bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cabozantinib (CABO) plus durvalumab (DURVA) in patients with advanced and chemotherapy-treated bladder carcinoma of urothelial and non-urothelial histology: An open-label, single-arm, phase 2 trial.
Authors: Necchi Andrea , Giannatempo Patrizia , Raggi Daniele , Anichini Andrea , Calareso Giuseppina , Crippa Flavio , Mariani Luigi 
Published: February 2018

TPS536 Background: DURVA and CABO have shown single-agent activity in patients (pts) with urothelial carcinoma (UC). Their combination may result in prolonging overall survival (OS) in pts who have failed prior platinum-based chemotherapy (CT). Additionally, DURVA+CABO may be an effective combination for treating subgroup of pts like those with bone metastases only (not having RECIST-measurable disease) or with non-UC histology. Methods: In an open-label, single-arm, multicenter, phase 2 trial, pts will assume CABO 40 mg daily, orally, and will be administered DURVA 1500 mg, intravenously, q28 days, until disease progression (PD, RECIST 1.1) or onset of unacceptable toxicity. Treatment beyond PD is not allowed. Key inclusion criteria: ECOG-PS 0-1, bladder or upper tract primary tumor, UC and non-UC histology, failure of 1 or 2 platinum-based CT for metastatic disease (2nd-to-3rd line only). Neoadjuvant/adjuvant CT is counted if relapse occurred ≤6 months (m) of the last CT cycle. Response is evaluated by RECIST criteria v.1.1 q2 cycles. The primary endpoint of the study is OS. The target is to detect an improvement in median OS from ≤6m (H0) to ≥9m(H1). To achieve 90% power with a one-sided non-parametric test at 5% significance, 122 pts must will be accrued over 36m and follow-up may be closed 12m after the end of accrual. PD-L1 expression will be assessed using with the Ventana SP142 assay, and categorized as high (≥25% of tumor cells [TC] or immune cells [IC]) or low/negative ( < 25% TC or IC). The decision on whether or not to undertake PD-L1+ cohort expansion will be based on predictive power (PP) calculation: a PP ≥30% will be regarded as promising and necessary to continue. An interim analysis is planned after 24m (50% expected events). This analysis will be based on PP. The criterion for stopping the trial because of futility will be a PP < 20%. Analyses on tissue/blood samples will include immune-cell profiling, cytokine assessment, gene expression analyses and next-generation sequencing (FoundationOne). FDG-PET response in bone metastases will represent another translational endpoint (EudraCT number 2017-000580-32). Clinical trial information: 2017-000580-32.
A phase 3, open-label, randomized study of nivolumab plus ipilimumab or standard of care (SOC) versus SOC alone in patients (pts) with previously untreated unresectable or metastatic urothelial carcinoma (mUC; CheckMate 901).
Authors: Galsky Matt D. , Powles Thomas , Li Shengting , Hennicken Delphine , Sonpavde Guru 
Published: February 2018

TPS539 Background: Cisplatin-containing regimens have been SOC for mUC for nearly 40 years, but durable responses are rare with such treatments. Furthermore, a large proportion of pts with unresectable/mUC are ineligible for cisplatin therapy. Treatment approaches conferring longer-term disease control and extending to broader mUC pt populations are urgently needed. Recently, the programmed death-1 (PD-1) inhibitor, nivolumab, induced durable responses in pts with unresectable/mUC progressing despite platinum-based chemotherapy, and nivolumab combined with ipilimumab (a CTLA-4 inhibitor) demonstrated acceptable safety and clinical activity. This phase 3 study will evaluate nivolumab + ipilimumab and nivolumab + SOC vs SOC in previously untreated pts with unresectable/mUC (NCT03036098). Methods: Key inclusion criteria: cisplatin-eligible and -ineligible pts with measurable disease, no prior systemic chemotherapy for unresectable/mUC, and evaluable tumor biopsy. Key exclusion criteria: active brain metastases, autoimmune disease, and prior treatment with drugs specifically targeting T-cell co-stimulation or checkpoint pathways. Cisplatin-eligible and -ineligible pts will be randomized 1:1 to arm A (nivolumab 1 mg/kg + ipilimumab 3 mg/kg every 3 weeks up to 4 doses, followed by nivolumab 480 mg every 4 weeks until disease progression or unacceptable toxicity) or arm B (gemcitabine-cisplatin or gemcitabine-carboplatin for up to 6 cycles). Additional cisplatin-eligible pts will be randomized to arm C (nivolumab 360 mg + gemcitabine-cisplatin every 3 weeks for up to 6 cycles, followed by nivolumab 480 mg) or arm D (gemcitabine-cisplatin for up to 6 cycles). Stratification factors: PD-1 ligand 1 status, cisplatin eligibility, and liver metastasis. Co-primary endpoints: overall and progression-free survival (OS and PFS) by blinded independent review committee (BIRC) in cisplatin-ineligible pts receiving nivolumab + ipilimumab vs SOC, and PFS by BIRC in cisplatin-eligible pts receiving nivolumab + SOC vs SOC. Enrollment began March 2017 with a target of 897 pts. Clinical trial information: NCT03036098.
A phase 3 trial to compare efficacy and safety of lenvatinib in combination with everolimus or pembrolizumab versus sunitinib alone in first-line treatment of patients with metastatic renal cell carcinoma.
Authors: Motzer Robert J. , Grünwald Viktor , Hutson Thomas E. , Porta Camillo , Powles Thomas , Eto Masatoshi , Dutcus Corina E. , Baig Mahadi Ali , Dutta Lea , Li Di , Choueiri Toni K. 
Published: February 2018

TPS706 Background: Lenvatinib (LEN) is a multikinase inhibitor of vascular endothelial growth factor (VEGF) receptor 1–3, fibroblast growth factor receptor 1–4, platelet-derived growth factor receptor alpha, and RET and KIT. Based on a phase 2 study (Motzer et al. Lancet Oncol. 2015), LEN was approved in combination with everolimus (EVE) for the treatment of metastatic renal cell carcinoma (RCC) following 1 prior VEGF-targeted therapy. A phase 1b/2 study of LEN in combination with pembrolizumab (PEM) in patients (pts) with RCC LEN is also underway. We report the design of a multicenter, open-label, phase 3 trial of LEN plus EVE or PEM vs sunitinib (SUN; a standard therapy for RCC) as first-line treatment for advanced RCC. Methods: Pts aged ≥ 18 years with confirmed advanced RCC diagnosis, ≥ 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Karnofsky Performance Status ≥ 70, controlled blood pressure, and adequate blood coagulation, renal, hepatic, and bone marrow function are eligible. Pts will be randomized 1:1:1 to receive LEN 18 mg/d + EVE 5 mg/d, LEN 20 mg/d + PEM 200 mg every 3 wks, or SUN 50 mg/d (on a schedule of 4 wks on treatment followed by 2 wks off) until disease progression, unacceptable toxicity, withdrawal of consent, or study end. The primary endpoint is to show superiority of LEN+EVE or LEN+PEM over single-agent SUN as first-line treatment for advanced RCC in improving progression-free survival (PFS). Secondary endpoints include comparison of objective response rate, overall survival, PFS on next-line therapy, health-related quality of life, and safety and tolerability in pts receiving LEN+EVE or LEN+PEM vs SUN. Exploratory endpoints include PFS in the LEN+PEM arm using immune-related RECIST, comparison of duration of response, disease control rate, and clinical benefit rate in pts treated with LEN+EVE or LEN+PEM vs SUN, and analysis of the relationship between blood biomarkers and outcome. No interim analysis is planned for efficacy or futility. Enrollment of 735 pts is planned to achieve 90% power at 2-sided α = 0.05 to detect a difference in ≥ 1 of the primary comparisons. Clinical trial information: NCT02811861.
A phase III randomized study comparing perioperative nivolumab vs. observation in patients with localized renal cell carcinoma undergoing nephrectomy (PROSPER RCC).
Authors: Harshman Lauren Christine , Puligandla Maneka , Haas Naomi B. , Allaf Mohamad , Drake Charles G. , McDermott David F. , Signoretti Sabina , Cella David , Gupta Rajan T , Bhatt Rupal Satish , Van Allen Eliezer Mendel , Choueiri Toni K. , Lara Primo , Kapoor Anil , Heng Daniel Yick Chin , Shuch Brian M. , Jewett Michael A.S. , George Daniel J. , Michaelson M. Dror , Carducci Michael Anthony ,   On Behalf of the EA8143 PROSPER RCC Investigators
Published: February 2018

TPS710 Background: The anti-PD-1 antibody nivolumab (nivo) improves overall survival (OS) in metastatic treatment refractory RCC and is generally tolerable. In 2017, there is no standard adjuvant therapy proven to increase OS over surgery alone in non-metastatic (M0) disease. Mouse solid tumor models have revealed an OS benefit with a short course of neoadjuvant PD-1 blockade compared to adjuvant therapy. Two ongoing phase 2 studies of perioperative nivo in RCC patients (pts) are showing preliminary feasibility and safety with no surgical delays/complications. PROSPER RCC will examine if the addition of perioperative nivo to radical or partial nephrectomy can improve clinical outcomes in pts with locally advanced RCC. We are implementing a three-pronged, multidisciplinary approach of presurgical priming with nivo followed by resection and adjuvant PD-1 blockade with the goal of increasing cure and recurrence-free survival (RFS) rates in M0 RCC. Methods: Tumor biopsy prior to randomization is mandatory to ensure RCC diagnosis but will also permit unparalleled correlative science in this global, unblinded, phase 3 National Clinical Trials Network randomized study. 766 pts with clinical stage ≥T2 or any node positive M0 RCC of any histology will be enrolled. The study arm will receive nivo 240mg IV for 2 doses prior to surgery followed by adjuvant dosing for 9 mo (q2 wks x 3 mo followed by q4 wks x 6 mo). The control arm will undergo the current standard of care: surgical resection followed by observation. Pts are stratified by clinical T stage, node positivity, and histology. There is 84.2% power to detect a 14.4% absolute increase in the primary endpoint of RFS from the ASSURE historical control of 55.8% to 70.2% at 5 yrs (HR 0.70). The study is also powered to detect a significant OS benefit (HR 0.67). Safety, feasibility, and quality of life are key secondary endpoints. PROSPER RCC exemplifies team science and incorporates a host of correlative work to examine the significance of the baseline immune milieu and changes induced by neoadjuvant priming and to identify predictive gene expression patterns. New collaborations welcomed. Clinical trial information: NCT03055013.
Η εικονολογία του Θανάτου: μια αντιπαραβολή
Authors: Ρασιδάκη Αλεξάνδρα 
Published: February 2018

Η παρούσα συγκριτολογική μελέτη προσπαθεί να συσχετίσει την μακάβρια παράδοση του δυτικού μεσαίωνα με την προσωποποίηση του θανάτου στα ελληνικά δημοτικά μοιρολόγια.Το πρώτο μέρος του άρθρου παρακολουθεί την εξέλιξη της σύλληψης του θανάτου κατά τον ευρωπαϊκό μεσαίωνα εστιάζοντας στην προσωποποίησή του ως αυτόνομης, βίαιης και ύπουλης μορφής και τους τρόπους αναπαράστασής αυτού. Ειδικότερα παρουσιάζονται, με τη βοήθεια κειμενικών και εικονικών παραδειγμάτων, τα νοερά σχήματα του «Θριάμβου του θανάτου» και του «Χορού των νεκρών» τα οποία χαρακτηρίζουν την λεγόμενη μακάβρια περίοδο του υψηλού και ύστερου μεσαίωνα και εκφράζουν την οικειότητα του ανθρώπου της εποχής εκείνης προς την ιδέα του θανάτου.Η υπόθεση εργασίας στην μελέτη αυτή είναι ότι μια ανάλογη οικειότητα εκφράζεται και στην ελληνική δημοτική παράδοση και ειδικότερα στα τόσο εντυπωσιακά τραγούδια του θανάτου, τα μοιρολόγια. Το δεύτερο μέρος επικεντρώνεται στα ελληνικά μοιρολόγια και ειδικότερα στα «μοιρολόγια του Χάρου» και στα «μοιρολόγια του κάτω κόσμου», καθώς αυτά κυρίως, πέρα από έκφραση θλίψης και πένθους, λειτουργούν ως θεματοποιηση του αναπόφευκτου της ανθρώπινης μοίρας, ως αναστοχασμός πάνω στο θέμα του θανάτου. Παρουσιάζονται τα βασικά μοτίβα των μοιρολογιών αυτών και αντιπαραβάλλονται με την δυτική εικονολογία περί θανάτου. Ειδικότερα εστιάζω στην προσωποποίηση του θανάτου στην μορφή του Χάρου και στα χαρακτηριστικά που του αποδίδονται, συγκρίνοντάς την με τις ποικίλες εκδοχές της δράσης του θανάτου της δυτικής μακάβριας παράδοσης. Με τον τρόπο αυτό φιλοδοξώ να συμπληρώσω με μια άλλη οπτική γωνία τη μελέτη των μοιρολογιών.
Developing WHO guidelines: Time to formally include evidence from mathematical modelling studies
Authors: Egger Matthias , Johnson Leigh , Althaus Christian , Schöni Anna , Salanti Georgia , Low Nicola , Norris Susan L. 
Published: February 2018

In recent years, the number of mathematical modelling studies has increased steeply. Many of the questions addressed in these studies are relevant to the development of World Health Organization (WHO) guidelines, but modelling studies are rarely formally included as part of the body of evidence. An expert consultation hosted by WHO, a survey of modellers and users of modelling studies, and literature reviews informed the development of recommendations on when and how to incorporate the results of modelling studies into WHO guidelines. In this article, we argue that modelling studies should routinely be considered in the process of developing WHO guidelines, but particularly in the evaluation of public health programmes, long-term effectiveness or comparative effectiveness. There should be a systematic and transparent approach to identifying relevant published models, and to commissioning new models. We believe that the inclusion of evidence from modelling studies into the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process is possible and desirable, with relatively few adaptations. No single “one-size-fits-all” approach is appropriate to assess the quality of modelling studies. The concept of the ‘credibility’ of the model, which takes the conceptualization of the problem, model structure, input data, different dimensions of uncertainty, as well as transparency and validation into account, is more appropriate than ‘risk of bias’.
An oxidation-resistant peptide mimic of surfactant protein B (B-YL) forms an amphipathic helix-hairpin in liposomes with high surface activity
Authors: Walther Frans J. , Gupta Monik , Gordon Larry M. , Waring Alan J. 
Published: February 2018

Background: Animal-derived surfactants containing surfactant proteins B (SP-B) and C (SP-C) are used to treat respiratory distress syndrome (RDS) in preterm infants. SP-B (79 residues) plays a pivotal role in lung function and the design of synthetic lung surfactant. Super Mini-B (SMB), a 41-residue peptide based on the N- and C-domains of SP-B joined with a turn and two disulfides, folds as an α-helix hairpin mimicking the properties of these domains in SP-B. Here, we studied ‘B-YL’, a 41-residue oxidation-resistant SMB variant that has its four Cys and two Met residues replaced by Tyr and Leu, respectively, to test whether these hydrophobic substitutions produce a surface-active, α-helix hairpin.Methods:Structure and function of B-YL and SMB in surfactant lipids were compared with CD and FTIR spectroscopy and molecular dynamic (MD) simulations, and surface activity with captive bubble surfactometry and in lavaged, surfactant-deficient adult rabbits.Results:CD and FTIR spectroscopy of B-YL in surfactant lipids showed secondary structures compatible with peptide folding as an α-helix hairpin, similar to SMB in lipids. MD simulations confirmed that B-YL maintained its α-helix hairpin in a lipid bilayer, matching the hairpin obtained from MD of SMB. Unlike the disulfide-reinforced helix-turn of SMB, the B-YL fold was stabilized by a core of clustered Tyr linking the N- and C-helices through noncovalent interactions involving aromatic rings. B-YL in surfactant lipids demonstrated excellentin vitrosurface activity and good oxygenation and dynamic compliance in lavaged, surfactant-deficient adult rabbits.Conclusions:‘Sulfur-free’ and ‘oxidation-resistant’ B-YL forms an amphipathic helix-hairpin in surfactant liposomes with high surface activity and is functionally similar to SMB and native SP-B. B-YL’s resistance against free oxygen radical damage provides an extra edge over oxidized SMB in the treatment of respiratory failure in preterm infants with RDS and children and adults with acute lung injury.
Evaluation of Phenol-Formaldehyde Resins Modified and Blended with Pyrolysis Bio-Oil for Plywood
Authors: Mao An , Xu Weitao , Xi Enhua , Li Qi , Wan Hui 
Published: February 2018

Abstract
The objective of this study was to compare the characteristics and bonding performance of phenol-formaldehyde (PF) resins modified and blended with crude bio-oil. For modified PF resins, crude bio-oil from the pyrolysis of pinewood was synthesized with phenol and formaldehyde at 10, 25, 50, and 75 percent phenol substitution percentages, respectively. For blended PF resins, crude bio-oil was physically blended with PF resin at 4, 13, 23, and 38 percent addition percentages, respectively. The physical properties of crude bio-oil and PF resins, such as viscosity, pH value, gel time, water content, and solid content, were measured. The bond strength of plywood was evaluated. The results indicated that incorporating crude bio-oil into PF resin either by synthesis or by blending at certain amounts could improve the bonding performance of PF resins. For blended PF resins, the best crude bio-oil addition percentage was 13 percent, while for synthesized (modified) PF resins, the best phenol substitution percentage was 25 percent. Further increment of the crude bio-oil content level decreased the bond performance of both modified and blended PF resins. This was mainly due to the increased viscosity and the acidity of blended PF resins at a high crude bio-oil addition percentage and a shortage of reactive phenolic compounds in modified PF resins at a high phenol substitution percentage. Plywood bonded with the resins could generally meet the requirement of Chinese National Standard GB/T 17657‐2013 and be suitable for outdoor applications.
Using Structural Analysis to Inform Peer Support Arrangements for High School Students With Severe Disabilities
Authors: Huber Heartley B. , Carter Erik W. , Lopano Sarah E. , Stankiewicz Kristen C. 
Published: February 2018

Abstract
We examined the effects of peer support arrangements as an alternative to exclusive direct support from paraprofessionals for three high school students with severe disabilities in general education classrooms. We also explored the use of structural analysis as a data-based approach for further refining the interventions to enhance their impact in particular classrooms. Peer support arrangements were associated with substantial increases in social outcomes; academic engagement maintained or improved modestly for all participants. Moreover, structural analyses yielded findings used to adapt peer support arrangements to address students' individual needs. Although the effects of structural analysis-based adaptations resulted in increases in social responses for only one participant, levels of social interactions maintained, and improvements in academic engagement occurred for two participants.
Individual and Contextual Correlates of Frequently Involved Special Olympics Athletes
Authors: Robinson Suzanne , Fraser-Thomas Jessica L. , Balogh Robert , Lunsky Yona , Weiss Jonathan A. 
Published: February 2018

Abstract
It is important to understand factors associated with sport participation for youth with intellectual and developmental disabilities (IDD). With a sample of 414 Special Olympics (SO) athletes, this study examined how frequently involved athletes differ from other youth who are less involved in SO. Results showed that frequently involved athletes are older, have more sport-specific parental support, stronger athlete-coach relationships, and more positive SO experiences than other athletes. These factors were predictive of SO involvement, even after controlling for athlete characteristics, including behavior problems and adaptive behavior. Athletes with IDD have the potential to be highly involved in sports when external supports (i.e., coaches and parents) are strong.
Pesticide Formulation and Delivery Systems: 37th Volume, Formulations with Ingredients on the EPA's List of Minimal Concern
Authors: Edlund Renee K. 
Published: February 2018

Description
Get detailed research on formulations with ingredients on the EPA list of minimal concern, including list 4 ingredients. This book includes 11 peer-reviewed papers that address a wide range of topics in the field of agrochemical inerts.
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The featured papers were presented at the 37th Symposium on Pesticide Formulation and Delivery Systems: “Formulations with Ingredients on the EPA’s List of Minimal Concern,” held October 25-27, 2016, in Washington, D.C._x000D_
Choice for Drug or Natural Reward Engages Largely Overlapping Neuronal Ensembles in the Infralimbic Prefrontal Cortex
Authors: Pfarr Simone , Schaaf Laura , Reinert Janine K. , Paul Elisabeth , Herrmannsdörfer Frank , Roßmanith Martin , Kuner Thomas , Hansson Anita C. , Spanagel Rainer , Körber Christoph , Sommer Wolfgang H. 
Published: February 2018

Cue-reward associations form distinct memories that can drive appetitive behaviors and are involved in craving for both drugs and natural rewards. Distinct sets of neurons, so-called neuronal ensembles, in the infralimbic area (IL) of the medial prefrontal cortex (mPFC) play a key role in alcohol seeking. Whether this ensemble is specific for alcohol or controls reward seeking in general remains unclear. Here, we compared IL ensembles formed upon recall of drug (alcohol) or natural reward (saccharin) memories in male Wistar rats. Using an experimental framework that allows identification of two distinct reward-associated ensembles within the same animal, we found that cue-induced seeking of either alcohol or saccharin activated ensembles of similar size and organization, whereby these ensembles consist of largely overlapping neuronal populations. Thus, the IL seems to act as a general integration hub for reward seeking behavior, but also contains subsets of neurons that encode for the different rewards.SIGNIFICANCE STATEMENTCue-reward associations form distinct memories that can act as drivers of appetitive behaviors and are involved in craving for natural rewards as well as for drugs. Distinct sets of neurons, so-called neuronal ensembles, in the infralimbic area of the mPFC play a key role in cue-triggered reward seeking. However, it is unclear whether these ensembles act as broadly tuned controllers of approach behavior or represent the learned associations between specific cues and rewards. Using an experimental framework that allows identification of two distinct reward-associated ensembles within the same animal we find largely overlapping neuronal populations. Repeated activation by two distinct events could reflect the linking of the two memory traces within the same neuron.