bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validated LC‐MS/MS method of Sphingosine 1‐phosphate quantification in human serum for evaluation of response to radiotherapy in lung cancer
Authors: Tang Xiaohui , Chen Haisheng , Chen Guanxuan , Duan Cunxian , Fan Qing , Li Hui , Wang Yanhong , Li Zhijun , Shi Wenna , Liu Yuguo 
Published: March 2020

AbstractBackgroundSphingosine 1‐phosphate (S1P), a bioactive lipid, has been shown to mediate cancer processes. Therefore, accurate qualitative and quantitative determination is essential. The current assay method is still cumbersome to be of practical use worldwide and the aim of this study was therefore to develop a fast, accurate, precise and efficient LC‐MS/MS method for targeted analyses of S1P in serum samples.MethodsLiquid chromatography‐tandem mass spectrometry (LC‐MS/MS) is an established method used for monitoring and analyzing S1P levels in serum. We determined the level of serum S1P in 256 patients with lung cancer and 36 healthy donors, and used Spearman';s rank correlation analysis to evaluate the difference in serum S1P levels between radiotherapy and nonradiotherapy patients.ResultsStandard curves were linear over ranges of 25–600 ng/mL for S1P with correlation coefficient (r2) greater than 0.9996. The lower limit of quantifications (LLOQs) was 25 ng/mL. The intra‐ and interbatch precisions and accuracy was less than 10% for S1P. The recoveries of the method were found to be 80%–98%. Serum S1P levels in healthy donors were different from those in patients (P < 0.001). Of 256 lung cancer patients, 124 (48.4%) received radiotherapy and were identified to have concomitant low serum S1P levels (222.13 ± 48.63), whereas 132 (51.6%) who had not received radiotherapy were identified to have high levels (315.16 ± 51.06). The serum S1P levels were therefore associated with radiotherapy (Spearman's Rho = −0.653, P < 0.001).ConclusionsOur results indicated that this new LC‐MS/MS method is rapid, sensitive, specific and reliable for the quantification of S1P levels in serum samples. The level of S1P in serum samples of patients with lung cancer who received radiotherapy was significantly lower than that in patients who did not receive radiotherapy.Key pointsAn improved method was established to quantify S1P levels in human serum by LC‐MS/MS, which enabled the change in serum S1P levels in lung cancer patients to be monitored, in combination with radiotherapy, and their clinical significance to be analyzed.
Knowing minds: Culture and perceptions of mental state access
Authors: Wice Matthew , Karasawa Minoru , Matsui Tomoko , Miller Joan G. 
Published: March 2020

How does culture influence the ways in which individuals reflect upon their knowledge of others’ mental states? We addressed this question in a two‐study cross‐cultural investigation examining perceptions of mental state access in the United States and Japan. Study 1 (n = 100) revealed that American participants reported greater mental state access than did Japanese participants. Study 2 (n = 146) showed that both Americans and Japanese perceived greater access to the mental states of a close friend relative to a casual friend and that the observed cultural differences in perceived mental state access to a close friend’s mental states were mediated by how much access was considered appropriate. Overall, the results indicate that culturally variable norms specifying appropriate levels of mental state access play an important role in how individuals estimate their knowledge of other people’s minds in close relationships.
Are existing self‐ratings of acute manic symptoms in adults reliable and valid?—A systematic review
Authors: Meyer Thomas D. , Crist Nicholas , La Rosa Nikki , Ye Biyu , Soares Jair C. , Bauer Isabelle E. 
Published: March 2020

AbstractBackgroundDepression research historically uses both self‐ and clinician ratings of symptoms with significant and substantial correlations. It is often assumed that manic patients lack insight and cannot accurately report their symptoms. This delayed the development of self‐rating scales for mania, but several scales now exist and are used in research. Our objective is to systematically review the literature to identify existing self‐ratings of symptoms of (hypo)mania and to evaluate their psychometric properties.MethodsPubMed, Web of Knowledge, and Ovid were searched up until June 2018 using the keywords: “(hypo)mania,” “self‐report,” and “mood disorder” to identify papers which included data on the validity and reliability of self‐rating scales for (hypo)mania in samples including patients with bipolar disorder.ResultsWe identified 55 papers reporting on 16 different self‐rating scales claiming to assess (hypo)manic symptoms or states. This included single item scales, but also some with over 40 items. Three of the scales, the Internal State Scale (ISS), Altman Self‐Rating Mania Scale (ASRM), and Self‐Report Manic Inventory (SRMI), provided data about reliability and/or validity in more than three independent studies. Validity was mostly assessed by comparing group means from individuals in different mood states and sometimes by correlation to clinician ratings of mania.ConclusionsASRM, ISS, and SRMI are promising self‐rating tools for (hypo)mania to be used in clinical contexts. Future studies are, however, needed to further validate these measures; for example, their associations between each other and sensitivity to change, especially if they are meant to be outcome measures in studies.
The anti‐mitotic agents PTC‐028 and PTC596 display potent activity in pre‐clinical models of multiple myeloma but challenge the role of BMI‐1 as an essential tumour gene
Authors: Bolomsky Arnold , Muller Joséphine , Stangelberger Kathrin , Lejeune Margaux , Duray Elodie , Breid Helene , Vrancken Louise , Pfeiffer Christina , Hübl Wolfgang , Willheim Martin , Weetall Marla , Branstrom Art , Zojer Niklas , Caers Jo , Ludwig Heinz 
Published: March 2020

SummaryFuture progress in the treatment of multiple myeloma (MM) requires both the characterisation of key drivers of the disease and novel, innovative approaches to tackle these vulnerabilities. The present study focussed on the pre‐clinical evaluation of a novel drug class, BMI‐1 modulators, in MM. We demonstrate potent activity of PTC‐028 and PTC596 in a comprehensive set of in vitro and in vivo models, including models of drug resistance and stromal support. Treatment of MM cells with PTC‐028 and PTC596 downregulated BMI‐1 protein levels, which was found to correlate with drug activity. Surprisingly, BMI‐1 was dispensable for the activity of BMI‐1 modulators and MM cell growth. Our data rather point to mitotic arrest accompanied by myeloid cell leukaemia‐1 (MCL‐1) loss as key anti‐MM mechanisms and reveal impaired MYC and AKT signalling activity due to BMI‐1 modulator treatment. Moreover, we observed a complete eradication of MM after PTC596 treatment in the 5TGM.1 in vivo model and define epigenetic compounds and B cell leukaemia/lymphoma 2 homology domain 3 (BH3) mimetics as promising combination partners. These results bring into question the postulated role of BMI‐1 as an essential MM gene and confirm BMI‐1 modulators as potent anti‐mitotic agents with encouraging pre‐clinical activity that supports their rapid translation into clinical trials.
Pemetrexed sensitizes human lung cancer cells to cytotoxic immune cells
Authors: Okimoto Tamio , Kotani Hitoshi , Iida Yuichi , Koyanagi Akira , Tanino Ryosuke , Tsubata Yukari , Isobe Takeshi , Harada Mamoru 
Published: March 2020

AbstractPemetrexed (PEM) is a useful drug that can be combined with immune checkpoint blockade therapy for treatment of patients with advanced non–small‐cell lung cancer (NSCLC). However, its effects on anti–cancer immunity, especially the sensitivity of NSCLC cells to cytotoxic immune cells, have not been fully investigated. In this study, we examined the effects of PEM on the sensitivity of human NSCLC cells to two different types of cytotoxic immune cells. Pre‐treatment with PEM increased the sensitivity of two NSCLC cell lines, PC9 and A549, to activated T cells and natural killer (NK) cells, and decreased the expression of anti–apoptotic proteins, including XIAP and Mcl‐1. In addition, PEM treatment increased the cell surface expression of programmed death‐ligand 1 (PD‐L1) on PC9 cells. PEM‐induced upregulation of PD‐L1 on PC9 cells was at least partially ascribed to activation of ERK and the NFκB pathway. In contrast, PEM treatment increased the expression of UL16‐binding proteins (ULBP), ligands for the NKG2D NK receptor, on PC9 and A549 cells, as well as the induction of senescence. Although the addition of anti–programmed cell death 1 antibody showed no effect on the sensitivity of PEM‐treated PC9 and A549 cells to activated T cells, that of anti–NKG2D antibody decreased the enhanced sensitivity of PEM‐treated A549 cells to NK cells. These results indicate that PEM can effectively sensitize human NSCLC cells to cytotoxic immune cells while modulating the expression of immune‐regulatory molecules.
Relationship among DNA double‐strand break (DSB), DSB repair, and transcription prevents genome instability and cancer
Authors: Ui Ayako , Chiba Natsuko , Yasui Akira 
Published: March 2020

AbstractDNA double‐strand break (DSB) is a serious type of DNA damage and is known to trigger multiple responses within cells. In these responses, novel relationships among DSB, DSB repair, and transcription machineries are created. First, transcription is repressed if DSB occurs near or at the transcription site, termed DSB‐induced transcriptional repression, which contributes to DSB repair with the aid of DNA damage‐signaling pathways, ATM‐ or DNA‐PKcs‐signaling pathways. DSB‐induced transcriptional repression is also regulated by transcriptional factors TLP1, NELF, and ENL, as well as chromatin remodeling and organizing factors ZMYND8, CDYL1, PBAF, and cohesin. Second, transcription and RNA promote DSB repair for genome integrity. Transcription factors such as LEDGF, SETD2, and transcriptionally active histone modification, H3K36, facilitate homologous recombination to overcome DSB. At transcriptional active sites, DNA:RNA hybrids, termed R‐loops, which are formed by DSB, are processed by RAD52 and XPG leading to an activation of the homologous recombination pathway. Even in a transcriptionally inactive non‐genic sites, noncoding RNAs that are produced by RNA polymerase II, DICER, and DROSHA, help to recruit DSB repair proteins at the DSB sites. Third, transcriptional activation itself, however, can induce DSB. Transcriptional activation often generates specific DNA structures such as R‐loops and topoisomerase‐induced DSBs, which cause genotoxic stress and may lead to genome instability and consequently to cancer. Thus, transcription and DSB repair machineries interact and cooperate to prevent genome instability and cancer.
Double positivity for anti‐N‐methyl‐d‐aspartate receptor and anti‐aquaporin‐4 antibodies in a patient presenting with hypersomnolence, personality change, and reduced spontaneity
Authors: Yoshimura Motoi , Uehara Taira , Tanaka Eizo , Okadome Toshiki , Yamaguchi Takahiro , Maeda Yasuhiro , Isobe Noriko , Matsushita Takuya , Yamasaki Ryo , Kira Jun‐ichi 
Published: March 2020

AbstractBackgroundRecently, the coexistence of anti‐aquaporin‐4 antibody (AQP4‐ab) and anti‐N‐methyl‐d‐aspartate receptor antibody (NMDAR‐ab) were reported in a single case. However, its clinical significance is not well defined.Case presentationA 42‐year‐old woman developed hypersomnolence, personality change, and childish or bizarre behavior. Four months later, she exhibited marked reduction of verbal and motor spontaneity. Serum AQP4‐ab was positive. Cerebrospinal fluid (CSF) was positive for oligoclonal bands. Brain magnetic resonance imaging (MRI) detected multiple T2‐hyperintense lesions without gadolinium enhancement in the pons, midbrain, bilateral internal capsule, basal ganglia, corpus callosum, and deep cerebral white matter. Spinal MRI was negative. Because clinical symptoms and clinical course were atypical for neuromyelitis optica spectrum disorders (NMOSD), CSF NMDAR‐ab was tested and found to be positive. Whole‐body examination revealed cystic lesions in the right ovary, which were later found not to be malignant tumors. In accordance with the proposed algorithm for the treatment of NMDAR encephalitis (NMDARE), she was treated with three courses of intravenous methylprednisolone pulse therapy, followed by oral prednisolone, intravenous immunoglobulin therapy, and five courses of bimonthly intravenous cyclophosphamide pulse therapy. Her symptoms gradually improved, and she returned to her daily life without major sequelae.ConclusionsAlthough her main symptoms were compatible with NMDARE, MRI findings were more compatible with NMOSD. Therefore, we interpreted her clinical and imaging features as a mixed phenotype of NMOSD and NMDARE. This case report provides additional evidence that double positivity for AQP4‐ab and NMDAR‐ab is associated with a mixed phenotype of NMOSD and NMDARE.
Changing Perspective: Building Creative Mindsets
Authors: Chou Yung‐Yi Juliet , Tversky Barbara 
Published: March 2020

AbstractThe search for new ideas often frustratingly cycles back to old ones, a phenomenon known as fixation. Recent research has shown ways to kick‐start finding new uses for familiar objects, a prototypical creativity task: wandering in the mind or the world or working on a messy desk. Those techniques seem to succeed by helping break fixation, but do not guide the search for new ideas. The perspective‐taking or human‐centric or empathic mindset championed by many in HCI and in design firms does provide a search strategy. We compared the mind‐wandering mindset to a perspective‐taking mindset, the latter priming thinking of ways that people in different roles (gardener, artist, etc.) might use the objects. In two studies, the Perspective‐Taking mindset yielded more ideas and more original ideas than Mind‐Wandering, which did not differ from a No‐Mindset control. Original ideas came late, rewarding persistence. The perspective‐taking mindset is productive for problem‐solving, forecasting, and social interactions as well as innovation.
SKA1 regulates actin cytoskeleton remodelling via activating Cdc42 and influences the migration of pancreatic ductal adenocarcinoma cells
Authors: Li Tong , Liu Xu , Xu Bin , Wu Wei , Zang Yi , Li Juanjuan , Wei Lumin , Qian Yuting , Xu Hui , Xie Mingping , Wang Qi , Wang Lifu 
Published: March 2020

AbstractObjectivesSpindle and kinetochore–associated protein 1(SKA1), originally identified as a protein essential for proper chromosome segregation, has been recently linked to multiple malignancies. This study aimed to explore the biological, clinical role and molecular mechanism of SKA1 in pancreatic carcinogenesis.Materials and MethodsSKA1 expression was detected in 145 pancreatic ductal adenocarcinoma (PDAC) specimens by immunohistochemistry. Biological behaviour assays were used to determine the role of SKA1 in PDAC progression in vitro and in vivo. Using isobaric tags for relative and absolute quantitation (iTRAQ), SKA1’s downstream proteins were examined. Moreover, cytochalasin B and ZCL278 were used to explore the changes of SKA1‐induced signalling and cell morphology, with further confirmation by immunoblotting and immunofluorescence assays.ResultsIncreased SKA1 expression was significantly correlated with tumour size and cellular differentiation degree in PDAC tissues. Furthermore, elevated levels of SKA1 reflected shorter overall survival (P = .019). As for biological behaviour, SKA1 acted as a tumour promotor in PDAC, overexpression of SKA1 facilitates cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, we demonstrated that SKA1 enhanced pancreatic cancer aggressiveness by inhibiting G2/M arrest and regulating actin cytoskeleton organization via activating Cdc42.ConclusionsThis study revealed novel roles for SKA1 as an important regulator of actin cytoskeleton organization and an oncogene in PDAC cells, which may provide insights into developing novel therapeutics.
Feasibility and acceptability of a volunteer peer fidelity assessment model in early psychosis intervention programmes in Ontario: Results from a pilot study
Authors: Selick Avra , Langill Gordon , Cheng Chiachen , Addington Donald , Archie Suzanne , Butt Shannel , Durbin Janet 
Published: March 2020

AbstractAimFidelity monitoring can support high‐quality service delivery but is resource‐intensive to implement. A fidelity assessment model utilizing volunteer assessors was trialled as a low‐cost strategy for conducting fidelity assessments. This article reports on the acceptability and feasibility of this model.MethodsTwenty volunteer assessors were trained to conduct fidelity assessments in nine Early Psychosis Intervention programmes across Ontario, Canada. Assessments were conducted using the First‐Episode Psychosis Services Fidelity Scale based on a 2‐day site visit, during which assessors interviewed staff, clients and families; reviewed charts; observed a team meeting and reviewed programme materials. The model was evaluated based on assessor focus groups, programme interviews, consensus meeting data and time‐tracking logs. General inductive analysis was used to code and synthesize qualitative data. Quantitative data were aggregated and summarized.ResultsParticipant feedback was positive and indicated that use of peer assessors and the in‐person site visit added value to the process. The model was perceived to provide valuable information to support internal quality improvement efforts. Assessors reported direct benefits from participating, including networking and learning opportunities. Key challenges were the high time demand on assessors and turnover in the assessor team.ConclusionsThe volunteer peer fidelity model was perceived to be a valuable improvement process by participants, but the high cost and reliance on ongoing volunteerism makes its sustainability uncertain. Next steps may include exploring remote assessment strategies or direct payments, although these strategies risk reducing the acceptability, and therefore uptake, of the assessment.
Effects of neuropsychiatric symptoms of dementia on reductions in activities of daily living in patients with Alzheimer's disease
Authors: Okabe Kiwamu , Nagata Tomoyuki , Shinagawa Shunichiro , Inamura Keisuke , Tagai Kenji , Nukariya Kazutaka , Shigeta Masahiro 
Published: March 2020

AimIn patients with Alzheimer's disease (AD), cognitive impairments cause a progressive reduction in Activities of Daily Living (ADL). Neuropsychiatric symptoms (NPS) also appear in most patients; however, the association between NPS and reductions in ADL remains unclear. The present study evaluated whether NPS influence such reductions using two different ADL measures in patients with AD.MethodsAmong 546 consecutive outpatients who visited the memory clinic at the Jikei University Kashiwa Hospital, we recruited 208 patients with AD and investigated the correlations between either the Physical Self‐Maintenance Scale (PSMS) score or the Instrumental ADL (IADL) level, and each of the Behavioral Pathology in AD (Behave‐AD) subscales. To clarify the causal relationships of these correlations, we then verified the associations between statistically significant demographic variables and the Behave‐AD subscales as well as the two ADL scales (PSMS score and IADL percentage) using a general linear model.ResultsNeither the PSMS nor the IADL results were significantly influenced by the aberrant motor behaviors score. However, the IADL was significantly influenced by the Mini‐Mental State Exam (MMSE) score. Furthermore, diurnal rhythm disturbances and the interaction between diurnal rhythm disturbances score and the MMSE score significantly influenced the PSMS results.ConclusionBasic ADL reductions may be influenced by diurnal rhythm disturbances, in addition to cognitive impairments in patients with AD. Furthermore, the interaction between the diurnal rhythm disturbances score and cognitive function may also influence basic ADL. Geriatr Gerontol Int 2020; ••: ••–••.
New histories of marronage in the Anglo‐Atlantic world and early North America
Authors: Nevius Marcus P. 
Published: March 2020

AbstractThis essay surveys the scholarship ofmarronage, the most pervasive form of fugitive slave community formation, resistance, negotiation, and enslaver accommodation in the history of the Atlantic world. It begins with a brief survey of the subject's historiographic roots, with particular emphasis on its foundational definition as slave resistance and rebellion; on scholarly debates of thegrand/petitmarronage binary; and on the validity and definitions of maroon identity, forged by processes of ethnogenesis and grounded in maroon communities, past and present. The essay then centers on recent histories of marronage in the Caribbean, the Global South, and in early North America. In doing so, it seeks to draw out explicit thematic connections otherwise implicit in new maroon studies. The essay closes with a brief mention of forthcoming works that, informed by extant maroon studies, examine the challenges contemporary maroon communities face and that signal present‐day maroon descended communities' contributions to an increasingly globalizing world.
From panopticon to heautopticon: A new form of surveillance introduced by quantified‐self practices
Authors: De Moya Jean‐François , Pallud Jessie 
Published: March 2020

AbstractIn this research, we investigate whether quantified‐self (QS) technologies, based on wearable technologies, enable individuals' empowerment or lead to their disempowerment. To understand better the potential paradoxical effects of QS technologies, we adopt a critical approach by mobilising the panopticon metaphor from Foucault's original writings and more precisely, his four core concepts, namely power, knowledge, body and space. Relying on a qualitative study that consists of the analysis of 12 interviews, 14 142 messages extracted from online forums, and 30 blogs, we explore the discourses associated with the usage of QS technologies. Our findings indicate that self‐quantification has ambivalent, conflicting effects—13 empowering and 11 disempowering—spanning the dimensions of power, knowledge, body and space. Our research also shows the emergence of micro‐surveillance of oneself, which we name the heautopticon. The implications of this critical research also offer possibilities for change by discussing social and individual emancipation.
Perovskite quantum dots growth in situ in transparent medium for short wavelength shielding
Authors: Yang Ze , Zhao Lei , Li Moxiang , Yang Qihua , Fang Zhaohui , Yang Liuli , Yu Xue , Qiu Jianbei , Yang Yang , Xu Xuhui 
Published: March 2020

AbstractHigh energy ultraviolet (UV) and blue light (short wavelength) radiation is proved to be harmful to human eyes, skin, and biological genomes. However, developing effective shielding materials providing protect from short wavelength is still a great challenge. Here, Eu3+‐doped CsPbBr3 embedded in a transparent glass medium is proved to shield the short wavelength from 200 to 475 nm with high performance, which is prepared by a facile and efficient melting‐quenching technique. The uniform distribution of the CsPbBr3 quantum dots (QDs) growth in situ from the transparent glass matrix ensures the high transmittance (>90%) at the long wavelength (520‐800 nm). In addition, the excellent short wavelength shielding ability of the Eu3+‐doped CsPbBr3 glass ceramics (EGC) is demonstrated even suffered with accelerated weathering tests as long as 480 hours. Moreover the cell viability of A549 cells is well preserved thanks to the completely blocked blue light by the as‐obtained EGC, which unambiguously demonstrates the promising application of EGC as short wavelength shielding materials.