bluuebunny/crossref_metadata_2025_split huggingface dataset:
An observational testbed for cosmological zoom-in simulations: constraining stellar migration in the solar cylinder using asteroseismology
Authors: Verma Kuldeep , Grand Robert J J , Silva Aguirre Víctor , Stokholm Amalie 
Published: June 2021

ABSTRACT
Large-scale stellar surveys coupled with recent developments in magneto-hydrodynamical simulations of the formation of Milky Way-mass galaxies provide an unparalleled opportunity to unveil the physical processes driving the evolution of the Galaxy. We developed a framework to compare a variety of parameters with their corresponding predictions from simulations in an unbiased manner, taking into account the selection function of a stellar survey. We applied this framework to a sample of over 7000 stars with asteroseismic, spectroscopic, and astrometric data available, together with six simulations from the Auriga project. We found that some simulations are able to produce abundance dichotomies in the [Fe/H]−[α/Fe] plane which look qualitatively similar to observations. The peak of their velocity distributions match the observed data reasonably well; however, they predict hotter kinematics in terms of the tails of the distributions and the vertical velocity dispersion. Assuming our simulation sample is representative of Milky Way-like galaxies, we put upper limits of 2.21 and 3.70 kpc on radial migration for young (&lt;4 Gyr) and old (∈[4, 8] Gyr) stellar populations in the solar cylinder. Comparison between the observed and simulated metallicity dispersion as a function of age further constrains migration to about 1.97 and 2.91 kpc for the young and old populations. These results demonstrate the power of our technique to compare numerical simulations with high-dimensional data sets, and paves the way for using the wider field TESS asteroseismic data together with the future generations of simulations to constrain the sub-grid models for turbulence, star formation, and feedback processes.
Genetic Admixture in the Culturally Unique Peranakan Chinese Population in Southeast Asia
Authors: Wu Degang , Li Peter Yiqing , Pan Bangfen , Tiang Zenia , Dou Jinzhuang , Williantarra Ivanna , Pribowo Amadeus Yeremia , Nurdiansyah Rizky ,   The SG Peranakan Project, Foo Roger S Y , Wang Chaolong 
Published: June 2021

AbstractThe Peranakan Chinese are culturally unique descendants of immigrants from China who settled in the Malay Archipelago ∼300–500 years ago. Today, among large communities in Southeast Asia, the Peranakans have preserved Chinese traditions with strong influence from the local indigenous Malays. Yet, whether or to what extent genetic admixture co-occurred with the cultural mixture has been a topic of ongoing debate. We performed whole-genome sequencing (WGS) on 177 Singapore (SG) Peranakans and analyzed the data jointly with WGS data of Asian and European populations. We estimated that Peranakan Chinese inherited ∼5.62% (95% confidence interval [CI]: 4.76–6.49%) Malay ancestry, much higher than that in SG Chinese (1.08%, 0.65–1.51%), southern Chinese (0.86%, 0.50–1.23%), and northern Chinese (0.25%, 0.18–0.32%). A sex-biased admixture history, in which the Malay ancestry was contributed primarily by females, was supported by X chromosomal variants, and mitochondrial (MT) and Y haplogroups. Finally, we identified an ancient admixture event shared by Peranakan Chinese and SG Chinese ∼1,612 (95% CI: 1,345–1,923) years ago, coinciding with the settlement history of Han Chinese in southern China, apart from the recent admixture event with Malays unique to Peranakan Chinese ∼190 (159–213) years ago. These findings greatly advance our understanding of the dispersal history of Chinese and their interaction with indigenous populations in Southeast Asia.
Dinuclear orthometallated gold(I)-gold(III) anticancer complexes with potent in vivo activity through an ROS-dependent mechanism
Authors: Mirzadeh Nedaossadat , Telukutla Srinivasa Reddy , Luwor Rodney , Privér Steven , Velma Ganga Reddy , Jakku Ranjith Kumar , Andrew N. Stephens , Plebanski Magdalena , Christian Hartinger , Bhargava Suresh 
Published: June 2021

Abstract
Increasingly explored over the last decade, gold complexes have shown great promise in the field of cancer therapeutics. A major obstacle to their clinical progression has been their lack of in vivo stability, particularly for gold(III) complexes, which often undergo a facile reduction in the presence of biomolecules such as glutathione. Herein, we report a new class of promising anticancer gold(I)–gold(III) complexes with the general formula [XAuI(μ-2-C6F4PPh2)(κ2-2-C6F4PPh2)AuIIIX] [X = Cl (1), Br (2), NO3 (3)] which feature two gold atoms in different oxidation states (I and III) in a single molecule. Interestingly, gold(I)–gold(III) complexes (1–3) are stable against glutathione reduction under physiological-like conditions. In addition, complexes 1–3 exhibit significant cytotoxicity (276-fold greater than cisplatin) toward the tested cancer cells compared to the noncancerous cells. Moreover, the gold(I)–gold(III) complexes do not interact with DNA-like cisplatin but target cellular thioredoxin reductase, an enzyme linked to the development of cisplatin drug resistance. Complexes 1–3 also showed potential to inhibit cancer and endothelial cell migration, as well as tube formation during angiogenesis. In vivo studies in a murine HeLa xenograft model further showed the gold compounds may inhibit tumor growth on par clinically used cisplatin, supporting the significant potential this new compound class has for further development as cancer therapeutic.
SARS-CoV-2 Nsp3 unique domain SUD interacts with guanine quadruplexes and G4-ligands inhibit this interaction
Authors: Lavigne Marc , Helynck Olivier , Rigolet Pascal , Boudria-Souilah Rofia , Nowakowski Mireille , Baron Bruno , Brülé Sébastien , Hoos Sylviane , Raynal Bertrand , Guittat Lionel , Beauvineau Claire , Petres Stéphane , Granzhan Anton , Guillon Jean , Pratviel Geneviève , Teulade-Fichou Marie-Paule , England Patrick , Mergny Jean-Louis , Munier-Lehmann Hélène 
Published: June 2021

AbstractThe multidomain non-structural protein 3 (Nsp3) is the largest protein encoded by coronavirus (CoV) genomes and several regions of this protein are essential for viral replication. Of note, SARS-CoV Nsp3 contains a SARS-Unique Domain (SUD), which can bind Guanine-rich non-canonical nucleic acid structures called G-quadruplexes (G4) and is essential for SARS-CoV replication. We show herein that the SARS-CoV-2 Nsp3 protein also contains a SUD domain that interacts with G4s. Indeed, interactions between SUD proteins and both DNA and RNA G4s were evidenced by G4 pull-down, Surface Plasmon Resonance and Homogenous Time Resolved Fluorescence. These interactions can be disrupted by mutations that prevent oligonucleotides from folding into G4 structures and, interestingly, by molecules known as specific ligands of these G4s. Structural models for these interactions are proposed and reveal significant differences with the crystallographic and modeled 3D structures of the SARS-CoV SUD-NM/G4 interaction. Altogether, our results pave the way for further studies on the role of SUD/G4 interactions during SARS-CoV-2 replication and the use of inhibitors of these interactions as potential antiviral compounds.
Salvage therapies for radiation-relapsed isocitrate dehydrogenase-mutant astrocytoma and 1p/19q codeleted oligodendroglioma
Authors: Ma Sirui , Rudra Soumon , Campian Jian L , Chheda Milan G , Johanns Tanner M , Ansstas George , Abraham Christopher D , Chicoine Michael R , Leuthardt Eric C , Dowling Joshua L , Dunn Gavin P , Kim Albert H , Huang Jiayi 
Published: June 2021

Abstract

Background
Optimal management for recurrent IDH-mutant glioma after radiation therapy (RT) is not well-defined. This study assesses practice patterns for managing recurrent IDH-mutant astrocytoma (Astro) and 1p/19q codeleted oligodendroglioma (Oligo) after RT and surveys their clinical outcomes after different salvage approaches.

Methods
Ninety-four recurrent Astro or Oligo patients after RT who received salvage systemic therapy (SST) between 2001 and 2019 at a tertiary cancer center were retrospectively analyzed. SST was defined as either alkylating chemotherapy (AC) or nonalkylating therapy (non-AC). Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method from the start of SST. Multivariable analysis (MVA) was conducted using Cox regression analysis.

Results
Recurrent Oligo (n = 35) had significantly higher PFS (median: 3.1 vs 0.8 years, respectively, P = .002) and OS (median: 6.3 vs 1.5 years, respectively, P &lt; .001) than Astro (n = 59). Overall, 90% of recurrences were local. Eight-three percent received AC as the first-line SST; 50% received salvage surgery before SST; approximately 50% with local failure &gt;2 years after prior RT received reirradiation. On MVA, non-AC was associated with worse OS for both Oligo and Astro; salvage surgery was associated with improved PFS and OS for Astro; early reirradiation was associated with improved PFS for Astro.

Conclusions
Recurrent radiation-relapsed IDH-mutant gliomas represent a heterogeneous group with variable treatment approaches. Surgery, AC, and reirradiation remain the mainstay of salvage options for retreatment.
Validation of diffusion MRI as a biomarker for efficacy using randomized phase III trial of bevacizumab with or without VB-111 in recurrent glioblastoma
Authors: Ellingson Benjamin M , Patel Kunal , Wang Chencai , Raymond Catalina , Brenner Andrew , de Groot John F , Butowski Nicholas A , Zach Leor , Campian Jian L , Schlossman Jacob , Rizvi Shan , Cohen Yael C , Lowenton-Spier Noa , Minei Tamar Rachmilewitz , Shmueli Shifra Fain , Wen Patrick Y , Cloughesy Timothy F 
Published: June 2021

Abstract

Background
Evidence from single and multicenter phase II trials have suggested diffusion MRI is a predictive imaging biomarker for survival benefit in recurrent glioblastoma (rGBM) treated with anti-VEGF therapy. The current study confirms these findings in a large, randomized phase III clinical trial.

Methods
Patients with rGBM were enrolled in a phase III randomized (1:1), controlled trial (NCT02511405) to compare the efficacy and safety of bevacizumab (BV) versus BV in combination with ofranergene obadenovec (BV+VB-111), an anti-cancer viral therapy. In 170 patients with diffusion MRI available, pretreatment enhancing tumor volume and ADC histogram analysis were used to phenotype patients as having high (&gt;1.24 µm2/ms) or low (&lt;1.24 µm2/ms) ADCL, the mean value of the lower peak of the ADC histogram, within the contrast enhancing tumor.

Results
Baseline tumor volume (P = .3460) and ADCL (P = .2143) did not differ between treatment arms. Univariate analysis showed patients with high ADCL had a significant survival advantage in all patients (P = .0006), as well as BV (P = .0159) and BV+VB-111 individually (P = .0262). Multivariable Cox regression accounting for treatment arm, age, baseline tumor volume, and ADCL identified continuous measures of tumor volume (P &lt; .0001; HR = 1.0212) and ADCL phenotypes (P = .0012; HR = 0.5574) as independent predictors of OS.

Conclusion
Baseline diffusion MRI and tumor volume are independent imaging biomarkers of OS in rGBM treated with BV or BV+VB-111.
Effects of different sources of dietary protein on markers of kidney function in individuals with diabetes: a systematic review and meta-analysis of randomized controlled trials
Authors: Eckert Igor , Koehler Igor C , Bauer Julia , Busnello Fernanda M , Silva Flávia M 
Published: June 2021

Abstract

Context
The type of dietary protein may modulate markers of diabetic kidney disease; however, no attempt to summarize the evidence from randomized controlled trials (RCTs) has been performed to date.

Objective
To assess the effects of different types of dietary protein on urinary albumin excretion and glomerular filtration rate in individuals with diabetes.

Data sources
MEDLINE, EMBASE, and Scopus were searched for all published RCTs, with no language restriction, up to July 2020.

Data Extraction
Study selection and data extraction were performed independently by 3 authors. Risk of bias was assessed independently by 2 authors, and the GRADE approach was used to assess the quality of the evidence.

Results
Twelve RCTs were included, of which 11 (involving 228 participants) were compiled in meta-analyses of random-effects models. Interventions consisted of diets emphasizing plant or white meat protein, with reduced intake of animal or red meat protein. Pooled data from crossover trials (n = 8) favored intervention diets for urinary albumin excretion (ratio of means, 0.86; 95% confidence interval 0.80 to 0.94; I2 = 4%) and glomerular filtration rate (ratio of means, 0.90; 95% confidence interval 0.87 to 0.94; I2 = 45%), compared with control diets. Results from parallel-design studies (n = 3), however, were not statistically significant for any outcome. The quality of the evidence ranged from very low to moderate, and most studies were judged with at least some concerns in terms of risk of bias.

Conclusion
This meta-analysis found weak evidence for small to moderate improvements in markers of kidney function in favor of interventions with lower animal protein (or red meat protein) compared with usual diets in short-term crossover trials. These findings require confirmation in well-designed randomized controlled trials.
The impact of humanoid robot presence in the paediatric emergency department waiting room: A prospective cohort study
Authors: Sivakumar Mithra , Ali Samina , Rajagopal Manasi , Yaskina Maryna , Drury Sharon , Wright Bruce 
Published: June 2021

AbstractBackgroundThe waiting room represents families’ first point of contact with the emergency department (ED). We wished to study if a humanoid robot technology presence in the waiting room would improve satisfaction and decrease anxiety for caregivers in the paediatric ED.MethodsThis observational cohort study was conducted from September to December 2018 at a Canadian paediatric ED. All caregivers and children &gt;11 years in the ED waiting room were eligible. We compared a robotic intervention (RI) to standard of care (SOC) education in the waiting room. The RI was a 5-minute psychoeducational program describing the ED process and flow. Specific days were designated for RI or SOC. An anonymous survey was administered twice, at the same times, on both SOC and RI days. The primary outcomes were (a) caregiver satisfaction with waiting room experience using a 5-point Likert scale; and (b) caregiver-reported anxiety in the waiting room, as measured by the State Trait Anxiety Inventory – State Scale.ResultsSix hundred and thirty-three caregivers participated, with a median age of 37 years (IQR 32 to 42); 80 children participated, with a median age of 15 years (IQR 13 to 16). Caregivers reported greater overall satisfaction in the RI cohort (174/200, 87.0%) compared to the SOC cohort (144/229, 62.9%; P&lt;0.0001). Caregivers also reported lower anxiety in the RI cohort (39.38±11.38) compared to the SOC cohort (42.04±11.99; P=0.009).ConclusionsA humanoid robot-based psycho educational intervention in the paediatric ED waiting room has a positive impact on caregiver satisfaction and anxiety.
Reaction Coronas at Olivine–Plagioclase Contacts in Host Rocks from the Nova–Bollinger Ni–Cu–Co Deposit, Albany–Fraser Orogen, Western Australia: Evidence of a Magmatic to Metamorphic Continuum
Authors: Torres-Rodriguez Natalia , Barnes Stephen J , Taranovic Valentina , Pearce Mark A , Verrall Michael , Schoneveld Louise E 
Published: June 2021

Abstract
A prominent feature of the cumulate rocks of the Nova intrusions is the presence of reaction coronas between olivine and plagioclase. A particular spatial arrangement of mineral textures, typical of olivine–plagioclase coronas in high-P troctolites and olivine gabbros worldwide, is almost universally observed: partially resorbed olivine with a cuspate margin, surrounded by orthopyroxene, surrounded by a zone of symplectite comprising hornblende + clinopyroxene, orthopyroxene and Cr-poor Al–(Fe, Mg) spinel, with a cuspate boundary against plagioclase. Where amphibole-free clinopyroxene–spinel symplectite is developed it is typically as an outer layer against plagioclase. The mineralogy and composition of these coronas has been revealed by a combination of scanning electron microscopy and synchrotron X-ray fluorescence microscopy. There is a close spatial association between reaction symplectites and Bowen reaction series sequences developed by reaction between cumulus phases and fractionated trapped interstitial melt, giving rise to local Cr and Ti enrichment within the coronas relative to olivine and plagioclase, accompanying enrichment in water recorded by stabilization of amphibole. These relationships imply that trapped liquid crystallization and corona formation were part of a process continuum, such that the coronas record mineral reactions close to the solidus temperature of the cumulates, initially developing in the presence of evolved hydrous interstitial liquid and continuing to develop in the solid state below the solidus. The symplectites owe their fine microstructure to diffusion-limited growth of the products of solid-state reactions below the solidus. The initial magmatic stage of corona formation records conditions of 0·76 and 0·96 GPa and around 1035 °C based on THERMOCALC pseudosections calculated for the bulk composition of the corona assemblage. Two-pyroxene assemblages within the symplectites record temperatures around 850–900 °C and pressures between 0·7 and 1·1 GPa. These pressure estimates are in good agreement with those obtained from regional metamorphism studies of the country rock paragneisses, confirming independent lines of evidence that the Nova intrusions were syn-metamorphic, emplaced under granulite-facies peak metamorphic conditions at crustal depths of 28–35 km. The unusually extensive development of the symplectites reflects the cooling history of the intrusions, which remained at temperatures close to solidus temperatures on the timescale of regional tectonic uplift and cooling of the deep roots of the orogen.
Looking for a safe haven: tail-anchored proteins and their membrane insertion pathways
Authors: Mehlhorn Dietmar G , Asseck Lisa Y , Grefen Christopher 
Published: June 2021

AbstractInsertion of membrane proteins into the lipid bilayer is a crucial step during their biosynthesis. Eukaryotic cells face many challenges in directing these proteins to their predestined target membrane. The hydrophobic signal peptide or transmembrane domain (TMD) of the nascent protein must be shielded from the aqueous cytosol and its target membrane identified followed by transport and insertion. Components that evolved to deal with each of these challenging steps range from chaperones to receptors, insertases, and sophisticated translocation complexes. One prominent translocation pathway for most proteins is the signal recognition particle (SRP)-dependent pathway which mediates co-translational translocation of proteins across or into the endoplasmic reticulum (ER) membrane. This textbook example of protein insertion is stretched to its limits when faced with secretory or membrane proteins that lack an amino-terminal signal sequence or TMD. Particularly, a large group of so-called tail-anchored (TA) proteins that harbor a single carboxy-terminal TMD require an alternative, post-translational insertion route into the ER membrane. In this review, we summarize the current research in TA protein insertion with a special focus on plants, address challenges, and highlight future research avenues.
Revisiting characteristics, treatment and outcome of cardiomyopathy in eosinophilic granulomatosis with polyangiitis (formerly Churg–Strauss)
Authors: Sartorelli Silvia , Chassagnon Guillaume , Cohen Pascal , Dunogué Bertrand , Puéchal Xavier , Régent Alexis , Mouthon Luc , Guillevin Loïc , Terrier Benjamin ,   for the French Vasculitis Study Group (FVSG)
Published: June 2021

AbstractObjectivesEosinophilic granulomatosis with polyangiitis (EGPA) is a necrotizing eosinophil-rich vasculitis. Specific cardiomyopathy (CM) was described in early studies as the most important predictor of mortality. We aimed to revisit EGPA-related CM and investigate its outcome in recent decades.MethodsWe reviewed all EGPA patients managed from 2000 to 2019 in our vasculitis clinic. Baseline characteristics and outcomes were analysed. EGPA-related CM was defined as clinical or extra-clinical manifestations of patent myocardial involvement, after exclusion of other causes.ResultsWe included 176 patients. The median age was 47 years [interquartile range (IQR) 36–58 years]. Specific CM was observed in 70 patients (40%). Cardiac symptoms were observed in 81% of CM+ patients, including mainly typical or atypical chest pain and peripheral oedema. Abnormal ECG, transthoracic echocardiography and cardiac MRI (CMRI) were found in 72%, 72% and 99% of CM+ patients, respectively, contrasting with abnormalities in 32%, 38% and 60% of CM-negative patients, respectively. Late gadolinium enhancement (LGE) was the most frequent abnormality on CMRI (70%). CM+ patients were less frequently ANCA-positive, had less frequent peripheral neuropathy and had higher eosinophil count. Major adverse cardiovascular events (MACEs) occurred in 13% of patients, both in CM+ and CM– patients. Abnormal ECG and LGE on CMRI were associated with the occurrence of MACEs. Four patients died, but none from cardiac causes.ConclusionSpecific cardiomyopathy is frequent in EGPA, especially in ANCA-negative patients with high eosinophil counts. Long-term outcome was better than previously reported. Abnormal ECG and LGE on CMRI were associated with the occurrence of MACEs.
Complexity in Employment and Coresidential Trajectories Among (Dis)Advantaged Social Groups in Chile
Authors: Madero-Cabib Ignacio , Cabello-Hutt Tania 
Published: June 2021

Abstract
Recent institutional and cultural changes have allowed individuals to gradually (but persistently) follow more complex, less uniform, and less predictable work and family patterns than the patterns often assumed to be the norm in Western settings. However, we identify important gaps in this literature: (i) a persistent focus on high-income countries in Western Europe and North America, (ii) an emphasis on narrowed periods of adulthood, and (iii) a disregard for coresidential histories when analyzing the family domain. In this paper, we aim to address these shortcomings in two ways. First, we identify lifetime employment and coresidential trajectories of individuals living currently in Santiago, Chile, born between 1944 and 1954—a cohort that faced several political, economic, and cultural changes across their lives. Second, we explore how gender and socioeconomic disadvantages are associated with individuals’ life trajectories. We conduct a multichannel sequence analysis of a comprehensive life history dataset and find that about a quarter of the sample (27.2%) follows a modal pattern of continuous formal full-time employment and coresidence with a partner and children. The remaining proportion of individuals follow more complex, unstable, and interrupted patterns, which vary in their levels of work attachment, work informality, solo parenthood, and intergenerational households. Our findings question the idea that socially advantaged individuals opt for more complex life courses and instead confirm the association between socially disadvantaged individuals, particularly women and those lower educated, and complex trajectories. Rather than deliberate individualistic choices, life course instability appears as an additional layer of social disadvantage.