bluuebunny/crossref_metadata_2025 huggingface dataset:
Observational Cost-Effectiveness Analysis Using Routine Data: Admission and Discharge Care Bundles for Patients with Chronic Obstructive Pulmonary Disease
Authors: Dixon Padraig , Hollingworth William , Benger Jonathan , Calvert James , Chalder Melanie , King Anna , MacNeill Stephanie , Morton Katherine , Sanderson Emily , Purdy Sarah
Published: March 2020

Background

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory disease, and accounts for a substantial proportion of unplanned hospital admissions. Care bundles for COPD are a set of standardised, evidence-based interventions that may improve outcomes in hospitalised COPD patients. We estimated the cost effectiveness of care bundles for acute exacerbations of COPD using routinely collected observational data.

Methods

Data were collected from implementation (n = 7) and comparator (n = 7) acute hospitals located in England and Wales. We conducted a difference-in-difference cost-effectiveness analysis using a secondary care (i.e. hospital) perspective to examine the effect on National Health Service (NHS) costs and 90-day mortality of implementing care bundles compared with usual care for patients admitted to hospital with an acute exacerbation of COPD. Adjusted models included as covariates patient age, sex, deprivation, ethnicity and seasonal effects and mixed effects for site.

Results

Outcomes and baseline characteristics of up to 12,532 patients were analysed using both complete case and multiply imputed models. Implementation of bundles varied. COPD care bundles were associated with slightly lower secondary care costs, but there was no evidence that they improved outcomes once adjustments were made for site and baseline covariates. Care bundles were unlikely to be cost effective for the NHS with an estimated net monetary benefit per 90-day death avoided from an adjusted multiply imputed model of −£1231 (95% confidence interval − £2428 to − £35) at a high cost-effectiveness threshold of £50,000 per 90-day death avoided.

Conclusion and Recommendations

Care bundles for COPD did not appear to be cost effective, although this finding may have been influenced by unmeasured variations in bundle implementation and other potential confounding factors.
An Integrated Bioarchaeological Approach to the Medieval ‘Agricultural Revolution’: A Case Study from Stafford, England,c.ad800–1200
Authors: Hamerow Helena , Bogaard Amy , Charles Michael , Forster Emily , Holmes Matilda , McKerracher Mark , Neil Samantha , Ramsey Christopher Bronk , Stroud Elizabeth , Thomas Richard
Published: March 2020

In much of Europe, the advent of low-input cereal farming regimes betweenc.ad800 and 1200 enabled landowners—lords—to amass wealth by greatly expanding the amount of land under cultivation and exploiting the labour of others. Scientific analysis of plant remains and animal bones from archaeological contexts is generating the first direct evidence for the development of such low-input regimes. This article outlines the methods used by the FeedSax project to resolve key questions regarding the ‘cerealization’ of the medieval countryside and presents preliminary results using the town of Stafford as a worked example. These indicate an increase in the scale of cultivation in the Mid-Saxon period, while the Late Saxon period saw a shift to a low-input cultivation regime and probably an expansion onto heavier soils. Crop rotation appears to have been practised from at least the mid-tenth century.
Tell Me Your Story: How Recruitment Practices Implementing Affirmative Action Laws May Undermine the Laws’ Goals
Authors: Buchter Lisa
Published: March 2020

Scholars pointed out that antidiscrimination laws do not fully undermine workplace discrimination and that affirmative action policies mostly benefit overqualified or advantaged individuals within minorities. To elucidate this paradox, this case study analyzes how some companies adopted specific selection and assessment processes for job seekers after the reinforcement of a quota for workers with disabilities in France. I observed the creation of alternative recruitment channels, the hiring of disability experts for recruitment, the refusal of resume sorting as a prescreening tool, and an emphasis on face-to-face interviews. While these changes circumvented practices that could have excluded people with disabilities (resume screening as a preselection tool, inaccessible venues for recruitment), they changed these practices only in limited spaces within the organizations. Additionally, while they did help more people get hired, they also compelled more personal disclosure that led to a more emotional assessment of job seekers and enabled “refined statistical discrimination” within pools of job seekers with disabilities. This research therefore reveals recruitment practices that may increase the number of individuals with disabilities hired but that, at the same time, may facilitate overselectivity and trigger significant risks associated with emotional recruitment of individuals with disabilities.
Music effects on phonological awareness development in 3-year-old children
Authors: Vidal Maria Manuel , Lousada Marisa , Vigário Marina
Published: March 2020

Music and language engage similar processing mechanisms, including auditory processing and higher cognitive functions, recruiting partially overlapping brain structures. It has been argued that both are related in child development and that linguistic functions can be positively influenced by music training above 4-years-old. In this randomized control study, with a test–training–retest methodology, 44 children (3–4 years old) were assessed with a phonological awareness test, prior and after an intervention period of a school year with weekly music classes (experimental group,n= 23) or visual arts classes (control group,n= 21) in kindergarten. In the preassessment there were no significant differences between groups. When comparing pre- and postassessment, results showed significant differences in both groups, but music classes’ students outperformed the control group, showing larger differences between the beginning and the end of the intervention. Improvement in both groups is expected due to general developmental reasons. However, the fact that children receiving music classes show greater improvement indicates that music lessons have influenced phonological awareness. Our results support the hypothesis that music training may promote language abilities, specifically phonological awareness, prior to the ages previously studied.
Feature-focusing constraints on implicit learning of function word and meaning associations
Authors: Pham Theresa , Kang Joel Hosung , Johnson Alisha , Archibald Lisa M. D.
Published: March 2020

Recent research has begun to investigate implicit learning at the level of meaning. The general consensus is that implicitly linking a word with a meaning is constrained by existing linguistic knowledge. However, another factor to consider is the extent to which attention is drawn to the relevant meanings in implicit learning paradigms. We manipulated the presence of cue saliency during implicit rule learning for a grammatical form (i.e., articles) linked to meaning (i.e., animacy vs. varying notions of size). In a series of experiments, participants learned four novel words but did not know that article usage also depended on a hidden rule, creating an opportunity for implicit rule learning. We found implicit learning through the use of a highly salient meaning (Experiment 1) or if image size was made salient by being explicitly cued (Experiment 3), but not in a low salient paradigm for intrinsic object size (Experiment 2). The findings suggest that implicit learning of semantic information might not be as constrained as previously argued. Instead, implicit learning might be additionally influenced by feature-focusing cues that make the meaning contrasts more salient and thereby more readily available to learning.
The influence of Totten Glacier on the Late Cenozoic sedimentary record
Authors: Donda Federica , Leitchenkov German , Brancolini Giuliano , Romeo Roberto , De Santis Laura , Escutia Carlota , O'Brien Philip , Armand Leanne , Caburlotto Andrea , Cotterle Diego
Published: March 2020

Analysis of multichannel seismic profiles collected on the continental rise off the Sabrina Coast, East Antarctica, has allowed the determination of the acoustic features that are indicative of major evolution steps of the East Antarctic Ice Sheet (EAIS) and highlights the role of meltwater that originated from Totten Glacier in shaping the margin architecture. The arrival of marine-terminating glaciers into the coastal region was recorded by an enhanced sediment input on the continental rise and the nucleation of channel-levees. Downslope sedimentary processes were dominant throughout the Late Cenozoic, testifying to the progressive growth of a highly dynamic, temperate ice sheet on the continent. The last evolutionary step marks the transition to when a full polar glacial regime occurred. The development of a prograding wedge with steeply dipping foresets on the continental shelf and slope exemplifies sedimentation at this time. Other sub-sea-floor observations indicate that downslope fluxes, triggered by glacial meltwater, were still able to deeply erode and deliver sediments to the rise area. This study's findings have led to the identification of expanded and well-preserved sedimentary successions, which we suggest should be considered as priority targets for future International Ocean Discovery Program deep drilling due to the sensitivity of the ice sheet in this area.
An estimate of the South Georgia diving petrelPelecanoides georgicuspopulation at Ile de la Possession, Crozet archipelago
Authors: Barbraud Christophe , Chaigne Adrien , Loubon Maxime , Lamy Olivier , Le Bouard Fabrice
Published: March 2020

Burrow-nesting seabirds constitute an important part of seabird diversity, yet accurate estimates of their abundance are largely lacking, limiting our understanding of their population dynamics and conservation status. We conducted a survey to estimate the number of South Georgia diving petrel (Pelecanoides georgicus) burrows during the 2013–14 breeding season on Ile de la Possession, Crozet archipelago, southern Indian Ocean. We used distance sampling and acoustic playback in order to estimate burrow densities ina priori-selected favourable nesting areas. A total of 855 burrows were detected. The mean altitude of burrows was 601.8 ± 69.4 m. The mean burrow detection distance was 1.77 ± 1.63 m. The burrow density was estimated at 15.649 burrows ha-1(95% confidence interval (CI): 10.245–23.903) and the slope-corrected total favourable area was 2365.53 ha, which yielded an estimate 37 018 burrows (95% CI: 24 235–56 544). The playback response rate was 15.8 ± 1.3%, and 40.8 ± 1.7% of burrows were occupied or showed signs of occupation. Occupancy rates were low compared to those measured by systematic burrow inspection in other studies. Assuming that laying occurred in 80–93% of the estimated number of burrows, as estimated by previous studies, gives an estimate of 29 614 (95% CI: 19 388–45 235) to 34 426 (95% CI: 22 538–52 585) breeding pairs.
Disappearance of the shunt and lower cardiac index during exercise in small, unrepaired ventricular septal defects
Authors: Maagaard Marie , Eckerström Filip , Heiberg Johan , Asschenfeldt Benjamin , Ringgaard Steffen , Hjortdal Vibeke E.
Published: March 2020

Objectives:

Clinical studies have revealed decreased exercise capacity in adults with small, unrepaired ventricular septal defects. Increasing shunt ratio and growing incompetence of the aortic and pulmonary valve with retrograde flow during exercise have been proposed as reasons for the previously found reduced exercise parameters. With MRI, haemodynamic shunt properties were measured during exercise in ventricular septal defects.

Methods:

Patients with small, unrepaired ventricular septal defects and healthy peers were examined with MRI during exercise. Quantitative flow scans measured blood flow through ascending aorta and pulmonary artery. Scans were analysed post hoc where cardiac index, retrograde flows, and shunt ratio were determined.

Results:

In total, 32 patients (26 ± 6 years) and 28 controls (27 ± 5 years) were included. The shunt ratio was 1.2 ± 0.2 at rest and decreased to 1.0 ± 0.2 at peak exercise, p < 0.01. Aortic cardiac index was lower at peak exercise in patients (7.5 ± 2 L/minute/m2) compared with controls (9.0±2L l/minute/m2), p<0.01. Aortic and pulmonary retrograde flow was larger in patients during exercise, p < 0.01. Positive correlation was demonstrated between aortic cardiac index at peak exercise and previously established exercise capacity for all patients (r = 0.5, p < 0.01).

Conclusions:

Small, unrepaired ventricular septal defects revealed declining shunt ratio with increasing exercise and lower aortic cardiac index. Patients demonstrated larger retrograde flow both through the pulmonary artery and the aorta during exercise compared with controls. In conclusion, adults with unrepaired ventricular septal defects redistribute blood flow during exercise probably secondary to a more fixed pulmonary vascular resistance compared with age-matched peers.
A systematic review, and meta-analysis, examining the prevalence of price promotions on foods and whether they are more likely to be found on less-healthy foods
Authors: Kaur Asha , Lewis Thomas , Lipkova Veronika , Fernando Santhushya , Rayner Mike , Harrington Richard A , Waterlander Wilma , Scarborough Peter
Published: March 2020

Objective:

There are concerns that price promotions encourage unhealthy dietary choices. This review aims to answer the following research questions (RQ1) what is the prevalence of price promotions on foods in high-income settings, and (RQ2) are price promotions more likely to be found on unhealthy foods?

Design:

Systematic review of articles published in English, in peer-review journals, after 1 January 2000.

Setting:

Included studies measured the prevalence of price promotions (i.e. percentage of foods carrying a price promotion out of the total number of foods available to purchase) in retail settings, in upper-mid to high-income countries.

Participants:

‘Price promotion’ was defined as a consumer-facing temporary price reduction or discount available to all customers. The control group/comparator was the equivalent products without promotions. The primary outcome for this review was the prevalence of price promotions, and the secondary outcome was the difference between the proportions of price promotions on healthy and unhealthy foods.

Results:

Nine studies (239 344 observations) were included for the meta-analysis for RQ1, the prevalence of price promotions ranged from 6 % (95 % CI 2 %, 15 %) for energy-dense nutrient-poor foods to 15 % (95 % CI 9 %, 25 %) for cereals, grains, breads and other starchy carbohydrates. However, the I-squared statistic was 99 % suggesting a very high level of heterogeneity. Four studies were included for the analysis of RQ2, of which two supported the hypothesis that price promotions were more likely to be found on unhealthy foods.

Conclusions:

The prevalence of price promotions is very context specific, and any proposed regulations should be supported by studies conducted within the proposed setting(s).
Effect of crop canopy and herbicide application on kochia (Bassia scoparia) density and seed production
Authors: Mosqueda Elizabeth G. , Lim Charlemagne A. , Sbatella Gustavo M. , Jha Prashant , Lawrence Nevin C. , Kniss Andrew R.
Published: March 2020

Understanding the effects of crop management practices on weed survival and seed production is imperative in improving long-term weed management strategies, especially for herbicide-resistant weed populations. Kochia [Bassia scoparia (L.) A.J. Scott] is an economically important weed in western North American cropping systems for many reasons, including prolific seed production and evolved resistance to numerous herbicide sites of action. Field studies were conducted in 2014 in a total of four field sites in Wyoming, Montana, and Nebraska to quantify the impact of different crop canopies and herbicide applications on B. scoparia density and seed production. Crops used in this study were spring wheat (Triticum aestivum L.), dry bean (Phaseolus vulgaris L.), sugar beet (Beta vulgaris L.), and corn (Zea mays L.). Herbicide treatments included either acetolactate synthase (ALS) inhibitors effective on non-resistant B. scoparia or a non–ALS inhibiting herbicide effective for both ALS-resistant and ALS-susceptible B. scoparia. Bassia scoparia density midseason was affected more by herbicide choice than by crop canopy, whereas B. scoparia seed production per plant was affected more by crop canopy compared with herbicide treatment. Our results suggest that crop canopy and herbicide treatments were both influential on B. scoparia seed production per unit area, which is likely a key indicator of long-term management success for this annual weed species. The lowest germinable seed production per unit area was observed in spring wheat treated with non–ALS inhibiting herbicides, and the greatest germinable seed production was observed in sugar beet treated with ALS-inhibiting herbicides. The combined effects of crop canopy and herbicide treatment can minimize B. scoparia establishment and seed production.
Suicide and Suicide Prevention From a Global Perspective
Authors: Arensman Ella , Scott Vanda , De Leo Diego , Pirkis Jane
Published: March 2020

Abstract. In this introductory chapter, we provide the background and rationale for the compilation of overviews of national suicide prevention strategies from all geographic regions globally. Currently, suicide is the second leading cause of death among young people aged 15–29 years at global level. Overall, suicide rates in low- and middle-income countries (LMIC) are lower than the rates in high-income countries (HIC) of 11.2 per 100,000 compared with 12.7 per 100,000 population, but the majority of suicide deaths worldwide occur in LMICs. However, there are ongoing challenges in relation to the accuracy of suicide figures in many countries. The rationale for the global approach to suicide prevention is linked to major strategic documents provided by the WHO, including the Global Mental Health Action Plan, 2013–2020, the WHO report Preventing Suicide: A Global Imperative, in 2014, and the United Nations Sustainable Development Goals (SDGs) for 2030, including a target of reducing premature mortality from noncommunicable diseases by one-third, with suicide mortality rate identified as an indicator for this target. In addition, a review is provided of the evidence base and best practice of suicide prevention programs.
Suicide Prevention in the Southeast Asia Region
Authors: Vijayakumar Lakshmi , Daly Caroline , Arafat Yasir , Arensman Ella
Published: March 2020

Abstract. This chapter provides an update on suicide and suicide prevention in the Southeast Asia Region, which covers 11 low- and middle-income countries, accounting for 26% of the world's population. More than one third (39%) of all suicides globally, occur in this region, with the highest suicide rate of 17.7 per 100,000, which is likely to be an underestimate due to differences in study populations, research methodology, and uncomprehensive data registration systems. The risk profile of people who die by suicide and the characteristics of suicides in Southeast Asia are distinctly different from other regions in many ways. In this region the male–female ratio for suicide is closer to 1, compared with 3:5 in higher-income countries, and the overall reported prevalence of mental disorders, such as depression or other psychiatric conditions, is lower. Both older people and adolescents show the highest rates of suicide. Suicide involving pesticide poisoning is the most common method used in both rural and urban areas in countries in this region. Updates are provided on national and regional suicide prevention activities in Bangladesh, Bhutan, Nepal, India, Sri Lanka, and Thailand.
Suicide Prevention in the African Region
Authors: Osafo Joseph , Asante Kwaku Oppong , Akotia Charity Sylvia
Published: March 2020

Abstract. This paper addresses national responses to suicide prevention in the African region. Eighteen countries responded, of which none had a national suicide prevention strategy in place and only three countries, namely Algeria, Congo, and Madagascar, were in the process of developing any kind of strategy, at the time of this survey. Official national statistics on suicide were available in four of the 18 AFRO countries, with two countries publishing figures on suicide attempts nationally. Training programs on suicide assessment and interventions for general practitioners or mental health professionals were very limited, available in just four countries. One country had a national center specifically dedicated to suicide research or prevention and four countries have at least one NGO dedicated to suicide prevention. Postvention bereavement support for families affected by suicide was available in three AFRO countries. In more than half of the countries, suicide is not an option to certify cause of death. Statistics on suicide and suicide prevention are poorly monitored in all the 18 AFRO countries. The present state of suicide prevention in the region will require cross-country efforts that will generate a critical mass to move suicide advocacy in establishing national prevention strategies in the region.
Suicide Prevention Programs
Authors: Platt Stephen , Niederkrotenthaler Thomas
Published: March 2020

Abstract. This chapter presents a narrative synthesis of the evidence relating to the effectiveness of 13 different approaches (interventions) that have been incorporated into national suicide prevention programs. These approaches are presented in an analytic framework that distinguishes between national and community-based multilevel programs, prevention, and treatment/maintenance. The primary source of evidence are six reviews of reviews published since 2005, supplemented by a small number of systematic reviews and primary studies. We report strongly supportive evidence concerning the effectiveness of structural interventions (restrictions on access to bridges, tall buildings, and railways) and restriction on access to pharmacological agents. Weakly supportive evidence of effectiveness is available for community-based multilevel programs; restrictions on access to firearms and ligature points in institutional settings; settings-based programs (in schools, communities, workplaces, prisons, and the armed forces); education and training targeted at primary care physicians; lithium; cognitive behavioral therapy and dialectical behavioral therapy; and brief contact. There is insufficient or conflicting evidence concerning the effectiveness of the remaining approaches. We conclude that the evidence base for effective suicide prevention is far from convincing. Major improvement in the extent and quality of collaboration between researchers, policymakers, and practitioners and a considerable increase in funding for evaluation studies in suicide prevention are required if the current knowledge gap about effective interventions is to be bridged.
Identifying Metasomatized Continental Lithospheric Mantle Involvement in Cenozoic Magmatism From Ta/Th Values, Southwestern North America
Authors: Farmer G. Lang , Fritz Diane E. , Glazner Allen F.
Published: March 2020

The accessory minerals rutile and apatite are rare or absent in the convecting upper mantle but occur in shallow, cooler, metasomatized continental lithospheric mantle (CLM) where they serve as carrier phases for the trace elements Ta (in rutile) and Th (in apatite). Because both minerals crystallize near‐solidus and are eliminated early during partial mantle melting, the relative abundances of rutile and apatite should control the Ta and Th abundances of mantle melts and provide a means of identifying the involvement of rutile‐ and/or apatite‐bearing metasomatized CLM in mafic continental magmatism. As a test, we investigated published Ta and Th abundances data from ~2,000 whole‐rock samples of mafic to intermediate composition, Cenozoic volcanic rocks in southwestern North America. Roughly half of the samples have Ta/Th values similar to those of island arc volcanic rocks (<0.2) or ocean island and mid‐ocean ridge basalts (>0.6). The remaining samples have intermediate and variable Ta/Th values between 0.2 and 0.6, independent of specific indices of crustal interaction (e.g., wt% P2O5/wt% K2O). We interpret the intermediate Ta/Th rocks as the products of direct melting of, or of extensive melt‐rock interaction with, rutile‐ and/or apatite‐bearing CLM. Intermediate Ta/Th rocks also have uniformly high 87Sr/86Sr (0.706 to 0.708) compared to oceanic basalts that, unlike their Nd isotopic compositions, do not covary with lithospheric age. These observations are consistent with widespread metasomatism of the CLM by Sr‐rich, Nd‐poor, aqueous fluids generated by dehydration of oceanic lithosphere, and its overlying tectonic mélange during early Cenozoic subduction beneath southwestern North America.
Absolute Centroid Location of Submarine Earthquakes from 3D Waveform Modeling of Water Reverberations
Authors: Castellanos Jorge C. , Zhan Zhongwen , Wu Wenbo
Published: March 2020

Oceanic transform faults (OTFs) represent an attractive tectonic environment to investigate how slip is accommodated within the crust. However, as most of these fault systems grow in the deep ocean, where few local seismic observations are available, characterizing their earthquake behavior is complicated and remains a formidable challenge. Here we present a novel approach for retrieving precise centroid locations of submarine earthquakes that is based on the modeling of water phases in teleseismic records. Using a hybrid method for simulating far‐field body waves with 3D source‐side structures, we demonstrate that the scattered energy generated by the continuous bounces of an earthquake's P‐wave trapped in the ocean is modelable and carries information about its source location. As a case study, we use a realistic bathymetry model of the Gofar transform fault on the East Pacific Rise and simulate the seismic wavefield at US Array stations for four of its moderate‐sized (Mw5.0+) earthquakes. Our modeling results show that water phases are sensitive to a ∼5 km change in the earthquake's horizontal location and that a remarkable agreement between observed and synthetic water phases is achieved when the location of an event is close to its true one. We then relocate three of these events by systematically computing their water phases in candidate locations until a satisfactory waveform fit is achieved. This analysis technique paves a new route for studying earthquake source properties in isolated marine environments and serves as a mean to investigate the seismic behavior of OTFs on a global scale.
Global Response of Evapotranspiration Ratio to Climate Conditions and Watershed Characteristics in a Changing Environment
Authors: Liu Zhiyong , Cheng Linyin , Zhou Guoyi , Chen Xiaohong , Lin Kairong , Zhang Wenfeng , Chen Xiuzhi , Zhou Ping
Published: March 2020

Understanding the complex relationship between evapotranspiration and climate conditions and land surface characteristics is important within the context of global warming and increasing anthropogenic stressors. Based on the Budyko theory, we derived general frameworks for describing how the evapotranspiration ratio (actual evapotranspiration/precipitation, AET/P) responds to changes in the aridity index (potential evapotranspiration/precipitation, PET/P) and watershed characteristics (m). The frameworks show that the sensitivity of AET/P to PET/P decreases with increasing aridity but such decreasing pattern also depends on different watershed characteristics. The sensitivity coefficient tends to be greater in the energy‐limited regimes (above 0.3) than in the water‐limited regimes. The slope of the sensitivity curve becomes steeper for larger m values (e.g., m > 2). In addition, the sensitivity of the AET/P to m shows an asymmetrical unimodal curve, while the strongest sensitivity (inflection point) of evapotranspiration ratio to m occurs at PET/P > 1. We further examined spatial patterns of these sensitivities and the relative roles of PET/P (RCPET/P) and m (RCm) to AET/P over 91 hydrological basins worldwide. The tropical humid basins present the strongest sensitivity of AET/P to PET/P, while higher sensitivity coefficients of AET/P to m can be found in very cold basins. The changes in the sensitivity of evapotranspiration ratio to PET/P and m between 1930–1970 and 1971–2008 were assessed for these basins across broad climatic gradients. Most of these basins show a positive change in RCPET/P but a negative shift in RCm in the warming world.
Nuclear DLC1 exerts oncogenic function through association with FOXK1 for cooperative activation of MMP9 expression in melanoma
Authors: Yang Xintao , Hu Feng , Liu Jessica Aijia , Yu Shan , Cheung May Pui Lai , Liu Xuelai , Ng Irene Oi-Lin , Guan Xin-Yuan , Wong Kelvin K. W. , Sharma Rakesh , Lung Hong Lok , Jiao Yufei , Lee Leo Tsz On , Cheung Martin
Published: March 2020

A Rho GTPase-activating protein (RhoGAP), deleted in liver cancer 1 (DLC1), is known to function as a tumor suppressor in various cancer types; however, whether DLC1 is a tumor-suppressor gene or an oncogene in melanoma remains to be clarified. Here we revealed that high DLC1 expression was detected in most of the melanoma tissues where it was localized in both the nuclei and the cytoplasm. Functional studies unveiled that DLC1 was both required and sufficient for melanoma growth and metastasis. These tumorigenic events were mediated by nuclear-localized DLC1 in a RhoGAP-independent manner. Mechanistically, mass spectrometry analysis identified a DLC1-associated protein, FOXK1 transcription factor, which mediated oncogenic events in melanoma by translocating and retaining DLC1 into the nucleus. RNA-sequencing profiling studies further revealed MMP9 as a direct target of FOXK1 through DLC1-regulated promoter occupancy for cooperative activation of MMP9 expression to promote melanoma invasion and metastasis. Concerted action of DLC1–FOXK1 in MMP9 gene regulation was further supported by their highly correlated expression in melanoma patients’ samples and cell lines. Together, our results not only unravel a mechanism by which nuclear DLC1 functions as an oncogene in melanoma but also suggest an unexpected role of RhoGAP protein in transcriptional regulation.
Regulation of the small GTPase Ran by miR-802 modulates proliferation and metastasis in colorectal cancer cells
Authors: Wang Xin , Li Danxiu , Sun Lina , Shen Gaofei , Liu Hao , Guo Hao , Ge Minghui , Liang Junrong , Chen Ping , Zhou Jinchi , Cao Tianyu , Wang Qi , Gao Xiaoliang , Tong Mingfu , Hu Sijun , Nie Yongzhan , Fan Daiming , wang xin , Zhao Xiaodi , Lu Yuanyuan
Published: March 2020

Background

The small GTPase Ran is upregulated in multiple cancers and fundamental for cancer cell survival and progression, but its significance and molecular mechanisms in colorectal cancer (CRC) remain elusive.

Methods

Ran expression was detected in CRC cell lines and tumour tissues. In vitro and in vivo functional assays were performed to examine the effects of Ran on cell proliferation and metastasis. The pathways and effectors regulated by Ran were explored by an unbiased screening. Bioinformatics prediction and experimental validation were used to identify the miRNA regulator for Ran.

Results

Ran expression was frequently increased in metastatic CRC cells and tissues, especially in metastatic tissues. The upregulation of Ran correlated with poor CRC patient prognosis. Ran silencing reduced proliferation and metastasis of CRC cells both in vitro and in vivo. Ran regulated the expression of EGFR and activation of ERK and AKT signalling pathways. miR-802 was identified as an upstream regulator of Ran and miR-802 overexpression resulted in antiproliferative and antimetastatic activities.

Conclusion

Our study demonstrates the oncogenic roles and underlying mechanisms of Ran in CRC and the novel miR-802/Ran/EGFR regulatory axis may provide potential biomarkers for the treatment of CRC.
Mapping anthropogenic mineral generation in China and its implications for a circular economy
Authors: Zeng Xianlai , Ali Saleem H. , Tian Jinping , Li Jinhui
Published: March 2020

Anthropogenic mineral is absorbing wide concern in the context of circular economy, but its generation mechanism and quantity from product to waste remain unclear. Here we consider three product groups, 30 products, and use the revised Weibull lifespan model to map the generation of anthropogenic mineral and 23 types of the capsulated materials by targeting their evolution from 2010 to 2050. Total weight of anthropogenic mineral on average in China reached 39 Mt in 2010, but it will double in 2022 and quadruple in 2045. Stocks of precious metals and rare earths will increase faster than most base materials. The total economic potential in yearly-generated anthropogenic mineral is anticipated to grow markedly from 100 billion US$ in 2020 to 400 billion US$ in 2050. Furthermore, anthropogenic mineral of around 20 materials will be capable to meet projected consumption of three product groups by 2050.
Microglial metabolic flexibility supports immune surveillance of the brain parenchyma
Authors: Bernier Louis-Philippe , York Elisa M. , Kamyabi Alireza , Choi Hyun B. , Weilinger Nicholas L. , MacVicar Brian A.
Published: March 2020

Microglia are highly motile cells that continuously monitor the brain environment and respond to damage-associated cues. While glucose is the main energy substrate used by neurons in the brain, the nutrients metabolized by microglia to support surveillance of the parenchyma remain unexplored. Here, we use fluorescence lifetime imaging of intracellular NAD(P)H and time-lapse two-photon imaging of microglial dynamics in vivo and in situ, to show unique aspects of the microglial metabolic signature in the brain. Microglia are metabolically flexible and can rapidly adapt to consume glutamine as an alternative metabolic fuel in the absence of glucose. During insulin-induced hypoglycemia in vivo or in aglycemia in acute brain slices, glutaminolysis supports the maintenance of microglial process motility and damage-sensing functions. This metabolic shift sustains mitochondrial metabolism and requires mTOR-dependent signaling. This remarkable plasticity allows microglia to maintain their critical surveillance and phagocytic roles, even after brain neuroenergetic homeostasis is compromised.
CDK1 dependent phosphorylation of hTERT contributes to cancer progression
Authors: Yasukawa Mami , Ando Yoshinari , Yamashita Taro , Matsuda Yoko , Shoji Shisako , Morioka Masaki Suimye , Kawaji Hideya , Shiozawa Kumiko , Machitani Mitsuhiro , Abe Takaya , Yamada Shinji , Kaneko Mika K. , Kato Yukinari , Furuta Yasuhide , Kondo Tadashi , Shirouzu Mikako , Hayashizaki Yoshihide , Kaneko Shuichi , Masutomi Kenkichi
Published: March 2020

The telomerase reverse transcriptase is upregulated in the majority of human cancers and contributes directly to cell transformation. Here we report that hTERT is phosphorylated at threonine 249 during mitosis by the serine/threonine kinase CDK1. Clinicopathological analyses reveal that phosphorylation of hTERT at threonine 249 occurs more frequently in aggressive cancers. Using CRISPR/Cas9 genome editing, we introduce substitution mutations at threonine 249 in the endogenous hTERT locus and find that phosphorylation of threonine 249 is necessary for hTERT-mediated RNA dependent RNA polymerase (RdRP) activity but dispensable for reverse transcriptase and terminal transferase activities. Cap Analysis of Gene Expression (CAGE) demonstrates that hTERT phosphorylation at 249 regulates the expression of specific genes that are necessary for cancer cell proliferation and tumor formation. These observations indicate that phosphorylation at threonine 249 regulates hTERT RdRP and contributes to cancer progression in a telomere independent manner.
A common MET polymorphism harnesses HER2 signaling to drive aggressive squamous cell carcinoma
Authors: Kong Li Ren , Mohamed Salleh Nur Afiqah Binte , Ong Richard Weijie , Tan Tuan Zea , Syn Nicholas L. , Goh Robby Miguel , Fhu Chee Wai , Tan Daniel S. W. , Iyer N. Gopalakrishna , Kannan Srinivasaraghavan , Verma Chandra S. , Lim Yaw Chyn , Soo Ross , Ho Jingshan , Huang Yiqing , Lim Joline S. J. , Yan Benedict Junrong , Nga Min En , Lim Seng Gee , Koeffler H. Phillip , Lee Soo Chin , Kappei Dennis , Hung Huynh The , Goh Boon Cher
Published: March 2020

c-MET receptors are activated in cancers through genomic events like tyrosine kinase domain mutations, juxtamembrane splicing mutation and amplified copy numbers, which can be inhibited by c-MET small molecule inhibitors. Here, we discover that the most common polymorphism known to affect MET gene (N375S), involving the semaphorin domain, confers exquisite binding affinity for HER2 and enables METN375S to interact with HER2 in a ligand-independent fashion. The resultant METN375S/HER2 dimer transduces potent proliferative, pro-invasive and pro-metastatic cues through the HER2 signaling axis to drive aggressive squamous cell carcinomas of the head and neck (HNSCC) and lung (LUSC), and is associated with poor prognosis. Accordingly, HER2 blockers, but not c-MET inhibitors, are paradoxically effective at restraining in vivo and in vitro models expressing METN375S. These results establish METN375S as a biologically distinct and clinically actionable molecular subset of SCCs that are uniquely amenable to HER2 blocking therapies.
Generating high quality libraries for DIA MS with empirically corrected peptide predictions
Authors: Searle Brian C. , Swearingen Kristian E. , Barnes Christopher A. , Schmidt Tobias , Gessulat Siegfried , Küster Bernhard , Wilhelm Mathias
Published: March 2020

Data-independent acquisition approaches typically rely on experiment-specific spectrum libraries, requiring offline fractionation and tens to hundreds of injections. We demonstrate a library generation workflow that leverages fragmentation and retention time prediction to build libraries containing every peptide in a proteome, and then refines those libraries with empirical data. Our method specifically enables rapid, experiment-specific library generation for non-model organisms, which we demonstrate using the malaria parasite Plasmodium falciparum, and non-canonical databases, which we show by detecting missense variants in HeLa.
Sustainability of global Golden Inland Waterways
Authors: Wang Yichu , Chen Xiabin , Borthwick Alistair G. L. , Li Tianhong , Liu Huaihan , Yang Shengfa , Zheng Chunmiao , Xu Jianhua , Ni Jinren
Published: March 2020

Sustainable inland waterways should meet the needs of navigation without compromising the health of riverine ecosystems. Here we propose a hierarchical model to describe sustainable development of the Golden Inland Waterways (GIWs) which are characterized by great bearing capacity and transport need. Based on datasets from 66 large rivers (basin area > 100,000 km2) worldwide, we identify 34 GIWs, mostly distributed in Asia, Europe, North America, and South America, typically following a three-stage development path from the initial, through to the developing and on to the developed stage. For most GIWs, the exploitation ratio, defined as the ratio of actual to idealized bearing capacity, should be less than 80% due to ecological considerations. Combined with the indices of regional development, GIWs exploitation, and riverine ecosystem, we reveal the global diversity and evolution of GIWs’ sustainability from 2015 to 2050, which highlights the importance of river-specific strategies for waterway exploitation worldwide.
A reflection on lithium-ion battery cathode chemistry
Authors: Manthiram Arumugam
Published: March 2020

Lithium-ion batteries have aided the portable electronics revolution for nearly three decades. They are now enabling vehicle electrification and beginning to enter the utility industry. The emergence and dominance of lithium-ion batteries are due to their higher energy density compared to other rechargeable battery systems, enabled by the design and development of high-energy density electrode materials. Basic science research, involving solid-state chemistry and physics, has been at the center of this endeavor, particularly during the 1970s and 1980s. With the award of the 2019 Nobel Prize in Chemistry to the development of lithium-ion batteries, it is enlightening to look back at the evolution of the cathode chemistry that made the modern lithium-ion technology feasible. This review article provides a reflection on how fundamental studies have facilitated the discovery, optimization, and rational design of three major categories of oxide cathodes for lithium-ion batteries, and a personal perspective on the future of this important area.
Automated highly multiplexed super-resolution imaging of protein nano-architecture in cells and tissues
Authors: Klevanski Maja , Herrmannsdoerfer Frank , Sass Steffen , Venkataramani Varun , Heilemann Mike , Kuner Thomas
Published: March 2020

Understanding the nano-architecture of protein machines in diverse subcellular compartments remains a challenge despite rapid progress in super-resolution microscopy. While single-molecule localization microscopy techniques allow the visualization and identification of cellular structures with near-molecular resolution, multiplex-labeling of tens of target proteins within the same sample has not yet been achieved routinely. However, single sample multiplexing is essential to detect patterns that threaten to get lost in multi-sample averaging. Here, we report maS3TORM (multiplexed automated serial staining stochastic optical reconstruction microscopy), a microscopy approach capable of fully automated 3D direct STORM (dSTORM) imaging and solution exchange employing a re-staining protocol to achieve highly multiplexed protein localization within individual biological samples. We demonstrate 3D super-resolution images of 15 targets in single cultured cells and 16 targets in individual neuronal tissue samples with <10 nm localization precision, allowing us to define distinct nano-architectural features of protein distribution within the presynaptic nerve terminal.
Thermophysical properties of a Si50Ge50 melt measured on board the International Space Station
Authors: Luo Yuansu , Damaschke Bernd , Lohöfer Georg , Samwer Konrad
Published: March 2020

Thermophysical properties of highly doped Si50Ge50 melt were measured contactlessly in the electromagnetic levitation facility ISS-EML on board the International Space Station. The sample could be melted, overheated by about 375 K, and cooled down in 350 mbar Argon atmosphere. A large undercooling of about 240 K was observed and a quasi-homogeneous nucleation on the droplet surface occurred. During the cooling phase, high-resolution videos were taken from the side and the top. The density and thermal expansion were evaluated with digital image processing; the viscosity and the surface tension were measured by means of the oscillating drop technique. Inductive measurements of the electrical resistivity were conducted by a dedicated electronics. All data were taken as a function of temperature T from the overheated melt down to the undercooled range. We found a nonlinear thermal expansion, suggesting a many body effect in the liquid beyond the regular pair interaction, an enhanced damping of surface oscillations likely related to an internal turbulent flow, and an increment of the electrical resistivity with decreased T in the undercooled range regarding a demixing of the components.
Nasal vaccine delivery attenuates brain pathology and cognitive impairment in tauopathy model mice
Authors: Takeuchi Hiroki , Imamura Keiko , Ji Bin , Tsukita Kayoko , Enami Takako , Takao Keizo , Miyakawa Tsuyoshi , Hasegawa Masato , Sahara Naruhiko , Iwata Nobuhisa , Inoue Makoto , Hara Hideo , Tabira Takeshi , Ono Maiko , Trojanowski John Q. , Lee Virginia M.-Y. , Takahashi Ryosuke , Suhara Tetsuya , Higuchi Makoto , Inoue Haruhisa
Published: March 2020

Pathological aggregates of tau proteins accumulate in the brains of neurodegenerative tauopathies including Alzheimer’s disease and frontotemporal lobar degeneration (FTLD-tau). Although immunotherapies of these disorders against tau are emerging, it is unknown whether nasal delivery, which offers many benefits over traditional approaches to vaccine administration, is effective or not for tauopathy. Here, we developed vaccination against a secreted form of pathological tau linked to FTLD-tau using a Sendai virus (SeV) vector infectious to host nasal mucosa, a key part of the immune system. Tau vaccines given as nasal drops induced tissue tau-immunoreactive antibody production and ameliorated cognitive impairment in FTLD-tau model mice. In vivo imaging and postmortem neuropathological assays demonstrated the suppression of phosphorylated tau accumulation, neurotoxic gliosis, and neuronal loss in the hippocampus of immunized mice. These findings suggest that nasal vaccine delivery may provide a therapeutic opportunity for a broad range of populations with human tauopathy.
Rapid flood and damage mapping using synthetic aperture radar in response to Typhoon Hagibis, Japan
Authors: Tay Cheryl W. J. , Yun Sang-Ho , Chin Shi Tong , Bhardwaj Alok , Jung Jungkyo , Hill Emma M.
Published: March 2020

During the aftermath of Typhoon Hagibis, we made flood and damage proxy maps, rapidly derived from synthetic aperture radar (SAR) data using change detection approaches. The maps have large spatial coverage over the Tokyo, Fukushima, Ibaraki, Iwate, and Nagano prefectures of Japan. The maps are also largely in agreement with various validation sources including aerial imagery, optical imagery and news sources. Apart from visual maps, we provide flood and damage extents in various formats compatible with geographic information system (GIS) applications. The data may potentially be used for applications such as typhoon risk modelling, investigating spatial correlations of typhoon impacts, and comparing alternative flood or damage mapping techniques.