bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cobomarsen, an Oligonucleotide Inhibitor of miR-155, Slows DLBCL Tumor Cell Growth In Vitro and In Vivo
Authors: Anastasiadou Eleni , Seto Anita G. , Beatty Xuan , Hermreck Melanie , Gilles Maud-Emmanuelle , Stroopinsky Dina , Pinter-Brown Lauren C. , Pestano Linda , Marchese Cinzia , Avigan David , Trivedi Pankaj , Escolar Diana M. , Jackson Aimee L. , Slack Frank J. 
Published: November 2020

Abstract

Purpose:
miRNA-155 is an oncogenic miRNA highly expressed in B-cell malignancies, particularly in the non–germinal center B-cell or activated B-cell subtype of diffuse large B-cell lymphoma (ABC-DLBCL), where it is considered a potential diagnostic and prognostic biomarker. Thus, miR-155 inhibition represents an important therapeutic strategy for B-cell lymphomas. In this study, we tested the efficacy and pharmacodynamic activity of an oligonucleotide inhibitor of miR-155, cobomarsen, in ABC-DLBCL cell lines and in corresponding xenograft mouse models. In addition, we assessed the therapeutic efficacy and safety of cobomarsen in a patient diagnosed with aggressive ABC-DLBCL.

Experimental Design:
Preclinical studies included the delivery of cobomarsen to highly miR-155–expressing ABC-DLBCL cell lines to assess any phenotypic changes, as well as intravenous injections of cobomarsen in NSG mice carrying ABC-DLBCL xenografts, to study tumor growth and pharmacodynamics of the compound over time. To begin to test its safety and therapeutic efficacy, a patient was recruited who underwent five cycles of cobomarsen treatment.

Results:
Cobomarsen decreased cell proliferation and induced apoptosis in ABC-DLBCL cell lines. Intravenous administration of cobomarsen in a xenograft NSG mouse model of ABC-DLBCL reduced tumor volume, triggered apoptosis, and derepressed direct miR-155 target genes. Finally, the compound reduced and stabilized tumor growth without any toxic effects for the patient.

Conclusions:
Our findings support the potential therapeutic application of cobomarsen in ABC-DLBCL and other types of lymphoma with elevated miR-155 expression.
Randomized Phase II Trial of Anthracycline-free and Anthracycline-containing Neoadjuvant Carboplatin Chemotherapy Regimens in Stage I–III Triple-negative Breast Cancer (NeoSTOP)
Authors: Sharma Priyanka , Kimler Bruce F. , O'Dea Anne , Nye Lauren , Wang Yen Y. , Yoder Rachel , Staley Joshua M. , Prochaska Lindsey , Wagner Jamie , Amin Amanda L. , Larson Kelsey , Balanoff Christa , Elia Manana , Crane Gregory , Madhusudhana Sheshadri , Hoffmann Marc , Sheehan Maureen , Rodriguez Roberto , Finke Karissa , Shah Rajvi , Satelli Deepti , Shrestha Anuj , Beck Larry , McKittrick Richard , Pluenneke Robert , Raja Vinay , Beeki Venkatadri , Corum Larry , Heldstab Jaimie , LaFaver Stephanie , Prager Micki , Phadnis Milind , Mudaranthakam Dinesh Pal , Jensen Roy A. , Godwin Andrew K. , Salgado Roberto , Mehta Kathan , Khan Qamar 
Published: November 2020

Abstract

Purpose:
Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response (pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in triple-negative breast cancer (TNBC). Aim of the NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens.

Patients and Methods:
Patients aged ≥18 years with stage I–III TNBC were randomized (1:1) to receive either paclitaxel (P) weekly × 12 plus carboplatin AUC6 every 21 days × 4 followed by doxorubicin/cyclophosphamide (AC) every 14 days × 4 (CbP → AC, arm A), or carboplatin AUC6 + docetaxel (D) every 21 days × 6 (CbD, arm B). Stromal tumor-infiltrating lymphocytes (sTIL) were assessed. Primary endpoint was pCR in breast and axilla. Other endpoints included residual cancer burden (RCB), toxicity, cost, and event-free (EFS) and overall survival (OS).

Results:
One hundred patients were randomized; arm A (n = 48) or arm B (n = 52). pCR was 54% [95% confidence interval (CI), 40%–69%] in arm A and 54% (95% CI, 40%–68%) in arm B. RCB 0+I rate was 67% in both arms. Median sTIL density was numerically higher in those with pCR compared with those with residual disease (20% vs. 5%; P = 0.25). At median follow-up of 38 months, EFS and OS were similar in the two arms. Grade 3/4 adverse events were more common in arm A compared with arm B, with the most notable differences in neutropenia (60% vs. 8%; P &lt; 0.001) and febrile neutropenia (19% vs. 0%; P &lt; 0.001). There was one treatment-related death (arm A) due to acute leukemia. Mean treatment cost was lower for arm B compared with arm A (P = 0.02).

Conclusions:
The two-drug CbD regimen yielded pCR, RCB 0+I, and survival rates similar to the four-drug regimen of CbP → AC, but with a more favorable toxicity profile and lower treatment-associated cost.
The Bromodomain Inhibitor PFI-3 Sensitizes Cancer Cells to DNA Damage by Targeting SWI/SNF
Authors: Lee Daye , Lee Da-Yeon , Hwang You-Son , Seo Hye-Ran , Lee Shin-Ai , Kwon Jongbum 
Published: November 2020

Abstract

Many chemotherapeutic drugs produce double-strand breaks (DSB) on cancer cell DNA, thereby inducing cell death. However, the DNA damage response (DDR) enables cancer cells to overcome DNA damage and escape cell death, often leading to therapeutic resistance and unsuccessful outcomes. It is therefore important to develop inhibitors that target DDR proteins to render cancer cells hypersensitive to DNA damage. Here, we investigated the applicability of PFI-3, a recently developed bromodomain inhibitor specifically targeting the SWI/SNF chromatin remodeler that functions to promote DSB repair, in cancer treatment. We verified that PFI-3 effectively blocks chromatin binding of its target bromodomains and dissociates the corresponding SWI/SNF proteins from chromatin. We then found that, while having little toxicity as a single agent, PFI-3 synergistically sensitizes several human cancer cell lines to DNA damage induced by chemotherapeutic drugs such as doxorubicin. This PFI-3 activity occurs only for the cancer cells that require SWI/SNF for DNA repair. Our mechanism studies show that PFI-3 exerts the DNA damage–sensitizing effect by directly blocking SWI/SNF's chromatin binding, which leads to defects in DSB repair and aberrations in damage checkpoints, eventually resulting in increase of cell death primarily via necrosis and senescence. This work therefore demonstrates the activity of PFI-3 to sensitize cancer cells to DNA damage and its mechanism of action via SWI/SNF targeting, providing an experimental rationale for developing PFI-3 as a sensitizing agent in cancer chemotherapy.

Implications:
This study, revealing the activity of PFI-3 to sensitize cancer cells to chemotherapeutic drugs, provides an experimental rationale for developing this bromodomain inhibitor as a sensitizing agent in cancer chemotherapy.
Efeito agudo de dois modelos de treinamento intervalado sobre a carga interna em atletas de futsal feminino
Authors: Silva Telmo Nunes da , Nunes Renan Felipe , Serpa Marília Cavalcanti , Coelho Tiago Martins , Guglielmo Luiz Guilherme 
Published: November 2020

O objetivo desse estudo foi analisar o efeito agudo em duas sessões de treinamento intervalado de alta intensidade (TIAI) sobre os valores de carga interna em atletas de futsal feminino. Treze jogadoras adultas (21,2±2,8 anos; 60,3±7,6 kg; 163±06 cm; 20,6%±5,7 gordura) foram submetidas a quatro sessões experimentais: 1) Antropometria e teste incremental em esteira rolante (TIER); 2) Futsal Intermittent Endurance Test (FIET); 3) Maximal Shuttle Run Test (40-m MST); 4) divididas randomicamente em dois grupos, aonde cada grupo completou um dos dois modelos de TIAI em duas sessões de treinamento, consistindo em 8 séries similares em relação esforço:pausa (1:1), distância relativa (m.min-1) de modo que gerasse a mesma intensidade de corrida relativa ao PV do FIET (100% do Pico de Velocidade), mas com número de mudanças de direção distintos (TIAI7,5x7,5=1 vs. TIAI15x15=3). Lactato sanguíneo (Lac), frequência cardíaca (FC) e percepção subjetiva de esforço (PSE) foram coletados. Não foram encontradas diferenças nas variáveis obtidas no TIER, FIET, 40-m MST e entre as médias de FC e PSE durante TIAI entre os grupos (p>0,05). Porém, mudanças foram reportadas ao longo do tempo para FC (F=15,207; p<0,05) e [Lac] (F=57,110; p<0,001) em ambos os grupos. Valores de [Lac] foram superiores no TIAI7,5x7,5 comparado ao TIAI15x15 na série 1 (F(2,28)=2,234; p<0,05), além disso, a análise de inferência demonstrou valores muito provavelmente maiores na série 1 (98/1/1) e provavelmente maiores na série 2 (93/5/2) ambos com grande tamanho do efeito(TE=1,31; TE=0,84). Com base nos resultados obtidos em uma sessão de treino, conclui-se que os ambos os modelos de TIAI são capazes de promover mudanças na carga interna em jogadoras de futsal em uma mesma proposta de sessão de treino.
C-reactive protein is inversely and independently associated with maximal oxygen uptake in adolescents with obesity
Authors: Nunes João Elias Dias , Cunha Heitor Santos , Teixeira Renata Roland , Espindola Foued S. , Cheik Nádia Carla 
Published: November 2020

The purposes of this study were: 1) investigate whether different markers of infl ammation (CRP and TNF-alpha) are correlated to cardiorespiratory fi tness in adolescents with obesity; 2) examine the association of these variables when adjusted by parameters of body composition. Were selected 57 individuals, 34 girls and 23 boys, with 16.4±1.56 years and body mass index 36.0±4.3 kg/m2. Anthropometric measurements (weight, height and abdominal circunference) and body composition (BMI, visceral fat, body fat) were assessment. Body composition was estimated by analyzer of tetrapolar bioelectrical impedance. Obesity was defi ned as BMI>95th percentile of the curve proposed by the Center for Diseases Control. Plasma TNF-alpha was measured by a quantitative two-site high-sensitivity enzyme immunoassay and CRP was measured by high-sensitivityimmunoturbidimetric assay. Graded maximal exercise testing was performed to obtain the maximum oxygen consumption (VO2max) and velocity associated with the VO2max (vVO2max). Signifi cant correlations of CRP with VO2max and vVO2max were found (r=-0.40 and r=-0,36, respectively). No correlations were observed between TNF-alpha and VO2max e vVO2max. CRP was associated to the VO2max and vVO2max independently of measurements of body composition. The CRP was independently and inversely associated with direct measurement of VO2max and the indirect variable of cardiorespiratory fitness vVO2max, in obese adolescents, even after adjustments in body composition, a potential confounding factor. No association was found between TNF-alpha and the parameters of cardiorespiratory fitness.
Revisão crítica da literatura brasileira sobre as coberturas jornalísticas esportivas do futebol feminino
Authors: Gabriel Bruno José , Paula Erica Fernanda de , Pedroso Bruno , Freitas Junior Miguel Archanjo de , Pinto Márcia Helena Baldani 
Published: November 2020

Os objetivos deste artigo foram revisar e analisar criticamente a estruturação da literatura, publicada em periódicos científicos nacionais, que estabeleceu as coberturas jornalísticas impressas e digitais acerca do futebol feminino e das jogadoras como objeto de estudo. Para tanto, optou-se pela adoção dos direcionamentos da Revisão Crítica, complementados pelos instrumentos metodológicos da Análise de Conteúdo, pois estes guiam os pesquisadores no processo analítico dos diversos tipos de discursos, dentre estes, o acadêmico/científico. Após a análise crítica dos seis artigos encontrados, chegou-se a três considerações preponderantes, nomeadamente, insufi ciência na apresentação das escolhas metodológicas, diálogo interdisciplinar insuficiente, sobretudo com as teorias do jornalismo, e necessidade de pesquisas complementares.
Os loucos estão soltos e as pontes estão caindo
Authors: Vieira Marina Cavalcante 
Published: November 2020

Gotham City e Metrópolis figuram entre as cidades imaginárias mais famosas do universo das histórias em quadrinhos. Criadas nos Estados Unidos em finais da década de 1930, elas são mais do que simples cenários para as aventuras do Batman e Super-Homem, são cidades ficcionais que refletem as questões vividas pelos grandes centros urbanos da época. O presente artigo debruça-se sobre a representação das cidades do Batman e SuperHomem, tomando como objeto de pesquisa a questão do crime e problemas urbanos nas primeiras histórias destes dois super-heróis, do período de 1938 a 1941.
Significações imaginárias do humor nos quadrinhos de Conceição Cahú
Authors: Pessoa Alberto Ricardo 
Published: November 2020

O artigo disserta acerca das significações imaginárias do humor no quadrinhos Uma História de Amor, premiada no 19º Salão de Humor de Piracicaba, de autoria de Conceição Cahú que assim como outras autoras foram esquecidas entre os pesquisadores e são desconsideradas como pioneiras em representações gráficas sequenciais com uma maneira peculiar de construção do humor e seu reflexo no cotidiano da sociedade. Conceição Cahú apresenta em sua obra um humor calcado no empoderamento social, na sexualidade e em sua própria biografia, com uma estética narrativa que ressoa entre artistas do mais variados gêneros. A nossa hipótese é que Conceição Cahú aponta em um discurso humorístico com traços ingênuos, grotescos e com diálogo de contraponto constante com os estereótipos femininos criados por autores masculinos. Apresentamos uma introdução à autora, contexto social do qual se desenvolve como quadrinista e o legado criativo para as histórias em quadrinhos.
O Livro de Falas no Brasil e nos E.U.A: percursos literários e tradutórios
Authors: Mello Giovana Cordeiro Campos de 
Published: November 2020

O objetivo deste trabalho é refletir, a partir de um prisma historiográfico e cultural, sobre o processo de publicação de O Livro de Falas ou Kalunbungu, de Edimilson de Almeida Pereira, no Brasil, em 1987, em edição do autor, e nos Estados Unidos, na revista Callaloo, em 1996. A voz do poeta começou seu caminho em 1985, com Dormundo, seguido pela publicação de O Livro de Falas, e continuou seu percurso com a publicação de poesias, ensaios e literatura infantojuvenil, entre outros, tendo o universo afro-brasileiro como tema de reflexão. Os textos do referido pesquisador, ensaísta e poeta conseguiram extrapolar as fronteiras nacionais, tendo sido traduzidos e publicados em países como a Inglaterra, Itália, Espanha Alemanha e Estados Unidos. A presente pesquisa ilumina parte dessa trajetória, tomando como base conceitos dos Estudos da Tradução e procurando pensar a tradução de elementos da cultura brasileira para o contexto norte-americano e o processo mais amplo da publicação de poesia afro-brasileira em solo nacional e estrangeiro.
Entre ingredientes, cozinhas e afetos: aspectos socioculturais de uma vida dedicada à comida
Authors: Altoé Isabella , Azevedo Elaine de 
Published: November 2020

É possível afirmar que, em alguma medida, todos os seres humanos são afetados pela culinária. Entre diferentes intensidades de afinidade com a comida, há um grupo que se destaca por nutrir uma relação mais intensa com a alimentação: os cozinheiros. Cozinheiras e cozinheiros podem ser vistos como humanos que trilham suas vidas junto à dos alimentos e dedicam-se a eles diariamente. Essa caminhada conjunta faz parte de uma jornada de vidas construída historicamente, composta por muitos momentos de experiência culinária, bem como por diversos aspectos simbólicos e culturais que antecedem a vivência dentro da cozinha. Nesse sentido, voltar a atenção para questões socioculturais e simbólicas que englobam a alimentação é essencial para compreender como a relação entre cozinheiros e culinária é formada. Cozinheiros não nasceram com uma conexão inata com os alimentos, eles criaram um poderoso afeto pela comida ao longo de suas vidas. Sendo assim, como é estabelecida esta íntima relação entre humanos que cozinham e a culinária? Quais aspectos socioculturais e simbólicos ajudam a construir essa rede de afetos? Este artigo se volta à análise teórica de três aspectos considerados importantes para essa relação: a memória, a comensalidade e o afeto. A comida deixa trilhas na vida dos seres humanos; cria memórias poderosas nos imaginários, convoca pessoas para o convívio e evoca sentimentos duradouros. Relatar esses aspectos mais abrangentes da alimentação é descrever uma parte da história da comida fundamental para todos os seres humanos, em especial, os cozinheiros.
Glucose Metabolism in the Kidney: Neurohormonal Activation and Heart Failure Development
Authors: Gronda Edoardo , Jessup Mariell , Iacoviello Massimo , Palazzuoli Alberto , Napoli Claudio 
Published: November 2020

Abstract
The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium‐glucose cotransporters sodium‐glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin‐angiotensin‐aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective.
The Greek language in Sicily between the Hellenistic Period and Late Antiquity: A contribution from an epigraphic corpus
Authors: Capano Marta 
Published: November 2020

Abstract
My PhD dissertation (Università degli Studi di Napoli L’Orientale), entitled “Il greco in Sicilia fra età ellenistica e tarda antichità. Un contributo da un corpus epigrafico” (transl. “The Greek language in Sicily between the Hellenistic Period and Late Antiquity. A contribution from an epigraphic corpus”) offers a comprehensive analysis of the Greek language in post-classical Sicilian inscriptions, paying specific attention to the contact with other languages—especially Latin—and to the lexical and formulaic specificities of Christian epigraphy.
Why Are You Talking Like That, Sir? Il-Limbi, Phonology and Class in Contemporary Egypt
Authors: Youssef Islam 
Published: November 2020

Abstract
This article investigates the phonological patternings in the speech of il-Limbi, an immensely popular character in Egyptian comedy; and it stands therefore at a crossroads between cultural studies and linguistics. Il-Limbi represents the urban working classes, and his speech often mocks social conventions through ludicrous parody of educated speech. Masquerading as socially superior personas, his speech highlights the diglossic situation in Egypt as well as the pretentious use of English into the elite register. My examination of il-Limbi’s pronunciation in four movies reveals a number of systematic patterns in both consonants and vowels, which construct a unique code. This code is based partly on exaggerated features of Cairene Arabic and partly on genuine features of illiterate, lower-class vernacular. And it is often the interplay between various registers via correspondence rules that creates humor in the films.
Maps, Language, and the Conceptual–Non-Conceptual Distinction
Authors: Aguilera Mariela , Castellano Federico 
Published: November 2020

Abstract
To make the case for non-conceptualism, Heck (2007) draws on an apparent dichotomy between linguistic and iconic representations. According to Heck, whereas linguistic representations have conceptual content, the content of iconic representations is non-conceptual. Based on the case of cartographic systems, the authors criticize Heck’s dichotomous distinction. They argue that maps are composed of semantically arbitrary elements that play different syntactic roles. Based on this, they claim that maps have a predicative structure and convey conceptual content. Finally, the authors argue that, despite their differences, maps and sentences can logically interact with each other through heterogeneous inferences. These considerations not only challenge the view that conceptual content and inferential processes necessarily involve linguistic representations; furthermore, they provide a new perspective for thinking about maps, their semantics and syntax, and their interaction with linguistic systems.
Leibniz’s Inductive Challenge
Authors: Pelletier Arnaud 
Published: November 2020

Abstract
Leibniz’s metaphysics is often interpreted as being based solely on reason, so that experience would not provide a true foundation but only an analogy to it. Against this reading, this article first recalls that, according to Leibniz, experiences are necessarily implied by the demonstrative nature of metaphysics, for they take the place of an infinite chain of demonstrative steps that we cannot explain. It then argues that what he calls the two “first experiences” – namely, that “I think” and “a variety of things are always thought by me” – play a decisive role in justifying the Monadology’s key propositions that “there are substances” and “there are composites”. Although Leibniz never uses the term induction in this context, this – often neglected – role of singular first-person experiences in the grasping of universal propositions constitutes a real inductive moment in his metaphysics.
Responsibility of the United Nations for Wrongful Acts Occurred in the Framework of Authorized Operations in Light of the Draft Articles on the Responsibility of International Organizations (dario)
Authors: Lozanorios Frédérique 
Published: November 2020

When the Security Council authorizes a State or an international organization to use force, it entrusts it with authority over the chain of command of the operation. That is why the un has always declined to assume responsibility for conduct occurring in the context such operations. While this position is widely supported by practice, and by the 2011 Draft Articles on the Responsibility of International Organizations (dario) of the International Law Commission (ilc), certain cases brought before the European Court of Human Rights (ECtHR) such as Behrami/Saramati have challenged this principle. These cases had the merit of bringing to the fore uncertainties about the rules of responsibility applicable to complex schemes of peacekeeping. This study aims to address the question: in the light of the dario, to what extent could responsibility be attributed to the un for conduct occurred in the framework of authorized operations, and what kind of responsibility would that be?
First, it argues that no basis can be found in the principles of independent responsibility to justify the attribution of wrongful conduct committed on the occasion of authorized operations to the un, unless in exceptional factual circumstances. Second, it contends that indirect responsibility could be an appropriate way to apprehend the specific relationships established between the un on the one hand and the operations it has authorized on the other hand.