bluuebunny/crossref_metadata_2025_split huggingface dataset:
ABT-737 synergizes with Bortezomib to kill melanoma cells
Authors: Reuland Steven N. , Goldstein Nathaniel B. , Partyka Katie A. , Smith Shilo , Luo Yuchun , Fujita Mayumi , Gonzalez Rene , Lewis Karl , Norris David A. , Shellman Yiqun G. 
Published: December 2011

Summary
The BH3 mimetic ABT-737 is a potent inhibitor of the anti-apoptotic proteins Bcl-2, Bcl-XL, and Bcl-w. The Bcl-2 family modulates sensitivity to anticancer drugs in many cancers, including melanomas. In this study, we examined whether ABT-737 is effective in killing melanoma cells either alone or in combination with a proteasome inhibitor already in clinical use (Bortezomib) in vitro and in vivo, and further evaluated the mechanisms of action. Results showed that ABT-737 alone induced modest cytotoxicity in melanoma cells, but only at higher doses. Knock-down of the anti-apoptotic proteins Bcl-2, Bcl-XL, or Mcl-1 with siRNAs demonstrated that Mcl-1 is the critical mediator of melanoma's resistance to ABT-737 treatment. However, ABT-737 displayed strong synergistic lethality when combined with Bortezomib. Immunoblot analyses demonstrated that Bortezomib increased expression of Noxa, a pro-apoptotic Bcl-2 member that antagonizes Mcl-1. Additionally, siRNA-mediated inhibition of Noxa expression protected melanoma cells from cytotoxicity induced by the combination treatment. These results demonstrate that Bortezomib synergizes with ABT-737 by neutralizing Mcl-1's function via increased levels of Noxa. In a xenograft mouse model, although drug doses were limited due to toxicity, ABT-737 or Bortezomib slowed melanoma tumor growth compared to the control, and the drug combination significantly decreased growth compared to either drug alone. These data imply that less toxic drugs fulfilling a function similar to Bortezomib to neutralize Mcl-1 are promising candidates for combination with ABT-737 for treating melanomas.
Digital tomosynthesis for aortic arch calcification evaluation: performance comparison with chest radiography with CT as the reference standard
Authors: Kim Eun Young , Chung Myung Jin , Choe Yeon Hyeon , Lee Kyung Soo 
Published: December 2011

Background Recently developed digital tomosynthesis has shown improved detection of pulmonary lesions with a radiation dose comparable to conventional CR but with a much lower radiation dose than CT. Purpose To compare the diagnostic performance of digital tomosynthesis (DT) with that of chest radiography (CR) for the detection of aortic arch calcification (AAC). Material and Methods The study included 100 patients who underwent multidetector computed tomography (MDCT), DT, and CR (DT and CR were obtained within one week of CT examination). We evaluated and compared the diagnostic performances of DT and CR for the detection of AAC with MDCT as the reference standard. The extent (four grades 0–3) of AAC on DT and CR was also compared with CT calcium score. Inter-observer agreement was analyzed by using kappa statistics. Results On DT, overall accuracy for AAC was superior to that of CR (94% and 71%, respectively, P < 0.01). Inter-observer agreement was good with DT and CR (kappa values = 0.74 and 0.62, respectively) for the presence of AAC, and good with DT and moderate with CR (kappa value = 0.64 and 0.53, respectively) for AAC grading. The overall correlation coefficient on AAC grading between DT and CT (calcium score) was superior to that between CR and CT (0.90 and 0.60, respectively). Conclusion DT is superior to CR for detection and extent evaluation of AAC.
The contribution of strain patterns in characterization of prostate peripheral zone lesions at transrectal ultrasonography
Authors: Zhang Yan , Tang Jie , Li Yan-mi , Fei Xiang , He En-hui , Li Qiu-yang , Shi Huai-yin 
Published: December 2011

Background Elasticity is an important characteristic of tissue. During an elastography examination, various strain images of lesions are observed, and a suitable classification of strain patterns (SP) may provide vital diagnostic information about lesions. Numerous studies have shown that ultrasound elastography can improve the detection of prostate cancer, but the diagnostic value of SP classification has not yet been fully evaluated. Purpose To investigate the contribution of SP on the characterization of prostate peripheral zone lesions by transrectal real-time tissue elastography (TRTE) in combination with conventional transrectal ultrasonography (TRUS). Material and Methods One hundred and seventy-one patients with suspected prostate cancer underwent TRUS and TRTE examinations. The SPs of the suspicious lesions were classified into five scores by TRTE according to the degree and distribution of strain. All findings were confirmed by transrectal systematic 12-core biopsies and targeted biopsies for suspicious areas detecting by TRUS and/or TRTE. Results One hundred and forty-eight of 171 patients had high-quality TRTE imaging and were included into the study. When a cut-off point of SP score III was used, the area under the receiver-operating characteristic curve (AUC) was, respectively, 0.75 (95% CI: 0.67–0.83), 0.85 (95% CI: 0.78–0.91) and 0.84 (95% CI: 0.77–0.91) for the diagnosis of prostate cancer by TRUS, TRTE and TRTE + TRUS. A linear tendency of SP and Gleason scores was observed in scores III-V. The detection rate of prostate cancer using TRTE-targeted biopsy (75.8%) was significantly higher than that of systematic 12-core biopsy plus TRUS-targeted biopsy (14.5%) ( P = 0.00). Conclusion This study suggests the significant contribution of SP on characterization of prostate peripheral zone lesions and the improvement of TRTE-targeted biopsy on detection of prostate cancer.
Early return to work and improved range of motion with modified relative motion splinting: a retrospective comparison with immobilization splinting for zones V and VI extensor tendon repairs
Authors: Hirth Melissa J , Bennett Kate , Mah Eldon , Farrow Hamish C , Cavallo Andrew V , Ritz Morris , Findlay Michael W 
Published: December 2011

Introduction There is a lack of evidence on the best method for rehabilitating extensor tendon injuries in zones V and VI. The purpose of this study was to evaluate the outcomes of modified relative motion splinting compared with immobilization following repair of extensor tendons in zones V and VI. Methods A retrospective analysis compared the outcomes of relative motion splinting with immobilization. Sixteen patients (16 fingers) were treated by conventional immobilization splinting for four weeks (immobilization group) followed by mobilization with avoidance of ‘at-risk/heavy’ activities for a further 4–6 weeks. Twenty-three patients (23 fingers) were treated with the modified relative motion splint (mRMS group) during the day and a resting splint worn overnight for the first four weeks. The relative motion splint was continued for ‘at-risk/heavy’ activities for a further 4–6 weeks. Results The mRMS group demonstrated statistically significant improvement in range of motion compared with the immobilization group. This effect was most marked at six weeks ( P = 0.0194, two-way mixed ANOVA) with the mRMS group achieving a 12% higher mean percentage total active motion ( P = 0.0076, Mann-Whitney U test). Results were similar for both groups 12 weeks postoperatively. Differences in return to work times between groups were statistically significant ( P = 0.0062, Mann-Whitney U test). Average return to work was 9.4 weeks for the immobilization group and 3.3 weeks for the mRMS group, equating to a 42 days earlier return to work for the mRMS group. There was no incidence of tendon rupture in either group. Conclusion This study demonstrates that modified relative motion splintage (finger based without wrist component) can be applied in the postoperative management of single zone V or VI extensor tendon repairs. The main advantages of this protocol, compared with immobilization include the small simple splint design, and straightforward patient instructions that enable earlier mobilization, functional hand use and return to both daily living and work.
When to “Fire” Customers: Customer Cost-Based Pricing
Authors: Shin Jiwoong , Sudhir K. , Yoon Dae-Hee 
Published: December 2011

The widespread adoption of activity-based costing enables firms to allocate common service costs to each customer, allowing for precise measurement of both the cost to serve a particular customer and the customer's profitability. In this paper, we investigate how pricing strategies based on customer cost information affects a firm's customer acquisition and retention dynamics, and ultimately its profit, using a two-period monopoly model with high- and low-cost customer segments. Although past purchase and cost information helps firms to increase profits through differential prices for good and bad customers in the second period (“price discrimination effect”), it can hurt firms because strategic forward-looking consumers may delay purchases to avoid higher future prices (“ratchet effect”). We find that when the customer cost heterogeneity is sufficiently large, it is optimal for firms to “fire” some of its high-cost customers, and customer cost-based pricing is profitable. Surprisingly, it is optimal to fire even some profitable customers. This result is robust even when the cost to serve is endogenous and determined by the consumer's choice of service level. We also shed insight on acquisition–retention dynamics, on when firms can improve their profitability by selectively firing known old “bad” customers, and on replacing the old “bad” customers with a mix of new “good” and “bad” customers. This paper was accepted by J. Miguel Villas-Boas, marketing.
How Does the Variance of Product Ratings Matter?
Authors: Sun Monic 
Published: December 2011

This paper examines the informational role of product ratings. We build a theoretical model in which ratings can help consumers figure out how much they would enjoy the product. In our model, a high average rating indicates a high product quality, whereas a high variance of ratings is associated with a niche product, one that some consumers love and others hate. Based on its informational role, a higher variance would correspond to a higher subsequent demand if and only if the average rating is low. We find empirical evidence that is consistent with the theoretical predictions with book data from Amazon.com and BN.com. A higher standard deviation of ratings on Amazon improves a book's relative sales rank when the average rating is lower than 4.1 stars, which is true for 35% of all the books in our sample. This paper was accepted by Pradeep Chintagunta, marketing.
Modeling Purchasing Behavior with Sudden “Death”: A Flexible Customer Lifetime Model
Authors: Bemmaor Albert C. , Glady Nicolas 
Published: December 2011

This study proposes a new customer lifetime model: the gamma/Gompertz distribution (G/G). The advantage of this model relative to the well-known Pareto distribution is twofold: (i) its probability density function can exhibit a mode at zero or an interior mode, and (ii) it can be skewed to the right or to the left. We combine the G/G with a negative binomial distribution (NBD) and obtain the moments of the distribution of the number of transactions over (0, T] and (T, T+T*]. Out of six data sets, the G/G/NBD model provides a notable improvement in the log-likelihood over the Pareto/NBD model in four data sets. It can indicate substantial differences in expected residual lifetimes compared to the Pareto/NBD and induce a retention rather than acquisition policy. On the average, the G/G/NBD exhibits slightly better forecasts of the mean number of transactions than the Pareto/NBD. This paper was accepted by Pradeep Chintagunta, marketing.
Aristotele, Teopompo e la politica macedone
Authors: Occhipinti Egidia 
Published: December 2011

Riassunto
La presente indagine nasce dagli spunti di riflessione offerti dalla lettura di alcune opere aristoteliche (il De mirabilibus auscultationibus e l’Athenaion Politeia) e dei frammenti del decimo libro dei Philippika di Teopompo. Si fa strada – anche se con molta cautela – la possibilità di un uso dell’opera dello storico di Chio da parte del contemporaneo Aristotele. Inoltre, le relazioni stabilite da Aristotele e da Teopompo con l’entourage di Filippo gettano nuova luce sui rapporti greco-macedoni intorno alla metà del IV secolo.
Infatti, intorno alla fine degli anni ’40 la Persia si limitò ad aiutare segretamente alcuni politici ateniesi e permise ai satrapi d’Asia Minore di soccorrere Perinto assediata da Filippo, ma non intervenne mai esplicitamente contro la Macedonia. Non sono chiari i rapporti tra la Macedonia e Atarneo e non si conoscono le vere intenzioni di Filippo; è, tuttavia, verosimile che il re mirasse a stabilire rapporti di buon vicinato in Asia Minore e che si servisse per tale scopo di intermediari greci, quali appunto Teopompo e Aristotele, è, addirittura, possibile che il Macedone si fosse avvicinato ad Ermia, tiranno di Atarneo, per intercessione dello stesso Aristotele. In definitiva, al di là delle continue denunce di Demostene, in questi anni non ci furono le reali condizioni per un’eventuale spedizione di Filippo contro la Persia.
La maschera del vincitore. Strategie propagandistiche di Filippo II e Alessandro Magno nella distruzione di città greche
Authors: Squillace Giuseppe 
Published: December 2011

Riassunto
Filippo e Alessandro, direttamente attraverso le loro praxeis, indirettamente attraverso i logoi coniati dagli intellettuali che li sostenevano, cercarono di trovare una giustificazione plausibile e generalmente accettabile alle distruzioni di poleis. Sfruttando la religione essi si mostrarono come paladini della giustizia divina contro l’empietà, rievocando le tradizioni storiche, attualizzandole e manipolandole in funzione delle circostanze essi crearono una linea di continuità tra passato e presente e si presentarono come legittime guide dei Greci in nome dei quali avevano sconfitto l’empietà, l’ingiustizia, il tradimento.
L. Tarquinius magister equitum (458 a. C.)
Authors: Martínez-Pinna Jorge 
Published: December 2011

Resumen
El magister equitum nombrado por el dictador L. Quinctio Cincinato en el 458 a. C. figura con el nombre de L. Tarquinio en la tradición analística y con el de L. Tarquetio Flaco en los fasti consulares. Suponiendo que los Tarquinios habrían desaparecido de Roma tras la expulsión de los reyes, la mayor parte de los modernos se inclina por la segunda versión, lo cual no me parece satisfactorio. A partir del análisis del contexto histórico y de la relación entre los Tarquinios, los Quinctios y los Mamilios de Tusculum, este artículo pretende demostrar la veracidad de la versión tradicional.
Kein Aberglaube in Hispellum
Authors: Clauss Manfred 
Published: December 2011

Zusammenfassung
Das Reskript von Hispellum (CIL 11, 5265 = D 705) aus den letzten Regierungsjahren Konstantins ist immer wieder als Beweis für seine antiheidnische Politik herangezogen worden, weil man den Aberglauben (superstitio), den Konstantin untersagt, zu beliebig interpretierte. Der Begriff ist aber eher traditionell im Abgrenzung zu religio zu verstehen und die Inschrift ein Beweis für den fortbestehenden Kaiserkult unter Konstantin.
„Gottferne“ – Zur Marginalisierung der Giulleria im Mittelalter
Authors: Kotte Andreas 
Published: December 2011

Abstract
There were always allegations against travelling entertainers. They were held responsible for the downfall of morals as well as for the parishoners’ lack of attention in mass. Travelling jugglers ran the danger of being excommunicated and often they were not protected by the law. But how real were the dangers posed by jugglers in the middle ages? And were they offered any opportunity to integrate into wider society? Using theories current in theatre studies, this contribution seeks to demonstrate the nature of the threat posed by jugglers: namely that, in his use of body, voice and gesture, and in the captivation of his audience, the juggler threatened to rival the clergyman, and thus risked effacing the boundary between the sacred and the secular. This is why marginalisation was a deliberate process. It was not only church doctors and academics such as Hugo of Saint Victor who influenced the public treatment of travelling jugglers, but also popularizers of Christian ideas such as the monk Honorius Augustodunensis whose ‘Elucidarium’ proposed a social classification based on ‘proximity to God’.
Fragmente des Balsamierungsrituals in der Eremitage von St. Petersburg
Authors: Töpfer Susanne 
Published: December 2011

Zusammenfassung
13 fragments of the recto side of pap. Petersburg ДВ 18128 can be identified as belonging to the ‘Embalming Ritual’. The preserved remains of the papyrus conform exactly to the most extensive source pap. Boulaq 3. It is to be assumed that pap. St. Petersburg ДВ 18128 belongs to pap. Durham 1983.11.
Toxicity as a Biomarker of Efficacy of Molecular Targeted Therapies: Focus on EGFR and VEGF Inhibiting Anticancer Drugs
Authors: Dienstmann Rodrigo , Braña Irene , Rodon Jordi , Tabernero Josep 
Published: December 2011

Abstract
In addition to being present in tumor cells, many targets of signal transduction inhibitors are also found in normal tissue. Side effects attributable to the mechanism of action of molecular targeted agents thus represent “on-target” modulation in normal tissues. These mechanism-based toxicities can be pharmacodynamic effects of pathway inhibition and, in tumors depending on the inhibited pathway for proliferation, might be biomarkers of efficacy. The development of rash with tyrosine kinase inhibitors or monoclonal antibodies targeting the epidermal growth factor receptor is associated with superior outcomes in lung, head and neck, colorectal, and pancreatic cancer studies. Correlated with superior efficacy in retrospective analyses of large studies in advanced colorectal, breast, and renal cell carcinoma, arterial hypertension as an adverse event of antiangiogenic agents may also be a marker of effective target inhibition. An association between hypothyroidism and the activity of multitargeted tyrosine kinase inhibitors has been identified in renal cell carcinoma patients. Tumor growth addiction to the specific pathway that is effectively targeted may be the link between a mechanism-based toxicity and efficacy. The biological basis for this correlation can be pharmacological, with higher drug exposure being associated with greater toxicity and antitumor activity, and can also be genetic, because single nucleotide polymorphisms play an important role in drug pharmacokinetic and pharmacodynamic processes. Investigators have proposed that interpatient differences and associated toxicities can be exploited for dose selection and titration, and clinical trials are currently exploring intrapatient “dosing-to-toxicity” strategies. Ultimately, the predictive value of a side effect of molecular targeted therapies requires validation in prospective trials.
The Effect of Cigarette Smoking on Cancer Treatment–Related Side Effects
Authors: Peppone Luke J. , Mustian Karen M. , Morrow Gary R. , Dozier Ann M. , Ossip Deborah J. , Janelsins Michelle C. , Sprod Lisa K. , McIntosh Scott 
Published: December 2011

Abstract

Learning Objectives
After completing this course, the reader will be able to: Describe the influence of cigarette smoking on side effects during cancer treatment and following the end of cancer treatment.Identify areas in your practice in which smoking status can be assessed on a regular basis and devise a plan for disseminating cessation information and free cessation aids.
CME This article is available for continuing medical education credit at CME.TheOncologist.com

Background.
Cigarette smoking has long been implicated in cancer development and survival. However, few studies have investigated the impact of smoking on symptom burden in cancer survivors during treatment and at survivorship stage. This study examines the influence of cigarette smoking on side effects among 947 cancer patients during and 6 months following treatment.

Methods.
Patients diagnosed with cancer and scheduled to receive chemotherapy and/or radiation therapy reported on current smoking status (yes, no) and total symptom burden [the sum of 12 common symptoms (fatigue, hair loss, memory, nausea, depression, sleep, pain, concentration, hot flashes, weight loss, skin problems, and dyspnea) scored on an 11-point scale ranging from 0 = “not present” to 10 = “as bad as you can imagine”] during treatment and at 6-month follow-up. The adjusted mean total symptom burden by smoking status was determined by analysis of covariance controlling for age, gender, race, education, occupation, treatment, cancer site, and Karnofsky performance score.

Results.
During treatment, smokers (S) had a significantly higher total symptom burden than nonsmokers (NS) (S = 46.3 vs. NS = 41.2; p &lt; 0.05). At 6-month follow-up, smokers continued to report a higher total symptom burden than nonsmokers (S = 27.7 vs. NS = 21.9; p &lt; 0.05). Participants who quit smoking before treatment levels had a total symptom burden similar to nonsmokers.

Conclusion.
Smoking was associated with an increased symptom burden during and following treatments for cancer. Targeted cessation efforts for smokers to decrease symptom burden may limit the likelihood of treatment interruptions and increase quality of life following treatment.
Renal Phosphate Loss in Long-Term Kidney Transplantation
Authors: Sirilak Supinda , Chatsrisak Kamonwan , Ingsathit Atiporn , Kantachuvesiri Surasak , Sumethkul Vasant , Stitchantrakul Wasana , Radinahamed Piyanuch , Disthabanchong Sinee 
Published: December 2011

Summary

Background and objectives
Renal phosphate wasting occurs early postkidney transplantation as a result of an accumulation of parathyroid hormone and fibroblast growth factor 23 from the CKD period. Serum phosphate, parathyroid hormone, and fibroblast growth factor 23 return to baseline 1 year postkidney transplantation. What happens beyond this period is unknown.

Design, setting, participants, & measurements
Mineral parameters were obtained from 229 kidney transplant recipients at least 1 year posttransplantation; 46 normal subjects and 202 CKD patients with similar GFR served as controls. Factors associated with phosphate metabolism were analyzed.

Results
Despite the reduced graft function, most kidney transplant recipients had lower serum phosphate than normal subjects accompanied by renal phosphate loss. Fibroblast growth factor 23 was mostly lower or comparable with normal subjects, whereas parathyroid hormone was elevated in most patients. Hyperparathyroidism is also more common among kidney transplant recipients compared with CKD patients. Both parathyroid hormone and fibroblast growth factor 23 showed relationships with renal phosphate excretion, but only parathyroid hormone displayed an independent association. Parathyroid hormone showed the highest area under the curve in predicting renal phosphate leak. When patients were categorized according to parathyroid hormone and fibroblast growth factor 23 levels, only subset of patients with high parathyroid hormone had an increased renal phosphate excretion.

Conclusions
Relatively low serum phosphate from renal phosphate leak continued to present in long-term kidney transplantation. Both parathyroid hormone and fibroblast growth factor 23 participated in renal tubular phosphate handling, but persistent hyperparathyroidism seemed to have a greater influence in this setting.