bluuebunny/crossref_metadata_2025_split huggingface dataset:
LINC00470 accelerates the proliferation and metastasis of melanoma through promoting APEX1 expression
Authors: Huang Ting , Wang Yong-Jie , Huang Mi-Tao , Guo Yu , Yang Li-Chang , Liu Xiao-Jin , Tan Wu-Yuan , Long Jian-Hong 
Published: April 2021

AbstractRecently studies found that APEX1 was abnormally expressed in melanoma, indicating that it might be involved in the development of melanoma. However, the underlying mechanism and the interaction between APEX1 and LINC00470 in melanoma are not clear. Therefore, we aimed to investigate the role of LINC00470 in the development of melanoma in this work. We discovered that LINC00470 was overexpressed in melanoma tissues and cells compared with the adjacent normal tissues and cells by qPCR. The overexpression of LINC00470 promoted the proliferation and migration of melanoma cells. The functional investigation demonstrated that LINC00470 activated the transcription factor, ZNF131, to regulate the APEX1 expression, which finally promoted cell proliferation and migration. In contrast, knockdown of LINC00470 could significantly inhibit the melanoma cell proliferation and migration, and suppress the growth of tumor in vivo. Overexpression of APEX1 could reverse the impact of the silence of LINC00470 in melanoma cells. In summary, our studies revealed that LINC00470 promoted melanoma proliferation and migration by enhancing the expression of APEX1, which indicated that LINC00470 might be a therapeutic target for the treatment of melanoma.
A 127 kb truncating deletion of PGRMC1 is a novel cause of X-linked isolated paediatric cataract
Authors: Jones Johanna L. , Corbett Mark A. , Yeaman Elise , Zhao Duran , Gecz Jozef , Gasperini Robert J. , Charlesworth Jac C. , Mackey David A. , Elder James E. , Craig Jamie E. , Burdon Kathryn P. 
Published: April 2021

AbstractInherited paediatric cataract is a rare Mendelian disease that results in visual impairment or blindness due to a clouding of the eye’s crystalline lens. Here we report an Australian family with isolated paediatric cataract, which we had previously mapped to Xq24. Linkage at Xq24–25 (LOD = 2.53) was confirmed, and the region refined with a denser marker map. In addition, two autosomal regions with suggestive evidence of linkage were observed. A segregating 127 kb deletion (chrX:g.118373226_118500408del) in the Xq24–25 linkage region was identified from whole-genome sequencing data. This deletion completely removed a commonly deleted long non-coding RNA gene LOC101928336 and truncated the protein coding progesterone receptor membrane component 1 (PGRMC1) gene following exon 1. A literature search revealed a report of two unrelated males with non-syndromic intellectual disability, as well as congenital cataract, who had contiguous gene deletions that accounted for their intellectual disability but also disrupted the PGRMC1 gene. A morpholino-induced pgrmc1 knockdown in a zebrafish model produced significant cataract formation, supporting a role for PGRMC1 in lens development and cataract formation. We hypothesise that the loss of PGRMC1 causes cataract through disrupted PGRMC1-CYP51A1 protein–protein interactions and altered cholesterol biosynthesis. The cause of paediatric cataract in this family is the truncating deletion of PGRMC1, which we report as a novel cataract gene.
Socio-economic differences in accessing NHS spectacles amongst children with differing refractive errors living in Scotland
Authors: Kearney Stephanie , Strang Niall C. , Lewsey Jim , Azuara-Blanco Augusto , Jonuscheit Sven 
Published: April 2021

Abstract
Background/objectives
Adults living in more deprived areas are less likely to attend an eye examination, resulting in greater visual impairment from undiagnosed eye disease and a widening of health inequalities. It is unknown if the introduction of free NHS eye examinations and help with spectacle costs has benefited children in Scotland. This study aimed to explore factors associated with accessing NHS spectacles including level of deprivation, refractive error, urbanity and age.

Subjects/methods
NHS-financed General Ophthalmic Services (GOS) 3 supplement the cost of spectacles for children under 16 years. Administrative data on the spectacle refraction dispensed were obtained from Information Services Division (ISD) for mainland Scotland, 2018, and categorised by: Emmetropes/low hyperopes (reference group), myopes and moderate/high hyperopes. Data were linked to the Scottish Index of Multiple Deprivation (SIMD) quintile.

Results
Data included 108, 043 GOS 3 claims. Greater deprivation was associated with greater GOS 3 claims p = 0.041. This was most evident in emmetropic/low hyperopic children and in moderate/high hyperopic children. GOS 3 claims in the myopes group increased with age across all SIMD and decreased with age in the moderate/high hyperope group (all p < 0.001). GOS 3 claims were not associated with urbanity for all Health Boards (p = 0.13).

Conclusions
Children in areas of greater deprivation and in more rural areas are not disadvantaged in accessing NHS spectacles. This did not vary by refractive error group. This suggests that health policy in Scotland is accessible to those from all deprivation levels and refractive errors.
Transcriptomic analysis to identify genes associated with selective hippocampal vulnerability in Alzheimer’s disease
Authors: Crist Angela M. , Hinkle Kelly M. , Wang Xue , Moloney Christina M. , Matchett Billie J. , Labuzan Sydney A. , Frankenhauser Isabelle , Azu Nkem O. , Liesinger Amanda M. , Lesser Elizabeth R. , Serie Daniel J. , Quicksall Zachary S. , Patel Tulsi A. , Carnwath Troy P. , DeTure Michael , Tang Xiaojia , Petersen Ronald C. , Duara Ranjan , Graff-Radford Neill R. , Allen Mariet , Carrasquillo Minerva M. , Li Hu , Ross Owen A. , Ertekin-Taner Nilüfer , Dickson Dennis W. , Asmann Yan W. , Carter Rickey E. , Murray Melissa E. 
Published: April 2021

AbstractSelective vulnerability of different brain regions is seen in many neurodegenerative disorders. The hippocampus and cortex are selectively vulnerable in Alzheimer’s disease (AD), however the degree of involvement of the different brain regions differs among patients. We classified corticolimbic patterns of neurofibrillary tangles in postmortem tissue to capture extreme and representative phenotypes. We combined bulk RNA sequencing with digital pathology to examine hippocampal vulnerability in AD. We identified hippocampal gene expression changes associated with hippocampal vulnerability and used machine learning to identify genes that were associated with AD neuropathology, including SERPINA5, RYBP, SLC38A2, FEM1B, and PYDC1. Further histologic and biochemical analyses suggested SERPINA5 expression is associated with tau expression in the brain. Our study highlights the importance of embracing heterogeneity of the human brain in disease to identify disease-relevant gene expression.
Bias free multiobjective active learning for materials design and discovery
Authors: Jablonka Kevin Maik , Jothiappan Giriprasad Melpatti , Wang Shefang , Smit Berend , Yoo Brian 
Published: April 2021

AbstractThe design rules for materials are clear for applications with a single objective. For most applications, however, there are often multiple, sometimes competing objectives where there is no single best material and the design rules change to finding the set of Pareto optimal materials. In this work, we leverage an active learning algorithm that directly uses the Pareto dominance relation to compute the set of Pareto optimal materials with desirable accuracy. We apply our algorithm to de novo polymer design with a prohibitively large search space. Using molecular simulations, we compute key descriptors for dispersant applications and drastically reduce the number of materials that need to be evaluated to reconstruct the Pareto front with a desired confidence. This work showcases how simulation and machine learning techniques can be coupled to discover materials within a design space that would be intractable using conventional screening approaches.
A large modulation of electron-phonon coupling and an emergent superconducting dome in doped strong ferroelectrics
Authors: Ma Jiaji , Yang Ruihan , Chen Hanghui 
Published: April 2021

AbstractWe use first-principles methods to study doped strong ferroelectrics (taking BaTiO3 as a prototype). Here, we find a strong coupling between itinerant electrons and soft polar phonons in doped BaTiO3, contrary to Anderson/Blount’s weakly coupled electron mechanism for "ferroelectric-like metals”. As a consequence, across a polar-to-centrosymmetric phase transition in doped BaTiO3, the total electron-phonon coupling is increased to about 0.6 around the critical concentration, which is sufficient to induce phonon-mediated superconductivity of about 2 K. Lowering the crystal symmetry of doped BaTiO3 by imposing epitaxial strain can further increase the superconducting temperature via a sizable coupling between itinerant electrons and acoustic phonons. Our work demonstrates a viable approach to modulating electron-phonon coupling and inducing phonon-mediated superconductivity in doped strong ferroelectrics and potentially in polar metals. Our results also show that the weakly coupled electron mechanism for "ferroelectric-like metals” is not necessarily present in doped strong ferroelectrics.
STING enhances cell death through regulation of reactive oxygen species and DNA damage
Authors: Hayman Thomas J. , Baro Marta , MacNeil Tyler , Phoomak Chatchai , Aung Thazin Nwe , Cui Wei , Leach Kevin , Iyer Radhakrishnan , Challa Sreerupa , Sandoval-Schaefer Teresa , Burtness Barbara A. , Rimm David L. , Contessa Joseph N. 
Published: April 2021

AbstractResistance to DNA-damaging agents is a significant cause of treatment failure and poor outcomes in oncology. To identify unrecognized regulators of cell survival we performed a whole-genome CRISPR-Cas9 screen using treatment with ionizing radiation as a selective pressure, and identified STING (stimulator of interferon genes) as an intrinsic regulator of tumor cell survival. We show that STING regulates a transcriptional program that controls the generation of reactive oxygen species (ROS), and that STING loss alters ROS homeostasis to reduce DNA damage and to cause therapeutic resistance. In agreement with these data, analysis of tumors from head and neck squamous cell carcinoma patient specimens show that low STING expression is associated with worse outcomes. We also demonstrate that pharmacologic activation of STING enhances the effects of ionizing radiation in vivo, providing a rationale for therapeutic combinations of STING agonists and DNA-damaging agents. These results highlight a role for STING that is beyond its canonical function in cyclic dinucleotide and DNA damage sensing, and identify STING as a regulator of cellular ROS homeostasis and tumor cell susceptibility to reactive oxygen dependent, DNA damaging agents.
Energy implications of the 21st century agrarian transition
Authors: Rosa Lorenzo , Rulli Maria Cristina , Ali Saleem , Chiarelli Davide Danilo , Dell’Angelo Jampel , Mueller Nathaniel D. , Scheidel Arnim , Siciliano Giuseppina , D’Odorico Paolo 
Published: April 2021

AbstractThe ongoing agrarian transition from small-holder farming to large-scale commercial agriculture is reshaping systems of production and human well-being in many regions. A fundamental part of this global transition is manifested in large-scale land acquisitions (LSLAs) by agribusinesses. Its energy implications, however, remain poorly understood. Here, we assess the multi-dimensional changes in fossil-fuel-based energy demand resulting from this agrarian transition. We focus on LSLAs by comparing two scenarios of low-input and high-input agricultural practices, exemplifying systems of production in place before and after the agrarian transition. A shift to high-input crop production requires industrial fertilizer application, mechanization of farming practices and irrigation, which increases by ~5 times fossil-fuel-based energy consumption compared to low-input agriculture. Given the high energy and carbon footprints of LSLAs and concerns over local energy access, our analysis highlights the need for an approach that prioritizes local resource access and incorporates energy-intensity analyses in land use governance.
Short-range quorum sensing controls horizontal gene transfer at micron scale in bacterial communities
Authors: van Gestel Jordi , Bareia Tasneem , Tenennbaum Bar , Dal Co Alma , Guler Polina , Aframian Nitzan , Puyesky Shani , Grinberg Ilana , D’Souza Glen G. , Erez Zohar , Ackermann Martin , Eldar Avigdor 
Published: April 2021

AbstractIn bacterial communities, cells often communicate by the release and detection of small diffusible molecules, a process termed quorum-sensing. Signal molecules are thought to broadly diffuse in space; however, they often regulate traits such as conjugative transfer that strictly depend on the local community composition. This raises the question how nearby cells within the community can be detected. Here, we compare the range of communication of different quorum-sensing systems. While some systems support long-range communication, we show that others support a form of highly localized communication. In these systems, signal molecules propagate no more than a few microns away from signaling cells, due to the irreversible uptake of the signal molecules from the environment. This enables cells to accurately detect micron scale changes in the community composition. Several mobile genetic elements, including conjugative elements and phages, employ short-range communication to assess the fraction of susceptible host cells in their vicinity and adaptively trigger horizontal gene transfer in response. Our results underscore the complex spatial biology of bacteria, which can communicate and interact at widely different spatial scales.
How dopants limit the ultrahigh thermal conductivity of boron arsenide: a first principles study
Authors: Fava Mauro , Protik Nakib Haider , Li Chunhua , Ravichandran Navaneetha Krishnan , Carrete Jesús , van Roekeghem Ambroise , Madsen Georg K. H. , Mingo Natalio , Broido David 
Published: April 2021

AbstractThe promise enabled by boron arsenide’s (BAs) high thermal conductivity (κ) in power electronics cannot be assessed without taking into account the reduction incurred when doping the material. Using first principles calculations, we determine the κ reduction induced by different group IV impurities in BAs as a function of concentration and charge state. We unveil a general trend, where neutral impurities scatter phonons more strongly than the charged ones. CB and GeAs impurities show by far the weakest phonon scattering and retain BAs κ values of over ~1000 W⋅K−1⋅m−1 even at high densities. Both Si and Ge achieve large hole concentrations while maintaining high κ. Furthermore, going beyond the doping compensation threshold associated to Fermi level pinning triggers observable changes in the thermal conductivity. This informs design considerations on the doping of BAs, and it also suggests a direct way to determine the onset of compensation doping in experimental samples.
A Chlamydia trachomatis VD1-MOMP vaccine elicits cross-neutralizing and protective antibodies against C/C-related complex serovars
Authors: Olsen Anja Weinreich , Rosenkrands Ida , Holland Martin J. , Andersen Peter , Follmann Frank 
Published: April 2021

AbstractOcular and urogenital infections withChlamydia trachomatis (C.t.) are caused by a range of different serovars. The firstC.t. vaccine in clinical development (CTH522/CAF®01) induced neutralizing antibodies directed to the variable domain 4 (VD4) region of major outer membrane protein (MOMP), covering predominantly B and intermediate groups of serovars. The VD1 region of MOMP contains neutralizing B-cell epitopes targeting serovars of the C and C-related complex. Using an immuno-repeat strategy, we extended the VD1 region of SvA and SvJ to include surrounding conserved segments, extVD1Aand extVD1J, and repeated this region four times. The extVD1A*4 was most immunogenic with broad cross-surface and neutralizing reactivity against representative members of the C and C-related complex serovars. Importantly, in vitro results for extVD1A*4 translated into in vivo biological effects, demonstrated by in vivo neutralization of SvA and protection/cross-protection against intravaginal challenge with both SvA and the heterologous SvIa strain.
Daily PM2.5 concentration estimates by county, ZIP code, and census tract in 11 western states 2008–2018
Authors: Reid Colleen E. , Considine Ellen M. , Maestas Melissa M. , Li Gina 
Published: April 2021

AbstractWe created daily concentration estimates for fine particulate matter (PM2.5) at the centroids of each county, ZIP code, and census tract across the western US, from 2008–2018. These estimates are predictions from ensemble machine learning models trained on 24-hour PM2.5 measurements from monitoring station data across 11 states in the western US. Predictor variables were derived from satellite, land cover, chemical transport model (just for the 2008–2016 model), and meteorological data. Ten-fold spatial and random CV R2 were 0.66 and 0.73, respectively, for the 2008–2016 model and 0.58 and 0.72, respectively for the 2008–2018 model. Comparing areal predictions to nearby monitored observations demonstrated overall R2 of 0.70 for the 2008–2016 model and 0.58 for the 2008–2018 model, but we observed higher R2 (>0.80) in many urban areas. These data can be used to understand spatiotemporal patterns of, exposures to, and health impacts of PM2.5 in the western US, where PM2.5 levels have been heavily impacted by wildfire smoke over this time period.
Dependence of the escape from an axially symmetric galaxy on the energy
Authors: Navarro Juan F. 
Published: April 2021

AbstractThe escape of a particle from a dynamical system depends on the intersection between the ingoing and outgoing asymptotic trajectories to certain periodic orbits placed at the openings of the curves of zero velocity of the system. Although many efforts have been devoted to the analysis of the escape from potentials presenting multiple openings, there are still few studies on potentials with only one opening. In this article, we clarify the way in which the energy affects the escape in this type of systems, showing that, contrary to what one could expect, there are several bifurcations for certain values of the energy.
Global dynamics of SARS-CoV-2 clades and their relation to COVID-19 epidemiology
Authors: Hamed Samira M. , Elkhatib Walid F. , Khairalla Ahmed S. , Noreddin Ayman M. 
Published: April 2021

AbstractExpansion of COVID-19 worldwide increases interest in unraveling genomic variations of novel SARS-CoV-2 virus. Metadata of 408,493 SARS-CoV-2 genomes submitted to GISAID database were analyzed with respect to genomic clades and their geographic, age, and gender distributions. Of the currently known SARS-CoV-2 clades, clade GR was the most prevalent worldwide followed by GV then GH. Chronological analysis revealed expansion in SARS-CoV-2 clades carrying D614G mutations with the predominance of the newest clade, GV, in the last three months. D614G clades prevail in countries with more COVID-19 cases. Of them, the clades GH and GR were more frequently recovered from severe or deceased COVID-19 cases. In contrast, G and GV clades showed a significantly higher prevalence among asymptomatic patients or those with mild disease. Metadata analysis showed higher (p < 0.05) prevalence of severe/deceased cases among males than females and predominance of GR clade in female patients. Furthermore, severe disease/death was more prevalent (p < 0.05) in elderly than in adults/children. Higher prevalence of the GV clade in children compared to other age groups was also evident. These findings uniquely provide a statistical evidence on the adaptation-driven evolution of SARS-CoV-2 leading to altered infectivity, virulence, and mortality.
Analysis of BRCA1/2 variants of unknown significance in the prospective Korean Hereditary Breast Cancer study
Authors: Kim Joo Heung , Park Sunggyun , Park Hyung Seok , Park Ji Soo , Lee Seung-Tae , Kim Sung-Won , Lee Jong Won , Lee Min Hyuk , Park Sue K. , Noh Woo-Chul , Choi Doo Ho , Han Wonshik , Jung Sung Hoo 
Published: April 2021

AbstractGenetic testing for BRCA1 and BRCA2 is crucial in diagnosing hereditary breast and ovarian cancer syndromes and has increased with the development of multigene panel tests. However, results classified as variants of uncertain significance (VUS) present challenges to clinicians in attempting to choose an appropriate management plans. We reviewed a total of 676 breast cancer patients included in the Korean Hereditary Breast Cancer (KOHBRA) study with a VUS on BRCA mutation tests between November 2007 and April 2013. These results were compared to the ClinVar database. We calculated the incidence and odds ratios for these variants using the Korean Reference Genome Database. A total of 58 and 91 distinct VUS in BRCA1 and BRCA2 were identified in the KOHBRA study (comprising 278 and 453 patients, respectively). A total of 27 variants in the KOHBRA study were not registered in the Single Nucleotide Polymorphism database. Among BRCA1 VUSs, 20 were reclassified as benign or likely benign, four were reclassified as pathogenic or likely pathogenic, and eight remained as VUSs according to the ClinVar database. Of the BRCA2 VUSs, 25 were reclassified as benign or likely benign, two were reclassified as pathogenic or likely pathogenic, and 33 remained as VUS according to the ClinVar database. There were 12 variants with conflicting interpretations of pathogenicity for BRCA1 and 18 for BRCA2. Among them, p.Leu1780Pro showed a particularly high odds ratio. Six pathogenic variants and one conflicting variant identified using ClinVar could be reclassified as pathogenic variants in this study. Using updated ClinVar information and calculating odds ratios can be helpful when reclassifying VUSs in BRCA1/2.
Evolution of antibody titres against Epstein–Barr virus and human herpesvirus 6A/B and expression of multiple sclerosis-associated retrovirus in the serum of pregnant multiple sclerosis patients
Authors: Pérez-Pérez Silvia , Cuello Juan Pablo , Martínez-Ginés Marisa , Pardo-Rodríguez Beatriz , García-Domínguez José Manuel , Domínguez-Mozo María Inmaculada , Lozano-Ros Alberto , García-Martínez María Ángel , Higueras Yolanda , Meldaña-Rivera Ariana , Goicochea-Briceño Haydee , Tejeda-Velarde Amalia , Fernández-Velasco Jose Ignacio , Medina Silvia , Arroyo Rafael , Villar Luisa María , Álvarez-Lafuente Roberto 
Published: April 2021

AbstractEpstein–Barr virus (EBV), human herpesvirus 6A/B (HHV-6A/B) and multiple sclerosis (MS)-associated retrovirus (MSRV) have been described as possible MS triggers. We analysed antibody titres against EBV and HHV-6, and MSRV envelope (env) mRNA expression, in the serum of pregnant multiple sclerosis patients (P-MS) to study their possible link to the clinical activity of MS during pregnancy and postpartum and their possible role as relapse predictors. For that purpose, serum samples were collected from 71 pregnant women (50 pregnant MS and 21 pregnant healthy controls—P-HC) during pregnancy and postpartum. Relating to antibody titres, IgM antibody titres against HHV-6A/B were significantly higher in P-MS than in P-HC both in each pregnancy trimester and in the postpartum period. Moreover, IgM antibody titres against HHV-6A/B were higher in P-MS who suffered a relapse during the postpartum. Regarding MSRV env mRNA expression, the prevalence in the first trimester of pregnancy was significantly higher in P-MS who suffered relapses during pregnancy. Summing it up, high IgM antibody titres against HHV-6A/B and MSRV env mRNA expression during the first trimester of pregnancy could act as relapse predictors for the gestation/postpartum periods.