bluuebunny/crossref_metadata_2025_split huggingface dataset:
Discordant and heterogeneous clinically relevant genomic alterations in circulating tumor cells vs plasma DNA from men with metastatic castration resistant prostate cancer
Authors: Gupta Santosh , Hovelson Daniel H. , Kemeny Gabor , Halabi Susan , Foo Wen‐Chi , Anand Monika , Somarelli Jason A. , Tomlins Scott A. , Antonarakis Emmanuel S. , Luo Jun , Dittamore Ryan V. , George Daniel J. , Rothwell Colin , Nanus David M. , Armstrong Andrew J. , Gregory Simon G. 
Published: November 2019

AbstractCirculating tumor cell (CTC) and cell‐free (cf) DNA‐based genomic alterations are increasingly being used for clinical decision‐making in oncology. However, the concordance and discordance between paired CTC and cfDNA genomic profiles remain largely unknown. We performed comparative genomic hybridization (CGH) on CTCs and cfDNA, and low‐pass whole genome sequencing (lpWGS) on cfDNA to characterize genomic alterations (CNA) and tumor content in two independent prospective studies of 93 men with mCRPC treated with enzalutamide/abiraterone, or radium‐223. Comprehensive analysis of 69 patient CTCs and 72 cfDNA samples from 93 men with mCRPC, including 64 paired samples, identified common concordant gains inFOXA1,AR, andMYC, and losses inBRCA1,PTEN, andRB1between CTCs and cfDNA. ConcordantPTENloss and discordantBRCA2gain were associated with significantly worse outcomes in Epic AR‐V7 negative men with mCRPC treated with abiraterone/enzalutamide. We identified and externally validated CTC‐specific genomic alternations that were discordant in paired cfDNA, even in samples with high tumor content. These CTC/cfDNA‐discordant regions included key genomic regulators of lineage plasticity, osteomimicry, and cellular differentiation, includingMYCNgain in CTCs (31%) that was rarely detected in cfDNA. CTCMYCNgain was associated with poor clinical outcomes in AR‐V7 negative men and small cell transformation. In conclusion, we demonstrated concordance of multiple genomic alterations across CTC and cfDNA platforms; however, some genomic alterations displayed substantial discordance between CTC DNA and cfDNA despite the use of identical copy number analysis methods, suggesting tumor heterogeneity and divergent evolution associated with poor clinical outcomes.
Molecular characteristics of terminal deoxynucleotidyl transferase negative precursor B‐cell phenotype Burkitt leukemia with IGH‐MYC rearrangement
Authors: Yoon Jung , Yun Jae Won , Jung Chul Won , Ju Hee Young , Koo Hong Hoe , Kim Sun‐Hee , Kim Hee‐Jin 
Published: November 2019

AbstractPrecursor B cell phenotype Burkitt lymphoma/leukemia with IGH‐MYC is a rare subtype of Burkitt lymphoma (BL). BL and B lymphoblastic leukemia/lymphoma (B‐ALL/LBL) differ as regards treatment and the distinction between these two entities is crucial. Patients demonstrating a terminal deoxynucleotidyl transferase (TdT)‐positive precursor B cell phenotype with IGH‐MYC rearrangement have been reported to be molecularly distinct from BL and closer to B‐ALL/LBL. We investigated the molecular characteristics of two cases of a rare but distinct TdT‐negative precursor B cell phenotype BL. Both patients showed FAB L3 morphology with IGH‐MYC translocation, but had precursor B cell immunophenotypes including dim to moderate expression of CD45 and absence of BCL6, CD20, monoclonal kappa, and lambda light chain expression. To characterize the molecular features, we performed exome sequencing and analyzed the breakpoint junction of the IGH‐MYC rearrangement. We detected KMT2D mutations in both cases, a rarely acquired chromatin modifying gene mutation in BL. The breakpoint analysis revealed that the IGH‐MYC rearrangement occurred due to an aberrant VDJ recombination in one case. The treatment protocols differed, including high‐grade lymphoma treatment and standard B‐ALL treatment. Complete remission was achieved in the patient who received B‐ALL treatment. The degree of resemblance of BL and B‐ALL differed between two cases, but the molecular pathogenesis and manifesting features of both TdT‐negative precursor B cell phenotype BL case were distinct from classic BL, which indicates the need for a better understanding of this uncommon entity that does not fit in current diagnostic and classification categories.
Role of astrocyte purinergic signaling in epilepsy
Authors: Nikolic Ljiljana , Nobili Paola , Shen Weida , Audinat Etienne 
Published: November 2019

AbstractEpilepsy is characterized by unpredictable recurrent seizures resulting from hypersynchronous discharges from neuron assemblies. Increasing evidence indicates that aberrant astrocyte signaling to neurons plays an important role in driving the network hyperexcitability. Purinergic signaling is central in neuron–glia and glia–glia interactions and dysfunctions in communication pathways involving purinergic receptors have been reported in various CNS pathologies, such as Alzheimer disease, stroke, major depression, schizophrenia, and epilepsy. In the present review we will first discuss the mechanisms by which astrocytes influence neuronal activity. We will then review in more details recent evidence indicating that dysregulation of astrocyte purinergic signaling actively contributes to the appearance of abnormal neuronal activity in epilepsy.
Evaluation of 18F‐FDG PET/CT as an early imaging biomarker for response monitoring after radiochemotherapy using cetuximab in head and heck squamous cell carcinoma
Authors: de Galiza Barbosa Felipe , Riesterer Oliver , Tanadini‐Lang Stephanie , Stieb Sonja , Studer Gabriela , Pruschy Martin , Huber Gerhard F. , Huellner Martin W. , Stolzmann Paul , Veit‐Haibach Patrick 
Published: November 2019

AbstractBackgroundTo determine whether 18F‐PET/CT is able to identify treatment response as early as 1 week after the end of chemoradiotherapy, whether 18F‐PET/CT can identify prognostic markers concerning progression free survival and can identify patients who need additional consolidation therapy.MethodsA total of 54 patients with head and neck cancer were prospectively enrolled in this single‐center, randomized study from 03/2012‐04/2015. Patients underwent FDG‐PET/CT imaging at three predefined time points: pretreatment (PET/CT1), 1 week postprimary radiochemotherapy (PET/CT2) and 3 months postprimary radiochemotherapy (PET/CT3). Tumors were assessed quantitatively based on size and glucose uptake (SUVmax) concerning response at each time point. Response assessment was correlated with progression free survival. All patients had a minimum follow‐up period of 18 months. Multivariate regression analysis was performed to find independent predictors for progression free survival (PFS).ResultsThirty‐two (32) patients (64%) overall remained disease free, 11 patients (22%) had recurrence and 7 patients (14%) had persistent disease. There was no significantly different metabolic parameter ratio found concerning responders and nonresponders at posttreatment (PET/CT2 and 3) time points (P > .05) during clinical follow‐up. Multivariate regression analysis demonstrated both SUVmax and diameter assessed at time point PET/CT3 represent independent predictors of progression free survival (PFS). There was also no statistically significant difference in PFS between responders and nonresponders by means of PET/CT2 in both study arms (P > .05). Imaging responders at time point PET/CT3 showed a significantly longer PFS compared to nonresponders after the end of consolidation therapy (P < .01).ConclusionsEarly response of head/neck cancer after radiochemotherapy can be accurately assessed with PET/CT 1 week after RCT. SUVmax and lesion diameter are independent predictors of PFS at time point PET/CT3. PET/CT2 has no prognostic value concerning PFS and cannot identify high risk patients for consolidation therapy. Imaging responders showed a significantly longer PFS compared to nonresponders and therefore PET/CT might serve as a prognostic biomarker.Trial registrationClinical Trials.gov identifier: NCT01435252.
Interleukin‐22 Ameliorates Neutrophil‐Driven Nonalcoholic Steatohepatitis Through Multiple Targets
Authors: Hwang Seonghwan , He Yong , Xiang Xiaogang , Seo Wonhyo , Kim Seung‐Jin , Ma Jing , Ren Tianyi , Park Seol Hee , Zhou Zhou , Feng Dechun , Kunos George , Gao Bin 
Published: November 2019

Background and Aims
Nonalcoholic fatty liver disease encompasses a spectrum of diseases ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and liver cancer. At present, how simple steatosis progresses to NASH remains obscure and effective pharmacological therapies are lacking. Hepatic expression of C‐X‐C motif chemokine ligand 1 (CXCL1), a key chemokine for neutrophil infiltration (a hallmark of NASH), is highly elevated in NASH patients but not in fatty livers in obese individuals or in high‐fat diet (HFD)‐fed mice. The aim of this study was to test whether overexpression of CXCL1 itself in the liver can induce NASH in HFD‐fed mice and to test the therapeutic potential of IL‐22 in this new NASH model.

Approach and Results
Overexpression of Cxcl1 in the liver alone promotes steatosis‐to‐NASH progression in HFD‐fed mice by inducing neutrophil infiltration, oxidative stress, and stress kinase (such as apoptosis signal‐regulating kinase 1 and p38 mitogen‐activated protein kinase) activation. Myeloid cell‐specific deletion of the neutrophil cytosolic factor 1 (Ncf1)/p47

phox
gene, which encodes a component of the NADPH oxidase 2 complex that mediates neutrophil oxidative burst, markedly reduced CXCL1‐induced NASH and stress kinase activation in HFD‐fed mice. Treatment with interleukin (IL)‐22, a cytokine with multiple targets, ameliorated CXCL1/HFD‐induced NASH or methionine‐choline deficient diet‐induced NASH in mice. Mechanistically, IL‐22 blocked hepatic oxidative stress and its associated stress kinases via the induction of metallothionein, one of the most potent antioxidant proteins. Moreover, although it does not target immune cells, IL‐22 treatment attenuated the inflammatory functions of hepatocyte‐derived, mitochondrial DNA‐enriched extracellular vesicles, thereby suppressing liver inflammation in NASH.

Conclusions
Hepatic overexpression of CXCL1 is sufficient to drive steatosis‐to‐NASH progression in HFD‐fed mice through neutrophil‐derived reactive oxygen species and activation of stress kinases, which can be reversed by IL‐22 treatment via the induction of metallothionein.
Corporate social responsibility and bankruptcy probability: Exploring the role of market competition, intellectual capital, and equity cost
Authors: Kamalirezaei Hashem , Anvary Rostamy Ali Asghar , Saeedi Ali , Khodaei Valeh Zaghard Mohammad 
Published: November 2019

AbstractThis research investigates the relationship between corporate social responsibility and the probability of bankruptcy and explains the moderating role of the structure of market competition, intellectual capital, and equity cost on this relationship. Using a sample of the Tehran Stock Exchange during 2009–2016, panel data, and logit‐ranking model, we find an inverse relationship between corporate social responsibility and the probability of bankruptcy. Results from additional analyses show that corporate social responsibility has a significant inverse relationship with the probability of bankruptcy and when the market structure moves to a monopoly, the probability of bankruptcy is reduced due to high market entry costs for other companies. Overall, we document that corporate social responsibility plays an important roles in reducing the probability of bankruptcy of companies.
Blockchain distributed ledger technology: An introduction and focus on smart contracts
Authors: Hamilton Marc 
Published: November 2019

AbstractThe rapid evolution of the blockchain and distributed ledger technology and the associated applications will require many changes in the way business is transacted and how transactions are recorded. Significant R&D investments in blockchain environments and the maturation of application uses of “smart contracts” and other types of self‐executing tools are establishing frameworks for expanded use, infrastructure growth, and further development. The realization of the impact of these investments is currently changing entire business processes, transforming industries, and impacting governments globally. This global disruptive impact is a major technology evolution and will be transformational to society over the next several decades much as the Internet has been over the last 30 years. As these changes will be especially transformational to fundamental accounting processes, tools, and methodologies of today, accounting and finance professionals would be wise to embrace the technological challenges associated with blockchain technology.
Enforcement trends in the city of St. Louis from 2007 to 2017: Exploring variability in arrests and criminal summonses over time and across communities
Authors: Slocum Lee A. , Huebner Beth M. , Greene Claire , Rosenfeld Richard 
Published: November 2019

AbstractThe goal of this study is twofold: (a) to describe trends in enforcement activity in the city of St. Louis from 2007 through 2017 and (b) to document community variation in these trends. Five types of enforcement actions are examined: felony, misdemeanor, municipal, and bench warrant arrests and criminal summonses‐in‐lieu of arrest. Results indicate that enforcement activity decreased over the study period, particularly for nonfelony arrests among Blacks. City‐wide trends obscure some variability in neighborhood enforcement. Neighborhood trends in enforcement varied by type of action, but in all cases, trends were conditioned by racial composition. For example, misdemeanor and bench warrant arrests exhibited steeper declines in neighborhoods with a higher percentage of Black residents, resulting in a narrowing of the race gap. In contrast, differences in criminal summonses across neighborhoods of varying racial compositions increased. The effects persisted net of measures of economic disadvantage, community location, residential mobility, household composition, calls for service, and population size. The findings highlight the importance of disaggregating enforcement trends by race and place and documenting changes in less serious, but more prevalent, types of law enforcement activity.
Hope and health‐related quality of life among chronically ill uninsured/underinsured adults
Authors: Wippold Guillermo M. , Roncoroni Julia 
Published: November 2019

AbstractAimsUninsured/underinsured individuals with chronic health conditions report low health‐related quality of life. Empowerment‐based strategies (e.g., hope) may improve the health‐related quality of life of uninsured/underinsured individuals with chronic health conditions by enabling them to take charge of their health.MethodsThe present study used structural equation modeling to examine the relationships among number of chronic health conditions, the components of hope (i.e., agency and pathways), and the health‐related quality of life of 197 uninsured/underinsured adults in the United States living with at least one chronic health condition.ResultsResults indicate that number of chronic health conditions negatively impacted health‐related quality of life and that agency significantly mediated that relationship.ConclusionsResults from this study can be used to promote health‐related quality of life by empowering individuals to take charge of their lives despite their unique contextual circumstances.
Promoting resilience in street connected young people in Guatemala: The role of psychological and educational protective factors
Authors: Oldfield Jeremy , Stevenson Andrew , Ortiz Emily 
Published: November 2019

AbstractStreet connected young people (SCYP) are at risk of encountering negative life experiences, such as abuse, neglect, violence and exploitation. Nonetheless, some demonstrate remarkable resilience. This study therefore aimed to explore protective factors that promote resilience in SCYP in Guatemala City. Using ethnographic interviews and image elicitation eight young people and four adult educational outreach project coordinators participated within this study. Three key protective factors emerged that help develop resilience; Empowerment, as educational projects support SCYP and provide opportunities; Belongingness, encapsulated creating positive relationships, a sense of affinity and positive family environments; and Motivation which highlighted the importance of the young peoples’ willpower, engagement with learning and help‐seeking behaviour. Educational projects working with SCYP can help to develop resilience by empowering them for change, providing a sense of belonging, while also acknowledging their individual motivation for change.
Reduction of large soft‐tissue Gaucheromas with substrate reduction therapy
Authors: Mahajan Neha , Warren Mikako , Yano Shoji 
Published: November 2019

AbstractSoft‐tissue masses are rarely seen in Gaucher disease. We previously reported a case of a 30‐year‐old patient with Gaucher disease type 3, receiving β‐glucocerebrosidase enzyme replacement therapy (ERT), who presented with slowly enlarging masses infiltrated with Gaucher cells along her back. Substrate reduction therapy introduced in addition to ERT, resulted in significant reduction of the large masses.
Contrasting drought impacts on the start of phenological growing season in Northern China during 1982–2015
Authors: Deng Haoyu , Yin Yunhe , Wu Shaohong , Xu Xiaofeng 
Published: November 2019

AbstractDrought is a widely occurring extreme climatic event that may have various effects on vegetation phenology and activity. The change of the start of the phenological growing season (SOS) is one key mechanism for ecosystem responses to droughts yet remain unknown at large scale. This study used abnormal changes in the ratio of reference evapotranspiration (ETO) and precipitation (P) to detect the pre‐season (defined as the 3 months before the growing season) monthly drought during 1982–2015. After that, the pre‐season drought impacts on SOS were analysed. Drought appeared frequently (>3.6 times/10 years) in the northern and southwest China, as well as the coastal area of south China during the last 34 years. The droughts generally accompany a higher temperature and a stronger radiation, but the drought effects on the SOS differ between humid/sub‐humid and semi‐arid zones in northern China. Specifically, in the temperate humid/sub‐humid zones, SOS under drought was 1.08–4.86 days earlier than during normal (no drought) years, and the response was greater to the droughts that appeared in the first two of the three pre‐season months. In addition, in the cold, mid‐, and warm temperate zones, the advance response was more concentrated in the SOS about DOY130‐140, DOY125‐150, and DOY80‐160, respectively. However, in the north semi‐arid zone, the SOS under drought was 0.66–3.45 days later than during normal years, and the response was greater to the droughts that appeared in the last two of the 3 months. These delay responses also concentrated in the SOS about DOY125‐150. The contrasting drought impacts on phenology suggest that we should move beyond the vegetation activity under droughts such as the growth, productivity, and mortality, and pay more attention to the timing of vegetation activity to better quantify the carbon budget at Northern Hemisphere.
Combined Injury to the ACL and Lateral Meniscus Alters the Geometry of Articular Cartilage and Meniscus Soon After Initial Trauma
Authors: Beynnon Bruce D. , Fiorentino Niccolo , Gardner‐Morse Mack , Tourville Timothy W. , Slauterbeck James R. , Sturnick Daniel R. , Argentieri Erin C. , Imhauser Carl W. 
Published: November 2019

ABSTRACTCombined injury to the anterior cruciate ligament (ACL) and meniscus is associated with earlier onset and increased rates of post‐traumatic osteoarthritis compared with isolated ACL injury. However, little is known about the initial changes in joint structure associated with these different types of trauma. We hypothesized that trauma to the ACL and lateral meniscus has an immediate effect on morphometry of the articular cartilage and meniscus about the entire tibial plateau that is more pronounced than an ACL tear without meniscus injury. Subjects underwent magnetic resonance imaging scanning soon after injury and prior to surgery. Those that suffered injury to the ACL and lateral meniscus underwent changes in the lateral compartment (increases in the posterior–inferior directed slopes of the articular cartilage surface, and the wedge angle of the posterior horn of the meniscus) and medial compartment (the cartilage‐to‐bone height decreased in the region located under the posterior horn of the meniscus, and the thickness of cartilage increased and decreased in the mid and posterior regions of the plateau, respectively). Subjects that suffered an isolated ACL tear did not undergo the same magnitude of change to these articular structures. A majority of the changes in morphometry occurred in the lateral compartment of the knee; however, change in the medial compartment of the knee with a normal appearing meniscus also occurred. Statement of clinical significance: Knee injuries that involve combined trauma to the ACL and meniscus directly affect both compartments of the knee, even if the meniscus and articular cartilage appears normal upon arthroscopic examination. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:759‐767, 2020
Capillary electrophoresis for the investigation of two novel aminoalkanol derivatives of 1,7‐diethyl‐8,9‐diphenyl‐4‐azatricyclo[5.2.1.02,6] dec‐8‐ene‐3,5,10‐trione as potential anticancer drugs in water solution and serum
Authors: Grodner Błażej , Napiórkowska Mariola 
Published: November 2019

AbstractA simple, rapid, capillary zone electrophoresis method was developed and validated for the analysis of two novel aminoalkanol derivatives (I) and (II) of 1,7‐diethyl‐8,9‐diphenyl‐4‐azatricyclo[5.2.1.02,6]dec‐8‐ene‐3,5,10‐trione, which were found in earlier studies as potential anticancer drugs. Samples were analyzed to demonstrate the specificity and stability indicating ability of the developed method. The samples were extracted using n‐hexane‐ethyl acetate mixture in the ratio of 90:10. Electrophoretic separation was performed on a eCAP fused silica capillary (37 cm length, 50 µm inside diameter) with a 50 mM tetraborate buffer as a background electrolyte adjusted to pH = 2.5. The separation time of (I) and (II) was achieved within 7 min. In addition, analysis of the two compounds in the serum was conducted. Limits of detection of (I) and (II) by UV absorbance at 200 nm were achieved in the range of 87.4–92.1 ng/mL. The sufficient recovery was observed in the range of 90.3–99.8%. The quantification limits for the compounds (I) and (II) were in the range of 279.71–291.03 ng/mL, respectively. The method has been successfully applied to the analysis of compounds (I) and (II) in serum samples.