bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perioperative chemoimmunotherapy with durvalumab (Durva) in combination with cisplatin/gemcitabine (Cis/Gem) for operable muscle-invasive urothelial carcinoma (MIUC): Preplanned interim analysis of a single-arm phase II trial (SAKK 06/17).
Authors: Cathomas Richard , Petrausch Ulf , Hayoz Stefanie , Schneider Martina , Schardt Julian Andreas , Seiler Roland , Erdmann Andreas , Rothschild Sacha , Aeppli Stefanie , Mach Nicolas , Strebel Raeto , Hadaschik Boris A. , Berthold Dominik R. , Pless Miklos , Zihler Deborah , Schmid Mathias , Biaggi Rudolf Christine , Spahn Martin 
Published: February 2020

499 Background: Cisplatin-based neoadjuvant chemotherapy followed by surgery is the standard of care for patients (pts) with MIUC but relapse rates remain high. Immune checkpoint inhibitors have demonstrated efficacy in advanced urothelial carcinoma (UC). We hypothesize that the integration of the PD-L1 inhibitor durvalumab into perioperative management of MIUC improves outcome. Methods: SAKK 06/17 is an open label single arm phase II study including 61 pts. Operable MIUC cT2-T4a cN0-1 pts without contraindication for Cis were eligible. Four cycles of preoperative Cis/Gem q3w are administered in combination with 4 cycles Durva 1500mg q3w starting at cycle 2. Durva is continued after surgery q4w for 10 cycles. Primary endpoint is event free survival at 2 years. We report a preplanned interim analysis of the secondary endpoints safety, pathological complete remission ypT0 N0 (pCR,) and pathological response rate (PaR, defined as ≤ypT1N0) on the first 30 resected pts. Results: Among 34 eligible pts (27M, 7F; median age 70, range 41-81 years) included from 07/18 – 02/19, 33 pts (97%) had primary bladder cancer and 1 pt had upper tract UC. Clinical T2, T3, T4 and TxN1 stage were present at diagnosis in 68%, 18%, 15% and 15%, respectively. Four cycles of chemo-immunotherapy were completed per protocol in 34 pts (100%). No tumor progression was noted at preoperative restaging. AE related to Durvalumab were G3 in 5 pts (15%) and G4 in 3 pts (9%). Surgery was performed as planned in 30 pts (88%), 3 pts refused surgery and 1 pt had a frozen pelvis. Operation technique was open in 20 pts (67%) and laparoscopic/robot-assisted in 10 pts (33%). Postoperative complications included Clavien-Dindo III in 6 pts (20%) and IV in 2 pts (7%) with infections being most common (5 pts, 17%). pCR was found in 9 pts (30%) and additional 6 pts (20%) had ypT1/ypTis for a PaR of 50%. Conclusions: The combination of Cis/Gem and Durva as neoadjuvant treatment for MIUC is feasible with manageable toxicities and pCR and PaR rates in the expected range. The rate of postoperative complications warrants further close follow up. Clinical trial information: 2017-003565-10.
Sensitive detection of renal cell carcinoma using plasma and urine cell-free DNA methylomes.
Authors: Nuzzo Pier Vitale , Berchuck Jacob E , Spisak Sandor , Korthauer Keegan , Nassar Amin , Abou Alaiwi Sarah , Chakravarthy Ankur , Shen Shu Yi , Bakouny Ziad , Boccardo Francesco , Baca Sylvan , Lee Gwo-Shu Mary , Chang Steven Lee , Waikar Sushrut , Sonpavde Guru , Irizarry Rafael A. , Pomerantz Mark , De Carvalho Daniel , Freedman Matthew L. , Choueiri Toni K. 
Published: February 2020

728 Background: Improving early cancer detection has the potential to significantly reduce cancer-related mortality. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMedDIP-seq) is a highly sensitive, low-input, cost-efficient and bisulfite-free assay capable of detecting and classifying various tumor types. We tested the feasibility of cfMeDIP-seq to detect RCC in plasma samples and, for the first time, in urine cell-free DNA (cfDNA), with an emphasis on early-stage disease. Methods: We performed cfMeDIP-seq on 117 samples (72 plasma and 45 urine samples): 68 stage I-IV RCC cases pre-nephrectomy, 21 stage IV urothelial bladder cancer (UBC) plasma samples from 15 patients, and 28 healthy cancer-free controls. 60.5% of plasma samples and 66.7% of urine samples came from patients with TNM Stage I/II disease. cfDNA was immunoprecipitated and enriched using an antibody targeting 5-methylcytosine and amplified to create a sequence-ready library. The top differentially methylated regions (DMRs) which partitioned RCC and control samples or UBC were used to train a regularized binomial generalized linear model using 80% of the samples as a training set. The 20% of withheld test samples were then assigned a probability of being RCC or control. This process was repeated 100 times. This was performed using both plasma and urine cfDNA samples. Results: We identified 89,799 DMRs in plasma samples and 38,462 DMRs in urine samples. Iterative training and classification of held out samples, using the 300 DMRs which partitioned RCC and control samples, resulted in a mean AUROC of 0.990 (95% CI 0.984-0.997) in plasma samples and 0.791 (95% CI 0.759-0.823) in urine samples. Classification performance between tumor types was evaluated comparing plasma cfDNA from patients with RCC and UBC, resulting in a mean AUROC of 0.954 (95% CI 0.940-0.969). Conclusions: cfMeDIP-seq is a powerful tool for genome-wide discovery of non-invasive DNA methylation biomarkers. This is the first independent validation of plasma cfMeDIP-seq, demonstrating near-perfect classification of RCC in a cohort enriched for patients with early-stage disease and the potential of urine cfDNA methylome-based biomarkers for cancer detection.
PT-112 in advanced metastatic castrate-resistant prostate cancer (mCRPC), as monotherapy or in combination with PD-L1 inhibitor avelumab: Findings from two phase I studies.
Authors: Bryce Alan Haruo , Dronca Roxana Stefania , Costello Brian Addis , Infante Jeffrey R. , Ames Tyler David , Jimeno Jose , Karp Daniel D. 
Published: February 2020

83 Background: PT-112, the first pyrophosphate conjugate in Phase I/II clinical development, induces robust immunogenic cell death and is osteotropic, prompting study in mCRPC during Phase I. We report safety and efficacy findings in the mCRPC sub-population given PT-112 monotherapy (NCT02266745) or in combination with avelumab (“PAVE”) (NCT03409458, ongoing). Methods: Patients (pts) received PT-112 days 1, 8, 15 of a 28d cycle; pts on the PAVE combination also received 800 mg avelumab days 1 and 15; all enrolled during dose escalation or at PT-112 doses previously deemed safe. Pts on therapy (Tx) for ≥2 cycles or who stopped Tx due to progressive disease or treatment-related adverse events (TRAEs) were evaluated for exploratory efficacy. Results: 10 pts on PT-112 (200-420 mg/m2) and 18 pts on PAVE (150-200 mg/m2 PT-112) were evaluable for safety. The most common PT-112 TRAEs were thrombocytopenia (70%, grade (Gr) ≤3) and fatigue (40%, Gr ≤2) with mono-Tx; nausea (50%, Gr ≤2) and fatigue (39%, Gr ≤2) with PAVE. Mono-Tx pts had 6.5 median prior lines of Tx; 2/7 pts with measurable disease (MD) had reductions in target lesions; prostate specific antigen (PSA) declined in 3/10 pts, 1 with ≥50% reduction; and serum alkaline phosphatase (ALP) reductions were seen in 9/10 pts. PAVE pts had 5.5 median prior lines of Tx; radiographic reductions were seen in 2/9 pts with MD; PSA declined in 6/14 pts, 3 with ≥50% decrease, with 1 responder progression free 11.3 months (microsatellite stable). An additional response is ongoing at 4 mos, with 93% PSA decrease and 48% reduction in target lesions (PIK3CBmut & PTEN loss). 13/14 pts with bone metastases had ALP reductions. Pain improvement, opioid cessation and improved performance status were noted in both cohorts. Conclusions: PT-112 was well-tolerated with evidence of efficacy in mCRPC as mono-Tx and in combination with avelumab in heavily pre-treated pts. Bone pain improvement and nearly universal observation of ALP reduction suggest marked therapeutic activity of PT-112 in bone metastases. Serologic / RECIST responses and prolonged disease control in multiple pts substantiate further development of PT-112 in mCRPC. Clinical trial information: NCT02266745, NCT03409458.
Demonstratives as indicators of interactional focus: Spatial and social dimensions of Spanish esta and esa
Authors: Shin Naomi , Hinojosa-Cantú Luis , Shaffer Barbara , Morford Jill P. 
Published: February 2020

Abstract
This paper adopts a cognitive linguistic framework to explore the influence of spatial and social factors on the use of Spanish demonstratives esta ‘this’ and esa ‘that’. Twenty adult Spanish speakers in Monterrey, Mexico, were asked questions prompting the selection of puzzle pieces for placement in a 25-piece puzzle located in the shared space between the participant and an addressee. Although participants were not explicitly instructed to produce demonstratives, the need to identify specific puzzle pieces naturally elicited a total of 523 tokens of esta and esa. Analyses of the distribution of esta versus esa show that demonstratives are not used in a categorical manner to mark differences in physical space. Although participants tended to produce proximal esta for referents near the speaker, both esta and esa were used for referents further from the speaker and closer to the addressee. Participants’ demonstrative selection was also influenced by interaction type: intersubjective misalignment between speakers promoted the use of proximal esta, whereas intersubjective alignment promoted the use of distal esa. These results support the view that nominal grounding is an intersubjective activity. Physical and social factors jointly shape speakers’ construal of the developing co-constructed communicative event as a whole, leading to increasingly variable usage of demonstratives as the referent is more distant both spatially and intersubjectively from the speaker.
The shear and compressive yield stress of fibrillated acacia pulp fiber suspensions
Authors: Sha Jiulong , Yang Yueyue , Wang Can , Li Wei , Lu Peng , Qin Chengrong , Wang Shuangfei 
Published: February 2020

AbstractThe degree of interactions between fibers and the tendency of fibers to form flocs play an important role in effective unit operation in pulp and paper industry. Mechanical treatments may damage the structure of the fiber cell wall and geometrical properties, and ultimately change the fiber-fiber interactions. In this study, the gel crowding number, compressive and shear yield stress of fibrillated acacia pulps were investigated, and the results showed that the gel crowding number of the refined pulp samples ranged from 8.7 to 10.7, which were much lower than that of un-refined pulps. As the concentration increased, both the compressive yield stressPy{P_{y}}and shear yield stressτy{\tau _{y}}of all suspensions increased accordingly, and the yield stress was found to depend on a power law of the crowding number. Moreover, the values ofτy/Py{\tau _{y}}/{P_{y}}were also examined and the variation ofτy/Py{\tau _{y}}/{P_{y}}became largely dependent on the fiber morphology and mass concentration.
Al3Ti/ADC12 Composite Synthesized by Ultrasonic Chemistry in Situ Reaction
Authors: Sun Yong-Hui , Yan Hong , Xiong Jun-Jie 
Published: February 2020

Abstract
Al3Ti/ADC12 composite was synthesized in situ using Al-fluoride potassium titanate (K2TiF6) as the reaction system and an ultrasonic assisted direct melt reaction. Results indicate ultrasonic chemistry reactions are both accelerated and more complete compared to traditional in situ reactions. Al3Ti reinforced particles with a regular shape and size of 1-2 μm were well distributed and as-cast microstructures of composites were superior. Composite particles under ultrasonic assistance were also refined to a greater extent. Tensile strength and elongation rate of the composites reached 255 MPa and 2.2%, an increase of 19.1% and 37.5% respectively to those without ultrasonic aid. Cleavage surface of the composite declined and the number of dimples increased while dimples became smaller and deeper, showing obvious ductile fracture.
Large-Scale Transgenic Drosophila Resource Collections for Loss- and Gain-of-Function Studies
Authors: Zirin Jonathan , Hu Yanhui , Liu Luping , Yang-Zhou Donghui , Colbeth Ryan , Yan Dong , Ewen-Campen Ben , Tao Rong , Vogt Eric , VanNest Sara , Cavers Cooper , Villalta Christians , Comjean Aram , Sun Jin , Wang Xia , Jia Yu , Zhu Ruibao , Peng Ping , Yu Jinchao , Shen Da , Qiu Yuhao , Ayisi Limmond , Ragoowansi Henna , Fenton Ethan , Efrem Senait , Parks Annette , Saito Kuniaki , Kondo Shu , Perkins Liz , Mohr Stephanie E , Ni Jianquan , Perrimon Norbert 
Published: February 2020

Abstract
The Transgenic RNAi Project (TRiP), a Drosophila melanogaster functional genomics platform at Harvard Medical School, was initiated in 2008 to generate and distribute a genome-scale collection of RNA interference (RNAi) fly stocks. To date, it has generated &gt;15,000 RNAi fly stocks. As this covers most Drosophila genes, we have largely transitioned to development of new resources based on CRISPR technology. Here, we present an update on our libraries of publicly available RNAi and CRISPR fly stocks, and focus on the TRiP-CRISPR overexpression (TRiP-OE) and TRiP-CRISPR knockout (TRiP-KO) collections. TRiP-OE stocks express single guide RNAs targeting upstream of a gene transcription start site. Gene activation is triggered by coexpression of catalytically dead Cas9 fused to an activator domain, either VP64-p65-Rta or Synergistic Activation Mediator. TRiP-KO stocks express one or two single guide RNAs targeting the coding sequence of a gene or genes. Cutting is triggered by coexpression of Cas9, allowing for generation of indels in both germline and somatic tissue. To date, we have generated &gt;5000 TRiP-OE or TRiP-KO stocks for the community. These resources provide versatile, transformative tools for gene activation, gene repression, and genome engineering.
Kryptoverwahrung nach dem KWG: Der Versuch einer Konturierung des neuen Erlaubnistatbestands
Authors: Resas Daniel , Ulrich Niklas , Geest André 
Published: February 2020

Zusammenfassung
Deutschland hat die Umsetzung der Änderungsrichtlinie zur Vierten EU-Geldwäscherichtlinie zum Anlass genommen, im Alleingang die Verwahrung von Kryptowerten als Finanzdienstleistung einer Erlaubnispflicht nach dem KWG zu unterstellen. In der praktischen Rechtsanwendung zeigt sich jedoch, dass der Tatbestand des Kryptoverwahrgeschäfts nicht zuletzt durch die komplexe technische Materie eine Reihe von (Abgrenzungs-)Fragen aufwirft, die die Verwaltungs- und Beratungspraxis noch länger beschäftigen werden.
On Color Energy of Few Classes of Bipartite Graphs and Corresponding Color Complements
Authors: Prajakta Bharat Joshi  , Mayamma Joseph  
Published: February 2020

For a given colored graph G, the color energy is defined as Ec(G) = Σλi, for i = 1, 2,…., n; where λi is a color eigenvalue of the color matrix of G, Ac (G) with entries as 1, if both the corresponding vertices are neighbors and have different colors; -1, if both the corresponding vertices are not neighbors and have same colors and 0, otherwise. In this article, we study color energy of graphs with proper coloring and L (h, k)-coloring. Further, we examine the relation between Ec(G) with the corresponding color complement of a given graph G and other graph parameters such as chromatic number and domination number.
AMS Subject Classification: 05C15, 05C50
A construção da identidade do aluno frente ao projeto lei de ideologia de gênero
Authors: Almeida Maiara Cristine Oliveira de , Vale Carolina Sena do , Silva Cristiano Cezar Gomes da 
Published: February 2020

RESUMO: O presente trabalho traz uma breve discussão acerca dos conceitos de ideologia, gênero e identidade a partir do debate a respeito da identidade do aluno frente ao projeto lei de ideologia de gênero. No decorrer do trabalho, tais conceitos foram correlacionados ao projeto lei de ideologia de gênero com a construção de identidade do aluno. Foram mobilizados autores, como: Althusser (1995), Arroyo (2004), Carvalho (2011), Foucault (1988), Hall (2005), Louro (2007), Souza e Silva (2018) e Silva (2017), além de algumas normas legais. Do ponto de vista metodológico, foram realizadas análises bibliográficas, para, a partir das leituras, trazer elementos para a presente discussão. Destaca-se que a escola deve possibilitar o desenvolvimento do pensamento crítico a partir da compreensão sobre as diferenças corporais e sexuais que culturalmente se constroem na sociedade, tendo papel fundamental na desmistificação dessas diferenças, além de ser um importante instrumento na construção de valores e atitudes, que permitam um olhar mais crítico e reflexivo sobre as identidades de gênero e sexual. Nesse sentido, este trabalho visa suscitar o debate e a reflexão sobre a ideologia de gênero na construção da identidade a partir da escola.
PALAVRAS-CHAVE: ideologia de gênero; identidade; escola.
A marca do tropeirismo e os caminhos do gado em Alagoas
Authors: Ferreira José Robson Gonçalves , Leite Angela Maria Araújo 
Published: February 2020

RESUMO: A plantation, no nordeste brasileiro, é introduzida após a invasão portuguesa, no início do século XVI. O cultivo da cana de açúcar vai ser inserido na zona da mata e os engenhos vão se espalhando pelo território canavieiro. Para dar suporte a esses engenhos, a produção de alimentos se desenvolverá no agreste e a pecuária bovina no sertão, dessa forma o interior vai sendo ocupado, especialmente no atual território alagoano. Será a partir desta abordagem que o presente trabalho se desenvolverá. O objetivo é apresentar resultados da primeira etapa de uma pesquisa sobre a formação das cidades, através de levantamentos documentais em cartórios, igrejas e órgãos públicos. Assim, constatou-se a importância do tropeirismo, que será fundamental para o surgimento das feiras livres e, consequentemente, das cidades do agreste. Da mesma forma, as fazendas de gado serão o marco inicial da ocupação dos municípios do sertão alagoano.
PALAVRAS-CHAVE: Tropeiro. Rio dos currais. Agreste. Sertão. Alagoas.
™Índice de germinação (IG) e índice de velocidade de germinação (IVG) do tomate cereja (Solanum lycopersicum var. cerasiforme, solanaceae) cultivadas em vasos sob diferentes substratos
Authors: Silva Luiz Francisco Tavares da , Lira Thaynnara Paula dos Santos , Araújo Victória Polyana Azevedo , Barbosa Lívia Gibrinde , Lima Letícia Paula Barros , Barros Rubens Pessoa de 
Published: February 2020

RESUMO: Objetivou-se com este estudo avaliar os índices de germinação (IG) e de velocidade de germinação (IVG) do Tomate Cereja (Solanum lycopersicum var. cerasiforme) em diferentes substratos em ambiente protegido. A área da pesquisa foi na casa de vegetação da Universidade Estadual de Alagoas, Campus I, em Arapiraca-AL durante o período de Março a abril/2019. Os substratos utilizados foram areia fina, areia lavada, solo de área agrícola e Bioplant®. A semeadura ocorreu em vasos em material plástico, e foram realizadas sendo 5 repetições em cada tipo de solo, totalizando 20 amostras. Foram analisados o IG e o IGV de cada amostra no período de 30 dias. Foi possível identificar que o tomate cereja apresentou melhor IG e IGV nos substratos Areia Fina e Bioplant.
PALAVRAS-CHAVE: desenvolvimento, sementes, solo.
Envelhecimento e educação: impressões advindas da oficina pedagógica de formação
Authors: Barbosa Edja Souza , Silva Maria Lays da , Araújo Mariana Ferreira Torres de , Bezerra Sara Jane Cerqueira 
Published: February 2020

RESUMO: Trata-se de relato da experiência da execução da Oficina Pedagógica Envelhecimento e Educação: tecendo caminhos possíveis no curso de Pedagogia do Campus III da Universidade Estadual de Alagoas. A Oficina teve como objetivo articular o conhecimento teórico do que seja envelhecimento tanto a nível médico quanto a nível psicológico, em um ambiente de formação de professores, tendo como meta a conscientização do que é ser idoso. A oficina foi desenvolvida em três momentos: palestra; participação de idosas e circuito do envelhecimento. Com a realização desta experiência as autoras afirmam que, frente às mudanças sociais e o aumento da população idosa, a pedagogia torna-se ciência propícia para interlocução de ações que deem visibilidade às necessidades dessa parcela da população. Ressaltam ainda o grande ganho da educação com a alteração na LDBEN 9394/96 através da Lei nº 13.632/2018 que acrescentou um inciso no artigo 37, garantindo a educação ao longo da vida, no cotidiano social e em diferentes espaços educacionais.
PALAVRAS-CHAVE: Educação; Envelhecimento; Gerontologia Educacional.
Relação campo-cidade e dinâmicas populacionais no município de Jaramataia-Alagoas.
Authors: Lima Júnior Admilton Barbosa , Amaral Guilherme Alves do , Nunes Maria Vitória Barbosa , Lima Noêmia Fernanda Azarias , Oliveira Matteus Freitas de 
Published: February 2020

RESUMO: O município de Jaramataia, localizado no Sertão de Alagoas, possui uma população de 5.558 habitantes (IBGE, 2010) e nele são estabelecidas relações campo-cidade mediadas pela articulação de fluxos que emergem dos seus espaços urbanos e rurais. O município é composto por sete povoados e um assentamento, apresentando cadeias produtivas ligadas à produção de leite, pescado e agricultura de subsistência temporal e permanente nos moldes do trabalho sustentável/familiar. Face ao exposto, o objetivo desta pesquisa foi compreender as dinâmicas populacionais que se estabelecem entre a sede de Jaramataia e as áreas onde se concentram os principais fluxos dessas cadeias produtivas que estão situadas no perímetro rural. Para além disso, o estudo coloca na agenda de análise a realidade de cidades pequenas que mantêm a complexa relação com o campo por meio da agricultura. Metodologicamente, foi realizado levantamento bibliográfico com base nas palavras-chave cidade-campo, cidade pequena, cadeia produtiva e agroindústria, e, em seguida, foram elaborados e aplicados questionários semiestruturados, e, por fim, procedeu-se à análise dos dados.
PALAVRAS-CHAVE: Cidades pequenas, Sertão alagoano, Rural-urbano.
“A batalha urbana para além do nome”: segregação urbana entre os Bairros Alto São Jorge e Avenida Governador Muniz Falcão, na cidade de Batalha-AL
Authors: Nobre Larissa Emanuely Silva , Farias Ana Raquel dos Santos , Aquino Heloisy Mafalda Vieira , Costa Sarah de Souza , Sales Artur Ferreira , Oliveira Matteus Freitas de 
Published: February 2020

RESUMO: O presente trabalho procurou analisar a segregação socioespacial que ocorre na cidade de Batalha, em Alagoas, comparando os bairros Avenida Governador Muniz Falcão e o Bairro Alto São Jorge. Foram verificados os arranjos espaciais e o perfil socioeconômico de seus moradores como marcadores da paisagem urbana, além de identificar os agentes que atuam modelando esses espaços e gerando formas e funções específicas na cena da urbe. Metodologicamente, a pesquisa foi realizada por meio de levantamento de literatura, dados primários oriundos de questionários e entrevistas semiestruturadas. Constatou-se que, mesmo sendo um fenômeno na escala da cidade pequena, os processos decorrentes do modo de produção capitalista nas cidades do ocidente reproduzem as mesmas lógicas de desigualdade e produção dialética das diferenças, intensificando as lutas e a segregação no cotidiano da cidade.
PALAVRAS-CHAVE: Cidade pequena, Capitalismo, Agentes produtores.