bluuebunny/crossref_metadata_2025 huggingface dataset:
A Quantitative Assessment of Staphylococcus aureus Community Carriage in Yuma, Arizona
Authors: Russakoff Benjamin , Wood Colin , Lininger Monica R , Barger Steven D , Trotter Robert T , Maltinsky Sara , Mbegbu Mimi , Coyne Briana , Panisello Yagüe David , Kyman Shari , Tucker-Morgan Kara , Ceniceros Kathya , Padilla Cristina , Hurtado Kevin , Menard Ashley , Villa Francisco , Wayment Heidi A , Hepp Crystal , Furstenau Tara , Fofanov Viacheslav , Liu Cindy M , Pearson Talima R
Published: November 2022

Background

Disease control relies on pathogen identification and understanding reservoirs. Staphylococcus aureus infection prevention is based upon decades of research on colonization and infection, but diminishing returns from mitigation efforts suggest significant knowledge gaps. Existing knowledge and mitigation protocols are founded upon culture-based detection, with almost no information about pathogen quantities.

Methods

We used culture and a quantitative polymerase chain reaction assay on samples from 3 body sites to characterize colonization more comprehensively than previous studies by describing both prevalence and pathogen quantity.

Results

We show a much higher overall prevalence (65.9%) than previously documented, with higher quantities and prevalence associated with the nares, non-Hispanic males (86.9%), and correlating with colonization in other body sites. These results suggest that research and clinical practices likely misclassify over half of colonized persons, limiting mitigation measures and their impact.

Conclusions

This work begins the process of rebuilding foundational knowledge of S aureus carriage with more accurate and wholistic approaches.
I had not time to make it shorter: an exploratory analysis of how physicians reduce note length and time in notes
Authors: Apathy Nate C , Hare Allison J , Fendrich Sarah , Cross Dori A
Published: November 2022

Objective

We analyze observed reductions in physician note length and documentation time, 2 contributors to electronic health record (EHR) burden and burnout.

Materials and Methods

We used EHR metadata from January to May, 2021 for 130 079 ambulatory physician Epic users. We identified cohorts of physicians who decreased note length and/or documentation time and analyzed changes in their note composition.

Results

37 857 physicians decreased either note length (n = 15 647), time in notes (n = 15 417), or both (n = 6793). Note length decreases were primarily attributable to reductions in copy/paste text (average relative change of –18.9%) and templated text (–17.2%). Note time decreases were primarily attributable to reductions in manual text (–27.3%) and increases in note content from other care team members (+21.1%).

Discussion

Organizations must consider priorities and tradeoffs in the distinct approaches needed to address different contributors to EHR burden.

Conclusion

Future research should explore scalable burden-reduction initiatives responsive to both note bloat and documentation time.
A probabilistic temporal epistemic logic: Strong completeness
Authors: Ognjanović Zoran , Ilić Stepić Angelina , Perović Aleksandar
Published: November 2022

The paper offers a formalization of reasoning about distributed multi-agent systems. The presented propositional probabilistic temporal epistemic logic $\textbf {PTEL}$ is developed in full detail: syntax, semantics, soundness and strong completeness theorems. As an example, we prove consistency of the blockchain protocol with respect to the given set of axioms expressed in the formal language of the logic. We explain how to extend $\textbf {PTEL}$ to axiomatize the corresponding first-order logic.
Volatility of Volatility Estimation: Central Limit Theorems for the Fourier Transform Estimator and Empirical Study of the Daily Time Series Stylized Facts
Authors: Toscano Giacomo , Livieri Giulia , Mancino Maria Elvira , Marmi Stefano
Published: November 2022

We study the asymptotic normality of two feasible estimators of the integrated volatility of volatility based on the Fourier methodology, which does not require the pre-estimation of the spot volatility. We show that the bias-corrected estimator reaches the optimal rate n1/4, while the estimator without bias-correction has a slower convergence rate and a smaller asymptotic variance. Additionally, we provide simulation results that support the theoretical asymptotic distribution of the rate-efficient estimator and show the accuracy of the latter in comparison with a rate-optimal estimator based on the pre-estimation of the spot volatility. Finally, using the rate-optimal Fourier estimator, we reconstruct the series of the daily volatility of volatility of the S&P500 and EUROSTOXX50 indices over long samples and provide novel insight into the existence of stylized facts about the volatility of volatility dynamics.
Hybrid mode atomic force microscopy of phase modulation and frequency modulation
Authors: Yamamoto Tatsuya , Miyazaki Masato , Nomura Hikaru , Li Yan Jun , Sugawara Yasuhiro
Published: November 2022

We propose hybrid phase modulation (PM)/frequency modulation (FM) atomic force microscopy (AFM) to increase the imaging speed of AFM in high-Q environments. We derive the relationship between the phase shift, the frequency shift and the tip–sample interaction force from the equation of motion for the cantilever in high-Q environments. The tip–sample conservative force is approximately given by the sum of the conservative force with respect to the phase shift in the PM mode and that with respect to the frequency shift in the FM mode. We preliminarily demonstrate that the hybrid PM/FM-AFM is a new and very promising AFM operation mode that can increase imaging speed.
Cis-regulatory variation expands the colour palette of the Brassicaceae
Authors: Fattorini Róisín , Ó’Maoiléidigh Diarmuid S
Published: November 2022

This article comments on:

Ye S, Hua S, Ma T, Ma X, Chen Y, Wu L, Zhao L, Yi B, Ma C, Tu J, Shen J, Fu T, Wen J. 2022. Genetic and multi-omics analyses reveal BnaA07.PAP2In-184-317 as the key gene conferring anthocyanin-based color in Brassica napus flowers. Journal of Experimental Botany 73,6630–6645.
In situcontrol of root–bacteria interactions using optical trapping in transparent soil
Authors: Ge Sisi , Dong Xingshui , Liu Yangminghao , Wright Kathryn M , Humphris Sonia N , Dupuy Lionel X , MacDonald Michael P
Published: November 2022

Bacterial attachment on root surfaces is an important step preceding the colonization or internalization and subsequent infection of plants by pathogens. Unfortunately, bacterial attachment is not well understood because the phenomenon is difficult to observe. Here we assessed whether this limitation could be overcome using optical trapping approaches. We have developed a system based on counter-propagating beams and studied its ability to guide Pectobacterium atrosepticum (Pba) cells to different root cell types within the interstices of transparent soils. Bacterial cells were successfully trapped and guided to root hair cells, epidermal cells, border cells, and tissues damaged by laser ablation. Finally, we used the system to quantify the bacterial cell detachment rate of Pba cells on root surfaces following reversible attachment. Optical trapping techniques could greatly enhance our ability to deterministically characterize mechanisms linked to attachment and formation of biofilms in the rhizosphere.
r-process nucleosynthesis and kilonovae from hypermassive neutron star post-merger remnants
Authors: Curtis Sanjana , Mösta Philipp , Wu Zhenyu , Radice David , Roberts Luke , Ricigliano Giacomo , Perego Albino
Published: November 2022

We investigate r-process nucleosynthesis and kilonova emission resulting from binary neutron star (BNS) mergers based on a three-dimensional (3D) general-relativistic magnetohydrodynamic (GRMHD) simulation of a hypermassive neutron star (HMNS) remnant. The simulation includes a microphysical finite-temperature equation of state (EOS) and neutrino emission and absorption effects via a leakage scheme. We track the thermodynamic properties of the ejecta using Lagrangian tracer particles and determine its composition using the nuclear reaction network SkyNet. We investigate the impact of neutrinos on the nucleosynthetic yields by varying the neutrino luminosities during post-processing. The ejecta show a broad distribution with respect to their electron fraction Ye, peaking between ∼0.25–0.4 depending on the neutrino luminosity employed. We find that the resulting r-process abundance patterns differ from solar, with no significant production of material beyond the second r-process peak when using luminosities recorded by the tracer particles. We also map the HMNS outflows to the radiation hydrodynamics code SNEC and predict the evolution of the bolometric luminosity as well as broadband light curves of the kilonova. The bolometric light curve peaks on the timescale of a day and the brightest emission is seen in the infrared bands. This is the first direct calculation of the r-process yields and kilonova signal expected from HMNS winds based on 3D GRMHD simulations. For longer-lived remnants, these winds may be the dominant ejecta component producing the kilonova emission.
ALMACAL VIII: a pilot survey for untargeted extragalactic CO emission lines in deep ALMA calibration data
Authors: Hamanowicz Aleksandra , Zwaan Martin A , Péroux Céline , Lagos Claudia del P , Klitsch Anne , Ivison Rob J , Biggs Andrew D , Szakacs Roland , Fresco Alejandra
Published: November 2022

We present a pilot, untargeted extragalactic carbon monoxide (CO) emission-line survey using ALMACAL, a project utilizing ALMA calibration data for scientific purposes. In 33 deep (Texp > 40 min) ALMACAL fields, we report six CO emission-line detections above S/N > 4, one-third confirmed by MUSE observations. With this pilot survey, we probe a cosmologically significant volume of ∼105 cMpc3, widely distributed over many pointings in the southern sky, making the survey largely insusceptible to the effects of cosmic variance. We derive the redshift probability of the CO detections using probability functions from the Shark semi-analytical model of galaxy formation. By assuming typical CO excitations for the detections, we put constraints on the cosmic molecular gas mass density evolution over the redshift range 0 < z < 1.5. The results of our pilot survey are consistent with the findings of other untargeted emission-line surveys and the theoretical model predictions and currently cannot rule out a non-evolving molecular gas mass density. Our study demonstrates the potential of using ALMA calibrator fields as a multi-sightline untargeted CO emission-line survey. Applying this approach to the full ALMACAL database will provide an accurate, free of cosmic variance, measurement of the molecular luminosity function as a function of redshift.
Unveiling polarized emission from interstellar dust of the Large Magellanic Cloud with Planck
Authors: Alina D , Bernard J-Ph , Yuen K H , Lazarian A , Hughes A , Iskakova M , Akimkhan A , Mukanova A
Published: November 2022

Polarization of interstellar dust emission is a powerful probe of dust properties and magnetic field structure. Yet studies of external galaxies are hampered by foreground dust contribution. The study aims at separating the polarized signal from the Large Magellanic Cloud (LMC) from that of the Milky Way (MW) to construct a wide-field, spatially complete map of dust polarization using the Planck 353 GHz data. To estimate the foreground polarization direction, we used velocity gradients in H i spectral line data and assessed the performance of the output by comparing to starlight extinction polarization. We estimate the foreground intensity using the dust-to-gas correlation and the average intensity around the LMC and we assume the foreground polarization to be uniform and equal to the average of the MW around the galaxy to derive foreground I, Q, and U parameters. After foreground removal, the geometry of the plane-of-the-sky magnetic field tends to follow the structure of the atomic gas. This is notably the case along the molecular ridges extending south and south-east of the 30 Doradus star-forming complex and along the more diffuse southern arm extending towards the Small Magellanic Cloud. There is also an alignment between the magnetic field and the outer arm in the western part. The median polarization fraction in the LMC is slightly lower than that observed for the MW as well as the anticorrelation between the polarization angle dispersion function and the polarization fraction. Overall, polarization fraction distribution is similar to that observed in the MW.
The effects of stellar rotation along the main sequence of the 100-Myr-old massive cluster NGC 1850
Authors: Kamann S , Saracino S , Bastian N , Gossage S , Usher C , Baade D , Cabrera-Ziri I , de Mink S E , Ekstrom S , Georgy C , Hilker M , Larsen S S , Mackey D , Niederhofer F , Platais I , Yong D
Published: November 2022

Young star clusters enable us to study the effects of stellar rotation on an ensemble of stars of the same age and across a wide range in stellar mass and are therefore ideal targets for understanding the consequences of rotation on stellar evolution. We combine MUSE spectroscopy with HST photometry to measure the projected rotational velocities (Vsin i) of 2184 stars along the split main sequence and on the main sequence turn-off (MSTO) of the 100 Myr-old massive ($10^5\, {\rm M_{\odot }}$) star cluster NGC 1850 in the Large Magellanic Cloud. At fixed magnitude, we observe a clear correlation between Vsin i and colour, in the sense that fast rotators appear redder. The average Vsin i values for stars on the blue and red branches of the split main sequence are $\sim \! 100\, {\rm km\, s^{-1}}$ and $\sim \! 200\, {\rm km\, s^{-1}}$, respectively. The values correspond to about $25-30{{\ \rm per\ cent}}$ and $50-60{{\ \rm per\ cent}}$ of the critical rotation velocity and imply that rotation rates comparable to those observed in field stars of similar masses can explain the split main sequence. Our spectroscopic sample contains a rich population of ∼200 fast rotating Be stars. The presence of shell features suggests that 23 per cent of them are observed through their decretion discs, corresponding to a disc opening angle of 15 degrees. These shell stars can significantly alter the shape of the MSTO, hence care should be taken when interpreting this photometric feature. Overall, our findings impact our understanding of the evolution of young massive clusters and provide new observational constraints for testing stellar evolutionary models.
Constraints on electron acceleration in gamma-ray bursts afterglows from radio peaks
Authors: Duncan Ruby A , van der Horst Alexander J , Beniamini Paz
Published: November 2022

Studies of gamma-ray bursts (GRBs) and their multiwavelength afterglows have led to insights in electron acceleration and emission properties from relativistic, high-energy astrophysical sources. Broad-band modelling across the electromagnetic spectrum has been the primary means of investigating the physics behind these sources, although independent diagnostic tools have been developed to inform and corroborate assumptions made in particle acceleration simulations and broad-band studies. We present a methodology to constrain three physical parameters related to electron acceleration in GRB blast waves: the fraction of shock energy in electrons, ϵe; the fraction of electrons that gets accelerated into a power-law distribution of energies, ξe; and the minimum Lorentz factor of the accelerated electrons, γm. These parameters are constrained by observations of the peaks in radio afterglow light curves and spectral energy distributions. From a sample of 49 radio afterglows, we are able to find narrow distributions for these parameters, hinting at possible universality of the blast wave microphysics, although observational bias could play a role in this. Using radio peaks and considerations related to the prompt gamma-ray emission efficiency, we constrain the allowed parameter ranges for both ϵe and ξe to within about one order of magnitude, 0.01 ≲ ϵe ≲ 0.2 and 0.1 ≲ ξe ≲ 1. Such stringent constraints are inaccessible for ξe from broad-band studies due to model degeneracies.
Chemical evolution of fluorine in the Milky Way
Authors: Womack Kate A , Vincenzo Fiorenzo , Gibson Brad K , Côté Benoit , Pignatari Marco , Brinkman Hannah E , Ventura Paolo , Karakas Amanda
Published: November 2022

Fluorine has many different potential sites and channels of production, making narrowing down a dominant site of fluorine production particularly challenging. In this work, we investigate which sources are the dominant contributors to the galactic fluorine by comparing chemical evolution models to observations of fluorine abundances in Milky Way stars covering a metallicity range of −2 < [Fe/H] < 0.4 and upper limits in the range of −3.4 < [Fe/H] < −2.3. In our models, we use a variety of stellar yield sets in order to explore the impact of varying both asymptotic giant branch (AGB) and massive star yields on the chemical evolution of fluorine. In particular, we investigate different prescriptions for initial rotational velocity in massive stars as well as a metallicity-dependent mix of rotational velocities. We find that the observed [F/O] and [F/Fe] abundance ratios at low metallicity and the increasing trend of [F/Ba] at [Fe/H] ≳ −1 can only be reproduced by chemical evolution models assuming, at all metallicities, a contribution from rapidly rotating massive stars with initial rotational velocities as high as 300 km s−1. A mix of rotational velocities may provide a more physical solution than the sole use of massive stars with vrot  =  300 km s−1, which are predicted to overestimate the fluorine and average s-process elemental abundances at [Fe/H] ≳ −1. The contribution from AGB stars is predicted to start at [Fe/H] ≈ −1 and becomes increasingly important at high metallicity, being strictly coupled to the evolution of the nitrogen abundance. Finally, by using modern yield sets, we investigate the fluorine abundances of Wolf–Rayet winds, ruling them out as dominant contributors to the galactic fluorine.
Blue Turns to Gray: Paleogenomic Insights into the Evolutionary History and Extinction of the Blue Antelope (Hippotragus leucophaeus)
Authors: Hempel Elisabeth , Bibi Faysal , Faith J Tyler , Koepfli Klaus-Peter , Klittich Achim M , Duchêne David A , Brink James S , Kalthoff Daniela C , Dalén Love , Hofreiter Michael , Westbury Michael V
Published: November 2022

The blue antelope (Hippotragus leucophaeus) is the only large African mammal species to have become extinct in historical times, yet no nuclear genomic information is available for this species. A recent study showed that many alleged blue antelope museum specimens are either roan (Hippotragus equinus) or sable (Hippotragus niger) antelopes, further reducing the possibilities for obtaining genomic information for this extinct species. While the blue antelope has a rich fossil record from South Africa, climatic conditions in the region are generally unfavorable to the preservation of ancient DNA. Nevertheless, we recovered two blue antelope draft genomes, one at 3.4× mean coverage from a historical specimen (∼200 years old) and one at 2.1× mean coverage from a fossil specimen dating to 9,800–9,300 cal years BP, making it currently the oldest paleogenome from Africa. Phylogenomic analyses show that blue and sable antelope are sister species, confirming previous mitogenomic results, and demonstrate ancient gene flow from roan into blue antelope. We show that blue antelope genomic diversity was much lower than in roan and sable antelope, indicative of a low population size since at least the early Holocene. This supports observations from the fossil record documenting major decreases in the abundance of blue antelope after the Pleistocene–Holocene transition. Finally, the persistence of this species throughout the Holocene despite low population size suggests that colonial-era human impact was likely the decisive factor in the blue antelope's extinction.
Rapid single-molecule characterisation of enzymes involved in nucleic-acid metabolism
Authors: Mueller Stefan H , Fitschen Lucy J , Shirbini Afnan , Hamdan Samir M , Spenkelink Lisanne M , van Oijen Antoine M
Published: November 2022

The activity of enzymes is traditionally characterised through bulk-phase biochemical methods that only report on population averages. Single-molecule methods are advantageous in elucidating kinetic and population heterogeneity but are often complicated, time consuming, and lack statistical power. We present a highly-generalisable and high-throughput single-molecule assay to rapidly characterise proteins involved in DNA metabolism. The assay exclusively relies on changes in total fluorescence intensity of surface-immobilised DNA templates as a result of DNA synthesis, unwinding or digestion. Combined with an automated data-analysis pipeline, our method provides enzymatic activity data of thousands of molecules in less than an hour. We demonstrate our method by characterising three fundamentally different enzyme activities: digestion by the phage λ exonuclease, synthesis by the phage Phi29 polymerase, and unwinding by the E. coli UvrD helicase. We observe the previously unknown activity of the UvrD helicase to remove neutravidin bound to 5′-, but not 3′-ends of biotinylated DNA.
TISCH2: expanded datasets and new tools for single-cell transcriptome analyses of the tumor microenvironment
Authors: Han Ya , Wang Yuting , Dong Xin , Sun Dongqing , Liu Zhaoyang , Yue Jiali , Wang Haiyun , Li Taiwen , Wang Chenfei
Published: November 2022

The Tumor Immune Single Cell Hub 2 (TISCH2) is a resource of single-cell RNA-seq (scRNA-seq) data from human and mouse tumors, which enables comprehensive characterization of gene expression in the tumor microenvironment (TME) across multiple cancer types. As an increasing number of datasets are generated in the public domain, in this update, TISCH2 has included 190 tumor scRNA-seq datasets covering 6 million cells in 50 cancer types, with 110 newly collected datasets and almost tripling the number of cells compared with the previous release. Furthermore, TISCH2 includes several new functions that allow users to better utilize the large-scale scRNA-seq datasets. First, in the Dataset module, TISCH2 provides the cell–cell communication results in each dataset, facilitating the analyses of interacted cell types and the discovery of significant ligand–receptor pairs between cell types. TISCH2 also includes the transcription factor analyses for each dataset and visualization of the top enriched transcription factors of each cell type. Second, in the Gene module, TISCH2 adds functions for identifying correlated genes and providing survival information for the input genes. In summary, TISCH2 is a user-friendly, up-to-date and well-maintained data resource for gene expression analyses in the TME. TISCH2 is freely available at http://tisch.comp-genomics.org/.
The nucleoplasmic phase of pre-40S formation prior to nuclear export
Authors: Cheng Jingdong , Lau Benjamin , Thoms Matthias , Ameismeier Michael , Berninghausen Otto , Hurt Ed , Beckmann Roland
Published: November 2022

Biogenesis of the small ribosomal subunit in eukaryotes starts in the nucleolus with the formation of a 90S precursor and ends in the cytoplasm. Here, we elucidate the enigmatic structural transitions of assembly intermediates from human and yeast cells during the nucleoplasmic maturation phase. After dissociation of all 90S factors, the 40S body adopts a close-to-mature conformation, whereas the 3' major domain, later forming the 40S head, remains entirely immature. A first coordination is facilitated by the assembly factors TSR1 and BUD23–TRMT112, followed by re-positioning of RRP12 that is already recruited early to the 90S for further head rearrangements. Eventually, the uS2 cluster, CK1 (Hrr25 in yeast) and the export factor SLX9 associate with the pre-40S to provide export competence. These exemplary findings reveal the evolutionary conserved mechanism of how yeast and humans assemble the 40S ribosomal subunit, but reveal also a few minor differences.
Structural insights into target DNA recognition and cleavage by the CRISPR-Cas12c1 system
Authors: Zhang Bo , Lin Jinying , Perčulija Vanja , Li Yu , Lu Qiuhua , Chen Jing , Ouyang Songying
Published: November 2022

Cas12c is the recently characterized dual RNA-guided DNase effector of type V-C CRISPR-Cas (clustered regularly interspaced short palindromic repeats and CRISPR-associated protein) systems. Due to minimal requirements for a protospacer adjacent motif (PAM), Cas12c is an attractive candidate for genome editing. Here we report the crystal structure of Cas12c1 in complex with single guide RNA (sgRNA) and target double-stranded DNA (dsDNA) containing the 5′-TG-3′ PAM. Supported by biochemical and mutation assays, this study reveals distinct structural features of Cas12c1 and the associated sgRNA, as well as the molecular basis for PAM recognition, target dsDNA unwinding, heteroduplex formation and recognition, and cleavage of non-target and target DNA strands. Cas12c1 recognizes the PAM through a mechanism that is interdependent on sequence identity and Cas12c1-induced conformational distortion of the PAM region. Another special feature of Cas12c1 is the cleavage of both non-target and target DNA strands at a single, uniform site with indistinguishable cleavage capacity and order. Location of the sgRNA seed region and minimal length of target DNA required for triggering Cas12c1 DNase activity were also determined. Our findings provide valuable information for developing the CRISPR-Cas12c1 system into an efficient, high-fidelity genome editing tool.
A forward genetic screen in C. elegans identifies conserved residues of spliceosomal proteins PRP8 and SNRNP200/BRR2 with a role in maintaining 5′ splice site identity
Authors: Cartwright-Acar Catiana H , Osterhoudt Kenneth , Suzuki Jessie M N G L , Gomez Destiny R , Katzman Sol , Zahler Alan M
Published: November 2022

The spliceosome undergoes extensive rearrangements as it assembles onto precursor messenger RNAs. In the earliest assembly step, U1snRNA identifies the 5′ splice site. However, U1snRNA leaves the spliceosome relatively early in assembly, and 5′ splice site identity is subsequently maintained through interactions with U6snRNA, protein factor PRP8, and other components during the rearrangements that build the catalytic site. Using a forward genetic screen in Caenorhabditis elegans, we have identified suppressors of a locomotion defect caused by a 5′ss mutation. Here we report three new suppressor alleles from this screen, two in PRP8 and one in SNRNP200/BRR2. mRNASeq studies of these suppressor strains indicate that they also affect specific native alternative 5′ss, especially for suppressor PRP8 D1549N. A strong suppressor at the unstructured N-terminus of SNRNP200, N18K, indicates a novel role for this region. By examining distinct changes in the splicing of native genes, examining double mutants between suppressors, comparing these new suppressors to previously identified splicing suppressors from yeast, and mapping conserved suppressor residues onto cryoEM structural models of assembling human spliceosomes, we conclude that there are multiple interactions at multiple stages in spliceosome assembly responsible for maintaining the initial 5′ss identified by U1snRNA for entry into the catalytic core.
PGG.MHC: toward understanding the diversity of major histocompatibility complexes in human populations
Authors: Zhao Xiaohan , Ma Sen , Wang Baonan , Jiang Xuetong ,   The Han100K Initiative, Xu Shuhua
Published: November 2022

The human leukocyte antigen (HLA) system, or the human version of the major histocompatibility complex (MHC), is known for its extreme polymorphic nature and high heterogeneity. Taking advantage of whole-genome and whole-exome sequencing data, we developed PGG.MHC to provide a platform to explore the diversity of the MHC in Asia as well as in global populations. PGG.MHC currently archives high-resolution HLA alleles of 53 254 samples representing 190 populations spanning 66 countries. PGG.MHC provides: (i) high-quality allele frequencies for eight classical HLA loci (HLA-A, -B, -C, -DQA1, -DQB1, -DRB1, -DPA1 and -DPB1); (ii) visualization of population prevalence of HLA alleles on global, regional, and country-wide levels; (iii) haplotype structure of 134 populations; (iv) two online analysis tools including ‘HLA imputation’ for inferring HLA alleles from SNP genotyping data and ‘HLA association’ to perform case/control studies for HLA-related phenotypes and (v) East Asian–specific reference panels for HLA imputation. Equipped with high-quality frequency data and user-friendly computer tools, we expect that the PGG.MHC database can advance the understanding and facilitate applications of MHC genomic diversity in both evolutionary and medical studies. The PGG.MHC database is freely accessible via https://pog.fudan.edu.cn/pggmhc or https://www.pggmhc.org/pggmhc.
Associations Between Race/Ethnicity, Language, and Enrollment on Cancer Research Studies
Authors: Ezeoke Ogochukwu M , Brooks Gary , Postow Michael A , Baxi Shrujal , Young Kim Soo , Narang Bharat , Diamond Lisa C
Published: November 2022

Purpose

The objective of this study was to determine whether differences in patients’ race/ethnicity, preferred language, and other factors were associated with patient enrollment in oncology research studies.

Patients and Methods

We conducted a retrospective cross-sectional analysis of all adults (>18 and ≤90) seen at a large, metropolitan cancer center from 2005 to 2015, examining if enrollment to a research study, varied by race/ethnicity, preferred language, comorbidities, gender, and age.

Results

A total of 233 604 patients were available for initial analysis. Of these, 93 278 (39.9%) were enrolled in a research protocol (therapeutic and non-therapeutic studies). Patients who self-reported their race/ethnicity as Native, Other, Unknown, or Refuse to Answer were less likely to be enrolled on a study. Patients with one or more comorbidities, and those whose preferred language was English, were more likely to be enrolled on a research study. A logistic regression model showed that, although Non-Hispanic Black patients were more likely to have one or more comorbidities and had a higher proportion of their subset selecting English as their preferred language, they were less likely to be enrolled on a study, than our largest population, Non-Hispanic/White patients.

Conclusions

We identified differences in research study enrollment based on preferred language, and within race/ethnicity categories including Native-Populations, Other, Unknown or Refuse to Answer compared to Non-Hispanic/White patients. We also highlighted the lower odds of enrollment among Non-Hispanic/Black patients, in the setting of factors such as comorbidities and English language preference, which were otherwise found to be positive predictors of enrollment. Further investigation is needed to design targeted interventions to reduce disparities in oncology research study enrollment, with particular focus on language diversity.
Is There a Right to Internet Access?
Authors: Cruft Rowan
Published: November 2022

This chapter asks whether the ideas of ‘rights’ and ‘human rights’ are useful concepts for getting to grips with moral questions about internet access. The values served by internet access—democratic participation, freedom of speech, privacy, the welfare state—are often understood in terms of rights, but they are also often taken more communally, as morally grounded fundamentally by their role in constituting an open society that serves us all collectively. Rights approaches highlight the individual right-holder as a party who is ‘wronged’ when a duty is violated. This chapter defends a rights-based approach to moral questions about internet access, and explores the practical implications of this approach for policy and law.
Timing and Petrogenesis of the Permo-Carboniferous Larvik Plutonic Complex, Oslo Rift, Norway: New Insights from U–Pb, Lu-Hf, and O Isotopes in Zircon
Authors: Rämö O Tapani , Andersen Tom , Whitehouse Martin J
Published: November 2022

The Permo-Carboniferous Oslo Rift is a narrow, aborted continental rift with comparatively little extension but voluminous magmatism, developed at a Proterozoic lithospheric discontinuity. On the southern flank of the onshore part of the rift, the multiple intrusive phase Larvik plutonic complex (LPC) encompasses almost the width of the rift with a conspicuous over- to undersaturated assemblage of monzonite (larvikite, tønsbergite) and nepheline syenite (lardalite, foyaite). We present new single-crystal U–Pb–, Lu–Hf–, and O–in–zircon isotope data for the intrusive centers of the complex. U–Pb ages of slightly over- to undersaturated monzonites show a shift in igneous activity from 299 Ma on the eastern edge of the complex to 289 Ma in the west. The western part of the complex is built of two consanguineous magmatic systems with a northward shift in the locus of magmatism, from 296 to 289 Ma (undersaturated monzonite) and 296 to ~288 Ma (nepheline syenite). Moreover, an early oversaturated monzonite was emplaced in the eastern part of the complex at ~302 Ma. The Hf and O isotope composition of the monzonites and nepheline syenites shows little variation with zircon εHf (295 Ma) values of +5.5 to +8 and δ18Ο values of +4.79‰ to +5.49‰. No change in isotope values is observed with varying alkalinity and the Hf and O isotope compositions are interpreted as mantle source values. The source of the precursors of the monzonitic and nepheline syenitic magmas was probably a mildly depleted, sublithospheric peridotite in the lithosphere-asthenosphere boundary zone (at 3–4 GPa). Rhyolite–MELTS modeling implies polybaric fractionation of weakly alkaline basaltic melts from the source having led to an oversaturated/saturated liquid line of descent at ~0.5 GPa and an undersaturated one at ~1 GPa. Magmatism had an imperative role in the evolution of the rift by localizing strain and weakening the lithosphere along the discontinuity. A fractionating crustal melt column was tapped at varying depths in the course of advancing rupturing with no significant mixing of the over- and undersaturated melts, and magma batches were emplaced as sequential nested plutons in response to differential opening of the rift. Among continental saturated-undersaturated alkaline complexes, the LPC may be unique in the emplacement of successive magma batches across a continental rift in the direction of opening, tapping of increasingly deeper parts of the melt column with advancing rifting, and intrusion of two contemporaneous, contrasting magmatic lineages at the end of igneous activity. The marked lithospheric step at the rift locus in the Precambrian basement of southeastern Norway was probably the driving force for the inception and evolution of the Larvik magmatic system.
Testing theoretical frameworks of zooplankton longitudinal distribution in a large reservoir
Authors: Detmer Thomas M , Roberts Hayden , Broadway Kyle , Parkos Joseph , Wahl David
Published: November 2022

Reservoirs are thought to contain three zones (riverine, transition and lacustrine) emerging from environmental gradients from the river to the dam where zooplankton are predicted to peak in the transitional zone. Few high spatial resolution studies, however, have surveyed zooplankton distribution in reservoirs, leading to limited knowledge regarding longitudinal abundance and composition of zooplankton. Using 44 samples from river to dam in a 35.7 km long reservoir, we explore spatial variability in zooplankton density, biomass, composition and relative bottom-up to top-down control. Broadly, density and biomass increased from the river to the dam. Variation occurred in the location and frequency of peaks among groups. Divergence between per unit volume and area within groups highlighted the importance of depth. Richness and turnover between sites were both greatest near the river. The ratio of zooplankton to phytoplankton biomass varied longitudinally, with a low near 20% of the distance from the river to the dam indicating spatial variability in bottom-up versus top-down control. This study highlights the complexity of longitudinal zooplankton composition and distribution in reservoirs and provides insight into reservoir ecosystem complexity and function, with important consequences for water quality, fish distribution, and productivity.
Preventive Effect of an Intervention Program with Increased Physical Activity on the Development of Musculoskeletal Pain in Community-Dwelling Older Adults: A Randomized Controlled Trial
Authors: Hirase Tatsuya , Inokuchi Shigeru , Koshikawa Shota , Shimada Hinata , Okita Minoru
Published: November 2022

Objective

To examine whether compared with a program without increased physical activity, an intervention program with increased physical activity can prevent the development of musculoskeletal pain in community-dwelling older adults.

Design

Randomized controlled trial.

Setting

Japanese community.

Subjects

Seventy-nine older adults without musculoskeletal pain were randomized into two groups: an intervention group (n = 40) that engaged in increased physical activity and an exercise class and a control group (n = 39) that participated only in the exercise class.

Methods

The exercise class consisted of weekly 60-min sessions over 24 weeks. The program to increase physical activity required the participants to record their daily step counts using pedometers. The primary outcome was the development of musculoskeletal pain, and secondary outcomes were physical function, psychological status, cognitive function, and physical activity levels.

Results

Twenty-four weeks after the intervention, the intervention group had a significantly lower prevalence of musculoskeletal pain (12.8%) than the control group (32.4%; P = .040). A time-by-group interaction emerged for cognitive function (P = .01) and physical activity levels (P < .001), both of which favored the intervention group. The intervention group also showed greater improvement in psychological status 24 weeks after the intervention than the control group (P = .018).

Conclusions

The intervention program with increased physical activity prevented the development of musculoskeletal pain and improved cognitive function, physical activity levels, and psychological status more effectively than the program without increased physical activity. Our intervention program may be an effective pain prevention approach for older adults.

Trial registration

UMIN000032768; registered on June 1, 2018.
Antibody-mediated delivery of CRISPR-Cas9 ribonucleoproteins in human cells
Authors: Ubiparipovic Stephanie , Christ Daniel , Rouet Romain
Published: November 2022

The CRISPR genome editing technology holds great clinical potential for the treatment of monogenetic disorders such as sickle cell disease. The therapeutic in vivo application of the technology relies on targeted delivery methods of the Cas9 and gRNA complex to specific cells or tissues. However, such methods are currently limited to direct organ delivery, preventing clinical application. Here, we show that monoclonal antibodies can be employed to deliver the Cas9/gRNA complex directly into human cells via cell-surface receptors. Using the SpyCatcher/SpyTag system, we conjugated the Fab fragment of the therapeutic antibodies Trastuzumab and Pertuzumab directly to the Cas9 enzyme and observed HER2-specific uptake of the ribonucleoprotein in a human HER2 expressing cell line. Following cellular uptake in the presence of an endosomolytic peptide, modest gene editing was also observed. This finding provides a blueprint for the targeted delivery of the CRISPR technology into specific cells using monoclonal antibodies.
The association of new-onset diabetes with subsequent diagnosis of pancreatic cancer—novel use of a large administrative database
Authors: White M J , Sheka A C , LaRocca C J , Irey R L , Ma S , Wirth K M , Benner A , Denbo J W , Jensen E H , Ankeny J S , Ikramuddin S , Tuttle T M , Hui J Y C , Marmor S
Published: November 2022

Background

Screening options for pancreatic ductal adenocarcinoma (PDAC) are limited. New-onset type 2 diabetes (NoD) is associated with subsequent diagnosis of PDAC in observational studies and may afford an opportunity for PDAC screening. We evaluated this association using a large administrative database.

Methods

Patients were identified using claims data from the OptumLabs® Data Warehouse. Adult patients with NoD diagnosis were matched 1:3 with patients without NoD using age, sex and chronic obstructive pulmonary disease (COPD) status. The event of PDAC diagnosis was compared between cohorts using the Kaplan–Meier method. Factors associated with PDAC diagnosis were evaluated with Cox’s proportional hazards modeling.

Results

We identified 640 421 patients with NoD and included 1 921 263 controls. At 3 years, significantly more PDAC events were identified in the NoD group vs control group (579 vs 505; P < 0.001). When controlling for patient factors, NoD was significantly associated with elevated risk of PDAC (HR 3.474, 95% CI 3.082–3.920, P < 0.001). Other factors significantly associated with PDAC diagnosis were increasing age, increasing age among Black patients, and COPD diagnosis (P ≤ 0.05).

Conclusions

NoD was independently associated with subsequent diagnosis of PDAC within 3 years. Future studies should evaluate the feasibility and benefit of PDAC screening in patients with NoD.
B-cell receptor profiling before and after IVIG monotherapy in newly diagnosed idiopathic inflammatory myopathies
Authors: Anang Dornatien C , Walter Hannah A W , Lim Johan , Niewold Ilse , van der Weele Linda , Aronica Eleonora , Eftimov Filip , Raaphorst Joost , van Schaik Barbera D C , van Kampen Antoine H C , van der Kooi Anneke J , de Vries Niek
Published: November 2022

Objective

To unravel B-cell receptor (BcR) characteristics in muscle tissues and peripheral blood and gain more insight into BcR repertoire changes in peripheral blood in idiopathic inflammatory myopathies (IIMs), and study how this correlates to the clinical response to IVIG.

Methods

Nineteen treatment-naive patients with newly diagnosed IIM were prospectively treated with IVIG monotherapy. RNA-based BcR repertoire sequencing was performed in muscle biopsies collected before, and in peripheral blood (PB) collected before and nine weeks after IVIG treatment. Results were correlated to patients’ clinical improvement based on the total improvement score (TIS).

Results

Prior to IVIG treatment, BcR clones found in muscle tissue could be retrieved in peripheral blood. Nine weeks after IVIG treatment, new patient-specific dominant BcR clones appeared in peripheral blood while pre-treatment dominant BcR clones disappeared. The cumulative frequency of all dominant BcR clones before treatment was significantly higher in individuals who responded to IVIG compared with those who did not respond to IVIG, and correlated with a higher CK. During follow-up, a decrease in the cumulative frequency of all dominant clones correlated with a higher TIS.

Conclusion

In treatment-naive patients with newly diagnosed IIM, muscle tissue and peripheral blood share expanded BcR clones. In our study a higher cumulative frequency of dominant BcR clones in blood before treatment was associated with a higher CK and better treatment response, suggesting that response to IVIG may depend on the composition of the pre-treatment BcR repertoire.
Relevance of leukaemia inhibitory factor to anti-melanoma differentiation-associated gene 5 antibody-positive interstitial lung disease
Authors: Ichimura Yuki , Ikei Hiroyuki , Konishi Risa , Zeniya Moko , Okai Takahiro , Nomura Toshifumi , Negishi Kousuke , Okiyama Naoko
Published: November 2022

Objectives

Anti-melanoma differentiation-associated gene 5 (MDA5) antibody-positive rapidly progressive interstitial lung disease (RP-ILD) is a life-threatening disease, the aetiology of which remains unclear. To detect potential diagnostic markers, a transcriptome analysis of the lung sample from a patient with anti-MDA5 antibody-positive RP-ILD was performed.

Methods

RNA sequencing analyses of an autopsy lung sample from a 74-year-old woman with anti-MDA5 antibody-positive RP-ILD was performed and compared with an age- and sex-matched normal lung sample. Genes with changes of gene expression ≥5-fold were considered differentially expressed genes and analysed by Metascape. The levels of leukaemia inhibitory factor (LIF) were measured in the serum samples from 12 cases of anti-MDA5 antibody-positive ILD, 12 cases of anti-aminoacyl tRNA synthetase (ARS) antibody-positive ILD, 10 cases of anti-transcription intermediary factor 1γ/anti-Mi-2 antibody DM and 12 healthy volunteers.

Results

Gene ontology enrichment analysis on the RNA sequencing data showed a strong association with antigen binding. Upregulated expressions of IL-1β, IL-6 and LIF were also detected. Serum LIF levels were significantly elevated in anti-MDA5 antibody-positive ILD patients {median 32.4 pg/ml [interquartile range (IQR) 13.2–125.7]} when compared with anti-ARS antibody-positive ILD patients [4.9 pg/ml (IQR 3.1–19.7), P < 0.05] and DM patients [5.3 pg/ml (IQR 3.9–9.7), P < 0.05].

Conclusion

Our present study suggested that upregulation of LIF might be a new potential disease marker specific for anti-MDA5 antibody-positive ILD.
EXAMINATION OF LENS EXPOSURE DOSES OF CARDIOLOGISTS, NEUROSURGEONS AND RADIOLOGISTS IN INTERVENTIONAL RADIOLOGY
Authors: Osawa Mitsuharu , Tawada Yuka , Kaneda Naoki , Fujita Naotoshi , Koyama Shuji
Published: November 2022

The International Commission on Radiological Protection (ICRP) 118th recommendation significantly reduced the threshold dose for cataract development from 8 to 0.5 Gy. Equivalent dose limits for the crystalline lenses of radiation workers are being reviewed for individual countries. Interventional radiology (IR) procedures are less invasive than surgery and have become widespread; however, there are concerns about exposure not only to patients but also to staff, including operators. Therefore, in this study, we used a human phantom to measure the near-lens dose of the operators (cardiologists, neurosurgeons and radiologists) and estimated the operator’s lens dose for every major procedure in each clinical department; this was found to vary. Owing to the different imaging and fluoroscopy conditions of each department, and the varying ratio of fluoroscopy to radiography, it is necessary to measure the lens dose for each condition, as in this study. In addition, this study explains the differences between the protective effect of various safety equipment and the appropriate use of protective plates; it can contribute to the reduction of lens doses for operators.
ESTIMATION OF PROTECTION FACTORS FOR SURROGATE VEHICLE MODELS IN ENVIRONMENTAL CONTAMINATION SCENARIOS
Authors: Dalak Sena , Asano Ethan , Dewji Shaheen
Published: November 2022

In the event of a nuclear or radiological incident involving the release of radioactive material, it may be critical to estimate doses to individuals who are transported through contaminated areas by vehicles. The radiation protection factor (RPF) for vehicles can be calculated to determine the level of shielding protection by the vehicle from external radiation sources. Prior studies evaluating RPFs demonstrate a lack of realistic vehicle configurations and the results cannot be extended directly to scenarios where a vehicle is surrounded by a contaminated environmental field. In this work, sex-averaged effective dose-rate coefficients were computed employing International Commission on Radiological Protection Publication 103 recommendations for radionuclides of interest and used to calculate the RPF as the ratio of unshielded to shielded dose for various radionuclides of interest in consequence management scenarios. Comparisons to dose reduction factors calculated using environmental measurement data from the 2011 Fukushima Daiichi nuclear incident were conducted to benchmark to experimental field measurements.