bluuebunny/crossref_metadata_2025_split huggingface dataset:
Embedded Regions 1 and 2 Field‐Aligned Currents: Newly Recognized From Low‐Altitude Spacecraft Observations
Authors: Liu Jiang , Lyons L. R. , Wang Chih‐Ping , Ma Yuzhang , Strangeway R. J. , Zhang Yongliang , Kivelson M. , Zou Ying , Khurana K. 
Published: May 2021

AbstractRegions 1 and 2 (R1 and R2) field‐aligned currents (FACs), manifestations of large‐scale convection in Earth's magnetosphere‐ionosphere (M‐I) system, often contain intense FAC layers of mesoscale latitudinal width near the R1/R2 interface. We refer to such layers as “embedded” R1 and R2 FACs. Likely resulting from enhanced magnetosphere‐ionosphere (M‐I) convection, these FACs may indicate M‐I configuration change and contribute significantly to substorm current wedges. We present several events in which embedded FACs were observed by low‐altitude spacecraft in the ionosphere. All the events occurred during active geomagnetic conditions or a substorm growth phase, and most map to an equatorial location on the nightside. When an embedded FAC is upward, it coincides with inverted‐V electron precipitation and a discrete auroral arc. If an upward embedded FAC is in the postmidnight‐to‐dawn sector, a dawnside auroral polarization stream appears immediately poleward of it, so it may be important for ionospheric heating, M‐I convection, and instabilities. Our results establish embedded FACs as a frequently appearing, fundamental phenomenon for understanding and modeling the magnetosphere‐ionosphere system.
Decoupling of Hf‐Nd Isotopes in Challenger Deep Sediments, Mariana Trench: Implications for Sedimentary Hf and Nd Recycling in Subduction Zones
Authors: Pang Chong‐Jin , Tian Liyan , Wang Xuan‐Ce , Zhang Hanyu , Wen Shu‐Nv , Krapež Bryan , Liu Wen‐Jing , Liu Zhi‐Xing , Wu Tao 
Published: May 2021

AbstractDecoupling between Hf and Nd isotopes in trench sediments is an important way to produce, via subduction‐related recycling, the mantle chemical heterogeneity that is evident in many arc‐related magmas. Sediments collected from >7,000 m water depths on the southern and northern slopes of the Challenger Deep were analyzed to understand the factors controlling the variation in Hf and Nd isotopic compositions. These sediments were transported to both flanks of the Challenger Deep by synchronous density currents. All sediment samples show positive ɛHf values and negative ɛNd values, mostly plotting above the seawater and terrestrial arrays in Hf‐Nd isotope space. Hafnium isotopic compositions in each depositional unit vary (high up to 9.2 ɛHf units) from lower, coarse‐grained laminae to upper, fine‐grained graded intervals, showing a good correspondence between ɛHf values and lamination within depositional units. Such variations are explained by the concentration of Fe‐Mn oxyhydroxide‐bearing clays in the upper graded intervals, whereas diatom fragments and arc‐volcanic detritus are preferentially sorted into lower laminae. These findings demonstrate that the decoupling of Hf‐Nd isotopes in trench sediments is not only linked to the nature of provenance but also to hydrodynamic sorting processes during sediment transport. Our results suggest that geographical and stratigraphic variations in sedimentary components (resedimented density‐current deposits vs. oceanic pelagites), as well as overall grain size, of the subduction wedge can complicate Hf‐Nd isotopic decoupling in resulting arc magmas.
Determining the Shoreline Retreat Rate of Australia Using Discrete and Hybrid Bayesian Networks
Authors: Mao Yongjing , Harris Daniel L. , Callaghan David P. , Phinn Stuart 
Published: May 2021

AbstractEvaluating shoreline retreat rate (SRR) on different spatial‐temporal scales is critical for effective coastal management. Large‐scale evaluations typically rely on data‐driven methods such as Discrete Bayesian networks (BNs). However, these BNs require discretization of continuous variables which can lead to information loss. Here, we propose a new method, the Hybrid BN to incorporate continuous variables without discretization. Both Discrete and Hybrid BNs were developed and compared to evaluate large‐scale (continental scale) SRR in Australia, using Digital Earth Australia data set. These BNs used forcing parameters (e.g., waves, tide, sediment sink/source, and sea level rise [SLR]) and geomorphic settings (e.g., geomorphology, backshore profile, and surfzone slope) to predict SRR. Validation of the BNs showed that Hybrid BNs, which provide a more realistic assessment of the range of SRR, outperform in predicting continuous variables, when compared with Discrete BNs. However, Discrete and Hybrid BNs provide consistent qualitative findings for the SRR of Australia. Among forcing parameters, the sediment sink/source was found to be the most informative variable to indicate the shoreline retreat, followed by tide, SLR rate, and wave processes. In the scenario of an increased SLR rate, tropical tidal flats were predicted as the most at risk coasts in Australia. We found that BNs can reflect the impact of different factors on coastal evolution, and predict future shoreline change by exploring historical data. The performance of these models can be further improved when more data sets become available.
Extratropical Low‐Frequency Variability With ENSO Forcing: A Reduced‐Order Coupled Model Study
Authors: Vannitsem Stéphane , Demaeyer Jonathan , Ghil Michael 
Published: May 2021

AbstractThe impact of the El Niño‐Southern Oscillation (ENSO) on the extratropics is investigated in an idealized, reduced‐order model that has a tropical and an extratropical module. Unidirectional ENSO forcing is used to mimick the atmospheric bridge between the tropics and the extratropics. The variability of the coupled ocean‐atmosphere extratropical module is then investigated through the analysis of its pullback attractors (PBAs). This analysis focuses on two types of ENSO forcing generated by the tropical module, one periodic and the other aperiodic. For a substantial range of the ENSO forcing, two chaotic PBAs are found to coexist for the same set of parameter values. Different types of extratropical low‐frequency variability (LFV) are associated with either PBA over the parameter ranges explored. For periodic ENSO forcing, the coexisting PBAs exhibit only weak nonlinear instability. For chaotic forcing, though, they are quite unstable and certain extratropical perturbations induce transitions between the two PBAs. These distinct stability properties may have profound consequences for extratropical climate predictions: in particular, ensemble averaging may no longer help isolate the LFV signal.
The balance between the intronic miR-342 and its host gene Evl determines hematopoietic cell fate decision
Authors: Herbst Friederike , Lang Tonio J. L. , Eckert Elias S. P. , Wünsche Peer , Wurm Alexander A. , Kindinger Tim , Laaber Karin , Hemmati Shayda , Hotz-Wagenblatt Agnes , Zavidij Oksana , Paruzynski Anna , Lu Junyan , von Kalle Christof , Zenz Thorsten , Klein Christoph , Schmidt Manfred , Ball Claudia R. , Glimm Hanno 
Published: May 2021

AbstractProtein-coding and non-coding genes like miRNAs tightly control hematopoietic differentiation programs. Although miRNAs are frequently located within introns of protein-coding genes, the molecular interplay between intronic miRNAs and their host genes is unclear. By genomic integration site mapping of gamma-retroviral vectors in genetically corrected peripheral blood from gene therapy patients, we identified theEVL/MIR342gene locus as a hotspot for therapeutic vector insertions indicating its accessibility and expression in human hematopoietic stem and progenitor cells. We therefore asked if and how EVL and its intronic miRNA-342 regulate hematopoiesis. Here we demonstrate that overexpression (OE) of Evl in murine primary Lin−Sca1+cKit+cells drives lymphopoiesis whereas miR-342 OE increases myeloid colony formation in vitro and in vivo, going along with a profound upregulation of canonical pathways essential for B-cell development or myelopoietic functions upon Evl or miR-342 OE, respectively. Strikingly, miR-342 counteracts its host gene by targeting lymphoid signaling pathways, resulting in reduced pre-B-cell output. Moreover, EVL overexpression is associated with lymphoid leukemia in patients. In summary, our data show that one common gene locus regulates distinct hematopoietic differentiation programs depending on the gene product expressed, and that the balance between both may determine hematopoietic cell fate decision.
Genomic analysis of cellular hierarchy in acute myeloid leukemia using ultrasensitive LC-FACSeq
Authors: Saygin Caner , Hu Eileen , Zhang Pu , Sher Steven , Lozanski Arletta , Doong Tzyy-Jye , Nicolet Deedra , Orwick Shelley , Labanowska Jadwiga , Skinner Jordan N. , Cempre Casey , Kauffman Tierney , Goettl Virginia M. , Heerema Nyla A. , Abruzzo Lynne , Miller Cecelia , Lapalombella Rosa , Behbehani Gregory , Mims Alice S. , Larkin Karilyn , Grieselhuber Nicole , Walker Alison , Bhatnagar Bhavana , Bloomfield Clara D. , Byrd John C. , Lozanski Gerard , Blachly James S. 
Published: May 2021

AbstractHematopoiesis is hierarchical, and it has been postulated that acute myeloid leukemia (AML) is organized similarly with leukemia stem cells (LSCs) residing at the apex. Limited cells acquired by fluorescence activated cell sorting in tandem with targeted amplicon-based sequencing (LC-FACSeq) enables identification of mutations in small subpopulations of cells, such as LSCs. Leveraging this, we studied clonal compositions of immunophenotypically-defined compartments in AML through genomic and functional analyses at diagnosis, remission and relapse in 88 AML patients. Mutations involving DNA methylation pathways, transcription factors and spliceosomal machinery did not differ across compartments, while signaling pathway mutations were less frequent in putative LSCs. We also provide insights into TP53-mutated AML by demonstrating stepwise acquisition of mutations beginning from the preleukemic hematopoietic stem cell stage. In 10 analyzed cases, acquisition of additional mutations and del(17p) led to genetic and functional heterogeneity within the LSC pool with subclones harboring varying degrees of clonogenic potential. Finally, we use LC-FACSeq to track clonal evolution in serial samples, which can also be a powerful tool to direct targeted therapy against measurable residual disease. Therefore, studying clinically significant small subpopulations of cells can improve our understanding of AML biology and offers advantages over bulk sequencing to monitor the evolution of disease.
SFRP2 induces a mesenchymal subtype transition by suppression of SOX2 in glioblastoma
Authors: Guo Min , Goudarzi Kaveh M. , Abedi Shiva , Pieber Melanie , Sjöberg Elin , Behnan Jinan , Zhang Xing-Mei , Harris Robert A. , Bartek Jiri , Lindström Mikael S. , Nistér Monica , Hägerstrand Daniel 
Published: May 2021

AbstractIntratumoral heterogeneity is a characteristic of glioblastomas that contain an intermixture of cell populations displaying different glioblastoma subtype gene expression signatures. Proportions of these populations change during tumor evolution, but the occurrence and regulation of glioblastoma subtype transition is not well described. To identify regulators of glioblastoma subtypes we utilized a combination of in vitro experiments and in silico analyses, using experimentally generated as well as publicly available data. Through this combined approach SOX2 was identified to confer a proneural glioblastoma subtype gene expression signature. SFRP2 was subsequently identified as aSOX2-antagonist, able to induce a mesenchymal glioblastoma subtype signature. A subset of patient glioblastoma samples with highSFRP2and lowSOX2expression was particularly enriched with mesenchymal subtype samples. Phenotypically, SFRP2 decreased tumor sphere formation, stemness as assessed by limiting dilution assay, and overall cell proliferation but increased cell motility, whereas SOX2 induced the opposite effects. Furthermore, an SFRP2/non-canonical-WNT/KLF4/PDGFR/phospho-AKT/SOX2 signaling axis was found to be involved in the mesenchymal transition. Analysis of human tumor tissue spatial gene expression patterns showed distinct expression ofSFRP2- and SOX2-correlated genes in vascular and cellular areas, respectively. Finally, conditioned media from SFRP2 overexpressing cells increased CD206 on macrophages. Together, these findings present SFRP2 as a SOX2-antagonist with the capacity to induce a mesenchymal subtype transition in glioma cells located in vascular tumor areas, highlighting its role in glioblastoma tumor evolution and intratumoral heterogeneity.
Facilitating improvements in young people’s social relationships to prevent or treat depression: A review of empirically supported interventions
Authors: Filia Kate , Eastwood Oliver , Herniman Sarah , Badcock Paul 
Published: May 2021

AbstractInterpersonal difficulties are often implicated in the onset of depressive disorders, and typically exacerbate depressive symptoms. This is particularly true for young people, given rapid changes in, and the increased importance of, their social relationships. The purpose of this narrative review was to identify empirically supported interventions that aim to prevent or treat depression in young people by facilitating improvements in their social environment. We conducted a search of controlled trials, systematic reviews and meta-analyses of such interventions, published between 1980 and June 2020. Our literature search and interpretation of results was informed by consultations with clinical experts and youth consumers and advocates. A number of promising approaches were identified with respect to prevention and treatment. Preliminary evidence was identified suggesting that school- and Internet-based approaches present a viable means to prevent the worsening of depressive symptoms in young people. Notably, delivering interpersonal psychotherapy—adolescent skills training (IPT-AST) in schools appears to be a promising early intervention strategy for young people at risk of full-threshold depressive disorder. In terms of treating depressive disorders in young people, there is strong evidence for the efficacy of interpersonal psychotherapy for adolescents (IPT-A), and preliminary evidence in favour of attachment-based family therapy (ABFT). Results are discussed with respect to recommendations for future research and practice.
Increased GFAP concentrations in the cerebrospinal fluid of patients with unipolar depression
Authors: Michel Maike , Fiebich Bernd L. , Kuzior Hanna , Meixensberger Sophie , Berger Benjamin , Maier Simon , Nickel Kathrin , Runge Kimon , Denzel Dominik , Pankratz Benjamin , Schiele Miriam A. , Domschke Katharina , van Elst Ludger Tebartz , Endres Dominique 
Published: May 2021

AbstractInflammatory processes involving altered microglial activity may play a relevant role in the pathophysiology of depressive disorders. Glial fibrillary acidic protein (GFAP) and calcium-binding protein S100B are considered microglial markers. To date, their role has been studied in the serum and tissue material of patients with unipolar depression but not in the cerebrospinal fluid (CSF). Therefore, the aim of the current study was to examine GFAP and S100B levels in the CSF of patients with major depression to better understand their role in affective disorders. In this retrospective study, 102 patients with unipolar depression and 39 mentally healthy controls with idiopathic intracranial hypertension were investigated. GFAP and S100B levels were measured using commercially available ELISA kits. CSF routine parameters were collected during routine clinical care. The mean values of GFAP and S100B were compared using age (and sex) corrected ANOVAs. Matched subgroups were analyzed by using an independent sample t-test. In addition, correlation analyses between GFAP/S100B levels and CSF routine parameters were performed within the patient group. Patients with unipolar depression had significantly higher levels of GFAP than controls (733.22 pg/ml vs. 245.56 pg/ml, p < 0.001). These results remained significant in a sub-analysis in which all controls were compared with patients suffering from depression matched 1:1 by age and sex (632.26 pg/ml vs. 245.56 pg/ml, p < 0.001). Levels of S100B did not differ significantly between patients and controls (1.06 ng/ml vs. 1.17 ng/ml, p = 0.385). GFAP levels correlated positively with albumin quotients (p < 0.050), S100B levels correlated positively with white blood cell counts (p = 0.001), total protein concentrations (p < 0.001), and albumin quotients (p = 0.001) in the CSF. The significance of the study is limited by its retrospective and open design, methodological aspects, and the control group with idiopathic intracranial hypertension. In conclusion, higher GFAP levels in patients with depression may be indicative of altered microglia activity, especially in astrocytes, in patients with unipolar depression. In addition, correlation analyses support the idea that S100B levels could be related to the integrity of the blood–brain/CSF barrier. Further multimodal and longitudinal studies are necessary to validate these findings and clarify the underlying biological processes.
Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial
Authors: Puig Noemi , Hernández Miguel T. , Rosiñol Laura , González Esther , de Arriba Felipe , Oriol Albert , González-Calle Verónica , Escalante Fernando , de la Rubia Javier , Gironella Mercedes , Ríos Rafael , García-Sánchez Ricarda , Arguiñano José M. , Alegre Adrián , Martín Jesús , Gutiérrez Norma. C. , Calasanz María J. , Martín María L. , Couto María del Carmen , Casanova María , Arnao Mario , Pérez-Persona Ernesto , Garzón Sebastián , González Marta S. , Martín-Sánchez Guillermo , Ocio Enrique M. , Coleman Morton , Encinas Cristina , Vale Ana M. , Teruel Ana I. , Cortés-Rodríguez María , Paiva Bruno , Cedena M. Teresa , San-Miguel Jesús F. , Lahuerta Juan J. , Bladé Joan , Niesvizky Ruben , Mateos María-Victoria 
Published: May 2021

AbstractAlthough case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.
IL-26 mediates epidermal growth factor receptor-tyrosine kinase inhibitor resistance through endoplasmic reticulum stress signaling pathway in triple-negative breast cancer cells
Authors: Itoh Takumi , Hatano Ryo , Horimoto Yoshiya , Yamada Taketo , Song Dan , Otsuka Haruna , Shirakawa Yuki , Mastuoka Shuji , Iwao Noriaki , Aune Thomas M. , Dang Nam H. , Kaneko Yutaro , Okumura Ko , Morimoto Chikao , Ohnuma Kei 
Published: May 2021

AbstractTriple-negative breast cancer (TNBC) has a poor prognosis compared to other breast cancer subtypes. Although epidermal growth factor receptor (EGFR) is overexpressed in TNBC, clinical trials with EGFR inhibitors including tyrosine kinase inhibitors (EGFR-TKI) in TNBC have heretofore been unsuccessful. To develop effective EGFR-targeted therapy for TNBC, the precise mechanisms of EGFR-TKI resistance in TNBC need to be elucidated. In this study, to understand the molecular mechanisms involved in the differences in EGFR-TKI efficacy on TNBC between human and mouse, we focused on the effect of IL-26, which is absent in mice. In vitro analysis showed that IL-26 activated AKT and JNK signaling of bypass pathway of EGFR-TKI in both murine and human TNBC cells. We next investigated the mechanisms involved in IL-26-mediated EGFR-TKI resistance in TNBC. We identified EphA3 as a novel functional receptor for IL-26 in TNBC. IL-26 induced dephosphorylation and downmodulation of EphA3 in TNBC, which resulted in increased phosphorylation of AKT and JNK against EGFR-TKI-induced endoplasmic reticulum (ER) stress, leading to tumor growth. Meanwhile, the blockade of IL-26 overcame EGFR-TKI resistance in TNBC. Since the gene encoding IL-26 is absent in mice, we utilized humanIL-26transgenic (hIL-26Tg) mice as a tumor-bearing murine model to characterize the role of IL-26 in the differential effect of EGFR-TKI in human and mice and to confirm our in vitro findings. Our findings indicate that IL-26 activates the bypass pathway of EGFR-TKI, while blockade of IL-26 overcomes EGFR-TKI resistance in TNBC via enhancement of ER stress signaling. Our work provides novel insights into the mechanisms of EGFR-TKI resistance in TNBC via interaction of IL-26 with its newly identified receptor EphA3, while also suggesting IL-26 as a possible therapeutic target in TNBC.
Intrinsic luminescence blinking from plasmonic nanojunctions
Authors: Chen Wen , Roelli Philippe , Ahmed Aqeel , Verlekar Sachin , Hu Huatian , Banjac Karla , Lingenfelder Magalí , Kippenberg Tobias J. , Tagliabue Giulia , Galland Christophe 
Published: May 2021

AbstractPlasmonic nanojunctions, consisting of adjacent metal structures with nanometre gaps, can support localised plasmon resonances that boost light matter interactions and concentrate electromagnetic fields at the nanoscale. In this regime, the optical response of the system is governed by poorly understood dynamical phenomena at the frontier between the bulk, molecular and atomic scales. Here, we report ubiquitous spectral fluctuations in the intrinsic light emission from photo-excited gold nanojunctions, which we attribute to the light-induced formation of domain boundaries and quantum-confined emitters inside the noble metal. Our data suggest that photoexcited carriers and gold adatom - molecule interactions play key roles in triggering luminescence blinking. Surprisingly, this internal restructuring of the metal has no measurable impact on the Raman signal and scattering spectrum of the plasmonic cavity. Our findings demonstrate that metal luminescence offers a valuable proxy to investigate atomic fluctuations in plasmonic cavities, complementary to other optical and electrical techniques.