bluuebunny/crossref_metadata_2025 huggingface dataset:
The propagation of linear waves in high-energy-density magnetoplasmas using a relativistic quantum magnetohydrodynamic model
Authors: Zhu Jun , Liu Xiaoshan , Jia Li
Published: March 2021

The propagation characteristics of linear waves in high-energy-density magnetoplasmas are investigated using a relativistic magnetohydrodynamic model based on the framework of relativistic quantum theory. Based on the covariant Wigner function approach, a relativistic quantum magnetohydrodynamic model is established. Starting from the relativistic quantum magnetohydrodynamic equations and the Maxwell equations, the dispersion equation for relativistic quantum magnetoplasmas is derived. The contributions of both quantum effects and relativistic effects are shown in the dispersion relations for perpendicular, parallel propagation with respect to a background magnetic field. Results show that the corrections of both quantum effects and relativistic effects are significant when choosing the plasma parameters of laser-based plasma compression schemes.
Significant association between intracranial volume and verbal intellectual abilities in patients with schizophrenia and a history of birth asphyxia
Authors: Wortinger Laura Anne , Jørgensen Kjetil Nordbø , Barth Claudia , Nerland Stener , Smelror Runar Elle , Vaskinn Anja , Ueland Torill , Andreassen Ole A. , Agartz Ingrid
Published: March 2021

Background

The etiology of schizophrenia (SZ) is proposed to include an interplay between a genetic risk for disease development and the biological environment of pregnancy and birth, where early adversities may contribute to the poorer developmental outcome. We investigated whether a history of birth asphyxia (ASP) moderates the relationship between intracranial volume (ICV) and intelligence in SZ, bipolar disorder (BD) and healthy controls (HC).

Methods

Two hundred seventy-nine adult patients (18–42 years) on the SZ and BD spectrums and 216 HC were evaluated for ASP based on information from the Medical Birth Registry of Norway. Participants underwent structural magnetic resonance imaging (MRI) to estimate ICV and intelligence quotient (IQ) assessment using the Wechsler Abbreviated Scale of Intelligence (WASI). Multiple linear regressions were used for analyses.

Results

We found a significant three-way interaction (ICV × ASP × diagnosis) on the outcome variable, IQ, indicating that the correlation between ICV and IQ was stronger in patients with SZ who experienced ASP compared to SZ patients without ASP. This moderation by ASP was not found in BD or HC groups. In patients with SZ, the interaction between ICV and a history of the ASP was specifically related to the verbal subcomponent of IQ as measured by WASI.

Conclusions

The significant positive association between ICV and IQ in patients with SZ who had experienced ASP might indicate abnormal neurodevelopment. Our findings give support for ICV together with verbal intellectual abilities as clinically relevant markers that can be added to prediction tools to enhance evaluations of SZ risk.
THE STRONG SILENT TYPE: MASCULINITY AND WANDELWEISER MUSIC
Authors: Cooper Ed
Published: March 2021

Masculinity is not just about being the loudest; it is a contradictory network of relationships relating to power, control and work. Deploying the methodology first developed in Raewyn Connell'sMasculinities(1995), this article argues that Wandelweiser works exhibit masculine social ordering. Silence presents apparent creative agency which is ultimately governed by the composer; fragile timbres strain the bodies of both the performers and listeners and encourage constant labour; openness displaces authorship, leaving interpreters to fill a composer-shaped hole. Analysis of these facets reveals a top-down power dynamic from these composers of the quiet that is integrally related to Connell's conception of hegemonic masculinity: the composer encourages reproduction and questioning of their dominant role from interpreters, which, counterintuitively, implicates their position of power. This investigation is interwoven with diary entries exposing and critiquing my own compositional process, demonstrating how masculinity is performed throughout my creative process and its subsequent documentation. This article explores how subversive, even if invisible, elements of masculinity lie within the process and product of composing instrumental music that initially may seem to counter typical ‘masculine’ musics.
THE MUSICAL DEPICTION OF A DISTORTED PLACE, SPACE AND TIME: AN INTERPRETATION OF JOHN ZORN'SINTERZONE
Authors: Windleburn Maurice
Published: March 2021

This article interprets John Zorn's compositionInterzone(2010) by comparing it to the eponymous place that is found throughout William S. Burroughs’ early novels. This is done through linking some of the ‘sound blocks’ that make up Zorn's composition to selected passages from Burroughs’ books as well as to specific events from the lives ofInterzone's two dedicatees: Burroughs, and his associate, the writer and painter Brion Gysin. Zorn's disjointed, chaotic arrangement of sound blocks, and by extension their extra-musical associations, is then shown to emulate the dream-like structure of the phantasmatic place that is Interzone, which Burroughs created for his novels with the aid of Gysin's ‘cut-up’ method. Through these extra-musical connotations, it is demonstrated that Zorn's composition imitates Interzone's distortion of place; of internal and external space; and, most importantly, of time.
THE CONCEPT ALBUM AS CURATORIAL ‘MEDIUM’: COLIN RILEY'S IN PLACE
Authors: McKeon Ed
Published: March 2021

Colin Riley's collaborative and curated project In Place (2015–18) – with its exploration of memory, place, language and identity – becomes a stimulus for considering the intertwining relationship between the song cycle and the album form. Featuring seven commissioned poets alongside found texts, In Place simultaneously assembles fragments of contemporary Britain and its broken tongues whilst reflecting on the current possibilities for binding these through song. Riley and his collaborators construct a sense of place in the movements between idiom, psychogeography, field recordings, samples, instrumental voices, speech and song, rather than from any fixed location, reference, identity or origin. I argue that this adapts and learns from the history of the album as a form of double binding, both of a finite set of materials and, crucially, of a community or interpersonal relations. With its development in the modern era through the poetry collection, song cycle, and recording, the album provides a model for living, collective remembrance, contrasting with the archival paradigm of preserving cultural authority. Its transformation and persistence are pursued with the emergence of the concept album through to music streaming, offering an historical framework in which In Place can be appreciated as a contribution to the contemporary ‘return to memory’.
Huddersfield Contemporary Music Festival 2020
Authors: Smith Neil Thomas
Published: March 2021

‘There has always been a state of crisis’, we are told in Ziad Nawfal's wonderful introduction to the underground music scene in Beirut. That the corona restrictions comprise a rather different crisis to that of Lebanon's capital should be stressed, yet it will have been no easy task creating any kind of Huddersfield festival this year. That any event could occur at all is an achievement on the part of the festival team and the ensembles, musicians, broadcasters and composers with whom they work. Adaptation and renewal are a vital part of a new musicians’ toolkit, even if the pace of change can be bewildering.
Dante Boon, Six Melodies (2020), 3×3 Concerts 5 June, 3 July and 7 August 2020.
Authors: Stone Sophie
Published: March 2021

The Covid-19 pandemic is an extremely difficult time for musicians, and some, out of necessity and perhaps curiosity and experimentation, have been exploring digital realisations of music, such as live streamed or pre-recorded concerts. Examples that I have experienced or have been a part of include the experimental music ensemble Bastard Assignment's Lockdown Jams involving Zoom experiments, the experimental Free Range Concert Series streamed on YouTube, the Montrose Composers’ Club Zoom collaborations, and The Ensemble Whose Name is Uhhhhmm … (formerly Lil’ Jürg Frey) who perform music in Animal Crossing using in-game sounds.
Managing the retention or divestment of material possessions in the transition to retirement: implications for sustainable consumption and for later-life wellbeing
Authors: Venn Susan , Burningham Kate
Published: March 2021

It has been argued that lifecourse transitions are transformative moments for individuals when lifestyles, habits and behaviours are potentially open to contemplation and change. Within sustainability research such ‘moments of change’ are regarded as offering potential to encourage less environmentally damaging consumption patterns. Research on consumption indicates that orientations to material goods and their affective significance are complex. Whilst sociological work understands attachment to things as integral to maintaining kinship relations, this is hard to reconcile with long-standing moral concerns about materialism and psychological research which indicates a negative relationship between the acquisition of material objects and wellbeing, and the environmental implications of acquiring and divesting ‘stuff’. Yet there has been little engagement with how older people orient to their material possessions and divestment, the implications of this for later-life wellbeing and for environmental sustainability. In this paper, we draw these different strands of work together to understand how retirees relate to their material possessions and their divestment. Drawing on serial interviews with individuals in the United Kingdom, we explore how the transition to retirement highlights the complexity of participants’ attachment to things. While some items had profound relational significance, others were experienced as troublesome. Decisions on what to divest were shaped by pragmatic considerations and levels of attachment, whilst modes of divestment were aligned with values of thrift.
Brain, musicality, and language aptitude: A complex interplay
Authors: Turker Sabrina , Reiterer Susanne M.
Published: March 2021

Music and language are highly intertwined auditory phenomena that largely overlap on behavioral and neural levels. While the link between the two has been widely explored on a general level, comparably few studies have addressed the relationship between musical skills and language aptitude, defined as an individual's (partly innate) capacity for learning foreign languages. Behaviorally, past research has provided evidence that individuals’ musicality levels (expressed by singing, instrument playing, and/or perceptive musical abilities) are significantly associated with their foreign language learning, particularly the acquisition of phonetic and phonological skills (e.g., pronunciation, speech imitation). On the neural level, both skills recruit a wide array of overlapping brain areas, which are also involved in cognition and memory.

The neurobiology of language aptitude is an area ripe for investigation, since there has been only limited research establishing neurofunctional and neuroanatomical markers characteristic of speech imitation and overall language aptitude (e.g., in the left/right auditory cortex and left inferior parietal areas of the brain). Thus, as noted above, in this short review for ARAL, the aim is to describe the most recent neuroscientific findings on the neurobiology of language aptitude, to discuss the complex interplay between language aptitude and musicality from neural and behavioral perspectives, and to briefly outline what the promise of future research in this area holds.
Configural frequency trees
Authors: Wiedermann Wolfgang , Herman Keith C. , Reinke Wendy , von Eye Alexander
Published: March 2021

Although variable-oriented analyses are dominant in developmental psychopathology, researchers have championed a person-oriented approach that focuses on the individual as a totality. This view has methodological implications and various person-oriented methods have been developed to test person-oriented hypotheses. Configural frequency analysis (CFA) has been identified as a prime method for a person-oriented analysis of categorical data. CFA searches for configurations in cross-classifications and asks whether the number of observed cases is larger (CFA type) or smaller (CFA antitype) than expected under a probability model. The present study introduces a combination of CFA and model-based recursive partitioning (MOB) to test for type/antitype heterogeneity in the population. MOB CFA is well suited to detect complex moderation processes and can distinguish between subpopulation and population types/antitypes. Model specifications are discussed for first-order CFA and prediction CFA. Results from two simulation studies suggest that MOB CFA is able to detect moderation processes with high accuracy. Two empirical examples are given from school mental health research for illustrative purposes. The first example evaluates heterogeneity in student behavior types/antitypes, the second example focuses on the effect of a teacher classroom management intervention on student behavior. An implementation of the approach is provided in R.
Mapping end-of-life and anticipatory medications in palliative care patients using a longitudinal general practice database
Authors: Khalil H. , Garett M. , Byrne A. , Poon P. , Gardner K. , Azar D. , Craig L. , Karimi L.
Published: March 2021

Objective

End-of-life and anticipatory medications (AMs) have been widely used in various health care settings for people approaching end-of-life. Lack of access to medications at times of need may result in unnecessary hospital admissions and increased patient and family distress in managing palliative care at home. The study aimed to map the use of end-of-life and AM in a cohort of palliative care patients through the use of the Population Level Analysis and Reporting Data Space and to discuss the results through stakeholder consultation of the relevant organizations.

Methods

A retrospective observational cohort study of 799 palliative care patients in 25 Australian general practice health records with a palliative care referral was undertaken over a period of 10 years. This was followed by stakeholders’ consultation with palliative care nurse practitioners and general practitioners who have palliative care patients.

Results

End-of-life and AM prescribing have been increasing over the recent years. Only a small percentage (13.5%) of palliative care patients received medications through general practice. Stakeholders’ consultation on AM prescribing showed that there is confusion about identifying patients needing medications for end-of-life and mixed knowledge about palliative care referral pathways.

Significance of results

Improved knowledge and information around referral pathways enabling access to palliative care services for general practice patients and their caregivers are needed. Similarly, the increased utility of screening tools to identify patients with palliative care needs may be useful for health care practitioners to ensure timely care is provided.
Prenatal programming of depression: cumulative risk or mismatch in the Ontario Child Health Study?
Authors: Savoy Calan , Van Lieshout Ryan J.
Published: March 2021

Consistent with cumulative risk hypotheses of psychopathology, studies examining prenatal adversity and later mental health largely suggest that pre and postnatal stress exposures have summative effects. Fewer data support that a mismatch in stress levels between pre- and postnatal life increases risk (the mismatch hypothesis). In this retrospective cohort study using data from the 1983 Ontario Child Health Study (OCHS), we examined interactions between birth weight status and childhood/adolescent stress to predict major depression in adulthood. Ninety-five participants born at low birth weight (LBW; <2500 g) and 972 normal birth weight (NBW) control participants completed the Composite International Diagnostic Interview Short-Form Major Depression module at 21–34 years of age. A youth risk scale consisting of five stressful exposures (family dysfunction, socioeconomic disadvantage, parental criminality, maternal mental illness, exposure to other life stresses) indexed child/adolescent adversity. Birth weight groups did not differ by childhood risk score nor depression levels. A significant interaction was observed between birth weight and the youth risk scale whereby exposure to increasing levels of exposure to childhood/adolescent adversity predicted increased levels of depression in the NBW group, but lower rates in those born at LBW. Consistent with the mismatch hypothesis, data from a large, longitudinally followed cohort suggest that the mental health of adults born LBW may be more resilient to the adverse effects of childhood/adolescent stress. Taken in the context of previous studies of low birth weight infants, these findings suggest that the nature of associations between gestational stress and later mental health may depend on the magnitude of prenatal stress exposure, as well as the degree of resilience and/or plasticity conferred by their early-life environment.
Potentially preventable hospitalisations for physical health conditions in community mental health service users: a population-wide linkage study
Authors: Sara G. , Chen W. , Large M. , Ramanuj P. , Curtis J. , McMillan F. , Mulder C.L. , Currow D. , Burgess P.
Published: March 2021

Aims

Mental health (MH) service users have increased prevalence of chronic physical conditions such as cardio-respiratory diseases and diabetes. Potentially Preventable Hospitalisations (PPH) for physical health conditions are an indicator of health service access, integration and effectiveness, and are elevated in long term studies of people with MH conditions. We aimed to examine whether PPH rates were elevated in MH service users over a 12-month follow-up period more suitable for routine health indicator reporting. We also examined whether MH service users had increased PPH rates at a younger age, potentially reflecting the younger onset of chronic physical conditions.

Methods

A population-wide data linkage in New South Wales (NSW), Australia, population 7.8 million. PPH rates in 178 009 people using community MH services in 2016–2017 were compared to population rates. Primary outcomes were crude and age- and disadvantage-standardised annual PPH episode rate (episodes per 100 000 population), PPH day rate (hospital days per 100 000) and adjusted incidence rate ratios (AIRR).

Results

MH service users had higher rates of PPH admission (AIRR 3.6, 95% CI 3.5–3.6) and a larger number of hospital days (AIRR 5.2, 95% CI 5.2–5.3) than other NSW residents due to increased likelihood of admission, more admissions per person and longer length of stay. Increases were greatest for vaccine-preventable conditions (AIRR 4.7, 95% CI 4.5–5.0), and chronic conditions (AIRR 3.7, 95% CI 3.6–3.7). The highest number of admissions and relative risks were for respiratory and metabolic conditions, including chronic obstructive airways disease (AIRR 5.8, 95% CI 5.5–6.0) and diabetic complications (AIRR 5.4, 95% CI 5.1–5.8). One-quarter of excess potentially preventable bed days in MH service users were due to vaccine-related conditions, including vaccine-preventable respiratory illness. Age-related increases in risk occurred earlier in MH service users, particularly for chronic and vaccine-preventable conditions. PPH rates in MH service users aged 20–29 were similar to population rates of people aged 60 and over. These substantial differences were not explained by socio-economic disadvantage.

Conclusions

PPHs for physical health conditions are substantially increased in people with MH conditions. Short term (12-month) PPH rates may be a useful lead indicator of increased physical morbidity and less accessible, integrated or effective health care. High hospitalisation rates for vaccine-preventable respiratory infections and hepatitis underline the importance of vaccination in MH service users and suggests potential benefits of prioritising this group for COVID-19 vaccination.
Spatiotemporal Assessment of GHG Emissions and Nutrient Sequestration Linked to Agronutrient Runoff in Global Wetlands
Authors: Pasut Chiara , Tang Fiona H. M. , Hamilton David , Riley William J. , Maggi Federico
Published: March 2021

Wetlands play a key role in regulating global greenhouse gas (GHG) emissions but anthropogenic impacts on nutrients may severely alter this balance. Recent assessments indicate that almost 22% of the global wetland area may be affected by agricultural runoff. In this work, we developed and applied a dynamic mechanistic reaction network model of soil organic matter linking the carbon (C), nitrogen (N), and sulfur (S) cycles at 0.5° × 0.5° spatial resolution across the globe. The model was used to estimate GHG emissions and nutrient sequestration rates in wetlands, driven by environmental stressors including N, P, and S fertilization. Wetland annual GHG emissions are estimated to be 136 ± 12.5 Tg C‐CH4, 589 ± 45.8 Tg C‐CO2, and 0.3 ± 0.04 Tg N‐N2O; in contrast, C, N, and S annual sequestration rates are estimated to be 576 ± 88.1 Tg C, 20 ± 4.4 Tg N, and 7.4 ± 0.8 Tg S, between 2000 and 2017. N fertilization inputs were responsible for 13% N2O emissions in wetlands in the Northern Hemisphere, while tropical wetlands were major reservoirs for C, N, and S. Temperature, net primary productivity, and methanogenic microorganisms exert the major control on GHG emissions. Wetland CH4 and CO2 emissions were found to have a hysteretic relationship with seasonal soil temperature, but not N2O. A global‐scale assessment is pivotal for best nutrient management practices, reducing nutrient losses, and controlling gas emissions.
Generation of Subauroral Longitudinally Extended Emissions Following Intensifications of the Poleward Boundary of the Substorm Bulge and Streamer Production
Authors: Henderson Michael G.
Published: March 2021

Observations showing the development of Subauroral Longitudinally Extended Emigerssions on a global scale are presented. It is demonstrated that they occur as a separation of an east‐west arc‐like band of luminosity that detaches away from the equatorward edge of the auroral distribution following episodes of auroral streamer production. They persist for time intervals on the order of ∼30 min and devolve into patchy disjointed segments before they fade. Emissions are seen in both 557.7 nm OI and 391.4 nm 1NG lines, and 630.0 nm emissions are often observed equatorward. The 391.4 nm emissions are typically weaker and fade away more quickly than the 557.7 nm emissions, suggesting that an auroral precipitation source is initially present but is rapidly depleted as the forms age. All cases are associated with enhanced Subauroral Polarization Stream (SAPS) flows, and one event shows clear association with large‐scale Giant Undulations (GUs) and the formation of spur‐like forms that fold equatorward under the main oval. A model is proposed for the production of subauroral longitudinally extended forms in which nonlinear growth of SAPS‐induced surface waves on the plasmapause results in a disruption of the boundary. It is suggested that hot plasma of plasma sheet origin becomes entrained in the plasmasphere to produce transient precipitation‐associated auroral emissions that may decay into STEVE emissions and that cold dense plasma from the plasmasphere becomes entrained onto open drift paths to feed long‐lived drainage plumes. This process may occur quasi periodically during intense substorms and storm‐time conditions.
History and Future of the Martian Dynamo and Implications of a Hypothetical Solid Inner Core
Authors: Hemingway Douglas J. , Driscoll Peter E.
Published: March 2021

Although Mars does not possess a global magnetic field today, regions of its crust are strongly magnetized, consistent with an early dynamo, likely powered by rapid heat flow from the core. If the core is undergoing crystallization, the associated compositional changes would provide an additional mechanism for driving convection—probably the dominant driver for Earth's dynamo today. This raises the question: does the lack of a global dynamo field on Mars suggest the absence of a partially crystallized core? More generally, what is the range of possibilities for the history and future of the Martian dynamo and which scenarios could be ruled out by the presence or absence of a solid inner core? Here we develop a new internal structure, thermal evolution, and buoyancy flux model to investigate the conditions under which the Martian core could experience compositionally driven convection, either in the past or the future. We show that the presence of a partially crystallized core is compatible with the lack of a dynamo today but that such a scenario implies the Martian dynamo could reactivate at some point in the future. We find that top‐down core crystallization (iron snow) requires weak light element partitioning, introduces limited buoyancy flux, and is unlikely to be effective at driving convection. Our model demonstrates how sulfur content & partitioning and core conductivity & expansivity determine which dynamo regimes are possible, can help in assessing implications of future observations relating to the Martian core, and forms the basis for further comparative study across rocky planets.
Interaction Between Oxygen Consumption and Carbon Dioxide Emission in a Subtropical Hypoxic Reservoir, Southeastern China
Authors: Yan Jing , Chen Nengwang , Wang Fenfang , Liu Qian , Wu Zetao , Middelburg Jack J. , Xie Yuyuan , Guo Weidong , Zhang Xin
Published: March 2021

It is well recognized that dam construction aggravates eutrophication and hypoxia in river reservoirs, but the interaction between oxygen dynamics and carbon cycling is often unclear. Here we investigated the external and internal controls on oxygen consumption and effects of hypoxia on carbon dioxide (CO2) emission in a subtropical reservoir in southeast China based on detailed field measurements during 2017 and 2018. Hypoxia lasted 4 months starting in mid‐July and expanded from the bottom to near surface water. Rainstorm hyperpycnal flow and unusual hydraulics (outflow exit 40 m from the bottom) resulted in two thermoclines and enhanced the oxygen deficit in deeper water. Microbial respiration accounted for 67.4%–96.5% of total oxygen consumption in the bottom water. The increased supply of organic matter from storm runoff and to a lesser extent primary production in summer enhanced subsequent oxygen consumption. We observed an imbalance between excess CO2 production and oxygen depletion in summer and winter which was likely associated with other processes in the hypolimnion (e.g., chemoautotrophy, anaerobic degradation of organic matter, proton buffering, and nitrification). The water‐air CO2 fluxes suggest that the surface reservoir usually served as a CO2 source, but was a sink in summer due to high primary productivity. CO2 was always oversaturated in the hypolimnion; this layer was at the depth of the dam outflow and ultimately released 68% of annual CO2 efflux to the atmosphere. This research confirmed that construction of a hydropower dam has substantially altered reservoir metabolism and regulated the CO2 emission pathway.
Phase characterisation of metalenses
Authors: Zhao Maoxiong , Chen Mu Ku , Zhuang Ze-Peng , Zhang Yiwen , Chen Ang , Chen Qinmiao , Liu Wenzhe , Wang Jiajun , Chen Ze-Ming , Wang Bo , Liu Xiaohan , Yin Haiwei , Xiao Shumin , Shi Lei , Dong Jian-Wen , Zi Jian , Tsai Din Ping
Published: March 2021

Metalenses have emerged as a new optical element or system in recent years, showing superior performance and abundant applications. However, the phase distribution of a metalens has not been measured directly up to now, hindering further quantitative evaluation of its performance. We have developed an interferometric imaging phase measurement system to measure the phase distribution of a metalens by taking only one photo of the interference pattern. Based on the measured phase distribution, we analyse the negative chromatic aberration effect of monochromatic metalenses and propose a feature size of metalenses. Different sensitivities of the phase response to wavelength between the Pancharatnam-Berry phase-based metalens and propagation phase-reliant metalens are directly observed in the experiment. Furthermore, through phase distribution analysis, it is found that the distance between the measured metalens and the brightest spot of focusing will deviate from the focal length when the metalens has a low nominal numerical aperture, even though the metalens is ideal without any fabrication error. We also use the measured phase distribution to quantitatively characterise the imaging performance of the metalens. Our phase measurement system will help not only designers optimise the designs of metalenses but also fabricants distinguish defects to improve the fabrication process, which will pave the way for metalenses in industrial applications.
Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts
Authors: Berdiel-Acer Mireia , Maia Ana , Hristova Zhivka , Borgoni Simone , Vetter Martina , Burmester Sara , Becki Corinna , Michels Birgitta , Abnaof Khalid , Binenbaum Ilona , Bethmann Daniel , Chatziioannou Aristotelis , Hasmann Max , Thomssen Christoph , Espinet Elisa , Wiemann Stefan
Published: March 2021

HER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes activation of AKT and ERK1/2, contributing to tumour progression and therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, and although they have shown favorable tolerability, their activity as a single agent has proven to be limited. Here we show that phosphorylation and activation of HER3 in luminal breast cancer cells occurs in a paracrine manner and is mediated by NRG1 expressed by cancer-associated fibroblasts (CAFs). Moreover, we uncover a HER3-independent NRG1 signaling in CAFs that results in the induction of a strong migratory and pro-fibrotic phenotype, describing a subtype of CAFs with elevated expression of NRG1 and an associated transcriptomic profile that determines their functional properties. Finally, we identified Hyaluronan Synthase 2 (HAS2), a targetable molecule strongly correlated with NRG1, as an attractive player supporting NRG1 signaling in CAFs.
Alternative approaches to target Myc for cancer treatment
Authors: Wang Chen , Zhang Jiawei , Yin Jie , Gan Yichao , Xu Senlin , Gu Ying , Huang Wendong
Published: March 2021

The Myc proto-oncogene family consists of three members, C-MYC, MYCN, and MYCL, which encodes the transcription factor c-Myc (hereafter Myc), N-Myc, and L-Myc, respectively. Myc protein orchestrates diverse physiological processes, including cell proliferation, differentiation, survival, and apoptosis. Myc modulates about 15% of the global transcriptome, and its deregulation rewires the cellular signaling modules inside tumor cells, thereby acquiring selective advantages. The deregulation of Myc occurs in >70% of human cancers, and is related to poor prognosis; hence, hyperactivated Myc oncoprotein has been proposed as an ideal drug target for decades. Nevertheless, no specific drug is currently available to directly target Myc, mainly because of its “undruggable” properties: lack of enzymatic pocket for conventional small molecules to bind; inaccessibility for antibody due to the predominant nucleus localization of Myc. Although the topic of targeting Myc has actively been reviewed in the past decades, exciting new progresses in this field keep emerging. In this review, after a comprehensive summarization of valuable sources for potential druggable targets of Myc-driven cancer, we also peer into the promising future of utilizing macropinocytosis to deliver peptides like Omomyc or antibody agents to intracellular compartment for cancer treatment.
Transitions in oral and gut microbiome of HPV+ oropharyngeal squamous cell carcinoma following definitive chemoradiotherapy (ROMA LA-OPSCC study)
Authors: Oliva Marc , Schneeberger Pierre H. H. , Rey Victor , Cho Matthew , Taylor Rachel , Hansen Aaron R. , Taylor Kirsty , Hosni Ali , Bayley Andrew , Hope Andrew J. , Bratman Scott V. , Ringash Jolie , Singh Simron , Weinreb Ilan , Perez-Ordoñez Bayardo , Chepeha Douglas , Waldron John , Xu Wei , Guttman David , Siu Lillian L. , Coburn Bryan , Spreafico Anna
Published: March 2021

Background

Oral and gut microbiomes have emerged as potential biomarkers in cancer. We characterised the oral and gut microbiomes in a prospective observational cohort of HPV+ oropharyngeal squamous cell carcinoma (OPSCC) patients and evaluated the impact of chemoradiotherapy (CRT).

Methods

Saliva, oropharyngeal swabs over the tumour site and stool were collected at baseline and post-CRT. 16S RNA and shotgun metagenomic sequencing were used to generate taxonomic profiles, including relative abundance (RA), bacterial density, α-diversity and β-diversity.

Results

A total of 132 samples from 22 patients were analysed. Baseline saliva and swabs had similar taxonomic composition (R2 = 0.006; p = 0.827). Oropharyngeal swabs and stool taxonomic composition varied significantly by stage, with increased oral RA of Fusobacterium nucleatum observed in stage III disease (p < 0.05). CRT significantly reduced the species richness and increased the RA of gut-associated taxa in oropharyngeal swabs (p < 0.05), while it had no effect in stool samples. These findings remained significant when adjusted by stage, smoking status and antibiotic use.

Conclusions

Baseline oral and gut microbiomes differ by stage in this HPV+ cohort. CRT caused a shift towards a gut-like microbiome composition in oropharyngeal swabs. Stage-specific features and the transitions in oral microbiome might have prognostic and therapeutic implications.
HNRNPA1-mediated exosomal sorting of miR-483-5p out of renal tubular epithelial cells promotes the progression of diabetic nephropathy-induced renal interstitial fibrosis
Authors: Liu DongWei , Liu FengXun , Li ZhengYong , Pan ShaoKang , Xie JunWei , Zhao ZiHao , Liu ZhenJie , Zhang JiaHui , Liu ZhangSuo
Published: March 2021

Diabetic nephropathy (DN) is a serious complication in type 1 and type 2 diabetes, and renal interstitial fibrosis plays a key role in DN progression. Here, we aimed to probe into the role and potential mechanism of miR-483-5p in DN-induced renal interstitial fibrosis. In this study, we corroborated that miR-483-5p expression was lessened in type 1 and type 2 diabetic mice kidney tissues and high glucose (HG)-stimulated tubular epithelial cells (TECs), and raised in the exosomes derived from renal tissues in type 1 and type 2 diabetic mice. miR-483-5p restrained the expressions of fibrosis-related genes in vitro and renal interstitial fibrosis in vivo. Mechanistically, miR-483-5p bound both TIMP2 and MAPK1, and TIMP2 and MAPK1 were bound up with the regulation of miR-483-5p on renal TECs under HG conditions. Importantly, HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine. Our results expounded that HNRNPA1-mediated exosomal sorting transported cellular miR-483-5p out of TECs into the urine, thus lessening the restraint of cellular miR-483-5p on MAPK1 and TIMP2 mRNAs, and ultimately boosting extracellular matrix deposition and the progression of DN-induced renal interstitial fibrosis.
Bioinformatic analysis of chromatin organization and biased expression of duplicated genes between two poplars with a common whole-genome duplication
Authors: Zhang Le , Zhao Jingtian , Bi Hao , Yang Xiangyu , Zhang Zhiyang , Su Yutao , Li Zhenghao , Zhang Lei , Sanderson Brian J. , Liu Jianquan , Ma Tao
Published: March 2021

The nonrandom three-dimensional organization of chromatin plays an important role in the regulation of gene expression. However, it remains unclear whether this organization is conserved and whether it is involved in regulating gene expression during speciation after whole-genome duplication (WGD) in plants. In this study, high-resolution interaction maps were generated using high-throughput chromatin conformation capture (Hi-C) techniques for two poplar species, Populus euphratica and Populus alba var. pyramidalis, which diverged ~14 Mya after a common WGD. We examined the similarities and differences in the hierarchical chromatin organization between the two species, including A/B compartment regions and topologically associating domains (TADs), as well as in their DNA methylation and gene expression patterns. We found that chromatin status was strongly associated with epigenetic modifications and gene transcriptional activity, yet the conservation of hierarchical chromatin organization across the two species was low. The divergence of gene expression between WGD-derived paralogs was associated with the strength of chromatin interactions, and colocalized paralogs exhibited strong similarities in epigenetic modifications and expression levels. Thus, the spatial localization of duplicated genes is highly correlated with biased expression during the diploidization process. This study provides new insights into the evolution of chromatin organization and transcriptional regulation during the speciation process of poplars after WGD.
Measuring human capital using global learning data
Authors: Angrist Noam , Djankov Simeon , Goldberg Pinelopi K. , Patrinos Harry A.
Published: March 2021

Human capital—that is, resources associated with the knowledge and skills of individuals—is a critical component of economic development1,2. Learning metrics that are comparable for countries globally are necessary to understand and track the formation of human capital. The increasing use of international achievement tests is an important step in this direction3. However, such tests are administered primarily in developed countries4, limiting our ability to analyse learning patterns in developing countries that may have the most to gain from the formation of human capital. Here we bridge this gap by constructing a globally comparable database of 164 countries from 2000 to 2017. The data represent 98% of the global population and developing economies comprise two-thirds of the included countries. Using this dataset, we show that global progress in learning—a priority Sustainable Development Goal—has been limited, despite increasing enrolment in primary and secondary education. Using an accounting exercise that includes a direct measure of schooling quality, we estimate that the role of human capital in explaining income differences across countries ranges from a fifth to half; this result has an intermediate position in the wide range of estimates provided in earlier papers in the literature5–13. Moreover, we show that average estimates mask considerable heterogeneity associated with income grouping across countries and regions. This heterogeneity highlights the importance of including countries at various stages of economic development when analysing the role of human capital in economic development. Finally, we show that our database provides a measure of human capital that is more closely associated with economic growth than current measures that are included in the Penn world tables version 9.014 and the human development index of the United Nations15.
Differential expression analysis and profiling of hepatic miRNA and isomiRNA in dengue hemorrhagic fever
Authors: de Oliveira Layanna Freitas , de Andrade Amanda Araújo Serrão , Pagliari Carla , de Carvalho Leda Viegas , Silveira Taiana S. , Cardoso Jedson Ferreira , Silva André Luiz Teles e , de Vasconcelos Janaina Mota , Moreira-Nunes Caroline Aquino , Burbano Rommel Mario Rodríguez , Nunes Márcio Roberto Teixeira , dos Santos Eduardo José Melo , Júnior João Lídio da Silva Gonçalves Viane
Published: March 2021

Dengue virus causes dengue hemorrhagic fever (DHF) and has been associated to fatal cases worldwide. The liver is one of the most important target tissues in severe cases, due to its intense viral replication and metabolic role. microRNAs role during infection is crucial to understand the regulatory mechanisms of DENV infection and can help in diagnostic and anti-viral therapies development. We sequenced the miRNome of six fatal cases and compared to five controls, to characterize the human microRNAs expression profile in the liver tissue during DHF. Eight microRNAs were differentially expressed, including miR-126-5p, a regulatory molecule of endothelial cells, miR-122-5p, a liver specific homeostasis regulator, and miR-146a-5p, an interferon-regulator. Enrichment analysis with predicted target genes of microRNAs revealed regulatory pathways of apoptosis, involving MAPK, RAS, CDK and FAS. Immune response pathways were related to NF- kB, CC and CX families, IL and TLR. This is the first description of the human microRNA and isomicroRNA profile in liver tissues from DHF cases. The results demonstrated the association of miR-126-5p, miR-122-5p and miR-146a-5p with DHF liver pathogenesis, involving endothelial repair and vascular permeability regulation, control of homeostasis and expression of inflammatory cytokines.
Exploratory study of the long-term footprint of deep brain stimulation on brain metabolism and neuroplasticity in an animal model of obesity
Authors: Casquero-Veiga Marta , Bueno-Fernandez Clara , Romero-Miguel Diego , Lamanna-Rama Nicolás , Nacher Juan , Desco Manuel , Soto-Montenegro María Luisa
Published: March 2021

Deep brain stimulation (DBS) is a powerful neurostimulation therapy proposed for the treatment of several neuropsychiatric disorders. However, DBS mechanism of action remains unclear, being its effects on brain dynamics of particular interest. Specifically, DBS reversibility is a major point of debate. Preclinical studies in obesity showed that the stimulation of the lateral hypothalamus (LH) and nucleus accumbens (NAcc), brain centers involved in satiety and reward circuits, are able to modulate the activity of brain structures impaired in this pathology. Nevertheless, the long-term persistence of this modulation after DBS withdrawal was unexplored. Here we examine the in vivo presence of such changes 1 month after LH- and NAcc-DBS, along with differences in synaptic plasticity, following an exploratory approach. Thus, both stimulated and non-stimulated animals with electrodes in the NAcc showed a common pattern of brain metabolism modulation, presumably derived from the electrodes’ presence. In contrast, animals stimulated in the LH showed a relative metabolic invariance, and a reduction of neuroplasticity molecules, evidencing long-lasting neural changes. Our findings suggest that the reversibility or persistence of DBS modulation in the long-term depends on the selected DBS target. Therefore, the DBS footprint would be influenced by the stability achieved in the neural network involved during the stimulation.
Author Correction: Desflurane anesthesia shifts the circadian rhythm phase depending on the time of day of anesthesia
Authors: Imai Ryo , Makino Hiroshi , Katoh Takasumi , Kimura Tetsuro , Kurita Tadayoshi , Hokamura Kazuya , Umemura Kazuo , Nakajima Yoshiki
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Author Correction: The sugar substitute Stevia shortens the lifespan of Aedes aegypti potentially by N-linked protein glycosylation
Authors: Sharma Arvind , Reyes Jeremiah , Borgmeyer David , Ayala-Chavez Cuauhtemoc , Snow Katie , Arshad Fiza , Nuss Andrew , Gulia-Nuss Monika
Published: March 2021

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
A theorized new class of polyhedral hydrocarbons of molecular formula CnHn and their bottom-up scaffold expansions into hyperstructures
Authors: Machado Camila M. B. , Lima Nathalia B. D. , Lins Sóstenes L. S. , Simas Alfredo M.
Published: March 2021

We address the use of Euler's theorem and topological algorithms to design 18 polyhedral hydrocarbons of general formula CnHn that exist up to 28 vertexes containing four- and six-membered rings only; compounds we call “nuggets”. Subsequently, we evaluated their energies to verify the likelihood of their chemical existence. Among these compounds, 13 are novel systems, of which 3 exhibit chirality. Further, the ability of all nuggets to perform fusion reactions either through their square faces, or through their hexagonal faces was evaluated. Indeed, they are potentially able to form bottom-up derived molecular hyperstructures with great potential for several applications. By considering these fusion abilities, the growth of the nuggets into 1D, 2D, and 3D-scaffolds was studied. The results indicate that nugget24a (C24H24) is predicted to be capable of carrying out fusion reactions. From nugget24a, we then designed 1D, 2D, and 3D-scaffolds that are predicted to be formed by favorable fusion reactions. Finally, a 3D-scaffold generated from nugget24a exhibited potential to be employed as a voxel with a chemical structure remarkably similar to that of MOF ZIF-8. And, such a voxel, could in principle be employed to generate any 3D sculpture with nugget24a as its level of finest granularity.
MicroRNAs modulate ethylene induced retrograde signal for rice endosperm starch biosynthesis by default expression of transcriptome
Authors: Panigrahi Sonam , Panigrahy Madhusmita , Kariali Ekamber , Dash Sushanta Kumar , Sahu Binod Bihari , Sahu Sushil Kumar , Mohapatra Pravat Kumar , Panigrahi Kishore Chandra Sekhar
Published: March 2021

Control of stage specific spike in ethylene production at anthesis has been a vauable route to potentially enhance genetic ceiling for grain filling of rice spikelet. A number of genes controlling ethylene homeostasis and starch synthesis have been identified so long, but lack of credible information on master modulation of gene expression by miRNAs and their target genes associated with hormonal dynamics obfuscate mechanisms controlling genotype difference in quantum of grain filling. The confusion accounts for consequent shrinkage of options for yield manipulation. In a two by two factorial design, miRNA regulation of spikelet specific grain development in low against high sterile recombinant inbred lines of riceOryza sativaL. namely CR 3856-62-11-3-1-1-1-1-1-1 (SR 157) and CR 3856-63-1-1-1-1-1-1-1 (SR 159) respectively, and inferior verses superior spikelets were compared during first 10 days after anthesis. Grain filling was poorer in SR159 than SR157 and inferior spikelets in the former were most vulnerable. Between the cultivars, overall expression of unique miRNAs with targets on ethylene pathway genes was higher in SR159 than SR157 and the situation was opposite for auxin pathway genes. Precision analysis in psTarget server database identified up-regulation of MIR2877 and MIR530-5p having Os11t0141000-02 and Os07t0239400-01 (PP2A regulatory subunit-like protein and ethylene-responsive small GTP-binding proteins) and MIR396h having Os01t0643300-02 (an auxin efflux carrier protein) and Os01t0643300-01 (a PIN1-like auxin transport protein), as targets with highest probability at anthesis and 5 days after anthesis respectively, in the inferior spikelet and the fold change values of DGE matched with pattern of gene expression (relative transcript level) in the qRT-PCR studies conducted for relevant miRNAs and protein factors for ethylene and auxin signalling. In conclusion, epigenetic regulation of both auxin and ethylene homeostasis control grain filling of rice spikelet was established, but evidences were more robust for the latter.