bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting STAT5 or STAT5-Regulated Pathways Suppresses Leukemogenesis of Ph+ Acute Lymphoblastic Leukemia
Authors: Minieri Valentina , De Dominici Marco , Porazzi Patrizia , Mariani Samanta A. , Spinelli Orietta , Rambaldi Alessandro , Peterson Luke F. , Porcu Pierluigi , Nevalainen Marja T. , Calabretta Bruno 
Published: August 2018

Abstract
Combining standard cytotoxic chemotherapy with BCR-ABL1 tyrosine kinase inhibitors (TKI) has greatly improved the upfront treatment of patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). However, due to the development of drug resistance through both BCR-ABL1–dependent and -independent mechanisms, prognosis remains poor. The STAT5 transcription factor is activated by BCR-ABL1 and by JAK2-dependent cytokine signaling; therefore, inhibiting its activity could address both mechanisms of resistance in Ph+ ALL. We show here that genetic and pharmacologic inhibition of STAT5 activity suppresses cell growth, induces apoptosis, and inhibits leukemogenesis of Ph+ cell lines and patient-derived newly diagnosed and relapsed/TKI-resistant Ph+ ALL cells ex vivo and in mouse models. STAT5 silencing decreased expression of the growth-promoting PIM-1 kinase, the apoptosis inhibitors MCL1 and BCL2, and increased expression of proapoptotic BIM protein. The resulting apoptosis of STAT5-silenced Ph+ BV173 cells was rescued by silencing of BIM or restoration of BCL2 expression. Treatment of Ph+ ALL cells, including samples from relapsed/refractory patients, with the PIM kinase inhibitor AZD1208 and/or the BCL2 family antagonist Sabutoclax markedly suppressed cell growth and leukemogenesis ex vivo and in mice. Together, these studies indicate that targeting STAT5 or STAT5-regulated pathways may provide a new approach for therapy development in Ph+ ALL, especially the relapsed/TKI-resistant disease.
Significance:Suppression of STAT5 by BCL2 and PIM kinase inhibitors reduces leukemia burden in mice and constitutes a new potential therapeutic approach against Ph+ ALL, especially in tyrosine kinase inhibitor-resistant disease. Cancer Res; 78(20); 5793–807. ©2018 AACR.
Patient-Derived Xenograft Models Reveal Intratumor Heterogeneity and Temporal Stability in Neuroblastoma
Authors: Braekeveldt Noémie , von Stedingk Kristoffer , Fransson Susanne , Martinez-Monleon Angela , Lindgren David , Axelson Håkan , Levander Fredrik , Willforss Jakob , Hansson Karin , Øra Ingrid , Backman Torbjörn , Börjesson Anna , Beckman Siv , Esfandyari Javanshir , Berbegall Ana P. , Noguera Rosa , Karlsson Jenny , Koster Jan , Martinsson Tommy , Gisselsson David , Påhlman Sven , Bexell Daniel 
Published: August 2018

Abstract
Patient-derived xenografts (PDX) and the Avatar, a single PDX mirroring an individual patient, are emerging tools in preclinical cancer research. However, the consequences of intratumor heterogeneity for PDX modeling of biomarkers, target identification, and treatment decisions remain underexplored. In this study, we undertook serial passaging and comprehensive molecular analysis of neuroblastoma orthotopic PDXs, which revealed strong intrinsic genetic, transcriptional, and phenotypic stability for more than 2 years. The PDXs showed preserved neuroblastoma-associated gene signatures that correlated with poor clinical outcome in a large cohort of patients with neuroblastoma. Furthermore, we captured spatial intratumor heterogeneity using ten PDXs from a single high-risk patient tumor. We observed diverse growth rates, transcriptional, proteomic, and phosphoproteomic profiles. PDX-derived transcriptional profiles were associated with diverse clinical characteristics in patients with high-risk neuroblastoma. These data suggest that high-risk neuroblastoma contains elements of both temporal stability and spatial intratumor heterogeneity, the latter of which complicates clinical translation of personalized PDX–Avatar studies into preclinical cancer research.
Significance: These findings underpin the complexity of PDX modeling as a means to advance translational applications against neuroblastoma. Cancer Res; 78(20); 5958–69. ©2018 AACR.
Spatially Resolved Transcriptomics Enables Dissection of Genetic Heterogeneity in Stage III Cutaneous Malignant Melanoma
Authors: Thrane Kim , Eriksson Hanna , Maaskola Jonas , Hansson Johan , Lundeberg Joakim 
Published: August 2018

Abstract
Cutaneous malignant melanoma (melanoma) is characterized by a high mutational load, extensive intertumoral and intratumoral genetic heterogeneity, and complex tumor microenvironment (TME) interactions. Further insights into the mechanisms underlying melanoma are crucial for understanding tumor progression and responses to treatment. Here we adapted the technology of spatial transcriptomics (ST) to melanoma lymph node biopsies and successfully sequenced the transcriptomes of over 2,200 tissue domains. Deconvolution combined with traditional approaches for dimensional reduction of transcriptome-wide data enabled us to both visualize the transcriptional landscape within the tissue and identify gene expression profiles linked to specific histologic entities. Our unsupervised analysis revealed a complex spatial intratumoral composition of melanoma metastases that was not evident through morphologic annotation. Each biopsy showed distinct gene expression profiles and included examples of the coexistence of multiple melanoma signatures within a single tumor region as well as shared profiles for lymphoid tissue characterized according to their spatial location and gene expression profiles. The lymphoid area in close proximity to the tumor region displayed a specific expression pattern, which may reflect the TME, a key component to fully understanding tumor progression. In conclusion, using the ST technology to generate gene expression profiles reveals a detailed landscape of melanoma metastases. This should inspire researchers to integrate spatial information into analyses aiming to identify the factors underlying tumor progression and therapy outcome.
Significance: Applying ST technology to gene expression profiling in melanoma lymph node metastases reveals a complex transcriptional landscape in a spatial context, which is essential for understanding the multiple components of tumor progression and therapy outcome. Cancer Res; 78(20); 5970–9. ©2018 AACR.
Gemcitabine Synergizes with Immune Checkpoint Inhibitors and Overcomes Resistance in a Preclinical Model and Mesothelioma Patients
Authors: Tallón de Lara Paulino , Cecconi Virginia , Hiltbrunner Stefanie , Yagita Hideo , Friess Martina , Bode Beata , Opitz Isabelle , Vrugt Bart , Weder Walter , Stolzmann Paul , Felley-Bosco Emanuela , Stahel Rolf A. , Tischler Verena , Britschgi Christian , Soldini Davide , van den Broek Maries , Curioni-Fontecedro Alessandra 
Published: August 2018

Abstract

Purpose:
Combination of immune checkpoint inhibitors with chemotherapy is under investigation for cancer treatment.

Experimental Design:
We studied the rationale of such a combination for treating mesothelioma, a disease with limited treatment options.

Results:
The combination of gemcitabine and immune checkpoint inhibitors outperformed immunotherapy alone with regard to tumor control and survival in a preclinical mesothelioma model; however, the addition of dexamethasone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response. Furthermore, treatment with gemcitabine plus anti-PD-1 resulted in an objective clinical response in two patients with mesothelioma, who were resistant to gemcitabine or anti-PD-1 as monotherapy.

Conclusions:
Thus, treatment of mesothelioma with a combination of gemcitabine with immune checkpoint inhibitors is feasible and results in synergistic clinical response compared with single treatment in the absence of steroids.
Additional information on Meloidogyne polycephannulata and its proposal as a junior synonym of M. incognita
Authors: Monteiro Jessica M.S. , Mattos Vanessa S. , Santos Marcilene F.A. , Gomes Ana C.M.M. , Correa Valdir R. , Sousa Daniela A. , Cares Juvenil E. , Pinheiro Jadir B. , Carneiro Regina M.D.G. 
Published: August 2018

SummaryThe type population ofMeloidogyne polycephannulatais synonymised withM. incognitabased on morphological and morphometric characters, as well as biochemical, molecular and phylogenetic studies. Morphological variability and a wide host range were reported forM. incognitaduring its first description and later re-description.Meloidogyne polycephannulatawas described in Brazil from specimens collected in a carrot field (type population). The esterase phenotype (Est) characterised for this species was identical to the phenotype Est I2 ofM. incognita, the most ubiquitous phenotype used for diagnostics. Morphological and morphometric characters of the descriptions of the two nominal species showed major similarities, as well as variability within the range of variation detected inM. incognita. In PCR assays, three SCAR markers species-specific forM. incognita(incK14 F/R, Mi/FR and incB06 F/R) amplified the same fragments of 399 bp, 955 bp and 1200 bp, respectively, for populations in both species. In phylogenetic studies based either on concatenated sequences of ITS1-5.8S-ITS2, D2-D3 rRNA, mitochondrialCOII regions or on RAPD and AFLP data, the populations of both species grouped in the same clade with high bootstrap support. Altogether, these results provide congruent evidence that theM. polycephannulatatype isolate deposited at the Embrapa Cryopreserved National Collection of Root-knot Nematodes is not a valid species but rather a junior synonym ofM. incognita.
Don’t Sleep on It: An Examination of Storm Naming and Potential Heuristic Effects on Twitter
Authors: Lin Xialing , Rainear Adam M. , Spence Patric R. , Lachlan Kenneth A. 
Published: August 2018

Abstract
Humans often prefer representations that are cognitively easier to store, and these representations are easier to retrieve later to make judgments about events. Exemplification theory draws on evolutionary logic and argues that simple, iconic, concrete, and emotionally arousing depictions of events (exemplars) are favored and thus more likely to be stored and used than are abstract, inconsequential depictions or representations. This study examined exemplified aspects of storm warnings in a Twitter feed. A three-condition study was completed, and variables examined included storm severity, susceptibility, hazard, outrage, and willingness to change or engage in specific behaviors. Results suggest the possibility of a sleeper effect impacting perceptions of severity. Results are discussed in theoretical and practical applications along with the consideration of other theories to be applied to future research.
Obstructive Sleep Apnea in Children with Down Syndrome: Demographic, Clinical, and Polysomnographic Features
Authors: Chamseddin Bahir H. , Johnson Romaine F. , Mitchell Ron B. 
Published: August 2018

ObjectivesTo evaluate demographic, clinical, and polysomnographic features of children with Down syndrome suspected of having obstructive sleep apnea. To identify factors that predict severe obstructive sleep apnea among children with Down syndrome.Study DesignCase series with chart review.SettingChildren's Medical Center Dallas / University of Texas Southwestern Medical Center.Subject and MethodsDemographic, clinical, and polysomnographic data were collected for children with Down syndrome aged 2 to 18 years. Simple and multivariable regression models were used to study predictors of severe obstructive sleep apnea (apnea‐hypopnea index ≥10). P≤. 05 was considered significant.ResultsA total of 106 children with Down syndrome were included, with 89 (84%) <12 years old, 56 (53%) male, 72 (68%) Hispanic, 15 (14%) African American, and 14 (13%) Caucasian. Ninety percent of children had ≥1 medical comorbidities; 95 (90%) patients had obstructive sleep apnea; and 46 (44%) had severe obstructive sleep apnea. The mean SaO2 nadir was lower among obese than nonobese children (80% vs 85%, P =. 02). Obese versus nonobese patients had a higher prevalence of severe obstructive sleep apnea (56% vs 35%, P =. 03). Severe OSA was associated with heavier weight (odds ratio = 1.0, 95% CI: 1.0‐1.1, P =. 002) and age ≥12 years (odds ratio = 1.2, 95% CI: 0.2‐2.5, P =. 02). The multivariable model showed that severe obstructive sleep apnea was associated only with weight (odds ratio = 1.1, 95% CI: 1.0‐1.1, P =. 02).ConclusionObese children with DS are at a high risk for severe OSA, with weight as the sole risk factor. The results of this study show the importance of monitoring the weight of children with DS and counseling parents of children with DS about weight loss.
Diagnostic significance of magnetic resonance imaging in patients with cervical cancer after brachytherapy: a meta-analysis
Authors: Zhang Ji , Tian Weizhong , Bu Xinhua , Wang Xiulan , Tian Fangzheng , Wu Linyun 
Published: August 2018

Background Patients with uterine cervical cancer suffer high mortality. Accurate detection of a residual tumor by magnetic resonance imaging (MRI) during and after directed brachytherapy (BCT) is crucial for the success of cancer treatment and is a significant predictor of patient survival. Purpose To determine the diagnostic significance of MRI in detecting residual tumor tissue after BCT. Material and Methods The Web of Knowledge, Cochrane Library, and PubMed were systematically searched (January 1997 to December 2016) for post-brachytherapy MRI studies that measured residual tumors in patients with uterine cervical cancer. All data were analyzed using the Meta-Disc 1.4 program. Results Four clinical studies consisting of 163 patients (147 of whom were included in the present analysis) who were diagnosed with uterine cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) staging system were included in the study. All the patients received BCT and underwent MRI detection of residual tumors tissue. In studies where the accuracy of MRI detection was confirmed by histological tests or gynecological tests, the summary estimates of specificity, sensitivity, positive predictive value, negative predictive value, and accuracy were 88.5%, 83.5%, 53.5%, 97.1%, and 84.3%, respectively. Conclusion MRI-directed BCT is commonly used for cervical cancer patients. Based on our investigation of four independent studies, MRI showed better prediction of positive results than negative results in patients with cervical cancer after BCT. However, more data on the greater numbers of patients are needed to establish the accuracy of MRI detection of cervical cancer after BCT.
A Model-Based Embedding Technique for Segmenting Customers
Authors: Jagabathula Srikanth , Subramanian Lakshminarayanan , Venkataraman Ashwin 
Published: August 2018

We consider the problem of segmenting a large population of customers into nonoverlapping groups with similar preferences, using diverse preference observations such as purchases, ratings, clicks, and so forth, over subsets of items. We focus on the setting where the universe of items is large (ranging from thousands to millions) and unstructured (lacking well-defined attributes) and each customer provides observations for only a few items. These data characteristics limit the applicability of existing techniques in marketing and machine learning. To overcome these limitations, we propose a model-based embedding technique, which takes the customer observations and a probabilistic model class generating the observations as inputs, and outputs an embedding—a low-dimensional vector representation in Euclidean space—for each customer. We then cluster the embeddings to obtain the segments. Theoretically, we derive precise necessary and sufficient conditions that guarantee asymptotic recovery of the true segments under a standard latent class setup. Empirically, we demonstrate the speed and performance of our method in two real-world case studies: (a) up to 84% improvement in accuracy of new movie recommendations on the MovieLens data set and (b) up to 8% improvement in the performance of similar product recommendations algorithm on an offline data set at eBay. We show that our method outperforms standard latent class, empirical Bayesian, and demographic-based techniques. The online appendix is available at https://doi.org/10.1287/opre.2018.1739 .
A SÚMULA 549 DO STJ: UM ATAQUE À VISÃO CONSTITUCIONAL DO DIREITO CIVIL CONTEMPORÂNEO
Authors: Faria Lucas Oliveira 
Published: August 2018

O artigo em questão visa analisar as razões de aprovação da Súmula 549 em outubro de 2015 pelo Superior Tribunal de Justiça, súmula esta que perpetua o entendimento de que é válida a penhora do bem de família do fiador de locação. O escrito pretende explicitar de forma minuciosa desde a razão de ser do instituto do bem de família, remetendo à sua origem, até mesmo ao modo como este tipo de instituto se fundamenta no ordenamento constitucional brasileiro, buscando entender se tanto a decisão jurisprudencial do Superior Tribunal de Justiça, quanto à decisão legislativa de inclusão da exceção de impenhorabilidade do único imóvel do fiador de locação em questão coadunam com a Constituição Federal de 1988 e com o Direito Civil moderno. Palavras-chave: Bem de Família; Fiador; Constituição; Súmula 549; Direito Civil
COLABORAÇÃO ENTRE AS FAZENDAS PÚBLICAS NA VIGÊNCIA DA LEI COMPLEMENTAR 105/2001
Authors: Campos Hélio Silvio Ourém , Oliveira Breno Duarte Ribeiro de 
Published: August 2018

A despeito do julgamento em 24.02.2016, pelo Supremo Tribunal Federal do RE 601.314 - SP, a questão do sigilo bancário e sua oponibilidade aos órgãos da Administração Tributária continuam a despertar a atenção da comunidade jurídica. A posição adotada pela Corte discrepou frontalmente de entendimento anterior justificado no RE 389.808 - PR, que poucos anos antes definira a necessidade de requisição judicial prévia como requisito ao acesso de dados bancários de contribuintes pela Administração Fazendária. O teor dos votos da minoria e maioria dos ministros do Supremo revela uma tendência de polarização ideológica, o que pode explicar a brusca alteração de posicionamento jurisprudencial em pouco tempo, sem qualquer alteração no plano legislativo.O objetivo do trabalho é o estudo das premissas argumentativas utilizadas nos julgados analisados e o confronto destas premissas com as bases estabelecidas nos cânones interpretativos clássicos(interpretação gramatical, lógico-sistemática e teleológica).O artigo parte da hipótese de que a utilização legal de mecanismos constitucionalmente previstos e regulamentados visando a eficiência e o aperfeiçoamento das ações fiscalizatórias não passa necessariamente por questão ideológica.Para a elaboração do artigo adotou-se a abordagem metodológica qualitativa, classificada em relação aos objetivos com exploratória, com a análise textual da fundamentação utilizada na elaboração de julgados específicos. Nesse aspecto fixa-se a abordagem da integração entre as fazendas públicas e o intercâmbio de informações anteriormente protegidas pelo sigilo em uma perspectiva jurídica iniciada por uma construção dogmática fundada na Constituição, nas Leis e normas regulamentares, a partir de cânones clássicos da interpretação jurídica, culminando por defender, em conclusão, a possibilidade da utilização das informações colhidas em limites estritamente controlados, de modo cooperativo entres os órgão integrantes das administração fazendária, em todas esferas integrantes do estado.
Simulation of Airflow in the Burning Cave of an Auxiliary Heating System in a Greenhouse
Authors: Xu Zhanyang , Liu Wenhe , Wang Tieliang , Yu Wei , Zhang Yuqing 
Published: August 2018

Abstract. In this study, numerical simulations of airflow were carried out in the burning cave of an auxiliary heating system. Experimental measurements were also conducted to verify the performance of the numerical model, and turbulent airflow in the burning cave was considered. The numerical simulation in the burning cave was performed for three cases:(1) with a baffle at the bottom of the burning cave entrance, (2) without a baffle at the burning cave entrance, and (3) with a baffle at the top of the burning cave entrance. The turbulent airflow was modeled using the realizable k-e turbulence model as well as the non-equilibrium wall function. The airflow velocity was assessed in the burning cave, and some suggestions were given to improve the performance of the burning cave. The results showed that the airflow entering the burning cave differed due to different positions of the baffle. The smoldering combustion was more even and the burning rate could be controlled more easily when the baffle was placed at the top of the burning cave entrance, making the airflow enter the burning cave through the bottom of the baffle. The results also showed that the maximum airflow velocity in the burning cave increased with increased distance between the baffle and the bottom of the burning cave. Keywords: Airflow, Burning cave, Greenhouse, Simulation.
Assessment of Water Quality and Fish Production in an Intensive Pond Aquaculture System
Authors: Bao Weijun , Zhu Songming , Guo Shuirong , Wang Li , Fang Han , Ke Bin , Ye Zhangying 
Published: August 2018

Abstract. Pond aquaculture plays a major role in world aquaculture production, especially in China. To make pond aquaculture more precise, ecologically sound, and efficient, in this study, an intensive pond aquaculture system (IPAS) was designed and built to produce freshwater fish that are commonly reared in China. Aquatic plants and filter-feeding, omnivorous fish were used to rehabilitate the aquaculture water quality, and the particle size distribution (PSD) model of suspended solids in the pond raceways was investigated. The results showed that the water quality in the purification pond was improved compared to that in the sedimentation basins, and it was close to the water quality in the raceways, which were within the acceptable range. The number distribution of suspended solids can be described by the power law model (R2 = 0.901 ± 0.032), which can provide guidance for solids removal using different methods. Moreover, during one production cycle, economic benefits of the IPAS were also evaluated; the return on investment (ROI) of 35.69% and benefit cost ratio (BCR) of 1.36 indicated that this kind of aquaculture mode has achieved a better profit. There are many fish species in China, so developing an IPAS with a wide application range requires further study in the future. Keywords: Airlift push-water aerator, Aquatic plant, Drum filter, Intensive pond aquaculture system, Particle size distribution, Purification pond.
The Cardrona Hotel: Creating a New Zealand heritage icon
Authors: Carpenter Lloyd William 
Published: August 2018

Abstract
On the road between the famed tourist hubs of Wanaka and Arrowtown on New Zealand’s South Island lies the former 1860s gold-rush-era town of Cardrona. There, beside an immaculately kept heritage precinct of nineteenth-century wooden buildings, tourists pause at the Cardrona Hotel, an architectural relic of the rush for gold in Central Otago. This hotel has emerged in guidebooks and local histories, and on social media sites and ratings guides, as a tourism and craft beer ‘must-do’ and, according to Heritage New Zealand, has become New Zealand’s most photographed hotel. Its popularity defies belief and even logic, and yet each new visitor to the region appears determined to leave with at least one photograph of its distinctive facade in their portfolio. The story behind the survival of the heritage-listed structure and its elevation to the heights of popular and tourist culture ‘icon’ status stems from a combination of its remote location, the enduring romanticization of the gold rush, a succession of eccentric owners, the mythopoeia of a popular book from the 1950s and its inclusion in a brewer’s marketing campaign. Each has scaffolded the Cardrona Hotel to become iconic to the gold-rush era, heritage tourism and New Zealand’s popular culture and identity.