bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCAAT enhancer binding protein alpha (CEBPA) biallelic acute myeloid leukaemia: cooperating lesions, molecular mechanisms and clinical relevance
Authors: Wilhelmson Anna S. , Porse Bo T. 
Published: February 2020

SummaryRecent advances in sequencing technologies have allowed for the identification of recurrent mutations in acute myeloid leukaemia (AML). The transcription factor CCAAT enhancer binding protein alpha (CEBPA) is frequently mutated in AML, and biallelic CEBPA‐mutant AML was recognised as a separate disease entity in the recent World Health Organization classification. However, CEBPA mutations are co‐occurring with other aberrations in AML, and together these lesions form the clonal hierarchy that comprises the leukaemia in the patient. Here, we aim to review the current understanding of co‐occurring mutations in CEBPA‐mutated AML and their implications for disease biology and clinical outcome. We will put emphasis on patterns of cooperation, how these lesions cooperate with CEBPA mutations and the underlying potential molecular mechanisms. Finally, we will relate this to patient outcome and future options for personalised medicine.
Detection of measurable residual disease may better predict outcomes than mutations based on next‐generation sequencing in acute myeloid leukaemia with biallelic mutations of CEBPA
Authors: Wang Jing , Lu RunQing , Wu Ying , Jia JinSong , Gong Lizhong , Liu XiaoHong , Lu ShengYe , Wang Yu , Yan ChenHua , Liu KaiYan , Zhang XiaoHui , Xu LanPing , Jiang Qian , Zhao XiaoSu , Shi HongXia , Lai YueYun , Huang XiaoJun , Ruan GuoRui , Jiang Hao 
Published: February 2020

SummaryAcute myeloid leukaemia (AML) patients with biallelic mutations of CEBPA (bi CEBPA) have a 30–50% relapse rate. This study established the value of mutations based on next‐generation sequencing (NGS) and multiparameter flow cytometric measurable residual disease (MFC‐MRD) detection and compared the outcomes. From 2014 to 2018, 124 newly diagnosed bi CEBPA AML patients were treated. The median age was 37·5 (16–69) years. The 3‐year cumulative incidence of relapse (CIR), relapse‐free survival (RFS) and overall survival (OS) were 33·0%, 64·7% and 84·3%, respectively. Patients without additional mutations and with GATA2 mutations were defined as ‘NGS low risk’, which was the only favourable independent factor for CIR and RFS of pretreatment parameters. Patients with sustained positive MRD after two consolidation cycles and MRD negative losses at any time were defined as ‘MRD high risk’, which was the only poor independent factor for CIR, RFS and OS, including pretreatment and post‐treatment parameters. In CR2 and non‐remission patients who underwent allo‐HSCT, superior OS was achieved. We conclude that NGS low risk was a favourable factor in the analysis of pretreatment parameters. MRD risk stratification was an independent prognostic factor in pretreatment and post‐treatment parameters. Relapsed patients still have a favourable outcome followed by allo‐HSCT.
OATP1A/1B, CYP3A, ABCB1, and ABCG2 limit oral availability of the NTRK inhibitor larotrectinib, while ABCB1 and ABCG2 also restrict its brain accumulation
Authors: Wang Yaogeng , Sparidans Rolf W. , Li Wenlong , Lebre Maria C. , Beijnen Jos H. , Schinkel Alfred H. 
Published: February 2020

Background and PurposeLarotrectinib is a FDA‐approved oral small‐molecule inhibitor for treatment of neurotrophic tropomyosin receptor kinase fusion‐positive cancer. We here investigated the functions of the multidrug efflux transporters ABCB1 and ABCG2, the SLCO1A/1B (OATP1A/1B) uptake transporters, and the multispecific drug‐metabolizing enzyme CYP3A in larotrectinib pharmacokinetic behaviour.Experimental ApproachIn vitro, transepithelial drug transport and uptake assays were performed.In vivo, larotrectinib (10 mg·kg−1) was administered orally to relevant genetically modified mouse models. Cell medium, plasma samples, and organ homogenates were measured by a sensitive and specific LC–MS/MS larotrectinib assay.Key ResultsIn vitro, larotrectinib was avidly transported by human (h) ABCB1 and mouse (m) Abcg2 efficiently by hABCG2 and modestly by hOATP1A2. In vivo, both mAbcb1a/1b and mAbcg2 markedly limited larotrectinib oral availability and brain and testis accumulation (by 2.1‐fold, 10.4‐fold, and 2.7‐fold, respectively), with mAbcb1a/1b playing a more prominent role. mOatp1a/1b also restricted larotrectinib oral availability (by 3.8‐fold) and overall tissue exposure, apparently by mediating substantial uptake into the liver, thus likely facilitating hepatobiliary excretion. Additionally, larotrectinib is an excellent substrate of CYP3A, which restricts the oral availability of larotrectinib and hence its tissue exposure.Conclusions and ImplicationsABCG2 and especially ABCB1 limit the oral availability and brain and testis penetration of larotrectinib, while OATP1A/1B transporters restrict its systemic exposure by mediating hepatic uptake, thus allowing hepatobiliary excretion. CYP3A‐mediated metabolism can strongly limit larotrectinib oral availability and hence its tissue concentrations. These insights may be useful in the further clinical development of larotrectinib.
The role of family centres in reducing social isolation in deprived communities
Authors: Mercer Fiona , Darbyshire Chris , Finlayson Janet , Kettle Martin , Dickson Adele 
Published: February 2020

AbstractSocial exclusion and isolation are worldwide social and health concerns with negative effects becoming exacerbated in deprived communities. There is limited understanding related to the role of community‐based centres in reducing social exclusion and isolation, so the aim of this research was to explore the role one family centre had in improving social inclusion in a deprived community in Glasgow, Scotland. Interpretative Phenomenological Analysis was utilized to analyse interviews from 10 parents to explore their lived experiences of creating and developing social networks through family centre attendance. Findings indicate that attending the family centre positively impacted on social inclusion and social support for all parents interviewed. Relationships created in the centre were proposed as being meaningful, non‐judgemental and produced social capital—rooted in reciprocity and trust. Findings can inform services that aim to reduce social isolation in deprived communities.
upd(20)mat is a rare cause of the Silver‐Russell‐syndrome‐like phenotype: Two unrelated cases and screening of large cohorts
Authors: Hjortshøj Tina D. , Sørensen Anna R. , Yusibova Melodi , Hansen Bo M. , Dunø Morten , Balslev‐Harder Marie , Grønskov Karen , van Hagen Johanna M. , Polstra Abeltje M. , Eggermann Thomas , Finken Martijn J.J. , Tümer Zeynep 
Published: February 2020

AbstractSilver‐Russell syndrome (SRS) is an imprinting disorder characterized by prenatal and postnatal growth retardation, relative macrocephaly, feeding difficulties and body asymmetry. Recently, upd(20)mat has been identified in few patients with SRS‐like features, suggestive of a new imprinting disorder characterized by prenatal and postnatal growth failure. Here, we describe two male patients with upd(20) and feeding difficulties, prenatal and postnatal growth retardation and normal cognitive development. During pregnancy, confined placental mosaicism for trisomy 20 was detected in one of the patients but was not investigated further until identification of upd(20)mat in the neonatal period. To evaluate whether upd(20)mat should be part of the first trier genetic diagnostic in patients with growth retardation, we screened a large cohort of patients (n = 673) referred to our laboratories for SRS‐testing without detecting any upd(20). Our results, along with the existing evidence, indicate that upd(20)mat is a very rare cause of growth retardation, but should be followed up when confined placental mosaicism for trisomy 20 mosaicism is observed during pregnancy.
Teleological Essentialism: Generalized
Authors: Rose David , Nichols Shaun 
Published: February 2020

AbstractNatural/social kind essentialism is the view that natural kind categories, both living and non‐living natural kinds, as well as social kinds (e.g., race, gender), are essentialized. On this view, artifactual kinds are not essentialized. Our view—teleological essentialism—is that a broad range of categories are essentialized in terms of teleology, including artifacts. Utilizing the same kinds of experiments typically used to provide evidence of essentialist thinking—involving superficial change (study 1), transformation of insides (study 2), and inferences about offspring (study 3)—we find support for the view that a broad range of categories—living natural kinds, non‐living natural kinds, and artifactual kinds—are essentialized in terms of teleology. Study 4 tests a unique prediction of teleological essentialism and also provides evidence that people make inferences about purposes which in turn guide categorization judgments.
Protection status and proximity to public‐private boundaries influence land use intensification near U.S. parks and protected areas
Authors: Vukomanovic Jelena , Singh Kunwar K. , Vogler John B. , Meentemeyer Ross K. 
Published: February 2020

AbstractPublic parks and protected areas are highly valued resources for recreation, education, and conservation of species and ecosystems. Increased demand for exurban lifestyles near protected areas may threaten these services, but to date research has been limited to case studies or considered only the most protected areas. We quantified changes (1990–2010) in the density of residential housing and impervious surface within 1, 10, 25, and 50 km of 6,644 U.S. protected areas, from highly protected national parks and wilderness areas to less protected game reserves and recreation areas. In almost all cases, housing density and impervious surface near protected areas were significantly higher than what would be expected by chance. Lands near protected areas with the highest level of protection (GAP I) experienced the greatest overall increase in housing and impervious area over time, but––contrary to earlier projections––little change occurred within 1 km of private‐public boundaries. An opposite pattern occurred near the least protected areas (GAP IV)––lands immediately adjacent to these parks experienced the largest rates of change, but this growth decreased further from their boundaries. Most of the changes near GAP IV areas occurred in the Eastern Temperate Forest ecoregion, though the greatest overall rates of land change occurred in the Southwest. Our findings suggest that previous studies may overestimate the extent to which housing growth broadly threatens conservation of U.S. protected areas. For the first time, we demonstrate that land change near protected areas varies by protection status, proximity to public‐private boundaries, and ecoregion. To make these data more accessible to practitioners, we have created an interactive, online mapping platform that allows anyone to explore location‐specific trends in land change near parks and protected areas.
A Doppler ghost in the pulmonary artery
Authors: Cagli Kumral , Ozbulbul Nilgun Isıksalan , Ozeke Ozcan , Calapkulu Muhammed Yunus , Golbasi Zehra 
Published: February 2020

AbstractLong‐standing left‐to‐right shunting across a patent ductus arteriosus (PDA) can result in Eisenmenger syndrome. In this report, we present echocardiographic findings of a 27‐year‐old female patient with pulmonary hypertension. In diagnostic work‐up especially Doppler findings of the pulmonary artery suggested the presence of a reversed PDA as a cause of pulmonary hypertension. The diagnosis was confirmed by contrast study and computed tomography.
It is more than Interference: Examining the neurohemodynamic correlates of the flanker task with functional near‐infrared spectroscopy
Authors: Geissler (Geißler) Christoph F. , Hofmann Markus J. , Frings Christian 
Published: February 2020

AbstractPrevious functional near‐infrared spectroscopy studies using the Eriksen flanker task, in contrast to functional magnetic resonance imaging studies, revealed the quite puzzling finding of an inverted conflict effect, that is, greater middle and superior frontal activation in response compatible than in response incompatible trials. However, since neither prior functional near‐infrared spectroscopy studies nor most previous functional magnetic resonance imaging studies separated between an identical and a compatible condition, it is hard to pinpoint whether this discrepancy occurs on the level of stimulus processing or response generation. By assigning two letters to both left (D, F) and right (J, K) hand reactions, we were able to separate identical (e.g., JJJ) and compatible (e.g., JKJ) conditions that solely differ in their stimulus congruency. Replicating prior functional magnetic resonance imaging findings, we found the standard conflict effect at the transition of superior and middle frontal gyrus, when comparing the activation in compatible trials to that in incompatible trials. Both changes in oxygenated and deoxygenated hemoglobin thus pointed to more effortful processing in incompatible trials. Interestingly, however, identical trials showed the highest activation in this region, according to both changes in oxygenated and deoxygenated blood. A finding that mirrors and extends prior functional near‐infrared spectroscopy findings, which only regarded oxygenated blood. We argue that this pattern of results does not reflect the standard conflict effect. We rather assume that other processes like perceptual familiarity or strategic readjustment might be at play.
The industries of the future in Mexico: Local and non‐local effects in the localization of “knowledge‐intensive services”
Authors: Santiago Luis Enrique 
Published: February 2020

AbstractThe current characteristics in the global economy have defined “knowledge‐intensive services” (KIS) as part of the so‐called “industries of the future” due to the attributes of their employment and central function in the development processes in science, technology, art, and culture. This study outlines as a central hypothesis that the localization of KIS depends on different factors according to the type of knowledge being developed (analytical, synthetic, and symbolic). The main objective in this work is to explore the spatial economic factors associated with the localization and changes (positive and negative) when using KIS in the “national urban system” in México between 2004 and 2014. To do so, the services sector is defined according to the “intensity” and the “types” of knowledge that they develop. An analysis of spatial econometrics is carried out that distinguishes between the geographic (local) effect and the spatial (non‐local) effect of the independent variables using data and microdata from the period 2004 to 2014. The results partly correspond with the central hypothesis of the study and offer possibilities of public policies to take advantage of and to promote the benefits of KIS, especially regarding cities in developing countries looking to become part of the 21st century economy.
Accuracy of the Enhanced Liver Fibrosis test, and combination of the Enhanced Liver Fibrosis and non‐invasive tests for the diagnosis of advanced liver fibrosis in patients with non‐alcoholic fatty liver disease
Authors: Inadomi Chika , Takahashi Hirokazu , Ogawa Yuji , Oeda Satoshi , Imajo Kento , Kubotsu Yoshihito , Tanaka Kenichi , Kessoku Takaomi , Okada Michiaki , Isoda Hiroshi , Akiyama Takumi , Fukushima Hideaki , Yoneda Masato , Anzai Keizo , Aishima Shinichi , Nakajima Atsushi , Eguchi Yuichiro 
Published: February 2020

AimThe Enhanced Liver Fibrosis (ELF) test comprises a logarithmic algorithm combining three serum markers of hepatic extracellular matrix metabolism. We aimed to evaluate the performance of ELF for the diagnosis of liver fibrosis and to compare it with that of liver stiffness measurement (LSM) by FibroScan in non‐alcoholic fatty liver disease.MethodsELF cut‐off values for the diagnosis of advanced fibrosis were obtained using receiver operating characteristic analysis in patients with biopsy‐confirmed non‐alcoholic fatty liver disease (training set; n = 200). Diagnostic performance was analyzed in the training set and in a validation set (n = 166), and compared with that of LSM in the FibroScan cohort (n = 224).ResultsThe area under receiver operating characteristic curve was 0.81 for the diagnosis of advanced fibrosis, and the ELF cut‐off values were 9.34 with 90.4% sensitivity and 10.83 with 90.6% specificity in the training set, and 89.8% sensitivity and 85.5% specificity in the validation set. There was no significant difference in the area under the receiver operating characteristic curve between ELF and LSM (0.812 and 0.839). A combination of ELF (cut‐off 10.83) and LSM (cut‐off 11.45) increased the specificity to 97.9% and the positive predictive value, versus ELF alone. Sequential use of the Fibrosis‐4 index (cut‐off 2.67) and ELF (cut‐off 9.34) increased the sensitivity to 95.9%.ConclusionsELF can identify advanced liver fibrosis in non‐alcoholic fatty liver disease, and its diagnostic accuracy is comparable to that of FibroScan. According to the clinical setting, combinations or sequential procedures using other non‐invasive tests complement the diagnostic performance of ELF for the identification of advanced fibrosis.
Biocompatible green tea extract‐stabilised zinc nanoparticles encapsulated by poly(butyl‐2‐cyanoacrylate) with control release profile and antioxidative capacity
Authors: Yao Jing‐Jing , Zhang Peng , Fu Zhou‐Ping , Xie Zhong‐Wen , Bao Guan‐Hu 
Published: February 2020

SummaryGreen tea extract‐stabilised Zn nanoparticles (GT‐Zn NPs) encapsulated by poly(butyl‐2‐cyanoacrylate) (PBCA@GT‐Zn NPs) were developed for control release of Zn. The crucial parameters, concentrations of GT‐Zn NPs and the monomer n‐butyl‐2‐cyanoacrylate (BCA), which affected the size, polydispersity indexes (PDI) and encapsulation efficiency (EE %), were evaluated to achieve the smaller size, higher EE (%) and stably and uniformly dispersed NPs. The optimised PBCA@GT‐Zn NPs with <100 nm diameter (46.38 ± 3.46 by SEM, 86.91 ± 3.66 by DLS), PDI (0.159 ± 0.042), zeta potential (−20.56 ± 2.53 mV) and EE (89.31 ± 1.09 %) were obtained. In vitro release of Zn ions was conducted at pH 7.4, showing that Zn from the self‐made tablets and lyophilised PBCA@GT‐Zn NPs is released significantly slower than that of GT‐Zn NPs. Additionally, the PBCA@GT‐Zn NP tablets are pH‐responsive, non‐toxic and antioxidative, suggesting that they could be used as safe food material or drug carriers, contributing to relieve Zn deficiency.
Over‐expression of RNA interference (RNAi) core machinery improves susceptibility to RNAi in silkworm larvae
Authors: You L. , Zhang F. , Huang S. , Merchant A. , Zhou X. , Li Z. 
Published: February 2020

AbstractRNA interference (RNAi), one of the strategies that organisms use to defend against invading viruses, is an important tool for functional genomic analysis. In insects, the efficacy of RNAi varies amongst taxa. Lepidopteran insects are, in large part, recalcitrant to RNAi. The overall goal of this study is to overcome such insensitivity in lepidopterans to RNAi. We hypothesize that over‐expression of core RNAi machinery enzymes can improve RNAi efficacy in traditionally recalcitrant species. A transgenic Bombyx mori strain, Baculovirus Immediate‐Early Gene, ie1, promoter driven expression of silkworm Dicer2 coding sequence (IE1‐BmDicer2), which over‐expresses BmDicer2, was generated by piggyBac transposon‐mediated transgenesis. Two indexes, the ratio of animals that showed a silencing phenotype and the duration of silencing, were used to evaluate silencing efficiency. Significant knockdown of target gene expression was observed at 48 h postinjection at both the transcriptional and translational levels. Furthermore, we coexpressed B. mori Argonaute 2 BmAgo2）and BmDicer 2 and found that 22% of the animals (n = 18) showed an obvious silencing effect even at 72 h, suggesting that coexpression of these two RNAi core machinery enzymes further increased the susceptibility of B. mori to injected double‐stranded RNAs. This study offers a new strategy for functional genomics research in RNAi‐refractory insect taxa in general and for lepidopterans in particular.
Group A streptococcal bacteraemia at a tertiary hospital in Melbourne: concern of an under‐reported risk group in Australia
Authors: Attwood Lucy O. , Spelman Denis 
Published: February 2020

AbstractBackgroundInvasive group A streptococcal (iGAS) infections are increasing worldwide with at‐risk groups being children, pregnant women and the elderly. In 2017, there was a rise in iGAS cases in Victoria, prompting a Chief Health Officer advisory.AimsTo describe the characteristics of patients with GAS bacteraemia admitted to a tertiary hospital. To compare at‐risk groups in our population with those identified in the Victorian Government health alert.MethodsRetrospective review of patients with GAS bacteraemia admitted between June 2014 and December 2017 at a tertiary hospital in Melbourne, Victoria.ResultsForty‐three cases of GAS bacteraemia occurred. Average age was 52 years (range 15–88 years) with 63% male. Average length of stay was 14 days (range 0–72 days) and all‐cause mortality occurred in two (5%) cases.Twelve (28%) patients presented with shock, 11 (26%) required intensive care unit admission and 13 (30%) surgical intervention. A history of intravenous drug use was documented in 18 (42%) cases and was commonly complicated by bone or joint involvement or thrombosis. Typing of GAS samples identified 22 different emm‐types.ConclusionGAS bacteraemia resulted in significant morbidity and prolonged hospitalisation. In contrast to the at‐risk groups identified in the Victorian Government health advisory, the commonest risk group in this series were people who inject drugs and most commonly middle‐aged men. Invasive GAS should be considered if a person who injects drugs presents with acute severe sepsis.
Infant‐directed speech to infants at risk for dyslexia: A novel cross‐dyad design
Authors: Kalashnikova Marina , Goswami Usha , Burnham Denis 
Published: February 2020

AbstractWhen mothers speak to infants at risk for developmental dyslexia, they do not hyperarticulate vowels in their infant‐directed speech (IDS). Here, we used an innovative cross‐dyad design to investigate whether the absence of vowel hyperarticulation in IDS to at‐risk infants is a product of maternal infant‐directed behavior or of infants’ parent‐directed cues. Interactions between mothers and infants who were at risk or not at risk for dyslexia were recorded in three conditions: when mothers interacted with (a) their own infants, (b) infants who were not their own but of the same risk status, and (c) infants who were not their own and of the opposite risk status. This design revealed both infant and parent effects. Mothers of not‐at‐risk infants hyperarticulated vowels significantly more when speaking to not‐at‐risk than to at‐risk infants. In contrast, mothers of at‐risk infants hyperarticulated vowels significantly less than NAR mothers, and this was irrespective of infant status. Mothers of not‐at‐risk infants thus adjusted their IDS to the infant's risk status, while mothers of at‐risk infants did not. We suggest that IDS is determined reciprocally by characteristics of both partners in the dyad: Both infant and maternal factors are essential for the vowel hyperarticulation component of IDS.