bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG‐ALL‐2002 study
Authors: Yeh Ting‐Chi , Liang Der‐Cherng , Hou Jen‐Yin , Jaing Tang‐Her , Lin Dong‐Tsamn , Yang Chao‐Ping , Peng Ching‐Tien , Hung Iou‐Jih , Lin Kai‐Hsin , Hsiao Chih‐Cheng , Jou Shiann‐Tarng , Chiou Shyh‐Shin , Chen Jiann‐Shiuh , Wang Shih‐Chung , Chang Te‐Kau , Wu Kang‐Hsi , Sheen Jiunn‐Ming , Yen Hsiu‐Ju , Chen Shih‐Hsiang , Lu Meng‐Yao , Li Meng‐Ju , Chang Tai‐Tsung , Huang Ting‐Huan , Chang Yu‐Hsiang , Chen Shu‐Huey , Yang Yung‐Li , Chang Hsiu‐Hao , Chen Bow‐Wen , Lin Pei‐Chin , Cheng Chao‐Neng , Chao Yu‐Hua , Yang Shang‐Hsien , Chao Yu‐Mei Y. , Liu Hsi‐Che 
Published: October 2018

BackgroundTo eliminate cranial irradiation (CrRT)–related sequelae and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous system (CNS)–directed regimen characterized by delayed triple intrathecal therapy (TIT) and the omission of CrRT for all children with newly diagnosed acute lymphoblastic leukemia (ALL).MethodsThis study compared the treatment outcomes of patients overall and patients with a non–CNS‐1 status (CNS‐2, CNS‐3, or TLP with blasts) in 2 treatment eras, one before and another after the revision of the TPOG‐ALL‐2002 protocol by the introduction of the modification (era 1 [2002‐2008] with CrRT and era 2 [2009‐2012] with delayed first TIT and no CrRT).ResultsThere were no statistically significant differences in major outcomes between the 903 patients treated in era 1 and the 444 patients treated in era 2: the 5‐year event‐free survival (EFS) rates were 75.7% ± 1.4% and 72.1% ± 2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse were 4.0% ± 0.7% and 4.1% ± 1.0%, respectively (P = .960). There were also no differences between non–CNS‐1 patients treated in era 1 (n = 76) and era 2 (n =28): the 5‐year EFS rates were 52.3% ± 5.8% and 62.9% ± 9.4%, respectively (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% ± 3.1% and 3.6% ± 3.5%, respectively (P = .639). Notably, TLP with blasts was completely eliminated after the first TIT was delayed in era 2.ConclusionsThe delay of the first TIT until the clearance of circulating blasts and the total omission of CrRT did not compromise survival or CNS control in patients with childhood ALL, including those with a non–CNS‐1 status.
The modular organization of the cerebral cortex: Evolutionary significance and possible links to neurodevelopmental conditions
Authors: Casanova Manuel F. , Casanova Emily L. 
Published: October 2018

AbstractThe recognition of discernible anatomical regularities that appear to self‐organize during development makes apparent the modular organization of the cerebral cortex. The metabolic cost engendered in sustaining interneuronal communications has emphasized the viability of short connections among neighboring neurons. This pattern of connectivity establishes a microcircuit which is repeated in parallel throughout the cerebral cortex. This canonical circuit is contained within the smallest module of information processing of the cerebral cortex; one which Vernon Mountcastle called the minicolumn. Plasticity within the brain is accounted, in part, by the presence of weak linkages that allow minicolumns to process information from a variety of sources and to quickly adapt to environmental exigencies without a need for genetic change. Recent research suggests that interlaminar correlated firing between minicolumns during the decision phase of target selection provides for the emergence of some executive functions. Bottlenecks of information processing within this modular minicolumnar organization may account for a variety of mental disorders observed in neurodevelopmental conditions.
Oncologist perspectives on chemotherapy‐induced nausea and vomiting (CINV) management and outcomes: A quantitative market research‐based survey
Authors: Aapro Matti , Ruffo Pierfrancesco , Panteri Roger , Costa Stefano , Piovesana Vittoria 
Published: October 2018

AbstractBackgroundChemotherapy‐induced nausea and vomiting (CINV) is a distressing side effect that can negatively impact patients' quality of life and could discourage completion of chemotherapy, thereby affecting overall treatment outcomes. Although adherence to antiemetic guidelines can reduce CINV incidence in patients receiving highly or moderately emetogenic chemotherapy, CINV control remains inadequate.AimsThe objectives of this survey were to determine oncologists' practice patterns in CINV management, identify factors that contribute to antiemetic treatment failure, and determine the outcomes of uncontrolled CINV on health care resource utilisation and on patients' attitude towards chemotherapy.Methods and resultsQuantitative market research was performed using an online questionnaire. Responses from 300 European oncologists who prescribe antiemetics and see ≥50 patients/month were analysed. Results showed that the main reasons reported by oncologists for antiemetic treatment failure were underestimating the emetogenic potential of chemotherapy, utilising weaker antiemetic regimens than required, and patient non‐adherence because of administration mistakes or missed/delayed doses. Educational initiatives for the oncology multidisciplinary team may help improve guideline‐consistent prescribing. Also, the availability of simpler, more convenient antiemetic therapies may improve guideline adherence and patient compliance during home administration.ConclusionAchieving effective CINV control is a crucial goal to improve patients' quality of life, which should optimise chemotherapy outcomes, and would ultimately reduce health care costs.
Selective sharing: The impact of patterns of communication in young people experiencing maternal cancer
Authors: Rodriguez Leonor 
Published: October 2018

AbstractBackgroundAdolescents that experience parental cancer can have significant difficulties and may be at a greater risk of emotional and behavioural problems; however, some studies have found that this experience can also be empowering and can promote positive growth. Open communication specifically has been associated with coping and less psychological distress in adolescents experiencing parental cancer.AimsThe aim of this study is to identify communication patterns in adolescents that faced maternal cancer to provide recommendations for practice on how best to support adolescents at this challenging time.MethodsAdolescents (n = 15) completed semistructured interviews with the main researcher to explore their experiences at the time of maternal cancer. Specifically, this study is a qualitative secondary thematic analysis.ResultsThe term “selective sharing” was coined to characterise adolescent communication patterns, as they selected who they wished to talk to and how much information about maternal illness they shared. Barriers for adolescent open communication included perceived unavailability of their mothers to talk, fear, geographical separation from their families, previous family communication patterns, and the time since maternal diagnosis. Benefits of open communication included access to affection, support and information, as well as validation of their emotions and improved coping. Adolescents also provided recommendations to peers and practitioners based on their own experiences.ConclusionsAdolescent communication patterns need to be evaluated as this can impact on their ability to cope with maternal cancer diagnosis. Practitioners can facilitate and encourage open communication, including both factual information about cancer and the emotions and thoughts adhered to this experience for adolescents, mothers, friends, and their families to support them at this challenging time.
Methods to Measure MDSC Immune Suppressive Activity In Vitro and In Vivo
Authors: Solito Samantha , Pinton Laura , De Sanctis Francesco , Ugel Stefano , Bronte Vincenzo , Mandruzzato Susanna , Marigo Ilaria 
Published: October 2018

AbstractThis unit presents methods to assess the immunosuppressive properties of immunoregulatory cells of myeloid origin, such as myeloid‐derived suppressor cells (MDSCs), both in vitro and in vivo in mice, as well as in biological samples from cancer patients. These methods could be adapted to test the impact of different suppressive populations on T cell activation, proliferation, and cytotoxic activity; moreover, they could be useful to assess the influence exerted by genetic modifications, chemical inhibitors, and drugs on immune suppressive pathways © 2018 by John Wiley & Sons, Inc.
Clients' experience of change: An exploration of the influence of reformulation tools in cognitive analytic therapy
Authors: Tyrer Rebecca , Masterson Ciara 
Published: October 2018

AbstractCase formulation is considered important in both the development of the therapeutic relationship and in starting the process of therapeutic change. Cognitive analytic therapy (CAT) describes the developmental origins and maintenance of a client's problems in both written (reformulation letter) and diagrammatic form (sequential diagrammatic reformulation). This study aimed to investigate the effects of these reformulation tools on insight and symptom change. A small‐N repeated measures design was employed with quantitative and qualitative measures collected from six therapist/client dyads. Participating therapists kept a record of their delivery of CAT reformulation tools. Participating clients completed the insight subscale of the Self‐Reflection and Insight Scale every fourth session and the Clinical Outcomes in Routine Evaluation‐10 every session. Qualitative data from client change interviews regarding their experiences of CAT and attributions of change was explored using template analysis. Participants demonstrated improvements (symptom reduction and insight increases) over the course of the intervention. Administration of reformulation tools did not consistently result in significant changes on insight and symptom measures. However, the tools were identified by participants as leading to insight and emotional change within the context of a good therapeutic relationship. These findings suggest that a genuine therapeutic relationship is an important change mechanism operating through, and strengthened by, CAT‐specific tools.
Structural Design of Ionic Liquids for Optimizing Aromatic Dissolution
Authors: Jiang Haihui Joy , Imberti Silvia , Simmons Blake A. , Atkin Rob , Warr Gregory G. 
Published: October 2018

AbstractCertain protic ionic liquids (PILs) are potentially low‐cost, high‐efficiency solvents for the extraction and processing of aromatic compounds. To understand the key design features of PILs that determine solubility selectivity at the atomic level, neutron diffraction was used to compare the bulk structure of two PILs with and without an aromatic solute, guaiacol (2‐methoxyphenol). Guaiacol is a common lignin residue in biomass processing, and a model compound for anisole‐ or phenol‐based food additives and drug precursors. Although the presence of amphiphilic nanostructure is important to facilitate the dissolution of solute nonpolar moieties, the local geometry and competitive interactions between the polar groups of the cation, anion, and solute are found to also strongly influence solvation. Based on these factors, a framework is presented for the design of PIL structure to minimize competition and to enhance driving forces for the dissolution of small aromatic species.
Application of Human‐Induced Pluripotent Stem Cells (hiPSCs) to Study Synaptopathy of Neurodevelopmental Disorders
Authors: Shen Xuting , Yeung Hoi Ting , Lai Kwok‐On 
Published: October 2018

AbstractSynapses are the basic structural and functional units for information processing and storage in the brain. Their diverse properties and functions ultimately underlie the complexity of human behavior. Proper development and maintenance of synapses are essential for normal functioning of the nervous system. Disruption in synaptogenesis and the consequent alteration in synaptic function have been strongly implicated to cause neurodevelopmental disorders such as autism spectrum disorders (ASDs) and schizophrenia (SCZ). The introduction of human‐induced pluripotent stem cells (hiPSCs) provides a new path to elucidate disease mechanisms and potential therapies. In this review, we will discuss the advantages and limitations of using hiPSC‐derived neurons to study synaptic disorders. Many mutations in genes encoding for proteins that regulate synaptogenesis have been identified in patients with ASDs and SCZ. We use Methyl‐CpG binding protein 2 (MECP2), SH3 and multiple ankyrin repeat domains 3 (SHANK3) and Disrupted in schizophrenia 1 (DISC1) as examples to illustrate the promise of using hiPSCs as cellular models to elucidate the mechanisms underlying disease‐related synaptopathy.
Disruption of MET Receptor Tyrosine Kinase, an Autism Risk Factor, Impairs Developmental Synaptic Plasticity in the Hippocampus
Authors: Ma Xiaokuang , Chen Ke , Lu Zhongming , Piechowicz Mariel , Liu Qiang , Wu Jie , Qiu Shenfeng 
Published: October 2018

AbstractAs more genes conferring risks to neurodevelopmental disorders are identified, translating these genetic risk factors into biological mechanisms that impact the trajectory of the developing brain is a critical next step. Here, we report that disrupted signaling mediated MET receptor tyrosine kinase (RTK), an established risk factor for autism spectrum disorders, in the developing hippocampus glutamatergic circuit leads to profound deficits in neural development, synaptic transmission, and plasticity. In cultured hippocampus slices prepared from neonatal mice, pharmacological inhibition of MET kinase activity suppresses dendritic arborization and disrupts normal dendritic spine development. In addition, single‐neuron knockdown (RNAi) or overexpression of Met in the developing hippocampal CA1 neurons leads to alterations, opposite in nature, in basal synaptic transmission and long‐term plasticity. In forebrain‐specific Met conditional knockout mice (Metfx/fx;emx1cre), an enhanced long‐term potentiation (LTP) and long‐term depression (LTD) were observed at early developmental stages (P12–14) at the Schaffer collateral to CA1 synapses compared with wild‐type littermates. In contrast, LTP and LTD were markedly reduced at young adult stage (P56–70) during which wild‐type mice show robust LTP and LTD. The altered trajectory of synaptic plasticity revealed by this study indicate that temporally regulated MET signaling as an intrinsic, cell autonomous, and pleiotropic mechanism not only critical for neuronal growth and functional maturation, but also for the timing of synaptic plasticity during forebrain glutamatergic circuits development.
Epithelial‐mesenchymal Transition and Cancer Stem Cells: At the Crossroads of Differentiation and Dedifferentiation
Authors: Wang Hanmin , Unternaehrer Juli J. 
Published: October 2018

AbstractIn this review, we explore the connections between epithelial‐mesenchymal transition (EMT) and differentiation status. EMTs in development have been described as differentiation events, while in most cases EMTs in cancer have been depicted as dedifferentiation events. We will briefly summarize both embryo development and cancer progression with regard to the involvement of EMT and cell differentiation status. We further present the studies that provide evidence that EMT results in both differentiation and dedifferentiation. Finally, we present our resolution to this dilemma by suggesting that EMT brings about dedifferentiation that enables subsequent differentiation. In normal development, EMT events may cause a partial reversal of differentiation to overcome differentiation barriers. When EMT is aberrantly activated in cancer, cells gain attributes of stem cells that contribute to self‐renewal capabilities and are able to differentiate to all cell types represented in the tumor. The resulting cancer stem cells attain hallmarks of cancer, including replicative immortality, resistance to cell death, and invasiveness. Developmental Dynamics 248:10–20, 2019. © 2018 Wiley Periodicals, Inc.
Policy dynamics and types of agency: From individual to collective patterns of action
Authors: Capano Giliberto , Galanti Maria Tullia 
Published: October 2018

Despite the relevance of structures and constraints to the outcomes of policy‐making, agency emerges as a key aspect in accounting for policy dynamics. Indeed, agency is a concept that may embrace different components according to their empirical reference and policy context.In policy studies, different agents are conceptualized to be relevant in policy‐making, but they address the issues of similar individuals who randomly jump into the policy process to make a specific contribution. This paper proposes to de‐personalize agency in policy dynamics by arguing that the different types of agents can be attributed to specific patterns of action and that related tasks are a necessary element of stability and change in policy dynamics. Thus, we propose three types of patterns—entrepreneurship, brokerage, and leadership—and we show how the use of these concepts can help to better order, describe, and grasp agency in policy dynamics.
Authentication of the geographical origin of patchouli oil using front‐face fluorescence spectroscopy and chemometric analysis
Authors: Al Riza Dimas Firmanda , Widodo Slamet , Purwanto Y. Aris , Kondo Naoshi 
Published: October 2018

AbstractIncreasing consumer awareness of the authenticity of products has led to a demand for rapid measurement methods to support the traceability of high‐value commodities. In this research, a front‐face method was used to obtain fluorescence excitation–emission matrix fingerprints of patchouli oil samples from different geographical origins in Indonesia. Principal component analysis (PCA) was then used to explore the excitation–emission matrix (EEM) data structure of the samples, and 3D eigenvector value thresholding was used to discriminate important variables. It was found that there were five important EEM regions representing the sample variation. A decision‐tree model with a subset of two important regions, i.e. regions 1 and 3, was then developed for the classification of patchouli oils from different Indonesian islands. These results show that front‐face fluorescence spectroscopy has the potential to be used as a supporting tool for the discrimination of the geographical origin of patchouli oils.
Recognition of UK Insolvency Proceedings Post‐Brexit: The Impact of a ‘No Deal’ Scenario
Authors: Umfreville Chris , Omar Paul , Lücke Heike , Fannon Irene Lynch , Veder Michael , Carballo Piñeiro Laura 
Published: October 2018

AbstractThis paper examines the impact of a ‘no deal’ or ‘hard’ Brexit on the recognition of insolvency proceedings commenced in the UK by the remaining Member States of the European Union (EU) post‐Brexit. The paper considers the framework currently implemented by the Recast European Insolvency Regulation and the possible approaches when it will cease to apply to proceedings commenced post‐Brexit. The paper identifies that there will be no overarching framework in the event that ‘no deal’ is reached between the UK and the EU for post‐Brexit arrangements, resulting in reliance on individual Member States' domestic laws to determine recognition of insolvency proceedings commenced in the UK. The paper sets out the contrasting approaches of five of the UK's key trading partners in the EU: France, Germany, Ireland, the Netherlands and Spain. The paper concludes that UK insolvency proceedings will not be recognised in a consistent manner in these Member States, which will be detrimental to stakeholders in, and ultimately the economies of, the UK and these Member States. In doing so, the paper underlines the importance of an agreement being reached between the UK and the EU on the recognition of cross‐border insolvency proceedings for the benefit of all parties. Copyright © 2018 The Authors International Insolvency Review published by INSOL International and John Wiley & Sons Ltd.
UCK2 upregulation might serve as an indicator of unfavorable prognosis of hepatocellular carcinoma
Authors: Yu Shuo , Li Xu , Guo Xingjun , Zhang Hang , Qin Renyi , Wang Ming 
Published: October 2018

AbstractUridine‐cytidine kinases (encoded by UCK1, UCKL1, and UCK2) catalyze the phosphorylation of uridine and cytidine to uridine monophosphate (UMP) and cytidine monophosphate (CMP). In this study, using data from the Cancer Genome Atlas (TCGA), we analyzed the expression profile of uridine‐cytidine kinase genes in hepatocellular carcinoma (HCC), their prognostic value, and the epigenetic alterations associated with their dysregulation. Results showed that UCKL1 and UCK2, but not UCK1 were significantly upregulated in HCC tissues than in adjacent normal tissues. Only UCK2 was significantly upregulated in the deceased group and the recurrence group, compared to the control groups. Multivariate analysis confirmed that increased UCK2 expression was an independent prognostic indicator of shorter overall survival (OS) (HR: 1.760, 95% CI: 1.398–2.216, P < 0.001) and recurrence‐free survival (RFS) (HR: 1.543, 95% CI: 1.232–1.933, P < 0.001). Two CpG sites (cg09277749 and cg21143899) were significantly hypomethylated in HCC tissues than in adjacent normal tissues and were negatively correlated with UCK2 expression. However, survival analysis showed that only high methylation of cg0927774 was associated with better OS and RFS of HCC patients. Based on the findings above, we infer that UCK2 upregulation might be a valuable prognostic marker in HCC. The methylation of status cg0927774 might play a critical role in its expression. © 2018 IUBMB Life, 71(1):105–112, 2019
Ex vivo induction of regulatory T cells from conventional CD4+ T cells is sensitive to substrate rigidity
Authors: Nataraj Neha M. , Dang Alex P. , Kam Lance C. , Lee Jounghyun H. 
Published: October 2018

AbstractThe immune system maintains a balance between protection and tolerance. Regulatory T cells (Tregs) function as a vital tolerance mechanism in the immune system to suppress effector immune cells. Additionally, Tregs can be utilized as a form of immunotherapy for autoimmune disorders. As T cells have previously been shown to exhibit sensitivity to the rigidity of an activating substrate upon activation via IL‐2 secretion, we herein explore the previously unknown effect of substrate rigidity on the induction of Tregs from conventional naïve mouse CD4+ T cells. Substrates with modulatable rigidities ranging from a hundred kilopascals to a few megapascals were fabricated via poly(dimethylsiloxane). We found that there was a significant increase in Treg induction at lower substrate rigidities (i.e., E ~ 100 kPa) compared to higher rigidity levels (i.e., E ~ 3 MPa). To confirm that this significant difference in induction rate was truly related to T‐cell mechanosensing, we administered compound Y‐27632 to inhibit myosin contractility. In the presence of Y‐27632, the myosin‐based contractility was disrupted and, as a result, the difference in Treg induction caused by the substrate rigidity was abrogated. This study demonstrates that mechanosensing is involved in Treg induction and raises questions about the underlying molecular mechanisms involved in this process. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3001–3008, 2018.