bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase 1/2 Randomized Study of the Immunogenicity, Safety, and Tolerability of a Respiratory Syncytial Virus Prefusion F Vaccine in Adults With Concomitant Inactivated Influenza Vaccine
Authors: Falsey Ann R , Walsh Edward E , Scott Daniel A , Gurtman Alejandra , Zareba Agnieszka , Jansen Kathrin U , Gruber William C , Dormitzer Philip R , Swanson Kena A , Jiang Qin , Gomme Emily , Cooper David , Schmoele-Thoma Beate 
Published: December 2021

Abstract

Background
Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults and adults with comorbidities. An effective vaccine is needed. An investigational bivalent prefusion F vaccine (RSVpreF) was assessed in healthy adults.

Methods
This phase 1/2 study randomized adults 18–85 years old to receive placebo or 60, 120, or 240 µg RSVpreF (with or without aluminum hydroxide) alone or concomitantly with seasonal inactivated influenza vaccine (SIIV). Safety and immunogenicity were assessed.

Results
In older adults, reactogenicity events were predominantly mild or moderate among RSVpreF recipients; adverse events through 1 month postvaccination were similar across formulations. Coadministration with SIIV did not appear to affect safety among younger or older adults. All RSVpreF formulations with or without concomitant SIIV elicited robust RSV serum-neutralizing responses in adults aged 50–85 years 1 month postvaccination. Neutralizing titers 1 and 12 months postvaccination were 6.9–14.9 and 2.9–4.5 times, respectively, those before vaccination. SIIV immune responses trended lower when coadministered with RSVpreF.

Conclusions
RSVpreF formulations administered alone or with SIIV were well tolerated and highly immunogenic in older adults, supporting the potential for RSVpreF to protect older adults from RSV disease.

Clinical Trials Registration
NCT03529773.
Transmission barrier of the blaKPC plasmid mediated by type I restriction-modification systems in Escherichia coli
Authors: Li Dan , Li Pei , Peng Mingjia , Zhao Xiaoyu , Jiang Xiaoying , Wang Dongliang , Yuan Yuan , Guo Qinglan , Wang Minghua , Xu Xiaogang , Wang Minggui 
Published: December 2021

Abstract

Background
Transportation of carbapenem-resistant plasmids contributes to carbapenem resistance in Gram-negative bacteria. KPC enzymes are the most clinically important enzymes among carbapenem-resistant Klebsiella pneumoniae, whereas the rate of blaKPC in Escherichia coli is low. The CRISPR-Cas system and restriction-modification system (R-M system) in bacteria defend against invading genomes. Currently, the role of the immune systems in the low rate of KPC-producing E. coli remains unclear.

Objectives
We investigated the relationship between immune systems and the low detection rate of blaKPC in E. coli.

Methods
We searched for blaKPC among 1039 E. coli whole genomes available in GenBank using nucleotide BLAST. CRISPR-Cas systems and the R-M system were detected in all strains having the ST as blaKPC-positive strains. Nucleotide BLAST was used to search for protospacers on blaKPC plasmids. A conjugation assay was performed to determine whether the R-M system influences the acquisition of blaKPC plasmids by E. coli.

Results
ST131 was the dominant ST of KPC-producing E. coli and IncN was the main plasmid type (12/32). CRISPR-Cas systems were frequently present in E. coli carrying blaKPC. Furthermore, CRISPR-Cas systems in E. coli didn’t target plasmids with blaKPC. Type I R-M systems were rare in KPC-producing E. coli, but significantly over-represented in KPC-negative strains. E. coli DH5α with hsdR deletion accepted blaKPC-carrying plasmids, whereas those with hsdR complementation impeded blaKPC-carrying plasmid conjugation.

Conclusions
Horizontal transmission of blaKPC occurs among E. coli. The type I R-M system is associated with the defence against blaKPC plasmid transport into E. coli.
Logic of informal provability with truth values
Authors: Pawlowski Pawel , Urbaniak Rafal 
Published: December 2021

AbstractClassical logic of formal provability includes Löb’s theorem, but not reflection. In contrast, intuitions about the inferential behavior of informal provability (in informal mathematics) seem to invalidate Löb’s theorem and validate reflection (after all, the intuition is, whatever mathematicians prove holds!). We employ a non-deterministic many-valued semantics and develop a modal logic T-BAT of an informal provability operator, which indeed does validate reflection and invalidates Löb’s theorem. We study its properties and its relation to known provability-related paradoxical arguments. We also argue that T-BAT is a fairly sensible candidate for a formal logic of informal provability.
Effect of carrier material on the thermodynamic properties and recrystallization kinetics of andrographolide-solid dispersion
Authors: Zhao Guowei , Zhang Junfang , Cai Ping , Ou Liquan , Liang Xinli , Dong Wei , Liao Zhenggen 
Published: December 2021

Abstract

Objectives
This work investigated the effect of the lipophilic long carbon chain of carrier material on the thermodynamic properties and the recrystallization kinetics of solid dispersion (SD).

Methods
The thermodynamic properties and recrystallization kinetic parameters of amorphous andrographolide (AG)-PEG8000 laurate (SM12)-SD, AG-PEG8000 palmitate (SM16)-SD and AG-PEG8000 behenate (SM22)-SD were determined and calculated by differential scanning calorimetry combining AGV equation and Avrami equation.

Key findings
From AG-SM12-SD to AG-SM22-SD with the increase of the carbon chain length of carrier material, the glass transition temperature, the maximum relaxation enthalpy and the mean relaxation time of SD increased at first and then decreased; the isothermal crystallization rate constants at different temperatures and non-isothermal crystallization rate constants at different heating rates of SD showed a trend of decreasing at first and then increasing.

Conclusions
Increasing the carbon chain length of polyethylene glycol fatty acid ester can improve the space-limiting effect of the carrier material on the AG molecule, but the carbon chain length of carrier was not the longer the better. SM16 had the appropriate spatial scale, which better limited the molecular mobility of AG in SD, so AG-SM16-SD has better thermodynamic stability and recrystallization kinetic stability.
Natural variation in stomatal dynamics drives divergence in heat stress tolerance and contributes to seasonal intrinsic water-use efficiency in Vitis vinifera (subsp. sativa and sylvestris)
Authors: Faralli Michele , Bontempo Luana , Bianchedi Pier Luigi , Moser Claudio , Bertamini Massimo , Lawson Tracy , Camin Federica , Stefanini Marco , Varotto Claudio 
Published: December 2021

Abstract
Stomata control CO2 uptake for photosynthesis and water loss through transpiration, thus playing a key role in leaf thermoregulation, water-use efficiency (iWUE), and plant productivity. In this work, we investigated the relationship between several leaf traits and hypothesized that stomatal behavior to fast (i.e. minutes) environmental changes co-determines, along with steady-state traits, the physiological response of grapevine to the surrounding fluctuating environment over the growing season. No relationship between iWUE, heat stress tolerance, and stomatal traits was observed in field-grown grapevine, suggesting that other physiological mechanisms are involved in determining leaf evaporative cooling capacity and the seasonal ratio of CO2 uptake (A) to stomatal conductance (gs). Indeed, cultivars that in the field had an unexpected combination of high iWUE but low sensitivity to thermal stress displayed a quick stomatal closure to light, but a sluggish closure to increased vapor pressure deficit (VPD) levels. This strategy, aiming both at conserving water under a high to low light transition and in prioritizing evaporative cooling under a low to high VPD transition, was mainly observed in the cultivars Regina and Syrah. Moreover, cultivars with different known responses to soil moisture deficit or high air VPD (isohydric versus anisohydric) had opposite behavior under fluctuating environments, with the isohydric cultivar showing slow stomatal closure to reduced light intensity but quick temporal responses to VPD manipulation. We propose that stomatal behavior to fast environmental fluctuations can play a critical role in leaf thermoregulation and water conservation under natural field conditions in grapevine.
The effects of lensing by local structures on the dipole of radio source counts
Authors: Murray Calum 
Published: December 2021

ABSTRACT
Our peculiar motion in a homogeneous and isotropic universe imprints a dipole in the cosmic microwave background (CMB) temperature field and similarly imprints a dipole in the distribution of extragalactic radio sources on the sky. Each of these effects have been measured; however, each of these measurements give different results for the velocity of our motion through the Universe: the radio dipole measurements finds the speed of our motion to be around three times larger than that of the CMB. Here we show the effects of the previously unconstrained lensing dipole, whereby necessarily local structures (required for large angular lensing scales) will distort the distribution of radio sources on the sky. We find that the inclusion of these effects does not reduce the tension between the CMB and radio source dipole measurements; however, without their inclusion future extragalactic number counts could lead to incorrect inferences of our peculiar motion. In addition we can constrain the size of the lensing dipole to be κ &lt; 3 · 10−2 at the 2σ level.
A selection function toolbox for subsets of astronomical catalogues
Authors: Boubert Douglas , Everall Andrew 
Published: December 2021

ABSTRACT
Large catalogues are ubiquitous throughout astronomy, but most scientific analyses are carried out on smaller samples selected from these catalogues by chosen cuts on catalogued quantities. The selection function of that scientific sample – the probability that a star in the catalogue will satisfy these cuts and so make it into the sample – is thus unique to each scientific analysis. We have created a general framework that can flexibly estimate the selection function of a sample drawn from a catalogue in terms of position, magnitude and colour. Our method is unique in using the binomial likelihood and accounting for correlations in the selection function across position, magnitude, and colour using Gaussian processes and spherical harmonics. We have created a new open-source python package selectionfunctiontoolbox that implements this framework and used it to make three different estimates of the APOGEE DR16 red giant sample selection function, as a subset of 2MASS, with each estimate using an increasing amount of technical knowledge of the APOGEE targeting. In a companion paper, we applied our methodology to derive estimates of the astrometric and spectroscopic selection functions of Gaia EDR3. Our framework will make it trivial for astrophysicists to estimate the selection function that they should be using with the custom sample of stars that they have chosen to answer their scientific question.
How cosmological merger histories shape the diversity of stellar haloes
Authors: Rey Martin P , Starkenburg Tjitske K 
Published: December 2021

ABSTRACT
We introduce and apply a new approach to probe the response of galactic stellar haloes to the interplay between cosmological merger histories and galaxy formation physics. We perform dark matter-only, zoomed simulations of two Milky Way-mass hosts and make targeted, controlled changes to their cosmological histories using the genetic modification technique. Populating each history’s stellar halo with a semi-empirical, particle tagging approach then enables a controlled study, with all instances converging to the same large-scale structure, dynamical and stellar mass at z = 0 as their reference. These related merger scenarios alone generate an extended spread in stellar halo mass fractions (1.5 dex) comparable to the observed population, with the largest scatter achieved by growing late (z ≤ 1) major mergers that spread out existing stars to create massive, in-situ dominated stellar haloes. Increasing a last major merger at z ∼ 2 brings more accreted stars into the inner regions, resulting in smaller scatter in the outskirts which are predominantly built by subsequent minor events. Exploiting the flexibility of our semi-empirical approach, we show that the diversity of stellar halo masses across scenarios is reduced by allowing shallower slopes in the stellar mass–halo mass relation for dwarf galaxies, while it remains conserved when central stars are born with hotter kinematics across cosmic time. The merger-dependent diversity of stellar haloes thus responds distinctly to assumptions in modelling the central and dwarf galaxies respectively, opening exciting prospects to constrain star formation and feedback at different galactic mass-scales with the coming generation of deep, photometric observatories.
Tracing the Origin and Evolutionary Fate of Recent Gene Retrocopies in Natural Populations of the House Mouse
Authors: Zhang Wenyu , Tautz Diethard 
Published: December 2021

AbstractAlthough the contribution of retrogenes to the evolution of genes and genomes has long been recognized, the evolutionary patterns of very recently derived retrocopies that are still polymorphic within natural populations have not been much studied so far. We use here a set of 2,025 such retrocopies in nine house mouse populations from three subspecies (Mus musculus domesticus, M. m. musculus, and M. m. castaneus) to trace their origin and evolutionary fate. We find that ancient house-keeping genes are significantly more likely to generate retrocopies than younger genes and that the propensity to generate a retrocopy depends on its level of expression in the germline. Although most retrocopies are detrimental and quickly purged, we focus here on the subset that appears to be neutral or even adaptive. We show that retrocopies from X-chromosomal parental genes have a higher likelihood to reach elevated frequencies in the populations, confirming the notion of adaptive effects for “out-of-X” retrogenes. Also, retrocopies in intergenic regions are more likely to reach higher population frequencies than those in introns of genes, implying a more detrimental effect when they land within transcribed regions. For a small subset of retrocopies, we find signatures of positive selection, indicating they were involved in a recent adaptation process. We show that the population-specific distribution pattern of retrocopies is phylogenetically informative and can be used to infer population history with a better resolution than with SNP markers.
Coronaviral RNA-methyltransferases: function, structure and inhibition
Authors: Nencka Radim , Silhan Jan , Klima Martin , Otava Tomas , Kocek Hugo , Krafcikova Petra , Boura Evzen 
Published: December 2021

Abstract
Coronaviral methyltransferases (MTases), nsp10/16 and nsp14, catalyze the last two steps of viral RNA-cap creation that takes place in cytoplasm. This cap is essential for the stability of viral RNA and, most importantly, for the evasion of innate immune system. Non-capped RNA is recognized by innate immunity which leads to its degradation and the activation of antiviral immunity. As a result, both coronaviral MTases are in the center of scientific scrutiny. Recently, X-ray and cryo-EM structures of both enzymes were solved even in complex with other parts of the viral replication complex. High-throughput screening as well as structure-guided inhibitor design have led to the discovery of their potent inhibitors. Here, we critically summarize the tremendous advancement of the coronaviral MTase field since the beginning of COVID pandemic.
Inference with Many Weak Instruments
Authors: Mikusheva Anna , Sun Liyang 
Published: December 2021

Abstract
We develop a concept of weak identification in linear instrumental variable models in which the number of instruments can grow at the same rate or slower than the sample size. We propose a jackknifed version of the classical weak identification-robust Anderson–Rubin (AR) test statistic. Large-sample inference based on the jackknifed AR is valid under heteroscedasticity and weak identification. The feasible version of this statistic uses a novel variance estimator. The test has uniformly correct size and good power properties. We also develop a pre-test for weak identification that is related to the size property of a Wald test based on the Jackknife Instrumental Variable Estimator. This new pre-test is valid under heteroscedasticity and with many instruments.
European bio-naïve spondyloarthritis patients initiating TNF inhibitor: time trends in baseline characteristics, treatment retention and response
Authors: Christiansen Sara Nysom , Ørnbjerg Lykke Midtbøll , Rasmussen Simon Horskjær , Loft Anne Gitte , Askling Johan , Iannone Florenzo , Zavada Jakub , Michelsen Brigitte , Nissen Michael , Onen Fatos , Santos Maria Jose , Pombo-Suarez Manuel , Relas Heikki , Macfarlane Gary J , Tomsic Matija , Codreanu Catalin , Gudbjornsson Bjorn , Van der Horst-Bruinsma Irene , Di Giuseppe Daniela , Glintborg Bente , Gremese Elisa , Pavelka Karel , Kristianslund Eirik Klami , Ciurea Adrian , Akkoc Nurullah , Barcelos Anabela , Sánchez-Piedra Carlos , Peltomaa Ritva , Jones Gareth T , Rotar Ziga , Ionescu Ruxandra , Grondal Gerdur , Van de Sande Marleen G H , Laas Karin , Østergaard Mikkel , Hetland Merete L 
Published: December 2021

Abstract

Objectives
To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating TNF inhibitor (TNFi) treatment.

Methods
Prospectively collected data on bio-naïve axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi initiation: A (1999–2008), B (2009–2014) and C (2015–2018). Retention, remission and response rates were assessed at 6, 12 and 24 months.

Results
In total, 27 149 axSpA and 17 446 PsA patients were included. Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A. Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C. For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months.

Conclusion
Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years.
Features of non-Hodgkin’s lymphoma diagnosed in minor salivary gland biopsies from primary Sjögren’s syndrome patients
Authors: Parreau Simon , Nocturne Gaétane , Mariette Xavier , Burroni Barbara , Lazure Thierry , Besson Florent L , Régent Alexis , Mouthon Luc , Terrier Benjamin , Seror Raphaele , Le Guern Véronique 
Published: December 2021

AbstractObjectiveTo evaluate the contribution of minor salivary gland biopsy (mSGB) histology in diagnosing primary SS (pSS)-associated non-Hodgkin B-cell lymphoma (NHL).MethodspSS patients with mSGB at NHL diagnosis were included.ResultsAmong the 24 patients (92.3% female, mean age 61.3 years) with an mSGB at NHL diagnosis, 13 (54.2%) had mSGB histology–revealed NHL (mSGB+); it was the only site enabling NHL diagnosis in 10/13 (76.9%) patients. Mucosa-associated lymphoid tissue (MALT) lymphoma was found in 23/24 (95.8%) patients; 100% of mSGB+ identified MALT lymphomas. pSS and lymphoma characteristics were comparable for mSGB+ and mSGB− patients. Eight (61.5%) of the 13 mSGB+ patients and all 11 mSGB− patients were treated for lymphoma. Between diagnosis and 1 year of follow-up, the ESSDAI without the NHL item remained stable (7.4 vs 5.0; P = 0.33) for the five untreated patients, while it decreased significantly for the 19 treated patients (15.8 vs 5.1; P = 0.004).ConclusionFor pSS patients with suspected NHL, mSGB histology enabled NHL diagnosis in half of them, MALT was found in 95.8% and all mSGB+ were MALT lymphomas, thereby avoiding more invasive biopsy. Our results suggest that mSGB should be obtained at pSS diagnosis and repeated during follow-up when NHL is suspected.
INDOOR RADON CONCENTRATION AND EXCESS LIFETIME CANCER RISK
Authors: Otansev Pelin , Bingöldağ Nesli 
Published: December 2021

Abstract
In this study, the indoor radon ( 222Rn) levels in summer and winter seasons were measured by using a total of 537 CR-39 detectors. The arithmetic mean values (ranges) of radon activity concentrations (RACs) in summer and winter seasons were found to be 71 Bq m −3 (27–313 Bq m−3) and 241 (89–1047 Bq m−3), respectively. In 20 houses, the RAC was higher than 400-Bq m−3 critical value declared by the Turkish Atomic Energy Authority (TAEK). The mean radon concentrations in summer and winter seasons were below the critical value declared by TAEK. According to normality test, the radon distributions in summer and winter seasons were determined as log-normal. The annual mean effective dose equivalent and the mean excess lifetime cancer risk were calculated as 8 mSv y−1 and 26 × 10−3.
The Frequency and Topology of Pseudoorthologs
Authors: Smith Megan L , Hahn Matthew W 
Published: December 2021

Abstract
Phylogenetics has long relied on the use of orthologs, or genes related through speciation events, to infer species relationships. However, identifying orthologs is difficult because gene duplication can obscure relationships among genes. Researchers have been particularly concerned with the insidious effects of pseudoorthologs—duplicated genes that are mistaken for orthologs because they are present in a single copy in each sampled species. Because gene tree topologies of pseudoorthologs may differ from the species tree topology, they have often been invoked as the cause of counterintuitive results in phylogenetics. Despite these perceived problems, no previous work has calculated the probabilities of pseudoortholog topologies or has been able to circumscribe the regions of parameter space in which pseudoorthologs are most likely to occur. Here, we introduce a model for calculating the probabilities and branch lengths of orthologs and pseudoorthologs, including concordant and discordant pseudoortholog topologies, on a rooted three-taxon species tree. We show that the probability of orthologs is high relative to the probability of pseudoorthologs across reasonable regions of parameter space. Furthermore, the probabilities of the two discordant topologies are equal and never exceed that of the concordant topology, generally being much lower. We describe the species tree topologies most prone to generating pseudoorthologs, finding that they are likely to present problems to phylogenetic inference irrespective of the presence of pseudoorthologs. Overall, our results suggest that pseudoorthologs are unlikely to mislead inferences of species relationships under the biological scenarios considered here.[Birth–death model; orthologs; paralogs; phylogenetics.]