idea of men acting like animals to describe when individuals or groups lose self-restraint, an idea found in Plato’s Republic. Plato uses θηριώδης to describe the ‘base desires’ of the soul that must be constrained by reason otherwise the individual will resort to crime or political revolution to satiate them. Polybius employs ἀποθηριόω in situations when individuals or groups lose part or all of their self-control, which results in self-destruction. The parallels in language and ideas indicate that Polybius’ idea of humans acting like animals derives from Plato. Recognizing this intellectual origin provides readers with a better understanding of the universal lessons of the Histories.
Al-Bīrūnī on Hermetic Forgery
Authors: van Bladel Kevin 
Published: April 2018

AbstractIn Central Asia in the early eleventh century, the Chorasmian scholar Abū Rayḥān al-Bīrūnī recognized that the Arabic works attributed to Hermes Trismegistus were inventions of recent centuries falsely written in the name of the ancient sage of legend. He did, however, accept the existence of a historical Hermes and even attempted to establish his chronology. This article presents al-Bīrūnī’s statements about this and contextualizes his view of the Arabic Hermetica as he derived it from Arabic chronographic sources. Al-Bīrūnī’s argument is compared with the celebrated seventeenth-century European criticism of the Greek Hermetica by Isaac Casaubon. It documents a hitherto unknown but significant event in the reception history of the Hermetica and helps to illustrate al-Bīrūnī’s attitude toward the history of science.
Early initiation of zoledronic acid does not impact bone healing or clinical outcomes of hallux valgus orthomorphia
Authors: Yang Lei , Yang Maowei 
Published: April 2018

Objective This prospective randomized controlled study was performed to determine whether early drug use for osteoporosis impacts bone healing after orthomorphic surgery for hallux valgus (HV) in menopausal patients with osteoporosis. Methods This study included 113 consecutive patients with osteoporosis who underwent a combination of Lapidus arthrodesis and Akin osteotomy for treatment of HV. The patients were randomly divided into a zoledronic acid (ZOL) group (5-mg intravenous injection of ZOL, n = 56) and a placebo group (n = 57); both ZOL and placebo were administered 1 week postoperatively. Radiographs were taken preoperatively and at 1, 6, 8, 10, and 12 weeks postoperatively to record the time of the first tarsometatarsal joint (FTJ) fusion and Akin osteotomy site healing. Clinical outcomes were evaluated using the American Orthopedic Foot and Ankle Society (AOFAS) scoring system 24 weeks after surgery. Results There were no statistically significant differences in the FTJ fusion time after Lapidus arthrodesis, healing time after Akin osteotomy, or postoperative AOFAS scores between the two groups. Conclusion Early initiation of ZOL does not impact the bone healing or clinical outcomes of orthomorphic surgery for HV in postmenopausal women diagnosed with osteoporosis after a combination of Lapidus arthrodesis and Akin osteotomy.
Therapy of cervical cancer using 131I-labeled nanoparticles
Authors: Li Wei , Sun Danyang , Li Ning , Shen Yiming , Hu Yiming , Tan Jian 
Published: April 2018

Objective To evaluate the effectiveness of two kinds of Arg-Gly-Asp (RGD)-targeted 131I-containing nanoliposomes for the treatment of cervical cancer in vitro and in vivo. Methods The nanoparticle liposomes designated RGD-131I-tyrosine peptide chain (TPC)-L and 131I-RGD-L were prepared. The emulsion solvent evaporation method was used to encapsulate the polypeptide into liposomes. The quantity of entrapped polypeptide was measured using UV spectrophotometry. The labeling rates, radiochemical purities, and total radioactivities were measured using paper chromatography. Cytotoxicity was assessed using the MTS assay and flow cytometry. Therapeutic efficacy was monitored using a mouse xenograft model of cervical cancer. Results The labeling efficiency, radiochemical purity, and specific radioactivity of RGD-131I-TPC-L were greater than those of 131I-RGD-L. The cytotoxicity test indicated that late apoptosis of cells treated with RGD-131I-TPC-L and 131I-RGD-L was higher than that of cells treated with Na131I. The therapeutic effect of RGD-131I-TPC-L was better than that of 31I-RGD-L in the mouse model. Conclusions The specific activity of liposome-encapsulated RGD-131I-TPC-L was higher than that of 131I-RGD-L, which labeled liposomes directly. Moreover, the RGD-131I-TPC-L liposomes were more effective for killing xenografted tumor cells.
Surgical Strategies in Colorectal Cancer Metastatic to the Liver
Authors: Bozzetti Federico , Bignami Paola , Baratti Dario 
Published: April 2018

Surgical resection remains a milestone in the treatment of colorectal metastases to the liver. There is a distinct subset of patients who benefit from surgical resection in terms of longer survival or definitive cure. The main effort of the surgical oncological regards the safety of the procedure and the adequacy of the recommendation. Many studies, some of them including multivariate analysis, have shown the presence of prognostic determinants of long-term survival and prognostic indexes of the outcome after hepatectomy. It is now accepted that liver resection should be done when the complete excision of all demonstrable tumor with clear resection margins is feasible. Major contra-indication is represented by the presence of extra-hepatic intra-abdominal disease or of unresectable lung metastatic deposits. There is a wide literature indicating that in very selected patients liver reresection and multiorgan synchronous or metachronous resections are beneficial. The role of neoadjuvant chemotherapy and especially postoperative adjuvant local (intra-hepatic) and systemic chemotherapy is promising and supported by recent multicenter randomised clinical trials.
Metastatic Renal Cell Carcinoma to the Head and Neck Area
Authors: Navarro Fátima , Vicente Javier , Villanueva Maria José , Sánchez Antonio , Provencio Mariano , España Pilar 
Published: April 2018

Aims and background Metastases of renal cell carcinoma to the head and neck are rare. We report on three cases with tumor spread to this area (nasal cavity, tongue and larynx) and present a review of the literature. Patients The first patient presented with lung and nasal cavity metastases five years after renal tumor resection. In patient 2 the diagnosis of primary renal carcinoma and lung and tongue metastases was concomitant. In case 3 a primary kidney tumor was not suspected until radical resection of a tongue lesion was performed. Results The first two patients received radiation therapy. They had been previously treated with interleukin + interferon and vinblastine + interleukin 2 and achieved a survival of 14 and 16 months, respectively. The third patient has not been given any treatment to date (apart from surgery) and remains asymptomatic four years after diagnosis. Conclusions In patients with cell carcinoma the occurrence of lesions in the head and neck area may suggest metastases. In some cases they may precede the diagnosis of a renal tumor and mimic a primary head and neck tumor; otolaryngologists should be aware of this possibility. An individualized treatment approach is recommended. In the case of solitary metastases a surgical excision should be performed as palliation, if not cure.
Evaluation of Cisplatin Combined with Ondansetron in Ehrlich Ascites Carcinoma in Vitro and in Vivo
Authors: Badary Osama Ahmed , Sharaby Sahar Moustafa , Kenawy Sanaa Abd El-Baky , El-Denshary Ezz El-Deen , Hamada Farid Mohamed Ahmed 
Published: April 2018

Aims and background Nausea and vomiting occur in the majority of patients receiving cisplatin (CDDP) chemotherapy. Ondansetron, a new 5-HT3 receptor antagonist, has been used effectively to control CDDP-induced nausea and vomiting. This study examined the potential of ondansetron to interfere with CDDP antitumor activity and toxicity in Ehrlich ascites carcinoma (EAC). Methods The influence of ondansetron on CDDP cytotoxicity was evaluated using EAC cells in culture. In addition, the influence of ondansetron pretreatment on CDDP-induced antitumor activity and host tissue toxicity was studied in EAC-bearing mice. Results Ondansetron (0.25 μM) enhanced CDDP (0–32 μM) cytotoxicity against EAC cells in vitro. In EAC-bearing mice ondansetron (0.2 mg/kg, ip) administered 1 h before CDDP (7 mg/kg, ip) did not modify the antitumor activity of CDDP. CDDP (7 mg/kg, ip) single treatment induced significant increases in blood urea nitrogen (2-fold) and serum creatinine (2.5-fold) and significant decreases in hematocrit (25%) and white blood cell count (39%) compared to saline treatment. Mice receiving ondansetron 1 h before CDDP showed no significant enhancement of CDDP-induced nephrotoxicity or myelosuppression compared to those pretreated with saline receiving the same dose of CDDP. Conclusions This study suggests that the use of ondansetron to control CDDP-induced nausea and vomiting does not affect CDDP antitumor efficacy.
Modulatory Effects of Melatonin and Vitamin E on Doxorubicin-Induced Cardiotoxicity in Ehrlich Ascites Carcinoma-Bearing Mice
Authors: Wahab Mohamed H. Abdel , Akoul El-Sayed E.M.S. , Abdel-Aziz Abdel-Aziz H. 
Published: April 2018

Doxorubicin (Dox), an anthracycline antibiotic, has a wide spectrum of antitumor activity with dose-limiting cardiotoxicity. The drug's toxicity is known to be closely related to the generation of active oxygen free radicals. In our study the normal cardiac tissue contents of total protein, glutathione (GSH) and malondialdehyde (MDA) were significantly decreased, by 25%, 33% and 92%, respectively, in the group of mice bearing Ehrlich ascites carcinoma (EAC) and treated with Dox (4 mg/kg/week x 2, ip). Administration of melatonin (5 mg/kg/day x 15, po) starting 24 hours prior to Dox treatment significantly increased the cardiac contents of total protein and GSH as well as the superoxide dismutase (SOD) activity, by 31%, 36% and 39%, respectively, compared to treatment with Dox only, while the content of MDA was decreased by 26%. Similarly, administration of vitamin E (250 mg/kg/day x 15, po) starting 24 hours prior to Dox treatment significantly increased the cardiac contents of total protein, GSH and SOD, by 23%, 26% and 42%, respectively, while the cardiac content of MDA was decreased by 35% compared with the Dox-only-treated group. As to the oncolytic activity of Dox, pretreatment of EAC-bearing mice with melatonin (5 mg/kg/day x 30, po) or vitamin E (250 mg/kg/day x 30, po) 24 hours prior to Dox administration (4 mg/kg/week x 4, ip) improved the antitumor activity of Dox as indicated by the increase in the average life span of the animals and the number of long-term survivors as well as the decrease in body weight loss induced by Dox treatment. It is clear from these results that administration of melatonin not only protects against the cardiotoxicity induced by Dox treatment but also enhances its antitumor activity to a more significant extent than does vitamin E.
Utility of Gallium-67 in Determining the Radicality of Lymph Node Dissections of the Neck for Metastatic Lymph Nodes with Extranodal Spread in Patients Affected by Carcinoma of the Head and Neck
Authors: Ricci Sante Basso , Chiti Arturo , Molinari Roberto , Borsa Giuseppe , Ricci Paolo Basso , Villa Sergio 
Published: April 2018

Aims and background Based on the fact that scintigraphy more readily reveals uptake of a radioisotope in a superficial position owing to incomplete surgical radicality, the authors examined by 67Ga scintigraphy a group of patients who had undergone dissection of lymph nodes of the neck from carcinoma with extranodal spread. They then checked the follow-up to ascertain the efficacy of 67Ga scintigraphy in relation to the eventual recurrences in the soft tissues of the neck. Methods A group of 136 patients were examined by 67Ga scintigraphy and followed for a minimum of 3 years after complementary radiotherapy. A group of 20 patients with no lymph node metastases was used as control to evaluate eventual false positives or false negatives. Results Recurrences in the soft tissues of the neck occurred in 35 (42.7%) of the 82 patients positive at 67Ga scintigraphy and in 6 (11.1%) of the 54 patients negative at the examination (P = 0.0001). All the patients in the control group were negative at 67Ga scintigraphy and without recurrences. Conclusions 67Ga scintigraphy can give reliable information on the risk of recurrences in the soft tissues of the neck. Since in spite of postoperative radiotherapy the percentage of local recurrences in cases with positive 67Ga scintigraphy was rather high (42.7%), the authors propose a scheme of radiotherapy based on administration of a higher dose per fraction on the scintigraphically positive area.
Different Sites and Modes of Tracer Injection for Mapping the Sentinel Lymph Node in Patients with Breast Cancer
Authors: Bianchi Pietro , Villa Giuseppe , Buffoni Ferdinando , Agnese Giuseppe , Gipponi Marco , Costa Rosario , Maragliano Cristina , Canavese Giuseppe , Mariani Giuliano 
Published: April 2018

Several studies have been published describing the techniques of identification of the “sentinel lymph node'’ (SN). There are marked differences in the techniques used by different investigators. Although agreement exists about the tracer particle size and the volume of injection, it is unknown what is the best site where to inject the tracer or the vital dye. The aim of the present study was to define the influence of different sites of injection on imaging of the lymphatic ducts and their SNs. We performed a pilot study in 30 consecutive patients with breast cancer who underwent SN biopsy by means of radioguided surgery and vital blue dye mapping. The patients were divided into six groups of five patients each; each patient was given a subdermal (ID) or peritumoral (IP) injection of radiotracer (300 μCi in 150 mL of 99mTc-HSA microcolloids; Albures, Amersham Sorin) above the tumor site in order to localize the SN. After the identification of the SN, a second injection of radiotracer was performed, which was different in each patient subset. In some cases more than one lymph node appeared on the lymphoscintigraphic scans after the second injection of radiotracer. When the peritumoral route was used it took longer to visualize the lymphatic pathways. For the ID route, injection at the exact skin projection over the tumor is optimal. Internal mammary lymph nodes were identified by both IP (2) and ID (1) injection, irrespective of the quadrant in which the tracer was injected. Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific SN. The subdermal route is more accurate than the intraparenchymal route, as it allows faster identification of the lymphatic vessels and SN. We believe these observations should be taken into account for the proper selection of the injection site of either vital dye or radiopharmaceuticals.
Soft Tissue Sarcomas in the General Population Living near a Chemical Plant in Northern Italy
Authors: Costani Gloria , Rabitti Paolo , Mambrini Adelmo , Bai Edoardo , Berrino Franco 
Published: April 2018

Background and objectives After the notification by a general practitioner of a high frequency of soft tissue sarcomas among subjects living close to the industrial area of the city of Mantua (northern Italy), the local Medical Association carried out a formal epidemiologic investigation to corroborate or falsify the hypothesized excess. Several industrial activities of the area were hypothesized to be a source of environmental pollution that might cause soft tissue sarcomas. Methods All general practitioners working in the area were requested to report the cases of soft tissue sarcoma diagnosed in the study area. Person-years of observation were computed for all subjects who ever resided in the area between 1984 and 1997. Expected incidence was computed from the cancer registry covering a nearby province (Varese) and from the pool of Italian cancer registries. Peripheral soft tissue sarcoma and visceral sarcomas were included in the analysis. Results and conclusions Overall, 20 cases were observed in a 13-year period, 8.87 were expected from the Varese province cancer registry and 7.72 from the pool of Italian registries. The corresponding standardized morbidity ratios were 2.25 (95% confidence interval, 1.34–3.47) and 2.6 (95% confidence interval, 1.6–4.0), respectively. A significant excess persisted after excluding 5 cases that had been the object of the original notification. We hypothesize that the soft tissue sarcoma excess may have resulted from environmental pollution by industrial toxic emissions, which likely included 2,3,7,8-tetra-chloro-dibenzo-dioxin.
Quality of Life in Patients with Early Stage Breast Carcinoma Treated with Conservation Surgery and Radiotherapy. An Italian Monoinstitutional Study
Authors: Amichetti Maurizio , Caffo Orazio 
Published: April 2018

Aims To evaluate the quality of life (QOL) in patients with early stage invasive carcinoma of the breast treated with conservative surgery and postoperative irradiation. Methods A mailed survey to examine QOL was conducted in 227 subjects with breast cancer treated in 1990 and 1994 with conservation surgery plus definitive irradiation. The self-compiled questionnaire was developed based on a series of 38 items assessing six core areas of QOL. Furthermore, the patients were requested to evaluate the degree of information provided by the medical staff concerning the disease, the treatment and related side effects and to evaluate the effects of the treatment on their social, overall QOL, and health status. Results The questionnaire was completed by 156 patients (68.7%) who had a median age of 56 years (range, 28–75 years) at the time of treatment and 59 years (range, 31–82 years) at the time of the study. The physical condition was reported to be good. Data relating to sexual life were provided by more than 90% of the patients. Some limitations in sexuality, some interference with sexual desire, and some modifications during intercourse were reported by 11, 11, and 10 patients, respectively. The subjective evaluations of the cosmetic results of the therapies were judged good-excellent by 56% of the patients, 12 (8%) only had a negative perception of their body image. Twenty-five percent of the sample declared that they felt tense, 19% nervous, 18% lonely, 27% anxious and 16% depressed. Only six patients (4%) declared that the treatment had had a bad on their social life, and 18 (11%) thought that their health status has been affected by the treatment. A worsening of QOL due to the disease or the treatment was reported by 8% of the responders. The amount of information received concerning the treatment and its side effects was considered sufficient by most of the patients. Conclusions The results of the study revealed a satisfactory health-related QOL in patients treated with breast conservation and postoperative irradiation. A preserved favorable body image and lack of a negative impact on sexuality was observed, even though about half of the patients reported a negative judgement on esthetic outcome. Some patients had persistent psychosocial concerns. No significant additional problems attributable to radiation therapy capable of affecting QOL outcomes were reported.