bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role of Metabolic Plasticity in Blood and Brain Stem Cell Pathophysiology
Authors: Landis Catherine J. , McConathy Jonathan , Darley-Usmar Victor , Hjelmeland Anita B. 
Published: October 2019

Abstract
Our understanding of intratumoral heterogeneity in cancer continues to evolve, with current models incorporating single-cell signatures to explore cell–cell interactions and differentiation state. The transition between stem and differentiation states in nonneoplastic cells requires metabolic plasticity, and this plasticity is increasingly recognized to play a central role in cancer biology. The insights from hematopoietic and neural stem cell differentiation pathways were used to identify cancer stem cells in leukemia and gliomas. Similarly, defining metabolic heterogeneity and fuel-switching signals in nonneoplastic stem cells may also give important insights into the corresponding molecular mechanisms controlling metabolic plasticity in cancer. These advances are important, because metabolic adaptation to anticancer therapeutics is rooted in this inherent metabolic plasticity and is a therapeutic challenge to be overcome.
Disparities in Cancer Incidence and Trends among American Indians and Alaska Natives in the United States, 2010–2015
Authors: Melkonian Stephanie C. , Jim Melissa A. , Haverkamp Donald , Wiggins Charles L. , McCollum Jeffrey , White Mary C. , Kaur Judith S. , Espey David K. 
Published: October 2019

Abstract

Background:
Cancer incidence rates for American Indian and Alaska Native (AI/AN) populations vary by geographic region in the United States. The purpose of this study is to examine cancer incidence rates and trends in the AI/AN population compared with the non-Hispanic white population in the United States for the years 2010 to 2015.

Methods:
Cases diagnosed during 2010 to 2015 were identified from population-based cancer registries and linked with the Indian Health Service (IHS) patient registration databases to describe cancer incidence rates in non-Hispanic AI/AN persons compared with non-Hispanic whites (whites) living in IHS purchased/referred care delivery area counties. Age-adjusted rates were calculated for the 15 most common cancer sites, expressed per 100,000 per year. Incidence rates are presented overall as well as by region. Trends were estimated using joinpoint regression analyses.

Results:
Lung and colorectal cancer incidence rates were nearly 20% to 2.5 times higher in AI/AN males and nearly 20% to nearly 3 times higher in AI/AN females compared with whites in the Northern Plains, Southern Plains, Pacific Coast, and Alaska. Cancers of the liver, kidney, and stomach were significantly higher in the AI/AN compared with the white population in all regions. We observed more significant decreases in cancer incidence rates in the white population compared with the AI/AN population.

Conclusions:
Findings demonstrate the importance of examining cancer disparities between AI/AN and white populations. Disparities have widened for lung, female breast, and liver cancers.

Impact:
These findings highlight opportunities for targeted public health interventions to reduce AI/AN cancer incidence.
A Prospective Analysis of Red and Processed Meat Consumption and Risk of Colorectal Cancer in Women
Authors: Mehta Suril S. , Arroyave Whitney D. , Lunn Ruth M. , Park Yong-Moon Mark , Boyd Windy A. , Sandler Dale P. 
Published: October 2019

Abstract

Background:
Red and processed meats have been implicated as risk factors in the development of colorectal cancer in U.S. women, but associations with cooking practices are less well established.

Methods:
Data are from the Sister Study, a cohort of women ages 35 to 74 years from the United States and Puerto Rico who have a sister diagnosed with breast cancer. Red and processed meat consumption, meat cooking practices, and intake of common meat products were collected at baseline using self-administered questionnaires (N = 48,704). Multivariable HRs (HRadj) and 95% confidence intervals (95% CI) were estimated.

Results:
During a median 8.7 years' follow-up (range &lt;1–12.7 years), 216 colorectal cancer cases were diagnosed. In categorical analyses, an increased risk of colorectal cancer was seen in the highest quartile of processed meat consumption compared with the lowest [HRadj = 1.52 (95% CI, 1.01–2.30); Ptrend = 0.02], and for specific meat products, including breakfast sausages [HRadj = 1.85 (95% CI, 1.30–2.64)] and bacon [HRadj = 1.46 (95% CI, 1.01–2.11)]. The HRadj for the highest quartile of red meat consumption was 1.04 (95% CI, 0.68–1.60), and little evidence of association was observed for cooking practices or doneness of red meat. We observed positive associations with specific red meat products when cooking methods were considered, for example, grilled/barbequed steaks [HRadj = 2.23 (95% CI, 1.20–4.14)] and hamburgers [HRadj = 1.98 (95% CI, 1.00–3.91)].

Conclusions:
Higher reported daily intake of processed meats and consumption of barbecued/grilled red meat products were associated with increased risk of colorectal cancer in women.

Impact:
Variability in colorectal risk risk by meat type and cooking method should be considered when evaluating meat consumption.
Differences in Pathology, Staging, and Treatment between HIV+ and Uninfected Patients with Microscopically Confirmed Hepatocellular Carcinoma
Authors: Torgersen Jessie , Taddei Tamar H. , Park Lesley S. , Carbonari Dena M. , Kallan Michael J. , Mitchell Richards Kisha , Zhang Xuchen , Jhala Darshana , Bräu Norbert , Homer Robert , D'Addeo Kathryn , Mehta Rajni , Skanderson Melissa , Kidwai-Khan Farah , Justice Amy C. , Lo Re Vincent 
Published: October 2019

AbstractBackground:The incidence of hepatocellular carcinoma (HCC) is substantially higher among HIV-infected (HIV+) than uninfected persons. It remains unclear if HCC in the setting of HIV infection is morphologically distinct or more aggressive.Methods:We evaluated differences in tumor pathology in a cohort of HIV+ and uninfected patients with microscopically confirmed HCC in the Veterans Aging Cohort Study from 2000 to 2015. We reviewed pathology reports and medical records to determine Barcelona Clinic Liver Cancer stage (BCLC), HCC treatment, and survival by HIV status. Multivariable Cox regression was used to determine the hazard ratio [HR; 95% confidence interval (CI)] of death associated with HIV infection after microscopic confirmation.Results:Among 873 patients with HCC (399 HIV+), 140 HIV+ and 178 uninfected persons underwent liver tissue sampling and had microscopically confirmed HCC. There were no differences in histologic features of the tumor between HIV+ and uninfected patients, including tumor differentiation (well differentiated, 19% vs. 28%, P = 0.16) and lymphovascular invasion (6% vs. 7%, P = 0.17) or presence of advanced hepatic fibrosis (40% vs. 39%, P = 0.90). There were no differences in BCLC stage (P = 0.06) or treatment (P = 0.29) by HIV status. After adjustment for risk factors, risk of death was higher among HIV-infected than uninfected patients (HR = 1.37; 95% CI, 1.02–1.85).Conclusions:We found no differences in HCC tumor characteristics or background hepatic parenchyma by HIV status, yet HIV was associated with poorer survival. Of note, pathology reports often omitted these characteristics.Impact:Systematic evaluation of HCC pathology by HIV status is needed to understand tumor characteristics associated with improved survival.
Identification of FES as a Novel Radiosensitizing Target in Human Cancers
Authors: Kim Byoung Hyuck , Kim Yong Joon , Kim Myung-Ho , Na Yi Rang , Jung Daun , Seok Seung Hyeok , Kim Joon , Kim Hak Jae 
Published: October 2019

Abstract

Purpose:
The identification of novel targets for developing synergistic drug–radiation combinations would pave the way to overcome tumor radioresistance. We conducted cell-based screening of a human kinome siRNA library to identify a radiation-specific kinase that has a synergistic toxic effect with radiation upon inhibition and is not essential for cell survival in the absence of radiation.

Experimental Design:
Unbiased RNAi screening was performed by transfecting A549 cells with a human kinome siRNA library followed by irradiation. Radiosensitizing effects of a target gene and involved mechanisms were examined.

Results:
We identified the nonreceptor protein tyrosine kinase FES (FEline Sarcoma oncogene) as a radiosensitizing target. The expression of FES was increased in response to irradiation. Cell viability and clonogenic survival after irradiation were significantly decreased by FES knockdown in lung and pancreatic cancer cell lines. In contrast, FES depletion alone did not significantly affect cell proliferation without irradiation. An inducible RNAi mouse xenograft model verified in vivo radiosensitizing effects. FES-depleted cells showed increased apoptosis, DNA damage, G2–M phase arrest, and mitotic catastrophe after irradiation. FES depletion promoted radiation-induced reactive oxygen species formation, which resulted in phosphorylation of S6K and MDM2. The radiosensitizing effect of FES knockdown was partially reversed by inhibition of S6K activity. Consistent with the increase in phosphorylated MDM2, an increase in nuclear p53 levels was observed, which appears to contribute increased radiosensitivity of FES-depleted cells.

Conclusions:
We uncovered that inhibition of FES could be a potential strategy for inducing radiosensitization in cancer. Our results provide the basis for developing novel radiosensitizers.
Whole–Genome Sequencing of Childhood Cancer Survivors Treated with Cranial Radiation Therapy Identifies 5p15.33 Locus for Stroke: A Report from the St. Jude Lifetime Cohort Study
Authors: Sapkota Yadav , Cheung Yin Ting , Moon Wonjong , Shelton Kyla , Wilson Carmen L. , Wang Zhaoming , Mulrooney Daniel A. , Zhang Jinghui , Armstrong Gregory T. , Hudson Melissa M. , Robison Leslie L. , Krull Kevin R. , Yasui Yutaka 
Published: October 2019

Abstract

Purpose:
To identify genetic factors associated with risk of stroke among survivors of childhood cancer treated with cranial radiotherapy (CRT).

Experimental Design:
We analyzed whole-genome sequencing (36.8-fold) data of 686 childhood cancer survivors of European ancestry [median (range), 40.4 (12.4–64.7) years old; 54% male] from the St. Jude Lifetime Cohort study treated with CRT, of whom 116 (17%) had clinically diagnosed stroke. Association analyses (single-variant and Burden/SKAT tests) were performed, adjusting for demographic characteristics and childhood cancer treatment exposures.

Results:
We identified a genome-wide significant association between 5p15.33 locus and stroke [rs112896372: HR = 2.55; P = 1.42 × 10–8], with a stronger association (HR = 3.68) among survivors treated with CRT dose 25–50 Gray (Gy) and weaker associations among those treated with CRT doses &lt;20 or 20–25 or &gt;50 Gy (HRs = 2.14, 2.40, and 2.28). The association was replicated in 90 CRT-exposed African survivors (HR = 3.05; P = 0.034). In CRT-exposed Europeans, rs112896372 significantly (P &lt; 0.001) improved predictive ability (AUC = 0.717) for determining stroke risk than nongenetic factors alone (AUC = 0.663) at 30 years since diagnosis, with significant improvement among African survivors (P = 0.047). SNP rs112896372 was further evaluated in three independent datasets including 1,641 European (HR = 1.54; P = 0.055) and 316 African survivors (HR = 1.88; P = 0.283) not treated with CRT, and 166,988 males in the UK Biobank (OR = 1.0012; P = 0.042).

Conclusions:
A novel locus 5p15.33 is associated with stroke risk among childhood cancer survivors, with a possible CRT dose-specific effect. The locus is of potential clinical utility in characterizing individuals who may benefit from surveillance and intervention strategies.
Acquired On-Target Clinical Resistance Validates FGFR4 as a Driver of Hepatocellular Carcinoma
Authors: Hatlen Megan A. , Schmidt-Kittler Oleg , Sherwin Cori Ann , Rozsahegyi Emily , Rubin Nooreen , Sheets Michael P. , Kim Joseph L. , Miduturu Chandrasekhar , Bifulco Neil , Brooijmans Natasja , Shi Hongliang , Guzi Timothy , Boral Andy , Lengauer Christoph , Dorsch Marion , Kim Richard D. , Kang Yoon-Koo , Wolf Beni B. , Hoeflich Klaus P. 
Published: October 2019

Abstract

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide with no clinically confirmed oncogenic driver. Although preclinical studies implicate the FGF19 receptor FGFR4 in hepatocarcinogenesis, the dependence of human cancer on FGFR4 has not been demonstrated. Fisogatinib (BLU-554) is a potent and selective inhibitor of FGFR4 and demonstrates clinical benefit and tumor regression in patients with HCC with aberrant FGF19 expression. Mutations were identified in the gatekeeper and hinge-1 residues in the kinase domain of FGFR4 upon disease progression in 2 patients treated with fisogatinib, which were confirmed to mediate resistance in vitro and in vivo. A gatekeeper-agnostic, pan-FGFR inhibitor decreased HCC xenograft growth in the presence of these mutations, demonstrating continued FGF19–FGFR4 pathway dependence. These results validate FGFR4 as an oncogenic driver and warrant further therapeutic targeting of this kinase in the clinic.

Significance:
Our study is the first to demonstrate on-target FGFR4 kinase domain mutations as a mechanism of acquired clinical resistance to targeted therapy. This further establishes FGF19–FGFR4 pathway activation as an oncogenic driver. These findings support further investigation of fisogatinib in HCC and inform the profile of potential next-generation inhibitors.
See related commentary by Subbiah and Pal, p. 1646.
This article is highlighted in the In This Issue feature, p. 1631
First-in-Human Phase I Study of Fisogatinib (BLU-554) Validates Aberrant FGF19 Signaling as a Driver Event in Hepatocellular Carcinoma
Authors: Kim Richard D. , Sarker Debashis , Meyer Tim , Yau Thomas , Macarulla Teresa , Park Joong-Won , Choo Su Pin , Hollebecque Antoine , Sung Max W. , Lim Ho-Yeong , Mazzaferro Vincenzo , Trojan Joerg , Zhu Andrew X. , Yoon Jung-Hwan , Sharma Sunil , Lin Zhong-Zhe , Chan Stephen L. , Faivre Sandrine , Feun Lynn G. , Yen Chia-Jui , Dufour Jean-Francois , Palmer Daniel H. , Llovet Josep M. , Manoogian Melissa , Tugnait Meera , Stransky Nicolas , Hagel Margit , Kohl Nancy E. , Lengauer Christoph , Sherwin Cori Ann , Schmidt-Kittler Oleg , Hoeflich Klaus P. , Shi Hongliang , Wolf Beni B. , Kang Yoon-Koo 
Published: October 2019

Abstract

Outcomes for patients with advanced hepatocellular carcinoma (HCC) remain poor despite recent progress in drug development. Emerging data implicate FGF19 as a potential HCC driver, suggesting its receptor, FGFR4, as a novel therapeutic target. We evaluated fisogatinib (BLU-554), a highly potent and selective oral FGFR4 inhibitor, in a phase I dose-escalation/dose-expansion study in advanced HCC using FGF19 expression measured by IHC as a biomarker for pathway activation. For dose escalation, 25 patients received 140 to 900 mg fisogatinib once daily; the maximum tolerated dose (600 mg once daily) was expanded in 81 patients. Fisogatinib was well tolerated; most adverse events were manageable, grade 1/2 gastrointestinal events, primarily diarrhea, nausea, and vomiting. Across doses, the overall response rate was 17% in FGF19-positive patients [median duration of response: 5.3 months (95% CI, 3.7–not reached)] and 0% in FGF19-negative patients. These results validate FGFR4 as a targetable driver in FGF19-positive advanced HCC.

Significance:
Fisogatinib elicited clinical responses in patients with tumor FGF19 overexpression in advanced HCC. These results validate the oncogenic driver role of the FGFR4 pathway in HCC and the use of FGF19 as a biomarker for patient selection.
See related commentary by Subbiah and Pal, p. 1646.
This article is highlighted in the In This Issue feature, p. 1631
Estudo da mineralização de cobre em basaltos do Grupo Serra Geral, utilizando difratometria de raios X, microscopia eletrônica de varreduraespectroscopia por energia dispersiva e tomografia com nêutrons
Authors: Garda Gianna Maria , Filgueira Diego Arruda , Pugliesi Reynaldo , Pereira Marco Antônio Stanojev , Sayeg Isaac Jamil 
Published: October 2019

Mineralizações de cobre do tipo Michigan ocorrem nos derrames basálticos do Grupo Serra Geral na região de Nova Prata do Iguaçu, sudoeste do estado do Paraná. Nessas mineralizações, o cobre nativo é o principal mineral de minério e, com a alteração supérgena, transforma-se em óxidos de cobre, malaquita e crisocola, sendo esta encontrada na forma de um precipitado gelatinoso que preenche amígdalas e impregna fraturas no basalto, além de recobrir minerais secundários e outros produtos de alteração. Neste estudo, foram utilizadas as técnicas de difratometria de raios X e microscopia eletrônica de varredura-espectroscopia por energia dispersiva (MEV-EDS) para a caracterização do grau de cristalinidade e composição química da crisocola e a identificação de outros materiais hidrogenados, como subsídio para o imageamento 3D por tomografia com nêutrons. A crisocola destacou-se como um eficiente atenuador de nêutrons, obtendo-se coeficiente de atenuação linear da ordem de 0,8–1,3 cm-1, ao passo que, para o corpo de minério (basalto), obteve-se 0,5–0,6 cm-1. O contraste entre os coeficientes permitiu a obtenção de imagens tomográficas e filmes de boa resolução, em que se pôde visualizar a distribuição da crisocola na amostra de basalto e estimar como fração volumétrica de crisocola no corpo de minério valores entre 0,9 e 1,4%, obtendo-se o valor de 7,8% em volume de crisocola para uma das amostras. A utilização integrada das três técnicas analíticas demonstrou que esta pode ser uma ferramenta para avaliação do potencial mineral nas fases iniciais da prospecção mineral, especialmente quando as substâncias de interesse são ricas em hidrogênio.
O parque agroambiental como nova categoria de sistema de espaços livres
Authors: Queiroz Alessandra Natali , Queiroga Eugênio Fernandes , Merlin José Roberto 
Published: October 2019

O presente artigo tem como tema o estudo de sistemas de espaços livres e a urbanização contemporânea na região de Limeira, integrante da Região Administrativa de Campinas - SP. De especial atenção é a configuração do território, como unidade de projeto para um “parque regional contemporâneo” ou, como se propôs chamar, “parque agroambiental”. O “parque agroambiental” não é uma solução simples, mas uma possibilidade de pensar e agir. Pode-se, por meio dele, ajustar o foco de leitura da realidade local, buscando-se mecanismos mais coerentes para nela atuar. Diferentemente de outras regiões de importantes recursos naturais, como a região metropolitana de São Paulo, o conceito do parque objetiva trabalhar uma área econômica e socialmente uniforme, onde a fauna e a flora são quase inexistentes, visto terem sido substituídas pela urbanização e pelas áreas destinadas à produção agrícola para o mercado global. O desafio aqui proposto é tornar o parque regional contemporâneo objeto de debate para políticas públicas de atendimento às necessidades sociais e ambientais. Podem ser práticas de lazer, esportes e/ou contemplativas, atividades culturais de identidade regional, de produção agrícola ou florestal, de conservação de ecossistemas, por meio das quais se definem diferentes níveis e escalas de intervenção e de acessibilidade aos lugares. Propõe-se o conceito de “parque agroambiental” como instrumento de planejamento regional e ambiental.
The Philippines in 2018: a Year of Disruption and Consolidation
Authors: Aguirre Arjan 
Published: October 2019

Abstract
2018 is a year of so much uneasiness and tension in Philippine politics. It saw one of the greatest crises in the Supreme Court, the bloodiest period in local politics of late, and successive attempts to silence critics of the president and the government. This year also witnessed major political alignments in the Duterte administration: a change in the leadership of the Senate, the election of Gloria Macapagal Arroyo as Speaker of the House, the rivalry between Hugpong ng Pagbabago and Partido Demokratiko ng Pilipinas-Lakas ng Bayan, and the eventual termination of the alliance with the radical left. This review aims to understand these developments in Philippine politics. It seeks to know why are there so many rifts and shifts in the political rule of Duterte. These changes can be interpreted as part of an ongoing transition toward democratic regression under the Duterte regime. The disruptive events that ensued throughout the year should be understood as the offshoot of the extant efforts to alter the political status quo since the election of Duterte in 2016. The administration uses these events to consolidate its power by rallying its supporters for the 2019 midterm elections and reconfiguring the alignments within the Duterte bloc.
Perspectives on Sea- and Lake-Effect Precipitation from Japan’s “Gosetsu Chitai”
Authors: Steenburgh W. James , Nakai Sento 
Published: October 2019

AbstractA remarkable snow climate exists on the Japanese islands of Honshu and Hokkaido near the Sea of Japan. Mean annual snowfall in this “gosetsu chitai” (heavy snow area) exceeds 600 cm (235 in.) in some near-sea-level cities and 1,300 cm (512 in.) in some mountain areas. Much of this snow falls from December to February during the East Asian winter monsoon when frequent cold-air outbreaks occur over the Sea of Japan. The resulting sea-effect precipitation systems share similarities with lake-effect precipitation systems of the Laurentian Great Lakes of North America, but are deeper, are modulated by the regional coastal geometry and topography, and can sometimes feature transversal mode snowbands. Snowfall can maximize in the lowlands or the adjoining mountains depending on the direction and strength of the boundary layer flow. Remarkable infrastructure exists in Japan for public safety, road and sidewalk maintenance, and avalanche mitigation, yet snow-related hazards claim more than 100 lives annually. For winter recreationists, there is no surer bet for deep powder than the mountains of Honshu and Hokkaido near the Sea of Japan in January, but the regional snow climate is vulnerable to global warming, especially in coastal areas. Historically, collaborative studies of sea- and lake-effect precipitation systems involving North American and Japanese scientists have been limited. Significant potential exists to advance our understanding and prediction of sea- and lake-effect precipitation based on studies from the Sea of Japan region and efforts involving meteorologists in North America, Japan, and other sea- and lake-effect regions.
The meagre outcomes of HoNOS
Authors: Bender Keith G 
Published: October 2019

Objective: To ask the Leginski question of an outcome measurement process. Method: Articles elicited by a literature search of ‘HoNOS’ are analysed for evidence of its value or cost effectiveness to consumers, clinicians or administrators. Results: None of the 260 studies elicited by the search attempted to assess the cost of the use of Health of the Nation Outcome Scale (HoNOS). One study investigated the effect of routine outcome measurement, finding that it failed to result in the provision of evidence-based care. One study reported positive outcomes. Conclusions: The ability of HoNOS to improve the health and social functioning of mentally ill people has not been demonstrated. The widespread use of HoNOS as a routine outcome measure is not justified by the evidence.