bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival outcomes following craniotomy for intracranial metastases from an unknown primary
Authors: Gough Melissa , Nielsen Molly , Coulter Ian C. , Holliman Damian 
Published: May 2020

Abstract
Introduction
Management of patients with intracranial metastases from an unknown primary tumor (CUP) varies compared to those with metastases of known primary tumor origin (CKP). The National Institute for Health and Care Excellence (NICE) recognizes the current lack of research to support the management of CUP patients with brain metastases. The primary aim was to compare survival outcomes of CKP and CUP patients undergoing early resection of intracranial metastases to understand the efficacy of surgery for patients with CUP.

Methods
A retrospective study was performed, wherein patients were identified using a pathology database. Data was collected from patient notes and trust information services. Surgically managed patients during a 10-year period aged over 18 years, with a histological diagnosis of intracranial metastasis, were included.

Results
298 patients were identified, including 243 (82.0%) CKP patients and 55 (18.0%) CUP patients. Median survival for CKP patients was 9 months (95%CI 7.475–10.525); and 6 months for CUP patients (95%CI 4.263–7.737, p = 0.113). Cox regression analyses suggest absence of other metastases (p = 0.016), age (p = 0.005), and performance status (p = 0.001) were positive prognostic factors for improved survival in cases of CUP. The eventual determination of the primary malignancy did not affect overall survival for CUP patients.

Conclusions
There was no significant difference in overall survival between the two groups. Surgical management of patients with CUP brain metastases is an appropriate treatment option. Current diagnostic pathways specifying a thorough search for the primary tumor pre-operatively may not improve patient outcomes.
Minimizing comprehensive geriatric assessment to identify deterioration of physical performance in a healthy community-dwelling older cohort: longitudinal data of the AEQUIPA Versa study
Authors: Diekmann R. , Hellmers S. , Elgert L. , Fudickar S. , Heinks A. , Lau S. , Bauer J. M. , Zieschang T. , Hein A. 
Published: May 2020

Abstract
Background
It is important to identify the relevant parameters of physical performance to prevent early functional decline and to prolong independent living. The aim of this study is to describe the development of physical performance in a healthy community-dwelling older cohort aged 70+ years using comprehensive assessment over two years and to subsequently identify the most relevant predictive tests for physical decline to minimize assessment.

Methods
Physical performance was measured by comprehensive geriatric assessment. Predictors for the individual decline of physical performance by Principal Component and k-means Cluster Analysis were developed, and sensitivity and specificity determined accordingly.

Results
251 subjects (Ø 75.4 years) participated in the study. Handgrip strength was low in 21.1%. The follow-up results of tests were divergent. Handgrip strength [− 16.95 (SD 11.55)] and the stair climb power test (power) [− 9.15 (SD 16.84)] yielded the highest percentage changes. Four most relevant tests (handgrip strength, stair climb power time, timed up & go and 4-m gait speed) were identified. A predictor based on baseline data was determined (sensitivity 82%, specificity 96%) to identify subjects characterized by a high degree of physical decline within two years.

Discussion
Although the cohort of older adults is heterogeneous, most of the individuals in the study exhibited high levels of physical performance; only a few subjects suffered a relevant decline within the 2-year follow-up. Four most relevant tests were identified to predict relevant decline of physical function.

Conclusion
In spite of ceiling effects of the geriatric assessment in high-performers, we assume that it is possible to predict an individual’s risk of physical decline within 2 years with four tests of a comprehensive geriatric assessment.
“El nen s'ha menjat una aranya”: The development of narratives in Catalan speaking children
Authors: CABALLERO Marta , APARICI Melina , SANZ-TORRENT Mònica , HERMAN Ros , JONES Anna , MORGAN Gary 
Published: May 2020

AbstractThe production of a well-constructed narrative is the culmination of several years of language acquisition and is an important milestone in children's development. There is no current description of narrative development for Catalan speaking children. This study collected elicited narratives in Catalan from 118 children aged 4;0–10;11. Narratives were scored for macrostructure and microstructure. Narrative scores improved with age with maximum performance for macrostructure by 9 years. Children's ability to use micro-structural components of Catalan is variable with some developments continuing beyond 9 years. The results are discussed in relation to theoretical arguments about universal and specific features of narrative development. We conclude by highlighting the usefulness of the new test for future language assessment of children acquiring Catalan.
EXPLAINING VARIABILITY IN ON-FLOOR ASSEMBLAGES: THE BEHAVIORAL-CONTEXTUAL METHOD
Authors: Lamoureux-St-Hilaire Maxime , Snetsinger Andrew Kent 
Published: May 2020

AbstractWe present a behavioral-contextual method for studying abandonment-related assemblages in order to ascribe them to a settlement abandonment scenario. Our approach examines the vertical and horizontal architectural contexts of assemblages, along with the nature of reconstructible vessels and other artifacts. This method accounts for gradual, rapid, mundane, and ceremonial abandonment scenarios, and for abandonment with anticipated return. Two advantages of this model are its replicability and its proposition of a shared taxonomy leading away from the concept of problematic deposits. The method is contextualized with two distinct case studies from the southern Maya lowlands: the palace of La Corona, Guatemala and an agricultural household group from greater Minanha, Belize. These dissimilar but contemporary (ca. A.D. 900) contexts revealed complex abandonment-related assemblages, including pre-abandonment middens,de factoand secondary material, and on-floor, exposed offerings. Both case studies are argued to reflect gradual, organized abandonment scenarios, although with significant temporal and behavioral distinctions.
Genome-wide association study identifies zonisamide responsive gene in Parkinson’s disease patients
Authors: Cha Pei-Chieng , Satake Wataru , Ando-Kanagawa Yuko , Yamamoto Ken , Murata Miho , Toda Tatsushi 
Published: May 2020

AbstractLong-term treatment of Parkinson’s disease (PD) by levodopa leads to motor complication “wearing-off”. Zonisamide is a nondopaminergic antiparkinsonian drug that can improve “wearing-off” although response to the treatment varies between individuals. To clarify the genetic basis of zonisamide responsiveness, we conducted a genome-wide association study (GWAS) on 200 PD patients from a placebo-controlled clinical trial, including 67 responders whose “off” time decreased ≥1.5 h after 12 weeks of zonisamide treatment and 133 poor responders. We genotyped and evaluated the association between 611,492 single nucleotide polymorphisms (SNPs) and “off” time reduction. We also performed whole-genome imputation, gene- and pathway-based analyses of GWAS data. For promising SNPs, we examined single-tissue expression quantitative trait loci (eQTL) data in the GTEx database. SNP rs16854023 (Mouse double minute 4, MDM4) showed genome-wide significant association with reduced “off” time (PAdjusted = 4.85 × 10−9). Carriers of responsive genotype showed >7-fold decrease in mean “off” time compared to noncarriers (1.42 h vs 0.19 h; P = 2.71 × 10−7). In silico eQTL data indicated that zonisamide sensitivity is associated with higher MDM4 expression. Among the 37 pathways significantly influencing “off” time, calcium and glutamate signaling have also been associated with anti-epileptic effect of zonisamide. MDM4 encodes a negative regulator of p53. The association between improved motor fluctuation and MDM4 upregulation implies that p53 inhibition may prevent dopaminergic neuron loss and consequent motor symptoms. This is the first genome-wide pharmacogenetics study on antiparkinsonian drug. The findings provide a basis for improved management of “wearing-off” in PD by genotype-guided zonisamide treatment.
The autophagy-independent role of BECN1 in colorectal cancer metastasis through regulating STAT3 signaling pathway activation
Authors: Hu Fuqing , Li Geng , Huang Changsheng , Hou Zhenlin , Yang Xi , Luo Xuelai , Feng Yongdong , Wang Guihua , Hu Junbo , Cao Zhixin 
Published: May 2020

AbstractBECN1 is a critical regulator of autophagy, which plays important roles in tumor formation and metastasis. However, the autophagy-independent role of BECN1 and the clinical prediction value of BECN1 still need to be explored. Here, we observed significantly lower expression of BECN1 in colorectal cancers (CRCs) compared with adjacent normal colon tissue, and downregulation of BECN1 was positively related to poor prognosis in CRC patients. In addition, we found that knockdown of BECN1 markedly promoted CRC cell motility and invasion. Bioinformatics gene set enrichment analysis (GSEA) revealed that low levels of BECN1 were significantly correlated with the STAT3 signaling pathway in CRC. Consistently, knockdown of BECN1 increased the phosphorylation of STAT3 and activated the STAT3 signaling pathway in CRC cells. Furthermore, we demonstrated that STAT3 was involved in the CRC metastasis mediated by knockdown of BECN1 in vitro and in vivo. Mechanistically, knockdown of BECN1 promoted the phosphorylation of STAT3 via regulation of the interaction between STAT and JAK2 but did not inhibit autophagy. Our study revealed that BECN1 served as a negative regulator of CRC metastasis by regulating STAT3 signaling pathway activation in an autophagy-independent manner. The BECN1/JAK2/STAT3 signaling pathway can be used as a potential therapeutic target for metastatic CRC.
A divisive model of evidence accumulation explains uneven weighting of evidence over time
Authors: Keung Waitsang , Hagen Todd A. , Wilson Robert C. 
Published: May 2020

AbstractDivisive normalization has long been used to account for computations in various neural processes and behaviours. The model proposes that inputs into a neural system are divisively normalized by the system’s total activity. More recently, dynamical versions of divisive normalization have been shown to account for how neural activity evolves over time in value-based decision making. Despite its ubiquity, divisive normalization has not been studied in decisions that require evidence to be integrated over time. Such decisions are important when the information is not all available at once. A key feature of such decisions is how evidence is weighted over time, known as the integration kernel. Here, we provide a formal expression for the integration kernel in divisive normalization, and show that divisive normalization quantitatively accounts for 133 human participants’ perceptual decision making behaviour, performing as well as the state-of-the-art Drift Diffusion Model, the predominant model for perceptual evidence accumulation.
Observation of the molecular response to light upon photoexcitation
Authors: Yong Haiwang , Zotev Nikola , Ruddock Jennifer M. , Stankus Brian , Simmermacher Mats , Carrascosa Andrés Moreno , Du Wenpeng , Goff Nathan , Chang Yu , Bellshaw Darren , Liang Mengning , Carbajo Sergio , Koglin Jason E. , Robinson Joseph S. , Boutet Sébastien , Minitti Michael P. , Kirrander Adam , Weber Peter M. 
Published: May 2020

AbstractWhen a molecule interacts with light, its electrons can absorb energy from the electromagnetic field by rapidly rearranging their positions. This constitutes the first step of photochemical and photophysical processes that include primary events in human vision and photosynthesis. Here, we report the direct measurement of the initial redistribution of electron density when the molecule 1,3-cyclohexadiene (CHD) is optically excited. Our experiments exploit the intense, ultrashort hard x-ray pulses of the Linac Coherent Light Source (LCLS) to map the change in electron density using ultrafast x-ray scattering. The nature of the excited electronic state is identified with excellent spatial resolution and in good agreement with theoretical predictions. The excited state electron density distributions are thus amenable to direct experimental observation.
Broadband frequency translation through time refraction in an epsilon-near-zero material
Authors: Zhou Yiyu , Alam M. Zahirul , Karimi Mohammad , Upham Jeremy , Reshef Orad , Liu Cong , Willner Alan E. , Boyd Robert W. 
Published: May 2020

AbstractSpace-time duality in paraxial optical wave propagation implies the existence of intriguing effects when light interacts with a material exhibiting two refractive indexes separated by a boundary in time. The direct consequence of such time-refraction effect is a change in the frequency of light while leaving the wavevector unchanged. Here, we experimentally show that the effect of time refraction is significantly enhanced in an epsilon-near-zero (ENZ) medium as a consequence of the optically induced unity-order refractive index change in a sub-picosecond time scale. Specifically, we demonstrate broadband and controllable shift (up to 14.9 THz) in the frequency of a light beam using a time-varying subwavelength-thick indium tin oxide (ITO) film in its ENZ spectral range. Our findings hint at the possibility of designing (3 + 1)D metamaterials by incorporating time-varying bulk ENZ materials, and they present a unique playground to investigate various novel effects in the time domain.
Inter-domain dynamics in the chaperone SurA and multi-site binding to its outer membrane protein clients
Authors: Calabrese Antonio N. , Schiffrin Bob , Watson Matthew , Karamanos Theodoros K. , Walko Martin , Humes Julia R. , Horne Jim E. , White Paul , Wilson Andrew J. , Kalli Antreas C. , Tuma Roman , Ashcroft Alison E. , Brockwell David J. , Radford Sheena E. 
Published: May 2020

AbstractThe periplasmic chaperone SurA plays a key role in outer membrane protein (OMP) biogenesis. E. coli SurA comprises a core domain and two peptidylprolyl isomerase domains (P1 and P2), but its mechanisms of client binding and chaperone function have remained unclear. Here, we use chemical cross-linking, hydrogen-deuterium exchange mass spectrometry, single-molecule FRET and molecular dynamics simulations to map the client binding site(s) on SurA and interrogate the role of conformational dynamics in OMP recognition. We demonstrate that SurA samples an array of conformations in solution in which P2 primarily lies closer to the core/P1 domains than suggested in the SurA crystal structure. OMP binding sites are located primarily in the core domain, and OMP binding results in conformational changes between the core/P1 domains. Together, the results suggest that unfolded OMP substrates bind in a cradle formed between the SurA domains, with structural flexibility between domains assisting OMP recognition, binding and release.
Skillful multiyear predictions of ocean acidification in the California Current System
Authors: Brady Riley X. , Lovenduski Nicole S. , Yeager Stephen G. , Long Matthew C. , Lindsay Keith 
Published: May 2020

AbstractThe California Current System (CCS) sustains economically valuable fisheries and is particularly vulnerable to ocean acidification, due to its natural upwelling of carbon-enriched waters that generate corrosive conditions for local ecosystems. Here we use a novel suite of retrospective, initialized ensemble forecasts with an Earth system model (ESM) to predict the evolution of surface pH anomalies in the CCS. We show that the forecast system skillfully predicts observed surface pH variations a year in advance over a naive forecasting method, with the potential for skillful prediction up to five years in advance. Skillful predictions of surface pH are mainly derived from the initialization of dissolved inorganic carbon anomalies that are subsequently transported into the CCS. Our results demonstrate the potential for ESMs to provide skillful predictions of ocean acidification on large scales in the CCS. Initialized ESMs could also provide boundary conditions to improve high-resolution regional forecasting systems.
Using apelin-based synthetic Notch receptors to detect angiogenesis and treat solid tumors
Authors: Wang Zhifu , Wang Fan , Zhong Junjie , Zhu Tongming , Zheng Yongtao , Zhao Tong , Xie Qiang , Ma Fukai , Li Ronggang , Tang Qisheng , Xu Feng , Tian Xueying , Zhu Jianhong 
Published: May 2020

AbstractAngiogenesis is a necessary process for solid tumor growth. Cellular markers for endothelial cell proliferation are potential targets for identifying the vasculature of tumors in homeostasis. Here we customize the behaviors of engineered cells to recognize Apj, a surface marker of the neovascular endothelium, using synthetic Notch (synNotch) receptors. We designed apelin-based synNotch receptors (AsNRs) that can specifically interact with Apj and then stimulate synNotch pathways. Cells engineered with AsNRs have the ability to sense the proliferation of endothelial cells (ECs). Designed for different synNotch pathways, engineered cells express different proteins to respond to angiogenic signals; therefore, angiogenesis can be detected by cells engineered with AsNRs. Furthermore, T cells customized with AsNRs can sense the proliferation of vascular endothelial cells. As solid tumors generally require vascular support, AsNRs are potential tools for the detection and therapy of a variety of solid tumors in adults.
Ultrathin 2 nm gold as impedance-matched absorber for infrared light
Authors: Luhmann Niklas , Høj Dennis , Piller Markus , Kähler Hendrik , Chien Miao-Hsuan , West Robert G. , Andersen Ulrik Lund , Schmid Silvan 
Published: May 2020

AbstractThermal detectors are a cornerstone of infrared and terahertz technology due to their broad spectral range. These detectors call for efficient absorbers with a broad spectral response and minimal thermal mass. A common approach is based on impedance-matching the sheet resistance of a thin metallic film to half the free-space impedance. Thereby, one can achieve a wavelength-independent absorptivity of up to 50%. However, existing absorber films typically require a thickness of the order of tens of nanometers, which can significantly deteriorate the response of a thermal transducer. Here, we present the application of ultrathin gold (2 nm) on top of a surfactant layer of oxidized copper as an effective infrared absorber. An almost wavelength-independent and long-time stable absorptivity of 47(3)%, ranging from 2 μm to 20 μm, can be obtained. The presented absorber allows for a significant improvement of infrared/terahertz technologies in general and thermal detectors in particular.
Mutational signatures are jointly shaped by DNA damage and repair
Authors: Volkova Nadezda V. , Meier Bettina , González-Huici Víctor , Bertolini Simone , Gonzalez Santiago , Vöhringer Harald , Abascal Federico , Martincorena Iñigo , Campbell Peter J. , Gartner Anton , Gerstung Moritz 
Published: May 2020

AbstractCells possess an armamentarium of DNA repair pathways to counter DNA damage and prevent mutation. Here we use C. elegans whole genome sequencing to systematically quantify the contributions of these factors to mutational signatures. We analyse 2,717 genomes from wild-type and 53 DNA repair defective backgrounds, exposed to 11 genotoxins, including UV-B and ionizing radiation, alkylating compounds, aristolochic acid, aflatoxin B1, and cisplatin. Combined genotoxic exposure and DNA repair deficiency alters mutation rates or signatures in 41% of experiments, revealing how different DNA alterations induced by the same genotoxin are mended by separate repair pathways. Error-prone translesion synthesis causes the majority of genotoxin-induced base substitutions, but averts larger deletions. Nucleotide excision repair prevents up to 99% of point mutations, almost uniformly across the mutation spectrum. Our data show that mutational signatures are joint products of DNA damage and repair and suggest that multiple factors underlie signatures observed in cancer genomes.
Chronic bee paralysis as a serious emerging threat to honey bees
Authors: Budge Giles E. , Simcock Nicola K. , Holder Philippa J. , Shirley Mark D. F. , Brown Mike A. , Van Weymers Pauline S. M. , Evans David J. , Rushton Steve P. 
Published: May 2020

AbstractChronic bee paralysis is a well-defined viral disease of honey bees with a global distribution that until recently caused rare but severe symptomatology including colony loss. Anecdotal evidence indicates a recent increase in virus incidence in several countries, but no mention of concomitant disease. We use government honey bee health inspection records from England and Wales to test whether chronic bee paralysis is an emerging infectious disease and investigate the spatiotemporal patterns of disease. The number of chronic bee paralysis cases increased exponentially between 2007 and 2017, demonstrating chronic bee paralysis as an emergent disease. Disease is highly clustered spatially within most years, suggesting local spread, but not between years, suggesting disease burnt out with periodic reintroduction. Apiary and county level risk factors are confirmed to include scale of beekeeping operation and the history of honey bee imports. Our findings offer epidemiological insight into this damaging emerging disease.
Fire deficit increases wildfire risk for many communities in the Canadian boreal forest
Authors: Parisien Marc-André , Barber Quinn E. , Hirsch Kelvin G. , Stockdale Christopher A. , Erni Sandy , Wang Xianli , Arseneault Dominique , Parks Sean A. 
Published: May 2020

AbstractThe top priority of fire management agencies in Canada is to protect human life and property. Here we investigate if decades of aggressive fire suppression in the boreal biome of Canada has reduced the proportion of recently burned forests (RBF; <30 years) near human communities, and thereby inadvertently increased the risk of wildfire. We measured the percentage of RBF, which are usually less flammable than older forests, up to a 25-km radius around communities compared to that in the surrounding regional fire regime zone. Our analysis of 160 communities across boreal Canada shows that 54.4% exhibited a deficit or lack of RBF, whereas only 15.0% showed a surplus. Overall, a majority (74.4%) of communities are surrounded by a low (≤10%) proportion of RBF, indicating a higher vulnerability of those communities to wildfire. These findings suggest that suppression policies are increasing flammability in the wildland–urban interface of boreal Canada.
Morphology and mobility as tools to control and unprecedentedly enhance X-ray sensitivity in organic thin-films
Authors: Temiño Inés , Basiricò Laura , Fratelli Ilaria , Tamayo Adrián , Ciavatti Andrea , Mas-Torrent Marta , Fraboni Beatrice 
Published: May 2020

AbstractOrganic semiconductor materials exhibit a great potential for the realization of large-area solution-processed devices able to directly detect high-energy radiation. However, only few works investigated on the mechanism of ionizing radiation detection in this class of materials, so far. In this work we investigate the physical processes behind X-ray photoconversion employing bis-(triisopropylsilylethynyl)-pentacene thin-films deposited by bar-assisted meniscus shearing. The thin film coating speed and the use of bis-(triisopropylsilylethynyl)-pentacene:polystyrene blends are explored as tools to control and enhance the detection capability of the devices, by tuning the thin-film morphology and the carrier mobility. The so-obtained detectors reach a record sensitivity of 1.3 · 104 µC/Gy·cm2, the highest value reported for organic-based direct X-ray detectors and a very low minimum detectable dose rate of 35 µGy/s. Thus, the employment of organic large-area direct detectors for X-ray radiation in real-life applications can be foreseen.