bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical significance of comprehensive genomic profiling tests covered by public insurance in patients with advanced solid cancers in Hokkaido, Japan
Authors: Kikuchi Junko , Ohhara Yoshihito , Takada Kohichi , Tanabe Hiroki , Hatanaka Kazuteru , Amano Toraji , C  Hatanaka Kanako , Hatanaka Yutaka , Mitamura Takashi , Kato Momoko , Shibata Yuka , Yabe Ichiro , Endoh Akira , Komatsu Yoshito , Matsuno Yoshihiro , Sugiyama Minako , Manabe Atsushi , Sakurai Akihiro , Takahashi Masato , Naruse Hirohito , Torimoto Yoshihiro , Dosaka-Akita Hirotoshi , Kinoshita Ichiro 
Published: December 2020

Abstract

Background
Comprehensive cancer genomic profiling has been used recently for patients with advanced solid cancers. Two cancer genomic profiling tests for patients with no standard treatment are covered by Japanese public health insurance since June 2019.

Methods
We prospectively analyzed data of 189 patients with solid cancers who underwent either of the two-cancer genomic profiling tests at Hokkaido University Hospital and its liaison hospitals and whose results were discussed in molecular tumor board at Hokkaido University Hospital between August 2019 and July 2020.

Results
All 189 patients had appropriate results. Actionable gene alterations were identified in 93 patients (49%). Frequent mutations included PIK3CA (12%) mutation, BRCA1/2 alteration (7%), ERBB2 amplification (6%) and tumor mutation burden-High (4%). The median turnaround time from sample shipping to acquisition by the expert panel was 26 days. Although 115 patients (61%) were provided with information for genotype-matched therapies, only 21 (11%) received them. Notably, four of eight patients below the age of 20 years were provided information for genotype-matched therapies, and three received them. Their response rates and disease control rates were 29% and 67%, respectively. Most patients who did not undergo the genotype-matched therapies were provided information for only investigational drugs in phases I and II at distant clinical trial sites in central Japan. Twenty-six patients were informed of suspected germline findings, while 11 patients (42%) received genetic counseling.

Conclusions
The publicly reimbursed cancer genomic profilings may lead to the modest but favorable therapeutic efficacy of genotype-matched therapy for solid cancer patients with no standard therapy. However, poor access to genotype-matched therapy needs to be resolved.
Ablation of Zfhx4 results in early postnatal lethality by disrupting the respiratory center in mice
Authors: Zhang Meiqin , Du Sichen , Ou Huayuan , Cui Renjie , Jiang Nan , Lin Yifeng , Ge Runsheng , Ma Duan , Zhang Jin 
Published: December 2020

Abstract
Breathing is an integrated motor behavior that is driven and controlled by a network of brainstem neurons. Zfhx4 is a zinc finger transcription factor and our results showed that it was specifically expressed in several regions of the mouse brainstem. Mice lacking Zfhx4 died shortly after birth from an apparent inability to initiate respiration. We also found that the electrical rhythm of brainstem‒spinal cord preparations was significantly depressed in Zfhx4-null mice compared to wild-type mice. Immunofluorescence staining revealed that Zfhx4 was co-expressed with Phox2b and Math1 in the brainstem and that Zfhx4 ablation greatly decreased the expression of these proteins, especially in the retrotrapezoid nucleus (RTN). Combined ChIP‒seq and mRNA expression microarray analysis identified Phox2b as the direct downstream target gene of Zfhx4, and this finding was validated by ChIP‒qPCR. Previous studies have reported that both Phox2b and Math1 play key roles in the development of the respiratory center, and Phox2b and Math1 knockout mice are neonatal lethal due to severe central apnea. On top of this, our study revealed that Zfhx4 is a critical regulator of Phox2b expression and essential for perinatal breathing.
A multiband map of the natural night sky brightness including Gaia
and Hipparcos integrated starlight
Authors: Masana Eduard , Carrasco Josep Manel , Bará Salvador , Ribas Salvador J 
Published: December 2020

ABSTRACT
The natural night sky brightness is a relevant input for monitoring the light pollution evolution at observatory sites, by subtracting it from the overall sky brightness determined by direct measurements. It is also instrumental for assessing the expected darkness of the pristine night skies. The natural brightness of the night sky is determined by the sum of the spectral radiances coming from astrophysical sources, including zodiacal light, and the atmospheric airglow. The resulting radiance is modified by absorption and scattering before it reaches the observer. Therefore, the natural night sky brightness is a function of the location, time, and atmospheric conditions. We present in this work the GAia Map of the Brightness Of the Natural Sky (GAMBONS), a model to map the natural night brightness of the sky in cloudless and moonless nights. Unlike previous maps, GAMBONS is based on the extra-atmospheric star radiance obtained from the Gaia catalogue. The Gaia-Data Release 2 (DR2) archive compiles astrometric and photometric information for more than 1.6 billion stars up to G = 21 mag. For the brightest stars, not included in Gaia-DR2, we have used the Hipparcos catalogue instead. After adding up to the star radiance the contributions of the diffuse galactic and extragalactic light, zodiacal light and airglow, and taking into account the effects of atmospheric attenuation and scattering, the radiance detected by ground-based observers can be estimated. This methodology can be applied to any photometric band, if appropriate transformations from the Gaia bands are available. In particular, we present the expected sky brightness for V (Johnson), and visual photopic and scotopic passbands.
Equation of state of hot dense hyperonic matter in the Quark–Meson-Coupling (QMC-A) model
Authors: Stone J R , Dexheimer V , Guichon P A M , Thomas A W , Typel S 
Published: December 2020

ABSTRACT
We report a new equation of state (EoS) of cold and hot hyperonic matter constructed in the framework of the quark–meson-coupling (QMC-A) model. The QMC-A EoS yields results compatible with available nuclear physics constraints and astrophysical observations. It covers the range of temperatures from T = 0 to 100 MeV, entropies per particle S/A between 0 and 6, lepton fractions from YL = 0.0 to 0.6, and baryon number densities nB = 0.05–1.2 fm−3. Applications of the QMC-A EoS are made to cold neutron stars (NSs) and to hot proto-neutron stars (PNSs) in two scenarios: (i) lepton-rich matter with trapped neutrinos (PNS-I) and (ii) deleptonized chemically equilibrated matter (PNS-II). We find that the QMC-A model predicts hyperons in amounts growing with increasing temperature and density, thus suggesting not only their presence in PNS but also, most likely, in NS merger remnants. The nucleon–hyperon phase transition is studied through the adiabatic index and the speed of sound cs. We observe that the lowering of (cs/c)2 to and below the conformal limit of 1/3 is strongly correlated with the onset of hyperons. Rigid rotation of cold and hot stars, their moments of inertia and Kepler frequencies are also explored. The QMC-A model results are compared with two relativistic models, the chiral mean field model (CMF), and the generalized relativistic density functional (GRDF) with DD2 (nucleon-only) and DD2Y-T (full baryon octet) interactions. Similarities and differences are discussed.
The role of faint population III supernovae in forming CEMP stars in ultra-faint dwarf galaxies
Authors: Jeon Myoungwon , Bromm Volker , Besla Gurtina , Yoon Jinmi , Choi Yumi 
Published: December 2020

ABSTRACT
Carbon enhanced metal poor (CEMP)-no stars, a subset of CEMP stars ($\rm [C/Fe]\ge 0.7$ and $\rm [Fe/H]\lesssim -1$) have been discovered in ultra-faint dwarf (UFD) galaxies, with $M_{\rm vir}\approx 10^8{\, \mathrm{ M}_\odot }$ and $M_{\ast }\approx 10^3-10^4{\, \mathrm{ M}_\odot }$ at z = 0, as well as in the halo of the Milky Way (MW). These CEMP-no stars are local fossils that may reflect the properties of the first (Pop III) and second (Pop II) generation of stars. However, cosmological simulations have struggled to reproduce the observed level of carbon enhancement of the known CEMP-no stars. Here, we present new cosmological hydrodynamic zoom-in simulations of isolated UFDs that achieve a gas mass resolution of $m_{\rm gas}\approx 60{\, \mathrm{ M}_\odot }$. We include enrichment from Pop III faint supernovae (SNe), with ESN = 0.6 × 1051 erg, to understand the origin of CEMP-no stars. We confirm that Pop III and Pop II stars are mainly responsible for the formation of CEMP and C-normal stars, respectively. New to this study, we find that a majority of CEMP-no stars in the observed UFDs and the MW halo can be explained by Pop III SNe with normal explosion energy (ESN = 1.2 × 1051 erg) and Pop II enrichment, but faint SNe might also be needed to produce CEMP-no stars with $\rm [C/Fe]\gtrsim 2$, corresponding to the absolute carbon abundance of $\rm A(C)\gtrsim 6.0$. Furthermore, we find that while we create CEMP-no stars with high carbon ratio $\rm [C/Fe]\approx 3-4$, by adopting faint SNe, it is still challenging to reproduce CEMP-no stars with extreme level of carbon abundance of $\rm A(C)\approx 7.0-7.5$, observed both in the MW halo and UFDs.
Evolution of dust porosity through coagulation and shattering in the interstellar medium
Authors: Hirashita Hiroyuki , Il’in Vladimir B , Pagani Laurent , Lefèvre Charlène 
Published: December 2020

ABSTRACT
The properties of interstellar grains, such as grain size distribution and grain porosity, are affected by interstellar processing, in particular, coagulation and shattering, which take place in the dense and diffuse interstellar medium (ISM), respectively. In this paper, we formulate and calculate the evolution of grain size distribution and grain porosity through shattering and coagulation. For coagulation, we treat the grain evolution depending on the collision energy. Shattering is treated as a mechanism of forming small compact fragments. The balance between these processes are determined by the dense-gas mass fraction ηdense, which determines the time fraction of coagulation relative to shattering. We find that the interplay between shattering supplying small grains and coagulation forming porous grains from shattered grains is fundamentally important in creating and maintaining porosity. The porosity rises to 0.7–0.9 (or the filling factor 0.3–0.1) around grain radii $a\sim 0.1~\rm{\mu m}$. We also find that, in the case of ηdense = 0.1 (very efficient shattering with weak coagulation) porosity significantly enhances coagulation, creating fluffy submicron grains with filling factors lower than 0.1. The porosity enhances the extinction by 10–20 per cent at all wavelengths for amorphous carbon and at ultraviolet wavelengths for silicate. The extinction curve shape of silicate becomes steeper if we take porosity into account. We conclude that the interplay between shattering and coagulation is essential in creating porous grains in the interstellar medium and that the resulting porosity can impact the grain size distributions and extinction curves.
The VVV near-IR galaxy catalogue beyond the Galactic disc
Authors: Baravalle Laura D , Alonso María Victoria , Minniti Dante , Nilo Castellón José Luis , Soto Mario , Valotto Carlos , Villalón Carolina , Graña Darío , Amôres Eduardo B , Milla Castro Fernanda 
Published: December 2020

ABSTRACT
Knowledge about the large-scale distribution of galaxies is far from complete in the Zone of Avoidance (ZoA), which is mostly due to high interstellar extinction and to source confusion at lower Galactic latitudes. Past near-infrared (NIR) surveys, such as the Two Micron All Sky Survey (2MASS), have shown the power of probing large-scale structure at these latitudes. Our aim is to map the galaxy distribution across the Southern Galactic plane using the VISTA Variables in the Vía Láctea Survey (VVV), which reach 2–4 mag deeper than 2MASS. We used SExtractor+PSFEx to identify extended objects and to measure their sizes, the light concentration index, magnitudes, and colours. Morphological and colour constraints and visual inspection were used to confirm galaxies. We present the resulting VVV NIR Galaxy Catalogue (VVV NIRGC) of 5563 visually confirmed galaxies, of which only 45 were previously known. This is the largest catalogue of galaxies towards the Galactic plane, with 99 per cent of these galaxies being new discoveries. We found that the galaxy density distribution closely resembled the distribution of low interstellar extinction of the existing NIR maps. We also present a description of the 185 2MASS extended sources observed in the region, of which 16 per cent of these objects had no previous description, which we have now classified. We conclude that interstellar extinction and stellar density are the main limitations for the detection of background galaxies in the ZoA. The VVV NIRGC is a new data set providing information for extragalactic studies in the Galactic plane.
Demographic History and Genomic Response to Environmental Changes in a Rapid Radiation of Wild Rats
Authors: Ge Deyan , Feijó Anderson , Wen Zhixin , Abramov Alexei V , Lu Liang , Cheng Jilong , Pan Shengkai , Ye Sicheng , Xia Lin , Jiang Xuelong , Vogler Alfried P , Yang Qisen 
Published: December 2020

AbstractFor organisms to survive and prosper in a harsh environment, particularly under rapid climate change, poses tremendous challenges. Recent studies have highlighted the continued loss of megafauna in terrestrial ecosystems and the subsequent surge of small mammals, such as rodents, bats, lagomorphs, and insectivores. However, the ecological partitioning of these animals will likely lead to large variation in their responses to environmental change. In the present study, we investigated the evolutionary history and genetic adaptations of white-bellied rats (Niviventer Marshall, 1976), which are widespread in the natural terrestrial ecosystems in Asia but also known as important zoonotic pathogen vectors and transmitters. The southeastern Qinghai-Tibet Plateau was inferred as the origin center of this genus, with parallel diversification in temperate and tropical niches. Demographic history analyses from mitochondrial and nuclear sequences of Niviventer demonstrated population size increases and range expansion for species in Southeast Asia, and habitat generalists elsewhere. Unexpectedly, population increases were seen in N. eha, which inhabits the highest elevation among Niviventer species. Genome scans of nuclear exons revealed that among the congeneric species, N. eha has the largest number of positively selected genes. Protein functions of these genes are mainly related to olfaction, taste, and tumor suppression. Extensive genetic modification presents a major strategy in response to global changes in these alpine species.
Loss of Mediator complex subunit 13 (MED13) promotes resistance to alkylation through cyclin D1 upregulation
Authors: Roliński Miłosz , Montaldo Nicola Pietro , Aksu Merdane Ezgi , Fordyce Martin Sarah L , Brambilla Alessandro , Kunath Nicolas , Johansen Jostein , Erlandsen Sten Even , Liabbak Nina-Beate , Rian Kristin , Bjørås Magnar , Sætrom Pål , van Loon Barbara 
Published: December 2020

Abstract
Alkylating drugs are among the most often used chemotherapeutics. While cancer cells frequently develop resistance to alkylation treatments, detailed understanding of mechanisms that lead to the resistance is limited. Here, by using genome-wide CRISPR–Cas9 based screen, we identify transcriptional Mediator complex subunit 13 (MED13) as a novel modulator of alkylation response. The alkylation exposure causes significant MED13 downregulation, while complete loss of MED13 results in reduced apoptosis and resistance to alkylating agents. Transcriptome analysis identified cyclin D1 (CCND1) as one of the highly overexpressed genes in MED13 knock-out (KO) cells, characterized by shorter G1 phase. MED13 is able to bind to CCND1 regulatory elements thus influencing the expression. The resistance of MED13 KO cells is directly dependent on the cyclin D1 overexpression, and its down-regulation is sufficient to re-sensitize the cells to alkylating agents. We further demonstrate the therapeutic potential of MED13-mediated response, by applying combinatory treatment with CDK8/19 inhibitor Senexin A. Importantly, the treatment with Senexin A stabilizes MED13, and in combination with alkylating agents significantly reduces viability of cancer cells. In summary, our findings identify novel alkylation stress response mechanism dependent on MED13 and cyclin D1 that can serve as basis for development of innovative therapeutic strategies.
The Pentatricopeptide Repeat Protein PGR3 Is Required for the Translation ofpetLandndhGby Binding Their 5′ UTRs
Authors: Higashi Haruka , Kato Yoshinobu , Fujita Tomoya , Iwasaki Shintaro , Nakamura Masayuki , Nishimura Yoshiki , Takenaka Mizuki , Shikanai Toshiharu 
Published: December 2020

AbstractPGR3 is a P-class pentatricopeptide repeat (PPR) protein required for the stabilization of petL operon RNA and the translation of the petL gene in plastids. Irrespective of its important roles in plastids, key questions have remained unanswered, including how PGR3 protein promotes translation and which plastid mRNA PGR3 activates the translation. Here, we show that PGR3 facilitates the translation from ndhG, in addition to petL, through binding to their 5′ untranslated regions (UTRs). Ribosome profiling and RNA sequencing in pgr3 mutants revealed that translation from petL and ndhG was specifically suppressed. Harnessing small RNA fragments protected by PPR proteins in vivo, we probed the PGR3 recruitment to the 5′ UTRs of petL and ndhG. The putative PGR3-bound RNA segments per se repress the translation possibly with a strong secondary structure and thereby block ribosomes’ access. However, the PGR3 binding antagonizes the effects and facilitates the protein synthesis from petL and ndhG in vitro. The prediction of the 3-dimensional structure of PGR3 suggests that the 26th PPR motif plays important roles in target RNA binding. Our data show the specificity of a plastidic RNA-binding protein and provide a mechanistic insight into translational control.
Kinetics of Fe–Ti Oxide Re-equilibration in Magmatic Systems: Implications for Thermo-oxybarometry
Authors: Hou Tong , Botcharnikov Roman , Moulas Evangelos , Just Tobias , Berndt Jasper , Koepke Jürgen , Zhang Zhaochong , Wang Meng , Yang Zongpeng , Holtz François 
Published: December 2020

Abstract
The combined Fe–Ti oxide geothermometry and oxygen barometry is an important tool in petrology and volcanology. However, its appropriate application to natural magmatic systems is still challenged by poorly constrained kinetics of the re-equilibration processes between magnetite, ilmenite, melt and other magmatic phases. In this study, we experimentally investigated how fast Fe–Ti oxides can re-equilibrate and how fast their compositions can adapt to changing temperature and/or redox conditions. A series of equilibrium crystallization experiments were conducted in internally heated gas pressure vessels using an evolved hydrous basaltic composition. These starting reference experiments were conducted at 200 MPa, at 900 and 1000°C and at two redox conditions, i.e. FMQ + 1 and FMQ + 3·3. The products of the starting experiments, all containing magnetite and/or ilmenite, were then placed at a different temperature (T) and/or oxygen fugacity (fO2) for time dependent experimental series (1, 10 and 100 hours) in an attempt to check for the time needed for re-equilibration of the oxide composition. The experimental results demonstrate that both magnetite and ilmenite start to respond chemically to the changing conditions quite rapidly in less than 1 h. The largest compositional deviations from the equilibrium compositions were observed in the runs with 1 and 10 h duration. After 100 h, the Fe–Ti oxide compositions were approaching the expected equilibrium values in almost all kinetic series, but still with significant deviation. Moreover, our results clearly show that the Mg/Mn ratio in magnetite and ilmenite can follow the nominal ‘equilibrium’ trend, although the Fe–Ti distribution between oxides may not have reached equilibrium. This observation implies that the use of the Mg/Mn criterion to check for the equilibrium distribution of Fe–Ti between magnetite and ilmenite should be reconsidered or at least applied with caution. The quick, within-100-hours re-equilibration of the Fe–Ti oxides at magmatic conditions imposes limitations on the reliable application of oxide thermobarometry to natural systems. We suggest that in basaltic to andesitic volcanic rocks ascending and cooling relatively slowly (more than 5 days), the compositional T–fO2 record in oxides is representative of a late evolution stage rather than the pre-eruptive conditions in a magmatic reservoir at depth. This ‘frozen’ late-stage T–fO2 record is controlled by changing element diffusion rates with cooling and degassing. Only magmatic/volcanic systems, which underwent very rapid cooling, resulting from magma ascent within minutes or few hours (e.g. Plinian eruptions), can deliver Fe–Ti oxides reflecting the pre-eruptive magmatic T–fO2 signature.
More Cops, Less Trust? Disentangling the Relationship between Police Numbers and Trust in the Police in the European Union
Authors: Nägel Christof , Vera Antonio 
Published: December 2020

Abstract
This paper investigates the relationship between number of police officers per inhabitant and trust in the police in the EU. By compiling data sources from the Eurobarometer, the Eurostat and the Corruption Perception Index, we test whether the number of police officers per inhabitant is a robust predictor of trust in the police on the country level. While there is a strong negative correlation between the two variables that justifies stating that the police are trusted most in countries where the number of police is minimal, controlling for relevant covariates reveals that the correlation is technically spurious. In line with distributive justice theory, perceptions of corruption in the respective countries explain most of the variation in trust in the police, which completely levels the influence of number of police officers per inhabitant. Implications for research and policy are discussed at the end of the paper.
Culture as a contributory factor in combatting the Covid-19 pandemic
Authors: Lagman James Darwin N , Vergara Raymond John D , Sarmiento Philip Joseph D 
Published: December 2020

Abstract
In a recent correspondence, the racial disparity was discussed regarding knowledge, attitudes and practices related to COVID-19. This paper highlights culture as a contributory factor in combatting the COVID-19 pandemic that is to be considered by each government around the world.
Building public trust: a response to COVID-19 vaccine hesitancy predicament
Authors: Vergara Raymond John D , Sarmiento Philip Joseph D , Lagman James Darwin N 
Published: December 2020

AbstractWith the rollout of vaccines against COVID-19, an optimistic and a negative attitude among people have arisen. Surprisingly, surveys among people reveal that there is a significant rate of distrust against the vaccines. In a recent short report published in this journal, vaccine hesitancy was found out among medical students. Hence, wide array of research has been springing, recommending various approaches in assisting authorities deal with vaccine hesitancy such as proper and effective strategic communication as a solution. This study suggests however that a more ‘localized’ public education and role-modelling from public officials and health authorities can help a lot in building public trust. The study aims to contribute to the further development of public health mechanisms in the rolling-out and distribution of vaccines against COVID-19.