bluuebunny/crossref_metadata_2025_split huggingface dataset:
A lost decade? A renewed case for adult social care reform in England
Authors: GLASBY JON , ZHANG YANAN , BENNETT MATTHEW R. , HALL PATRICK 
Published: August 2020

AbstractDrawing on a 2010 analysis of the reform and costs of adult social care commissioned by Downing Street and the UK Department of Health, this paper sets out projected future costs under different reform scenarios, reviews what happened in practice from 2010-19, explores the impact of the growing gap between need and funding, and explores the relationship between future spending and economic growth. In the process, it identifies a ‘lost decade’ in which policy makers failed to act on the warnings which they received in 2010, draws attention to the disproportionate impact of cuts on older people (compared to services for people of working age) and calls for urgent action before the current system becomes unsustainable.
Adaptive Plasticity Under Adverse Listening Conditions is Disrupted in Developmental Dyslexia
Authors: Gabay Yafit , Holt Lori L. 
Published: August 2020

AbstractObjective:Acoustic distortions to the speech signal impair spoken language recognition, but healthy listeners exhibit adaptive plasticity consistent with rapid adjustments in how the distorted speech input maps to speech representations, perhaps through engagement of supervised error-driven learning. This puts adaptive plasticity in speech perception in an interesting position with regard to developmental dyslexia inasmuch as dyslexia impacts speech processing and may involve dysfunction in neurobiological systems hypothesized to be involved in adaptive plasticity.Method:Here, we examined typical young adult listeners (N= 17), and those with dyslexia (N= 16), as they reported the identity of native-language monosyllabic spoken words to which signal processing had been applied to create a systematic acoustic distortion. During training, all participants experienced incremental signal distortion increases to mildly distorted speech along with orthographic and auditory feedback indicating word identity following response across a brief, 250-trial training block. During pretest and posttest phases, no feedback was provided to participants.Results:Word recognition across severely distorted speech was poor at pretest and equivalent across groups. Training led to improved word recognition for the most severely distorted speech at posttest, with evidence that adaptive plasticity generalized to support recognition of new tokens not previously experienced under distortion. However, training-related recognition gains for listeners with dyslexia were significantly less robust than for control listeners.Conclusions:Less efficient adaptive plasticity to speech distortions may impact the ability of individuals with dyslexia to deal with variability arising from sources like acoustic noise and foreign-accented speech.
“The Right of Suffrage Has Been Thrust on Me”: The Reluctant Suffragists of the American West
Authors: Kodumthara Sunu 
Published: August 2020

AbstractFrom nearly the moment the woman's suffrage movement began at Seneca Falls in 1848, anti-suffragists actively campaigned against it, claiming that woman suffrage would only destroy both American politics and the American family. However, despite their best efforts, states in the American West passed equal suffrage laws. Interestingly, once it passed in their states, anti-suffragists in the American West—albeit begrudgingly—exercised their right to vote. As equal suffrage continued to expand, the Western anti-suffragist strategy became the strategy of anti-suffragists everywhere. This essay examines three states that represent pivotal moments in the development of the anti-suffrage movement: Colorado, California, and Oklahoma. Shortly after Colorado passed equal suffrage in 1893 and California passed equal suffrage in 1911, anti-suffragists organized state and national associations. By the time Oklahoma passed its equal suffrage law in 1918, anti-suffragists were not only voting—they were also willing to run for office. Anti-suffragist strategy and rhetoric relied on how suffrage worked in the West, or at least anti-suffrage perceptions of it. In other words, women's suffrage in the West served as a catalyst for the anti-suffragist movement.
Comprehending global governance: International regime complexity vs. global constitutionalism
Authors: ALTER KAREN J. 
Published: August 2020

AbstractThe After Fragmentation special issue unites political science conversations about regime complexity with legal/normative conversations about global constitutionalism through a focus on the generation and resolution of interface conflicts, defined as moments when overlapping elements or rule incompatibilities generate actual conflicts. Yet scholars choosing among these two perspectives actually have different objectives. After reviewing the two literatures, I argue that this special issue is closer to the global constitutionalism perspective, which generally seeks legitimated order. By contrast, the regime complexity literature asks how does the fact that global governance is spread across multiple institutions in itself shape cooperation politics. Investigating what it means to get ‘beyond fragmentation’, I suggest that the potential or actuality of rule conflicts is not necessarily a problem because conflicts are a normal and even salutary aspect of politics. If conflict is not the concern, then what should we be worrying about? Both perspectives, I argue, are amoral because they normalise and help justify an international order where responsibility is spread across institutions, promoting order while failing to address fundamental problems affecting people and the world. In this respect, resolving rule conflicts does not get us beyond fragmentation.
A Novel Ensemble Design for Probabilistic Predictions of Fine Particulate Matter Over the Contiguous United States (CONUS)
Authors: Kumar Rajesh , Alessandrini Stefano , Hodzic Alma , Lee Jared A. 
Published: August 2020

AbstractThis study examines the benefit of using a dynamical ensemble for 48 hr deterministic and probabilistic predictions of near‐surface fine particulate matter (PM2.5) over the contiguous United States (CONUS). Our ensemble design captures three key sources of uncertainties in PM2.5 modeling including meteorology, emissions, and secondary organic aerosol (SOA) formation. Twenty‐four ensemble members were simulated using the Community Multiscale Air Quality (CMAQ) model during January, April, July, and October 2016. The raw ensemble mean performed better than most of the ensemble members but underestimated the observed PM2.5 over the CONUS with the largest underestimation over the western CONUS owing to negative PM2.5 bias in nearly all the members. To improve the ensemble performance, we calibrated the raw ensemble using model output statistics (MOS) and variance deficit methods. The calibrated ensemble captured the diurnal and day‐to‐day variability in observed PM2.5 very well and exhibited almost zero mean bias. The mean bias in the calibrated ensemble was reduced by 90–100% in the western CONUS and by 40–100% in other parts of the CONUS, compared to the raw ensemble in all months. The corresponding reduction in root‐mean‐square error (RMSE) was 13–40%. The calibrated ensemble also showed 30% improvement in the RMSE and spread matching compared to the raw ensemble. We have also shown that a nine‐member ensemble based on combinations of three meteorological and three anthropogenic emission scenarios can be used as a smaller subset of the full ensemble when sufficient computational resources are not available in the operational setting.
Composition and activity of nitrifier communities in soil are unresponsive to elevated temperature and CO2, but strongly affected by drought
Authors: Séneca Joana , Pjevac Petra , Canarini Alberto , Herbold Craig W , Zioutis Christos , Dietrich Marlies , Simon Eva , Prommer Judith , Bahn Michael , Pötsch Erich M , Wagner Michael , Wanek Wolfgang , Richter Andreas 
Published: August 2020

Abstract
Nitrification is a fundamental process in terrestrial nitrogen cycling. However, detailed information on how climate change affects the structure of nitrifier communities is lacking, specifically from experiments in which multiple climate change factors are manipulated simultaneously. Consequently, our ability to predict how soil nitrogen (N) cycling will change in a future climate is limited. We conducted a field experiment in a managed grassland and simultaneously tested the effects of elevated atmospheric CO2, temperature, and drought on the abundance of active ammonia-oxidizing bacteria (AOB) and archaea (AOA), comammox (CMX) Nitrospira, and nitrite-oxidizing bacteria (NOB), and on gross mineralization and nitrification rates. We found that N transformation processes, as well as gene and transcript abundances, and nitrifier community composition were remarkably resistant to individual and interactive effects of elevated CO2 and temperature. During drought however, process rates were increased or at least maintained. At the same time, the abundance of active AOB increased probably due to higher NH4+ availability. Both, AOA and comammox Nitrospira decreased in response to drought and the active community composition of AOA and NOB was also significantly affected. In summary, our findings suggest that warming and elevated CO2 have only minor effects on nitrifier communities and soil biogeochemical variables in managed grasslands, whereas drought favors AOB and increases nitrification rates. This highlights the overriding importance of drought as a global change driver impacting on soil microbial community structure and its consequences for N cycling.
A large-scale assessment of lakes reveals a pervasive signal of land use on bacterial communities
Authors: Kraemer S A , Barbosa da Costa N , Shapiro B J , Fradette M , Huot Y , Walsh D A 
Published: August 2020

Abstract
Lakes play a pivotal role in ecological and biogeochemical processes and have been described as “sentinels” of environmental change. Assessing “lake health” across large geographic scales is critical to predict the stability of their ecosystem services and their vulnerability to anthropogenic disturbances. The LakePulse research network is tasked with the assessment of lake health across gradients of land use on a continental scale. Bacterial communities are an integral and rapidly responding component of lake ecosystems, yet large-scale responses to anthropogenic activity remain elusive. Here, we assess the ecological impact of land use on bacterial communities from over 200 lakes covering more than 660,000 km2 across Eastern Canada. In addition to community variation between ecozones, land use across Eastern Canada also appeared to alter diversity, community composition, and network structure. Specifically, increasing anthropogenic impact within the watershed lowered diversity. Likewise, community composition was significantly correlated with agriculture and urban development within a watershed. Interaction networks showed decreasing complexity and fewer keystone taxa in impacted lakes. Moreover, we identified potential indicator taxa of high or low lake water quality. Together, these findings point to detectable bacterial community changes of largely unknown consequences induced by human activity within lake watersheds.
The TP53 mutation rate differs in breast cancers that arise in women with high or low mammographic density
Authors: Cheasley Dane , Devereux Lisa , Hughes Siobhan , Nickson Carolyn , Procopio Pietro , Lee Grant , Li Na , Pridmore Vicki , Elder Kenneth , Bruce Mann G. , Kader Tanjina , Rowley Simone M. , Fox Stephen B. , Byrne David , Saunders Hugo , Fujihara Kenji M. , Lim Belle , Gorringe Kylie L. , Campbell Ian G. 
Published: August 2020

AbstractMammographic density (MD) influences breast cancer risk, but how this is mediated is unknown. Molecular differences between breast cancers arising in the context of the lowest and highest quintiles of mammographic density may identify the mechanism through which MD drives breast cancer development. Women diagnosed with invasive or in situ breast cancer where MD measurement was also available (n = 842) were identified from the Lifepool cohort of >54,000 women participating in population-based mammographic screening. This group included 142 carcinomas in the lowest quintile of MD and 119 carcinomas in the highest quintile. Clinico-pathological and family history information were recorded. Tumor DNA was collected where available (n = 56) and sequenced for breast cancer predisposition and driver gene mutations, including copy number alterations. Compared to carcinomas from low-MD breasts, those from high-MD breasts were significantly associated with a younger age at diagnosis and features associated with poor prognosis. Low- and high-MD carcinomas matched for grade, histological subtype, and hormone receptor status were compared for somatic genetic features. Low-MD carcinomas had a significantly increased frequency of TP53 mutations, higher homologous recombination deficiency, higher fraction of the genome altered, and more copy number gains on chromosome 1q and losses on 17p. While high-MD carcinomas showed enrichment of tumor-infiltrating lymphocytes in the stroma. The data demonstrate that when tumors were matched for confounding clinico-pathological features, a proportion in the lowest quintile of MD appear biologically distinct, reflective of microenvironment differences between the lowest and highest quintiles of MD.
Using whole-genome sequencing data to derive the homologous recombination deficiency scores
Authors: de Luca Xavier M. , Newell Felicity , Kazakoff Stephen H. , Hartel Gunter , McCart Reed Amy E. , Holmes Oliver , Xu Qinying , Wood Scott , Leonard Conrad , Pearson John V. , Lakhani Sunil R. , Waddell Nicola , Nones Katia , Simpson Peter T. 
Published: August 2020

AbstractThe homologous recombination deficiency (HRD) score was developed using whole-genome copy number data derived from arrays as a way to infer deficiency in the homologous recombination DNA damage repair pathway (in particular BRCA1 or BRCA2 deficiency) in breast cancer samples. The score has utility in understanding tumour biology and may be indicative of response to certain therapeutic strategies. Studies have used whole-exome sequencing to derive the HRD score, however, with increasing use of whole-genome sequencing (WGS) to characterise tumour genomes, there has yet to be a comprehensive comparison between HRD scores derived by array versus WGS. Here we demonstrate that there is both a high correlation and a good agreement between array- and WGS-derived HRD scores and between the scores derived from WGS and downsampled WGS to represent shallow WGS. For samples with an HRD score close to threshold for stratifying HR proficiency or deficiency there was however some disagreement in the HR status between array and WGS data, highlighting the importance of not relying on a single method of ascertaining the homologous recombination status of a tumour.
Identity by descent analysis identifies founder events and links SOD1 familial and sporadic ALS cases
Authors: Henden Lyndal , Twine Natalie A. , Szul Piotr , McCann Emily P. , Nicholson Garth A. , Rowe Dominic B. , Kiernan Matthew C. , Bauer Denis C. , Blair Ian P. , Williams Kelly L. 
Published: August 2020

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterised by the loss of upper and lower motor neurons resulting in paralysis and eventual death. Approximately 10% of ALS cases have a family history of disease, while the remainder present as apparently sporadic cases. Heritability studies suggest a significant genetic component to sporadic ALS, and although most sporadic cases have an unknown genetic aetiology, some familial ALS mutations have also been found in sporadic cases. This suggests that some sporadic cases may be unrecognised familial cases with reduced disease penetrance in their ancestors. A powerful strategy to uncover a familial link is identity-by-descent (IBD) analysis, which detects genomic regions that have been inherited from a common ancestor. IBD analysis was performed on 83 Australian familial ALS cases from 25 families and three sporadic ALS cases, each of whom carried one of three SOD1 mutations (p.I114T, p.V149G and p.E101G). We defined five unique 350-SNP haplotypes that carry these mutations in our cohort, indicative of five founder events. This included two founder haplotypes that carry SOD1 p.I114T; linking familial and sporadic cases. We found that SOD1 p.E101G arose independently in each family that carries this mutation and linked two families that carry SOD1 p.V149G. The age of disease onset varied between cases that carried each SOD1 p.I114T haplotype. Linking families with identical ALS mutations allows for larger sample sizes and increased statistical power to identify putative phenotypic modifiers.
Effect of allosteric inhibition of non-muscle myosin 2 on its intracellular diffusion
Authors: Horváth Ádám I. , Gyimesi Máté , Várkuti Boglárka H. , Képiró Miklós , Szegvári Gábor , Lőrincz István , Hegyi György , Kovács Mihály , Málnási-Csizmadia András 
Published: August 2020

AbstractSubcellular dynamics of non-muscle myosin 2 (NM2) is crucial for a broad-array of cellular functions. To unveil mechanisms of NM2 pharmacological control, we determined how the dynamics of NM2 diffusion is affected by NM2′s allosteric inhibitors, i.e. blebbistatin derivatives, as compared to Y-27632 inhibiting ROCK, NM2′s upstream regulator. We found that NM2 diffusion is markedly faster in central fibers than in peripheral stress fibers. Y-27632 accelerated NM2 diffusion in both peripheral and central fibers, whereas in peripheral fibers blebbistatin derivatives slightly accelerated NM2 diffusion at low, but markedly slowed it at high inhibitor concentrations. In contrast, rapid NM2 diffusion in central fibers was unaffected by direct NM2 inhibition. Using our optopharmacological tool, Molecular Tattoo, sub-effective concentrations of a photo-crosslinkable blebbistatin derivative were increased to effective levels in a small, irradiated area of peripheral fibers. These findings suggest that direct allosteric inhibition affects the diffusion profile of NM2 in a markedly different manner compared to the disruption of the upstream control of NM2. The pharmacological action of myosin inhibitors is channeled through autonomous molecular processes and might be affected by the load acting on the NM2 proteins.
Identification and characterization of cytosolic malate dehydrogenase from the liver fluke Fasciola gigantica
Authors: Chetri Purna Bahadur , Shukla Rohit , Tripathi Timir 
Published: August 2020

AbstractThe liver fluke zoonoses, Fasciola spp. are parasitic helminths infecting humans and animals globally. Recent sequencing of the genome of Fasciola gigantica has provided a basis to understand the biochemistry of this parasite. Here, we identified the cytosolic malate dehydrogenase in F. gigantica (FgMDH) and characterized the enzyme biochemically and structurally. F. gigantica encodes a single cytosolic MDH, a key enzyme of the citric acid cycle. It catalyzes the reversible oxidation of malate to oxaloacetate using NAD+. The Fgmdh gene was amplified and cloned for expression of the recombinant protein. The purified protein showed a molecular weight of ~ 36 kDa that existed in a dimeric form in solution. The recombinant enzyme was catalytically active as it catalyzed both forward and reverse reactions efficiently. The kinetic parameters were determined for both directions. The structure of FgMDH and human MDH were modeled and validated. The superimposition of both the model structures showed overall structural similarity in the active site loop region, however, the conformation of the residues was different. Molecular docking elucidated the binding sites and affinities of the substrates and cofactors to the enzyme. Simulation of molecular dynamics and principal component analysis indicated the stability of the systems and collective motions, respectively. Understanding the structural and functional properties of MDH is important to better understand the roles of this enzyme in the biochemistry of the parasite.
Red phosphorus decorated electrospun carbon anodes for high efficiency lithium ion batteries
Authors: Liberale Francesco , Fiore Michele , Ruffo Riccardo , Bernasconi Roberto , Shiratori Seimei , Magagnin Luca 
Published: August 2020

AbstractElectrospinning is a powerful and versatile technique to produce efficient, specifically tailored and high-added value anodes for lithium ion batteries. Indeed, electrospun carbon nanofibers (CNFs) provide faster intercalation kinetics, shorter diffusion paths for ions/electrons transport and a larger number of lithium insertion sites with respect to commonly employed powder materials. With a view to further enhance battery performances, red phosphorous (RP) is considered one of the most promising materials that can be used in association with CNFs. RP/CNFs smart combinations can be exploited to overcome RP low conductivity and large volume expansion during cycling. In this context, we suggest a simple and cost effective double-step procedure to obtain high-capacity CNFs anodes and to enhance their electrochemical performances with the insertion of red phosphorous in the matrix. We propose a simple dropcasting method to confine micro- and nanosized RP particles within electrospun CNFs, thus obtaining a highly efficient, self-standing, binder-free anode. Phosphorous decorated carbon mats are characterized morphologically and tested in lithium ion batteries. Results obtained demonstrate that the reversible specific capacity and the rate capability of the obtained composite anodes is significantly improved with respect to the electrospun carbon mat alone.
The effects of intravitreal injections on intraocular pressure and retinal nerve fiber layer: a systematic review and meta-analysis
Authors: de Vries Victor. A. , Bassil Fabiana L. , Ramdas Wishal. D. 
Published: August 2020

AbstractThe number of eye diseases treated with intravitreal injections is increasing. Obviously, an injection of fluid into the eye results in an increase of intraocular pressure (IOP), the main risk factor for glaucoma. However, the effect of these repeated IOP increases on the eye is unclear. Therefore, we performed a systematic review with meta-analyses. PubMed, Embase and Clinical Trials Registries were searched for articles investigating the relationship between intravitreal injections (anti-vascular endothelial growth factor [anti-VEGF] or steroids) and either IOP, retinal nerve fiber layer (RNFL)-thickness and glaucoma. Multiple meta-analyses were performed, combining data on intravitreal injection of anti-VEGF medication and dexamethasone implants. A total of 74 articles were eligible for meta-analyses. The short-term effect of an intravitreal injection of anti-VEGF showed a statistically significant increase in IOP. One day after injection of anti-VEGF, however, IOP was significantly lower than baseline. The long-term time-intervals showed no significant difference in IOP. After intravitreal injection of a dexamethasone implant, IOP was significantly higher than baseline 1 month post-injection. RNFL-thickness was significantly reduced 6 and 12 months post-injection of anti-VEGF, as well as at end of follow up. Caution is advised when using intravitreal medication, especially when treating patients with advanced glaucoma; in these cases, prophylactic IOP-lowering medication may be considered.