bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circulating Tumor Cell Biomarker Panel As an Individual-Level Surrogate for Survival in Metastatic Castration-Resistant Prostate Cancer
Authors: Scher Howard I. , Heller Glenn , Molina Arturo , Attard Gerhardt , Danila Daniel C. , Jia Xiaoyu , Peng Weimin , Sandhu Shahneen K. , Olmos David , Riisnaes Ruth , McCormack Robert , Burzykowski Tomasz , Kheoh Thian , Fleisher Martin , Buyse Marc , de Bono Johann S. 
Published: March 2015

Purpose Trials in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrogates for survival. We evaluated circulating tumor cell (CTC) enumeration as a surrogate outcome measure. Patients and Methods Examining CTCs alone and in combination with other biomarkers as a surrogate for overall survival was a secondary objective of COU-AA-301, a multinational, randomized, double-blind phase III trial of abiraterone acetate plus prednisone versus prednisone alone in patients with metastatic CRPC previously treated with docetaxel. The biomarkers were measured at baseline and 4, 8, and 12 weeks, with 12 weeks being the primary measure of interest. The Prentice criteria were applied to test candidate biomarkers as surrogates for overall survival at the individual-patient level. Results A biomarker panel using CTC count and lactate dehydrogenase (LDH) level was shown to satisfy the four Prentice criteria for individual-level surrogacy. Twelve-week surrogate biomarker data were available for 711 patients. The abiraterone acetate plus prednisone and prednisone-alone groups demonstrated a significant survival difference (P = .034); surrogate distribution at 12 weeks differed by treatment (P < .001); the discriminatory power of the surrogate to predict mortality was high (weighted c-index, 0.81); and adding the surrogate to the model eliminated the treatment effect on survival. Overall, 2-year survival of patients with CTCs < 5 (low risk) versus patients with CTCs ≥ 5 cells/7.5 mL of blood and LDH > 250 U/L (high risk) at 12 weeks was 46% and 2%, respectively. Conclusion A biomarker panel containing CTC number and LDH level was shown to be a surrogate for survival at the individual-patient level in this trial of abiraterone acetate plus prednisone versus prednisone alone for patients with metastatic CRPC. Additional trials are ongoing to validate the findings.
Human Epidermal Growth Factor Receptor 2 (HER2) –Specific Chimeric Antigen Receptor–Modified T Cells for the Immunotherapy of HER2-Positive Sarcoma
Authors: Ahmed Nabil , Brawley Vita S. , Hegde Meenakshi , Robertson Catherine , Ghazi Alexia , Gerken Claudia , Liu Enli , Dakhova Olga , Ashoori Aidin , Corder Amanda , Gray Tara , Wu Meng-Fen , Liu Hao , Hicks John , Rainusso Nino , Dotti Gianpietro , Mei Zhuyong , Grilley Bambi , Gee Adrian , Rooney Cliona M. , Brenner Malcolm K. , Heslop Helen E. , Wels Winfried S. , Wang Lisa L. , Anderson Peter , Gottschalk Stephen 
Published: March 2015

PurposeThe outcome for patients with metastatic or recurrent sarcoma remains poor. Adoptive therapy with tumor-directed T cells is an attractive therapeutic option but has never been evaluated in sarcoma.Patients and MethodsWe conducted a phase I/II clinical study in which patients with recurrent/refractory human epidermal growth factor receptor 2 (HER2) –positive sarcoma received escalating doses (1 × 104/m2to 1 × 108/m2) of T cells expressing an HER2-specific chimeric antigen receptor with a CD28.ζ signaling domain (HER2-CAR T cells).ResultsWe enrolled 19 patients with HER2-positive tumors (16 osteosarcomas, one Ewing sarcoma, one primitive neuroectodermal tumor, and one desmoplastic small round cell tumor). HER2-CAR T-cell infusions were well tolerated with no dose-limiting toxicity. At dose level 3 (1 × 105/m2) and above, we detected HER2-CAR T cells 3 hours after infusion by quantitative polymerase chain reaction in 14 of 16 patients. HER2-CAR T cells persisted for at least 6 weeks in seven of the nine evaluable patients who received greater than 1 × 106/m2HER2-CAR T cells (P = .005). HER2-CAR T cells were detected at tumor sites of two of two patients examined. Of 17 evaluable patients, four had stable disease for 12 weeks to 14 months. Three of these patients had their tumor removed, with one showing ≥ 90% necrosis. The median overall survival of all 19 infused patients was 10.3 months (range, 5.1 to 29.1 months).ConclusionThis first evaluation of the safety and efficacy of HER2-CAR T cells in patients with cancer shows the cells can persist for 6 weeks without evident toxicities, setting the stage for studies that combine HER2-CAR T cells with other immunomodulatory approaches to enhance their expansion and persistence.
Survival, Durable Response, and Long-Term Safety in Patients With Previously Treated Advanced Renal Cell Carcinoma Receiving Nivolumab
Authors: McDermott David F. , Drake Charles G. , Sznol Mario , Choueiri Toni K. , Powderly John D. , Smith David C. , Brahmer Julie R. , Carvajal Richard D. , Hammers Hans J. , Puzanov Igor , Hodi F. Stephen , Kluger Harriet M. , Topalian Suzanne L. , Pardoll Drew M. , Wigginton Jon M. , Kollia Georgia D. , Gupta Ashok , McDonald Dan , Sankar Vindira , Sosman Jeffrey A. , Atkins Michael B. 
Published: March 2015

Purpose Blockade of the programmed death-1 inhibitory cell-surface molecule on immune cells using the fully human immunoglobulin G4 antibody nivolumab mediates tumor regression in a portion of patients with advanced treatment-refractory solid tumors. We report clinical activity, survival, and long-term safety in patients with advanced renal cell carcinoma (RCC) treated with nivolumab in a phase I study with expansion cohorts. Patients and Methods A total of 34 patients with previously treated advanced RCC, enrolled between 2008 and 2012, received intravenous nivolumab (1 or 10 mg/kg) in an outpatient setting once every two weeks for up to 96 weeks and were observed for survival and duration of response after treatment discontinuation. Results Ten patients (29%) achieved objective responses (according to RECIST [version 1.0]), with median response duration of 12.9 months; nine additional patients (27%) demonstrated stable disease lasting > 24 weeks. Three of five patients who stopped treatment while in response continued to respond for ≥ 45 weeks. Median overall survival in all patients (71% with two to five prior systemic therapies) was 22.4 months; 1-, 2-, and 3-year survival rates were 71%, 48%, and 44%, respectively. Grade 3 to 4 treatment-related adverse events occurred in 18% of patients; all were reversible. Conclusion Patients with advanced treatment-refractory RCC treated with nivolumab demonstrated durable responses that in some responders persisted after drug discontinuation. Overall survival is encouraging, and toxicities were generally manageable. Ongoing randomized clinical trials will further assess the impact of nivolumab on overall survival in patients with advanced RCC.
Early Versus Delayed Initiation of Concurrent Palliative Oncology Care: Patient Outcomes in the ENABLE III Randomized Controlled Trial
Authors: Bakitas Marie A. , Tosteson Tor D. , Li Zhigang , Lyons Kathleen D. , Hull Jay G. , Li Zhongze , Dionne-Odom J. Nicholas , Frost Jennifer , Dragnev Konstantin H. , Hegel Mark T. , Azuero Andres , Ahles Tim A. 
Published: March 2015

Purpose Randomized controlled trials have supported integrated oncology and palliative care (PC); however, optimal timing has not been evaluated. We investigated the effect of early versus delayed PC on quality of life (QOL), symptom impact, mood, 1-year survival, and resource use. Patients and Methods Between October 2010 and March 2013, 207 patients with advanced cancer at a National Cancer Institute cancer center, a Veterans Affairs Medical Center, and community outreach clinics were randomly assigned to receive an in-person PC consultation, structured PC telehealth nurse coaching sessions (once per week for six sessions), and monthly follow-up either early after enrollment or 3 months later. Outcomes were QOL, symptom impact, mood, 1-year survival, and resource use (hospital/intensive care unit days, emergency room visits, chemotherapy in last 14 days, and death location). Results Overall patient-reported outcomes were not statistically significant after enrollment (QOL, P = .34; symptom impact, P = .09; mood, P = .33) or before death (QOL, P = .73; symptom impact, P = .30; mood, P = .82). Kaplan-Meier 1-year survival rates were 63% in the early group and 48% in the delayed group (difference, 15%; P = .038). Relative rates of early to delayed decedents' resource use were similar for hospital days (0.73; 95% CI, 0.41 to 1.27; P = .26), intensive care unit days (0.68; 95% CI, 0.23 to 2.02; P = .49), emergency room visits (0.73; 95% CI, 0.45 to 1.19; P = .21), chemotherapy in last 14 days (1.57; 95% CI, 0.37 to 6.7; P = .27), and home death (27 [54%] v 28 [47%]; P = .60). Conclusion Early-entry participants' patient-reported outcomes and resource use were not statistically different; however, their survival 1-year after enrollment was improved compared with those who began 3 months later. Understanding the complex mechanisms whereby PC may improve survival remains an important research priority.
Benefits of Early Versus Delayed Palliative Care to Informal Family Caregivers of Patients With Advanced Cancer: Outcomes From the ENABLE III Randomized Controlled Trial
Authors: Dionne-Odom J. Nicholas , Azuero Andres , Lyons Kathleen D. , Hull Jay G. , Tosteson Tor , Li Zhigang , Li Zhongze , Frost Jennifer , Dragnev Konstantin H. , Akyar Imatullah , Hegel Mark T. , Bakitas Marie A. 
Published: March 2015

Purpose To determine the effect of early versus delayed initiation of a palliative care intervention for family caregivers (CGs) of patients with advanced cancer. Patients and Methods Between October 2010 and March 2013, CGs of patients with advanced cancer were randomly assigned to receive three structured weekly telephone coaching sessions, monthly follow-up, and a bereavement call either early after enrollment or 3 months later. CGs of patients with advanced cancer were recruited from a National Cancer Institute cancer center, a Veterans Administration Medical Center, and two community outreach clinics. Outcomes were quality of life (QOL), depression, and burden (objective, stress, and demand). Results A total of 122 CGs (early, n = 61; delayed, n = 61) of 207 patients participated; average age was 60 years, and most were female (78.7%) and white (92.6%). Between-group differences in depression scores from enrollment to 3 months (before delayed group started intervention) favored the early group (mean difference, −3.4; SE, 1.5; d = −.32; P = .02). There were no differences in QOL (mean difference, −2; SE, 2.3; d = −.13; P = .39) or burden (objective: mean difference, 0.3; SE, .7; d = .09; P = .64; stress: mean difference, −.5; SE, .5; d = −.2; P = .29; demand: mean difference, 0; SE, .7; d = −.01; P = .97). In decedents' CGs, a terminal decline analysis indicated between-group differences favoring the early group for depression (mean difference, −3.8; SE, 1.5; d = −.39; P = .02) and stress burden (mean difference, −1.1; SE, .4; d = −.44; P = .01) but not for QOL (mean difference, −4.9; SE, 2.6; d = −.3; P = .07), objective burden (mean difference, −.6; SE, .6; d = −.18; P = .27), or demand burden (mean difference, −.7; SE, .6; d = −.23; P = .22). Conclusion Early-group CGs had lower depression scores at 3 months and lower depression and stress burden in the terminal decline analysis. Palliative care for CGs should be initiated as early as possible to maximize benefits.
The Supply Chain Effects of Bankruptcy
Authors: Yang S. Alex , Birge John R. , Parker Rodney P. 
Published: March 2015

This paper examines how a firm’s financial distress and the legal environment regarding the ease of bankruptcy reorganization can alter product market competition and supplier–buyer relationships. We identify three effects—predation, bail-out, and abetment—that can change firms’ behavior from their actions in the absence of financial distress. The predation effect increases competition before potential bankruptcy as the nondistressed competitor behaves as if it has some first-mover advantage that could benefit a supplier with price control. The bail-out effect reflects the supplier’s incentive to grant the distressed firm concessions to preserve competition, improving supply chain efficiency and providing support for the exclusivity rule in Chapter 11 of the United States Bankruptcy Code when the supplier and the distressed firm are financially linked. The abetment effect is that the supplier may deliberately abet the competitor’s predation, leading to increased operational disadvantages for the distressed firm before bankruptcy. Together these effects stress that a firm’s bankruptcy potential can hurt its competitors and benefit its suppliers/customers. They also provide guidelines for firms’ operational decisions in such situations, a rationale for observed firm actions surrounding bankruptcies, and motivation for policies supporting reorganization and relaxing broad enforcement of nondiscriminatory pricing regulations. This paper was accepted by Serguei Netessine, operations management.
Violence in Illicit Markets: Unintended Consequences and the Search for Paradoxical Effects of Enforcement
Authors: Prieger James E. , Kulick Jonathan 
Published: March 2015

Abstract
The textbook competitive model of drug markets predicts that greater law enforcement leads to higher black market prices, but also to the unintended consequences of greater revenue and violence. These predictions are not in accord with the paradoxical outcomes evinced by recent history in some drug markets, where enforcement rose even as prices fell. We show that predictions of the textbook model are not unequivocal, and that when bandwagon effects among scofflaws are introduced, the simple predictions are more likely to be reversed. We next show that even simple models of noncompetitive black markets can elicit paradoxical outcomes. Therefore, we argue that instead of searching for assumptions that lead to paradoxical outcomes, which is the direction the literature has taken, it is better for policy analysis to choose appropriate assumptions for the textbook model. We finish with performing such an analysis for the case of banning menthol cigarettes. Under the most plausible assumptions enforcement will indeed spur violence, although the legal availability of electronic cigarettes may mitigate or reverse this conclusion.
The contribution of methionine to the stability of the Escherichia coli MetNIQ ABC transporter-substrate binding protein complex
Authors: Nguyen Phong T. , Li Qi Wen , Kadaba Neena S. , Lai Jeffrey Y. , Yang Janet G. , Rees Douglas C. 
Published: March 2015

Abstract
Despite the ubiquitous role of ATP-binding cassette (ABC) importers in nutrient uptake, only the Escherichia coli maltose and vitamin B12 ABC transporters have been structurally characterized in multiple conformations relevant to the alternating access transport mechanism. To complement our previous structure determination of the E. coli MetNI methionine importer in the inward facing conformation (Kadaba et al. (2008) Science 321, 250–253), we have explored conditions stabilizing the outward facing conformation. Using two variants, the Walker B E166Q mutation with ATP+EDTA to stabilize MetNI in the ATP-bound conformation and the N229A variant of the binding protein MetQ, shown in this work to disrupt methionine binding, a high affinity MetNIQ complex was formed with a dissociation constant measured to be 27 nm. Using wild type MetQ containing a co-purified methionine (for which the crystal structure is reported at 1.6 Å resolution), the dissociation constant for complex formation with MetNI is measured to be ∼40-fold weaker, indicating that complex formation lowers the affinity of MetQ for methionine by this amount. Preparation of a stable MetNIQ complex is an essential step towards the crystallographic analysis of the outward facing conformation, a key intermediate in the uptake of methionine by this transport system.
Co-optimization of Energy and Demand-Side Reserves in Day-Ahead Electricity Markets
Authors: Surender Reddy S. , Abhyankar A. R. , Bijwe P. R. 
Published: March 2015

Abstract
This paper presents a new multi-objective day-ahead market clearing (DAMC) mechanism with demand-side reserves/demand response (DR) offers, considering realistic voltage-dependent load modeling. The paper proposes objectives such as social welfare maximization (SWM) including demand-side reserves, and load served error (LSE) minimization. In this paper, energy and demand-side reserves are cleared simultaneously through co-optimization process. The paper clearly brings out the unsuitability of conventional SWM for DAMC in the presence of voltage-dependent loads, due to reduction of load served (LS). Under such circumstances multi-objective DAMC with DR offers is essential. Multi-objective Strength Pareto Evolutionary Algorithm 2+ (SPEA 2+) has been used to solve the optimization problem. The effectiveness of the proposed scheme is confirmed with results obtained from IEEE 30 bus system.
Multipurpose Power Converter for Non-Grid-Connected Microsystems
Authors: Vovos Panagis N. , Georgakas Konstantinos G. 
Published: March 2015

Abstract
The aim of this paper is to present a multipurpose converter, appropriate for non-grid-connected microsystems, which are prone to harmonic distortion. The converter suppresses harmonics by injecting mirror harmonics in the modulation stage. An important property is that it continuously monitors and significantly reduces the harmonic content without the use of active or passive low-frequency filters. This is under constant switching frequency, no matter if the harmonics are mainly created by the source, the loads or even its own operation. The converter is regulating output voltage using typical fuzzy control. The two types of control (harmonic and voltage) do not seem to affect each other during operation. Furthermore, it can supply either dc or ac loads from a dc source. The versatility of the converter is a useful property for remote or mobile micropower systems, where neither sources nor loads are of a single type. The converter has been tested successfully for a combination of harmonic-injecting electric appliances and various load step changes.
How effective is ultrasound-based screening for trisomy 18 without the addition of biochemistry at the time of late first trimester?
Authors: Wiechec Marcin , Knafel Anna , Nocun Agnieszka , Matyszkiewicz Anna , Wiercinska Ewa , Latała Emilia 
Published: March 2015

AbstractTrisomy 18 (T18) remains the second most common aneuploidy. It is associated with multiple congenital anomalies and causes intrauterine fetal demise in the most severe cases.To examine the screening performance of ultrasound-based protocols for detecting T18, we aimed to determine the most common signs and their prevalence in fetuses with T18 to develop logistic regression model.This was a prospective study based on singleton pregnancies examined at gestation 11+0 to 13+6. The referrals constituted 6210 patients. Scan protocol enclosed a systematic review of the entire early fetal anatomy, including fetal cardiac evaluation and sonographic signs of aneuploidy.Our study population comprised 5650 pregnancies: 5613 cases with a normal karyotype and 37 cases with T18. The mean nuchal translucency (NT) thickness in the subgroup of euploidy was 1.7 and in the subgroup of T18 it was 5.4. No statistically significant differences were found in terms of maternal age. One case of T18 (2.7%) demonstrated no markers of aneuploidy as opposed to 5111 cases of euploidy (91.1%). Extracardiac malformations were identified in 13 cases of T18 (35.1%) and in 48 cases of euploidy (0.8%). Congenital heart defects were observed in 26 cases of T18 (70.3%) and in 27 cases of euploidy (0.5%).Our results showed good screening performance of ultrasound-based risk calculation models. When the first trimester pattern of T18 is considered, an increased NT, tricuspid regurgitation, single umbilical artery, omphalocele and right dominant heart should be specifically searched for.
Qualitätssicherung der Analytik von Wachstumshormon und Insulin-Like Growth Factor I bei Erkrankungen der somatotropen Achse
Authors: Bidlingmaier Martin , Hauffa Berthold P. , Trainer Peter J. , Etzrodt-Walter Gwendolin , Sauer Joachim , Kratzsch Jürgen , Petersenn Stephan , Ranke Michael B. , Wallaschofski Henri , Strasburger Christian J. 
Published: March 2015

Zusammenfassung

Hintergrund: Eine zuverlässige Laboranalytik bildet einen Grundpfeiler für die Diagnostik, Therapie und Verlaufskontrolle von Wachstumsstörungen und Störungen der Sekretion von Wachstumshormon (GH) und Insulin-Like Growth Factor I (IGF-I). Die gegenwärtig verfügbaren kommerziellen Assays weisen jedoch Defizite auf, die zu großen Unterschieden der gemessenen Hormonkonzentrationen führen.

Methode: Empfehlungen eines Expertenworkshops mit klinisch tätigen Endokrinologen aus Pädiatrie und Innerer Medizin sowie mit Labormedizinern unter Bezugnahme auf die Ergebnisse der interdisziplinären Konsensus-Konferenz in Keswick (Virginia, USA) aus dem Jahr 2009.

Ergebnisse: Zu den von den Workshopteilnehmern geforderten Qualitätskriterien für GH- und IGF-I-Assays zählen die Verwendung einheitlicher Referenzstandards, die Dokumentation der analytischen Bedingungen – unter anderem in Bezug auf Kalibratoren, Bindungsepitope, Kreuzreaktivität und Methoden zur Trennung von Bindungsproteinen –, die Chargenkonstanz und eine geringe Interassay-Variabilität. Die Teilnehmer empfehlen, Grenzwerte und Referenzintervalle assayspezifisch unter Verwendung großer und gut charakterisierter Referenzpopulationen zu erarbeiten und die Assayqualität insbesondere im Bereich klinisch wichtiger Entscheidungsgrenzen zu beschreiben.

Schlussfolgerungen: Diagnostikahersteller sollten verpflichtet werden, die Umsetzung der Qualitätskriterien regelmäßig zu überwachen und darüber Bericht zu erstatten. Nur Assays, die nach einheitlichen Qualitätsstandards evaluiert sind und im klinischen Kontext eingesetzt werden, erlauben eine rational begründete Diagnostik und Therapie von Patienten mit Störungen der GH-Sekretion und vermeiden unnötige Belastungen der Patienten und Kostenträger.
Soret and Dufour Effects in the Flow of Williamson Fluid over an Unsteady Stretching Surface with Thermal Radiation
Authors: Hayat Tasawar , Saeed Yusra , Asad Sadia , Alsaedi Ahmed 
Published: March 2015

Abstract
This paper looks at the simultaneous effects of heat and mass transfer in the flow of Williamson fluid over an unsteady stretching surface. The effects of thermal radiation and viscous dissipation are considered in an energy equation. Besides, the energy and concentration equations are coupled with the combined effects of Soret and Dufour. The convective conditions for both temperature and mass concentration are employed. The transformation procedure reduces the time-dependent boundary layer equations of momentum, energy, and concentration to the non-linear ordinary differential equations. Through graphs and numerical values, the velocity, temperature, and concentration fields are discussed for different physical parameters. It is found that the thermal and concentration Biot numbers have an increasing impact on both temperature and concentration fields, respectively.