bluuebunny/crossref_metadata_2025_split huggingface dataset:
PROTEUS: A randomized, double-blind, placebo (PBO)-controlled, phase III trial of apalutamide (APA) plus androgen deprivation therapy (ADT) versus PBO plus ADT prior to radical prostatectomy (RP) in patients with localized high-risk or locally advanced prostate cancer (PC).
Authors: Taplin Mary-Ellen , Gleave Martin , Evans Christopher P. , Efstathiou Eleni , Kantoff Philip W. , Ross Ashley , Shore Neal D. , Briganti Alberto , Hadaschik Boris A. , Heidenreich Axel , Rooney Oliver Brendan , Tian Shaozhou Ken , Wetherhold Lisa , Xu Weichun , Cheng Shinta , Brookman-May Sabine Doris , Lopez-Gitlitz Angela , Kibel Adam S. 
Published: February 2020

TPS383 Background: Patients (pts) with localized high-risk PC have disease progression rates of ~50% after RP (Kane et al. J Urol. 2007). Neoadjuvant studies show that androgen blockade can improve local disease control at the time of RP (McKay et al. Prostate Cancer Prostatic Dis. 2017; Taplin et al. JCO. 2014; Efstathiou et al. Eur Urol. 2019). This study will determine if treatment with APA + ADT before RP in pts with localized high-risk or locally advanced PC improves pathologic complete response (pCR) rate and if neoadjuvant and adjuvant peri-operative treatment with APA + ADT improves metastasis-free survival (MFS) compared with PBO + ADT. Methods: This international multicenter trial is enrolling candidates for RP with localized high-risk or locally advanced PC. Eligibility criteria: any combination of Gleason score (GS) 4 + 3 (= Grade Group [GG] 3) and GS 8 (4 + 4 or 5 + 3) from ≥ 6 systematic biopsy cores (SB) or targeted biopsy cores (TB) (with ≥ 1 core GS 8 [4 + 4 or 5 + 3] included); any combination of GS 4 + 3 (= GG 3) and GS 8 (4 + 4 or 5 + 3) from ≥ 3 SB or TB (with ≥ 1 core GS 8 [4 + 4 or 5 + 3]) included and prostate-specific antigen (PSA) ≥ 20 ng/mL; GS ≥ 9 (GG 5) in ≥ 1 SB or TB; or ≥ 2 SB or TB with continuous GS ≥ 8 (GG 4), each with ≥ 80% involvement. Stratification: GS (7 or ≥ 8), cN0 or N1, and region. Randomization: 1:1 to APA (240 mg) + ADT or PBO + ADT. Pts will receive 6 months neoadjuvant treatment and RP + 6 months adjuvant treatment. Dual primary end points: pCR rate (assessed by blinded independent central pathology review) and MFS (assessed by blinded independent central radiology review). Secondary end points: PSA-free survival and progression-free survival. Imaging with CT or MRI and bone scan at screening, after RP, and then every 6 months following biochemical failure until documented distant metastasis, or death. ~1500 pts will be enrolled globally over 3 years at 240 sites in 19 countries. An independent data monitoring committee is commissioned to review trial data. Clinical trial information: NCT03767244.
A phase II study assessing the safety and efficacy of ASP1650 in male patients with incurable platinum refractory germ cell tumors.
Authors: Adra Nabil , Vaughn David J. , Einhorn Lawrence , Hanna Nasser H. , Rosales Matt , Arozullah Ahsan , Feldman Darren R. 
Published: February 2020

TPS424 Background: Testicular cancer (TC) is the most common solid malignancy in men aged 15-35 yrs; germ cell tumors (GCTs) account for 95% of TC. Claudin 6 (CLDN6) is a tight junction membrane protein whose expression in normal tissue is confined to embryonic cells but is frequently aberrantly expressed in GCTs. ASP1650 (also known as IMAB027) is a monoclonal antibody targeted against CLDN6 that can induce antibody-dependent cell-mediated and complement-dependent cytotoxicity in CLDN6-expressing cells and has demonstrated potent antitumor effects in preclinical models of TC. Methods: This phase 2 study with a safety run-in (NCT03760081) will enroll ≤46 male patients (pts) with advanced GCTs who have had prior cisplatin-based combination chemotherapy and ≥1 salvage regimen. In the safety run-in, an initial ASP1650 dose level will be evaluated in 3 pts. If tolerated, a new cohort of 3 pts will begin at the next dose level per the Bayesian Optimal Interval Design. A Dose Evaluation Committee will assess tolerability and determine maximum tolerated dose. Once the recommended phase 2 dose (RP2D) has been established, ≤34 pts will be enrolled in phase 2 and will receive ASP1650 in 2-week cycles for up to 12 cycles or until study discontinuation criteria is met. Phase 2 of the study will utilize a Simon’s 2-stage design to allow for early termination. In stage I, 13 pts, including pts from the RP2D cohort of the safety run-in, will be evaluated for response. If there is ≤1 response among these 13 pts, the study will be stopped, otherwise an additional 21 pts will be enrolled in stage II. Primary endpoints of the study include establishment of the RP2D and confirmation of overall response rate, as assessed by modified RECIST v1.1 response criteria (RECIST v1.1 + serum tumor markers [βhCG and AFP]). Secondary endpoints include the determination of safety/tolerability and pharmacokinetic profiles as well as other efficacy measures (eg, clinical benefit rate; progression-free survival; change in serum tumor biomarkers). Enrollment is currently ongoing; as of Sept 12, 2019, 6 pts have enrolled and 2 are still on active treatment. Clinical trial information: NCT03760081.
PIVOT-10: A phase II study of bempegaldesleukin (NKTR-214) in combination with nivolumab (NIVO) in cisplatin (cis) ineligible patients with previously untreated locally advanced or metastatic urothelial cancer (mUC).
Authors: Huddart Robert A. , Siefker-Radtke Arlene O. , Balar Arjun Vasant , Bilen Mehmet Asim , Powles Thomas , Bamias Aristotelis , Castellano Daniel , Khalil Maged F. , Van Der Heijden Michiel Simon , Koshkin Vadim S , Pook David William , Ozguroglu Mustafa , Santiago Linda , Saab Rabih , Li Pao-Chen , Tagliaferri Margit Cecile , Lin Wei , Tagliaferri Mary Ann , Loriot Yohann 
Published: February 2020

TPS589 Background: Checkpoint inhibitors can achieve durable responses in cis-ineligible 1L mUC. However, use is restricted to patients whose tumors are PD-L1 high. Approximately 70% of cis-ineligible patients have tumors with low PD-L1 expression, leaving a significant proportion of 1L mUC patients in need of new treatment options. Bempegaldesleukin (BEMPEG; NKTR-214) is a CD122-preferential IL-2 pathway agonist designed to provide sustained signaling through the IL-2 βγ receptor. NIVO is an anti-PD-1 antibody that is approved for treatment in several types of cancers, including 2L mUC after treatment with a platinum agent. Early BEMPEG plus NIVO data in 1L mUC (cis-eligible and -ineligible) patients found an objective response rate (ORR) of 48% (13/27) in the efficacy evaluable population (defined as having undergone at least one post-baseline scan) and a CR rate of 19%, prompting this further exploration of BEMPEG plus NIVO in a phase 2 study (Siefker-Radke, 2019). Methods: This Phase 2 multi-national trial evaluates BEMPEG plus NIVO in previously untreated patients with cis-ineligible mUC. Eligibility also requires tumor tissue be analyzed by central laboratory to document PD-L1 status. Approximately 205 patients will be enrolled. BEMPEG (0.006 mg/kg) and NIVO (360 mg) are given intravenously (IV) on Day 1 of each 3-week cycle. The primary endpoint is ORR assessed per RECIST 1.1 by blinded independent central review (BICR) in patients with low PD-L1 expression (defined as Combined Positive Score [CPS] < 10). Secondary endpoints include ORR and duration of response in all treated patients, safety, and tolerability. Tumor and blood samples will be collected for biomarker analyses. Enrollment is ongoing. Clinical trial information: NCT03785925.
GEMINI: An open-label, single-arm, phase II trial of intraoperative gemcitabine intravesical instillation in patients undergoing radical nephroureterectomy for upper tract urothelial carcinoma.
Authors: Packiam Vignesh T. , Leibovich Bradley C. , Thompson R. Houston , Potretzke Aaron M. , Chow George K. , Tollefson Matthew K. , Schulte Phillip J. , Tyson Mark , Lyon Timothy D. , Boorjian Stephen A. 
Published: February 2020

TPS594 Background: The standard treatment for upper tract urothelial carcinoma (UTUC) is radical nephroureterectomy (RNU) with bladder cuff resection. Subsequent intravesical recurrence is common and results in patient morbidity and increased healthcare cost. Level 1 evidence has demonstrated reduction of intravesical recurrence with instillation of intravesical Mitomycin C at 10 days following RNU. However, there has been limited adoption of Mitomycin C due to concerns for toxicity and logistics of postoperative drug delivery. Meanwhile, immediate intravesical gemcitabine has been shown to reduce intravesical recurrence following transurethral resection of bladder cancers without increasing toxicity compared to placebo. Moreover, small series have suggested improved efficacy of intraoperative intravesical chemotherapy for RNU. The purpose of the GEMINI trial, therefore, is to prospectively establish the safety and efficacy of intraoperative instillation of intravesical gemcitabine in patients undergoing RNU for UTUC. Methods: GEMINI is a multi-center open-label, single-arm, Phase II study that aims to enroll 90 patients with cTa-T4N0M0 UTUC. Patients receive intraoperative intravesical instillation of gemcitabine at the beginning of RNU, to be held in the bladder for at least 1 hour. The instilled drug will be drained prior to resection of the bladder cuff. Patients will undergo standard of care postoperative surveillance, including cystoscopy at 3, 6, 12, 18, and 24 months. The primary endpoint is 1-year intravesical recurrence-free survival. The historical event rate for no treatment is 30%, and we estimated a 40% relative reduction in event rate with gemcitabine. The study is powered to provide 80% power to detect this difference based on a one-sided exact test of proportions with alpha level 0.05. Secondary endpoints include time to recurrence and stratification of recurrence free survival by tumor grade, tumor stage, neoadjuvant chemotherapy, ureteral tumor location, and history of bladder cancer. Safety and adverse event endpoints will be evaluated. Complete accrual is expected within 3 years.
Utilization of Antineoplastic Agents and Medicare Spending in Elderly Patients With Extensive-Stage Small-Cell Lung Cancer Between 2001 and 2013
Authors: Shah Chintan , Hong Young-Rock , Bishnoi Rohit , Jones Dennie , Huo Jinhai 
Published: February 2020

PURPOSE: Some elderly patients (≥ 65 years old) with small-cell lung cancer (SCLC) do not receive chemotherapy likely because of fear of toxicity and uncertainty regarding benefits. Thus, we aimed to study real-world trends in utilization of antineoplastics over the years and predictors of utilization, survival, and Medicare expenditure in elderly patients with extensive-stage (ES) SCLC. PATIENTS AND METHODS: Using the linked SEER and Medicare database, we identified elderly patients with newly diagnosed ES-SCLC between 2001 and 2013. The Wald test was used to determine the significance of trends. Cox proportional hazards models were applied for survival analyses. We used SAS, version 9.4 (SAS Institute, Cary, NC). RESULTS: We identified 15,763 patients with newly diagnosed ES-SCLC. Approximately 6,838 patients (43.38%) received antineoplastics, and 8,925 patients (56.61%) received supportive care only. Every year since 2001, the percentage of patients receiving antineoplastics has decreased (45.8% v 36.6% in 2001 and 2013, respectively; Ptrend < .0001). Patients with advanced age ( P < .001), patients from high-poverty areas ( P < .001) or rural areas ( P = .005), patients with Charlson comorbidity index ≥ 3 ( P < .001), and non-Hispanic blacks ( P = .003) and Hispanics ( P = .001) were less likely to receive antineoplastics. Mean Medicare spending per patient decreased over the study period for patients treated with antineoplastics ($45,998 in 2001 and $35,053 in 2013; Ptrend < .001) and for those receiving supportive care only ($34,197 in 2001 and $25,265 in 2013; Ptrend < .001). CONCLUSION: Decreasing utilization of antineoplastics in elderly patients with ES-SCLC since 2001 could be partly secondary to higher comorbidities and physiologic age, leading to poor candidacy. Medicare expenditures decreased likely as a result of value-based treatment initiatives by the Centers for Medicaid and Medicare Services. However, expenditures are likely to increase with use of expensive novel agents.
Development and conservative treatment of spinal deformities in cerebral palsy
Authors: Brunner Reinald 
Published: February 2020

Incidence and cause Cerebral palsy (CP) is characterized by poor motor control. The more severe the affection is, the more patients are prone to deformities. Patients with Gross Motor Function Classification System level V run an up to 90% risk for spinal deformities. These are caused by poor trunk control under load. Although trunk tone is impossible to assess it seems to be low in the majority of patients, leading to collapse under gravity. The constant malposition results in growth asymmetry which leads to fixation and deterioration of the deformity. Brace treatment Brace treatment has a poor reputation in respect to the final outcome. Conventional braces as constructed for other spinal deformities are indeed difficult for patients with CP as they cannot change position in the brace and do not tolerate pressure on the belly for reflux problems. Respecting these points improves the tolerance of braces but still the time of use is far from the necessary when the trunk is upright. Nevertheless, they can help to postpone surgery for scoliosis, but they are very inefficient for sagittal plane deformities. Aim of treatment The lack of trunk control further leads to an impairment of head control and upper extremity function. Providing stability improves these problems. Braces are superior to seating shells for both treating deformity and providing stability as they remain close to the skin and follow movements. Supports on seating shells in contrast are too far away for controlling the deformity and provide stability only if the patient doesn't move forward.
Tectono-stratigraphic correlations between Northern Evvoia, Skopelos and Alonnisos, and the postulated collision of the Pelagonian carbonate platform with the Paikon forearc basin (Pelagonian-Vardar zones, Internal Hellenides)
Authors: Scherreiks Rudolph , Boudagher-Fadel Marcelle 
Published: February 2020

The Pelagonian stratigraphy of the study area consists of a Permo-Triassic basement and an Upper Triassic and Jurassic carbonate platform formation that had been overthrust by the Eohellenic ophiolite sheet during the Early Cretaceous. Intensive erosion, during the Cretaceous, removed most of the ophiolite and partly the Jurassic formation. It is hypothesised that uplift and erosion of eastern Pelagonia had been triggered by the break-off of the subducted oceanic leading edge of the Pelagonian plate.
An investigation of the rocks that succeed the erosional unconformity shows that they constitute a shear-zone-formation which is tectonically overlain by Cretaceous platform carbonates that characterise the Palouki series of Skopelos and Alonnisos. Geochemical analyses of the shear-zone rocks substantiate that they are of mid ocean ridge and island arc provenience.
Eastern Pelagonia collided with a Cretaceous carbonate platform, probably the Paikon-Paeonian forearc basin, as the Almopias ocean subducted beneath that island-arc-complex. The Cretaceous platform, together with a substrate of sheared-off ocean floor mélange, overthrust eastern Pelagonia as subduction continued, and the substrate was dynamically metamorphosed to cataclastic rocks, mylonite, phyllonite and interpreted pseudotachylite. This complex of Cretaceous platform rocks and a brittle-ductile shear-zone-substrate constitute the here named
Paikon-Palouki nappe which was emplaced during Early Palaeocene. The
Paikon-Palouki nappe did not reach Evvoia.
Seismic tomographic models of the Aegean region apparently depict images of two broken-off ocean-plate-slabs, interpreted as Almopias-lithosphere-slabs: the western Almopias slab began to sink during the Early Cretaceous, the eastern Almopias slab broke off and sank after the Paikon-Palouki nappe was emplaced in Early Palaeocene time.
At first sight: robots’ subtle eye movement parameters affect human attentional engagement, spontaneous attunement and perceived human-likeness
Authors: Ghiglino Davide , Willemse Cesco , Tommaso Davide De , Bossi Francesco , Wykowska Agnieszka 
Published: February 2020

AbstractHuman-robot interaction research could benefit from knowing how various parameters of robotic eye movement control affect specific cognitive mechanisms of the user, such as attention or perception. In the present study, we systematically teased apart control parameters of Trajectory Time of robot eye movements (rTT) between two joint positions and Fixation Duration (rFD) on each of these positions of the iCub robot. We showed recordings of these behaviors to participants and asked them to rate each video on how human-like the robot’s behavior appeared. Additionally, we recorded participants’ eye movements to examine whether the different control parameters evoked different effects on cognition and attention. We found that slow but variable robot eye movements yielded relatively higher human-likeness ratings. On the other hand, the eye-tracking data suggest that the human range of rTT is most engaging and evoked spontaneous involvement in joint attention. The pattern observed in subjective ratings was paralleled only by one measure in the implicit objective metrics, namely the frequency of spontaneous attentional following. These findings provide significant clues for controller design to improve the interaction between humans and artificial agents.
Segregação urbana na cidade de Major Izidoro: o caso do Bairro de Fátima em comparação com o loteamento Terra do Leite
Authors: Santana Julliana Rocha , Farias Cláudio José Godoi Silva de , Oliveira Gabriel Cazuza dos Santos , Moraes Júnior Fúlvio Mácio Correia de , Silva Lara Fabian Cordeiro , Lopes Letícia Beatriz Silva , Oliveira Matteus Freitas de 
Published: February 2020

RESUMO: O trabalho consistiu em avaliar a segregação urbana na cidade de Major Izidoro - Alagoas, analisando os casos do Bairro de Fátima e do loteamento Terra do Leite nas variações de suas paisagens urbanas marcadas pela segregação. O estudo foi embasado na metodologia de Silva et al (2017) e Oliveira et al (2017) que a partir de dados primários analisaram a atuação dos agentes produtores e a geração de áreas desiguais em cidades pequenas. A revisão de literatura nos ajudou a compreender as questões sociais e econômicas de ambos os bairros, além da sua formação, organização, desenvolvimento e a intervenção estatal através de obras e políticas públicas. Notamos que a cidade se fragmenta quando não se oportuniza uma gestão sustentável e inteligente gerando espaços de pouca democracia, paisagem marcadas por injustas e intensas diferenças além de fragilidade dos direitos sociais. Em suma, a cidade de Major Izidoro apresenta-se fragmentada e articulada, reflexo e condicionante social, isto é, os mesmos esquemas que imperam nas cidades grandes do mundo capitalista.
PALAVRAS-CHAVE: Desigualdades. Organização social. Intervenção Estatal.
Criptomoedas: apontamentos sob a ótica macroeconômica
Authors: Silva Fábio Correia da , Baro Andreia Rodrigues Ferreira , Soares Fany Pereira de Araújo 
Published: February 2020

RESUMO Criptomoedas são moedas digitais descentralizadas que podem ter novas unidades geradas como recompensa pelo uso de capacidade computacional, representando assim, uma ruptura em relação ao modelo “tradicional” de moedas ao substituir a confiança existente nas mesmas devido a um ente regulador por um sistema eletrônico de pagamentos baseado em prova criptográfica. A expansão na adoção e volume de criptomoedas é uma tendência no contexto atual. Diante de tal panorama, e tendo em consideração o fato de serem descentralizadas, as criptomoedas poderiam trazer alguma instabilidade do ponto de vista da relação entre Estado e economia? Deste modo, o presente trabalho objetiva identificar em que medida o advento das criptomoedas e sua recente expansão podem interferir nas políticas e atividades econômicas.
PALAVRAS CHAVE: Moedas virtuais, Economia, Regulação.
Tradicional feira livre de Arapiraca: análise do perfil socioeconômico e a atuação do poder público governamental
Authors: Santos Diego Monteiro dos 
Published: February 2020

RESUMO: A presente pesquisa discute, sob a perspectiva da economia popular e políticas públicas, a percepção dos atores presentes na atividade feira livre, feirantes, consumidores e comerciantes do entorno. O objeto encontra-se no município de Arapiraca, situado no agreste alagoano, onde sua principal atividade é o comércio, reconhecimento adquirido por meio da histórica e tradicional feira livre de Arapiraca, realizada as segundas-feiras. É na feira livre que muitos encontram uma forma de obter emprego e renda para o sustento familiar e o Estado precisa promover condições para o desenvolvimento dessa atividade e consequentemente do cidadão que dela depende. Os objetivos centrais deste artigo foram: analisar os aspectos econômicos e sociais da feira livre bem como sua influência no comércio ao redor e identificar a presença/ausência do poder público na feira livre. A metodologia utilizada foi a pesquisa bibliográfica além da aplicação de questionários com feirantes, consumidores e comerciantes não identificados. No desenvolvimento constatamos que 59% dos feirantes possuem apenas o ensino fundamental incompleto, 28% residem em cidades circunvizinhas, 55% depende exclusivamente da feira como fonte de renda e 77% faturam até R$ 300,00 por feira. Dada a capacidade geradora de renda, a feira desempenha um papel sócio financeiro capaz de tirar famílias da extrema pobreza e que, por sua vez, o poder público não cumpre seu papel de promover o desenvolvimento dessa atividade.
PALAVRAS-CHAVE: Economia Popular, Feira-Livre, Políticas Públicas.
Causas de descarte de vacas e novilhas dos pecuaristas da agricultura familiar de Jacaré dos Homens- AL
Authors: Silva Wesley Reniberg Timoteo , Santos Daniel Vianei dos , Silva José Crisólogo de Sales , Albuquerque Ariane Loudemila Silva de , Carvalho Cláudia Csekö Nolasco de 
Published: February 2020

RESUMO: Na agricultura familiar, ainda existe barreiras que impedem que o produtor faça um descarte pontual, podemos citar: a falta de conhecimentos zootécnicos; baixo capital disponível para reposição das fêmeas bovinas e manutenção das recrias. Assim sendo, o objetivo deste trabalho foi estudar e levantar as principais causas de descarte de fêmeas bovinas leiteiras do rebanho da agricultura familiar do município de Jacaré dos Homens- AL. Foi realizado uma pesquisa quantitativa de caráter exploratório na zona rural do município, aplicando-se 40 questionários para caracterização do produtor de leite. Os questionários continham informações relacionadas à índices zootécnicos, dentre os quais, a causa de descarte de vacas e novilhas leiteiras, formas de reposição, dentre outros aspectos correlacionados a atividade leiteira. As maiores causas de descarte relatadas pelos produtores foram: problemas reprodutivos, presente em 37,5% das propriedades, seca e escassez de alimentos que obteve prevalência em 27,5% dos casos, mastite e outras causas que incluem baixa na produção de leite, idade avançada e incrementação de renda, incidindo em 10% cada, respectivamente.
PALAVRAS - CHAVE: Fêmeas, bovinas, leite.