bluuebunny/crossref_metadata_2025 huggingface dataset:
Segmental aneuploid hotspots identified across the genome concordant on reanalysis
Authors: McCarty Keelee J , Haywood Mary E , Lee Rachel , Henry Lauren , Arnold Alison , McReynolds Susanna , McCallie Blair , Schoolcraft Bill , Katz-Jaffe Mandy
Published: December 2022

The aim of this study was to characterize a large set of full segmental aneuploidies identified in trophectoderm (TE) biopsies and evaluate concordance in human blastocysts. Full segmental aneuploid errors were identified in TE biopsies (n = 2766) from preimplantation genetic testing for aneuploid (PGT-A) cycles. Full segmental deletions (n = 1872; 66.1%) presented twice as many times as duplications (n = 939; 33.9%), mapped more often to the q-arm (n = 1696; 61.3%) than the p-arm (n = 847; 31.0%) or both arms (n = 223; 8.1%; P < 0.05), and were eight times more likely to include the distal end of a chromosome than not (P < 0.05). Additionally, 37 recurring coordinates (each ≥ 10 events) were discovered across 17 different chromosomes, which were also significantly enriched for distal regions (P = 4.1 × 10−56). Blinded concordance analysis of 162 dissected blastocysts validated the original TE PGT-A full segmental result for a concordance of 96.3% (n = 156); remaining dissected blastocysts were identified as mosaic (n = 6; 3.7%). Origin of aneuploid analysis revealed full segmental aneuploid errors were mostly paternally derived (67%) in contrast to whole chromosome aneuploid errors (5.8% paternally derived). Errors from both parental gametes were observed in 6.5% of aneuploid embryos when multiple whole chromosomes were affected. The average number of recombination events was significantly less in paternally derived (1.81) compared to maternally derived (3.81) segmental aneuploidies (P < 0.0001). In summary, full segmental aneuploidies were identified at hotspots across the genome and were highly concordant upon blinded analysis. Nevertheless, future studies assessing the reproductive potential of full (non-mosaic) segmental aneuploid embryos are critical to rule out potential harmful reproductive risks.
Deciphering RNA G-quadruplex function during the early steps of HIV-1 infection
Authors: Amrane Samir , Jaubert Chloé , Bedrat Amina , Rundstadler Tiffany , Recordon-Pinson Patricia , Aknin Cindy , Guédin Aurore , De Rache Aurore , Bartolucci Laura , Diene Ibra , Lemoine Frédéric , Gascuel Olivier , Pratviel Geneviève , Mergny Jean-Louis , Andreola Marie-Line
Published: December 2022

G-quadruplexes (G4s) are four-stranded nucleic acid structures formed by the stacking of G-tetrads. Here we investigated their formation and function during HIV-1 infection. Using bioinformatics and biophysics analyses we first searched for evolutionary conserved G4-forming sequences in HIV-1 genome. We identified 10 G4s with conservation rates higher than those of HIV-1 regulatory sequences such as RRE and TAR. We then used porphyrin-based G4-binders to probe the formation of the G4s during infection of human cells by native HIV-1. The G4-binders efficiently inhibited HIV-1 infectivity, which is attributed to the formation of G4 structures during HIV-1 replication. Using a qRT-PCR approach, we showed that the formation of viral G4s occurs during the first 2 h post-infection and their stabilization by the G4-binders prevents initiation of reverse transcription. We also used a G4-RNA pull-down approach, based on a G4-specific biotinylated probe, to allow the direct detection and identification of viral G4-RNA in infected cells. Most of the detected G4-RNAs contain crucial regulatory elements such as the PPT and cPPT sequences as well as the U3 region. Hence, these G4s would function in the early stages of infection when the viral RNA genome is being processed for the reverse transcription step.
Spontaneous binding of single-stranded RNAs to RRM proteins visualized by unbiased atomistic simulations with a rescaled RNA force field
Authors: Krepl Miroslav , Pokorná Pavlína , Mlýnský Vojtěch , Stadlbauer Petr , Šponer Jiří
Published: December 2022

Recognition of single-stranded RNA (ssRNA) by RNA recognition motif (RRM) domains is an important class of protein–RNA interactions. Many such complexes were characterized using nuclear magnetic resonance (NMR) and/or X-ray crystallography techniques, revealing ensemble-averaged pictures of the bound states. However, it is becoming widely accepted that better understanding of protein–RNA interactions would be obtained from ensemble descriptions. Indeed, earlier molecular dynamics simulations of bound states indicated visible dynamics at the RNA–RRM interfaces. Here, we report the first atomistic simulation study of spontaneous binding of short RNA sequences to RRM domains of HuR and SRSF1 proteins. Using a millisecond-scale aggregate ensemble of unbiased simulations, we were able to observe a few dozen binding events. HuR RRM3 utilizes a pre-binding state to navigate the RNA sequence to its partially disordered bound state and then to dynamically scan its different binding registers. SRSF1 RRM2 binding is more straightforward but still multiple-pathway. The present study necessitated development of a goal-specific force field modification, scaling down the intramolecular van der Waals interactions of the RNA which also improves description of the RNA–RRM bound state. Our study opens up a new avenue for large-scale atomistic investigations of binding landscapes of protein–RNA complexes, and future perspectives of such research are discussed.
DDX17 helicase promotes resolution of R-loop-mediated transcription–replication conflicts in human cells
Authors: Boleslavska Barbora , Oravetzova Anna , Shukla Kaustubh , Nascakova Zuzana , Ibini Oluwakemi Ngozi , Hasanova Zdenka , Andrs Martin , Kanagaraj Radhakrishnan , Dobrovolna Jana , Janscak Pavel
Published: December 2022

R-loops are three-stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced DNA strand. These structures can halt DNA replication when formed co-transcriptionally in the opposite orientation to replication fork progression. A recent study has shown that replication forks stalled by co-transcriptional R-loops can be restarted by a mechanism involving fork cleavage by MUS81 endonuclease, followed by ELL-dependent reactivation of transcription, and fork religation by the DNA ligase IV (LIG4)/XRCC4 complex. However, how R-loops are eliminated to allow the sequential restart of transcription and replication in this pathway remains elusive. Here, we identified the human DDX17 helicase as a factor that associates with R-loops and counteracts R-loop-mediated replication stress to preserve genome stability. We show that DDX17 unwinds R-loops in vitro and promotes MUS81-dependent restart of R-loop-stalled forks in human cells in a manner dependent on its helicase activity. Loss of DDX17 helicase induces accumulation of R-loops and the formation of R-loop-dependent anaphase bridges and micronuclei. These findings establish DDX17 as a component of the MUS81–LIG4–ELL pathway for resolution of R-loop-mediated transcription–replication conflicts, which may be involved in R-loop unwinding.
The RNA-binding protein RBP33 dampens non-productive transcription in trypanosomes
Authors: Gómez-Liñán Claudia , Gómez-Díaz Elena , Ceballos-Pérez Gloria , Fernández-Moya Sandra M , Estévez Antonio M
Published: December 2022

In-depth analysis of the transcriptomes of several model organisms has revealed that genomes are pervasively transcribed, giving rise to an abundance of non-canonical and mainly antisense RNA polymerase II-derived transcripts that are produced from almost any genomic context. Pervasive RNAs are degraded by surveillance mechanisms, but the repertoire of proteins that control the fate of these non-productive transcripts is still incomplete. Trypanosomes are single-celled eukaryotes that show constitutive RNA polymerase II transcription and in which initiation and termination of transcription occur at a limited number of sites per chromosome. It is not known whether pervasive transcription exists in organisms with unregulated RNA polymerase II activity, and which factors could be involved in the process. We show here that depletion of RBP33 results in overexpression of ∼40% of all annotated genes in the genome, with a marked accumulation of sense and antisense transcripts derived from silenced regions. RBP33 loss does not result in a significant increase in chromatin accessibility. Finally, we have found that transcripts that increase in abundance upon RBP33 knockdown are significantly more stable in RBP33-depleted trypanosomes, and that the exosome complex is responsible for their degradation. Our results provide strong evidence that RBP33 dampens non-productive transcription in trypanosomes.
PBSIM3: a simulator for all types of PacBio and ONT long reads
Authors: Ono Yukiteru , Hamada Michiaki , Asai Kiyoshi
Published: December 2022

Long-read sequencers, such as Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) sequencers, have improved their read length and accuracy, thereby opening up unprecedented research. Many tools and algorithms have been developed to analyze long reads, and rapid progress in PacBio and ONT has further accelerated their development. Together with the development of high-throughput sequencing technologies and their analysis tools, many read simulators have been developed and effectively utilized. PBSIM is one of the popular long-read simulators. In this study, we developed PBSIM3 with three new functions: error models for long reads, multi-pass sequencing for high-fidelity read simulation and transcriptome sequencing simulation. Therefore, PBSIM3 is now able to meet a wide range of long-read simulation requirements.
Molecular mimicry among human proteinase 3 and bacterial antigens: implications for development of c-ANCA associated vasculitis
Authors: Chavez Y , Garces J , Díaz R , Escobar M , Sanchez A , Buendía E , Múnera M
Published: December 2022

Wegener’s granulomatosis is an autoimmune disease where autoantibodies target human autoantigen PR3, a serine protease locates on the neutrophil membrane. This disease affects blood small vessels and could be deadly. The origin of these autoantibodies is unknown, but infections have been implicated with autoimmune disease. In this study, we explored potential molecular mimicry between human PR3 and homologous pathogens through in silico analysis. Thirteen serine proteases from human pathogens (Klebsiella pneumoniae, Acinetobacter baumannii, Salmonella sp., Streptococcus suis, Vibrio parahaemolyticus, Bacteroides fragilis, Enterobacter ludwigii, Vibrio alginolyticus, Staphylococcus haemolyticus, Enterobacter cloacae, Escherichia coli and Pseudomonas aeruginosa) shared structural homology and amino acid sequence identity with human PR3. Epitope prediction found an only conserved epitope IVGG, located between residues 59–74. However, multiple alignments showed conserved regions that could be involved in cross-reactivity between human and pathogens serine proteases (90–98, 101–108, 162–169, 267 and 262 residues positions). In conclusion, this is the first report providing in silico evidence about the existence of molecular mimicry between human and pathogens serine proteases, that could explain the origins of autoantibodies found in patients suffering from Wegener’s granulomatosis.
XMM-Newton view of the shock heating in an early merging cluster, CIZA J1358.9−4750
Authors: Omiya Yuki , Nakazawa Kazuhiro , Matsushita Kyoko , Kobayashi Shogo B , Okabe Nobuhiro , Sato Kosuke , Tamura Takayuki , Fujita Yutaka , Gu Liyi , Kitayama Tetsu , Akahori Takuya , Kurahara Kohei , Yamaguchi Tomohiro
Published: December 2022

CIZA J1358.9−4750 is a nearby galaxy cluster in the early phase of a major merger. The two-dimensional temperature map using XMM-Newton EPIC-PN observation confirms the existence of a high-temperature region, which we call the “hot region,” in the “bridge region” connecting the two clusters. The ∼500 kpc wide region between the south-east and north-west boundaries also has higher pseudo-pressure compared to the unshocked regions, suggesting the existence of two shocks. The southern shock front is clearly visible in the X-ray surface brightness image and has already been reported by Kato et al. (2015, PASJ, 67, 71). The northern one, on the other hand, is newly discovered. To evaluate their Mach number, we constructed a three-dimensional toy merger model with overlapping shocked and unshocked components in the line of sight. The unshocked and pre-shock intracluster medium (ICM) conditions are estimated based on those outside the interacting bridge region, assuming point symmetry. The hot-region spectra are modeled with two-temperature thermal components, assuming that the shocked condition follows the Rankin–Hugoniot relation with the pre-shock condition. As a result, the shocked region is estimated to have a line-of-sight depth of ∼1 Mpc with a Mach number of ∼1.3 in the south-east shock and ∼1.7 in the north-west shock. The age of the shock waves is estimated to be ∼260 Myr. This three-dimensional merger model is consistent with the Sunyaev–Zel’dovich signal obtained using the Planck observation within the cosmic microwave background fluctuations. The total flow of the kinetic energy of the ICM through the south-east shock was estimated to be ∼2.2 × 1042 erg s−1. Assuming that $10\%$ of this energy is converted into ICM turbulence, the line–of–sight velocity dispersion is calculated to be ∼200 km s−1, which is basically resolvable via upcoming high spectral resolution observations.
Assessing good environmental status through mesozooplankton biodiversity: a step forward
Authors: Theodorou I , Zervoudaki S , Varkitzi I , Tsirtsis G
Published: December 2022

We developed a zooplankton-based water-quality evaluating method using indices of alpha diversity. Two key objectives were set: (i) the comparison of two—different quality—samples from different areas, and the verification of their differentiation, based on mesozooplankton biodiversity indices; and (ii) the development of a methodology, which was able to assess the quality of new marine water samples. Our analysis was based on a 24-year-long in situ dataset (1987–2010) of 139 samples in which 86 mesozooplankton taxa were identified. High-diversity and high evenness values were reported in the case of the “good” status sample, while low diversity, low evenness and high dominance values occurred at the lower quality one. A linear discriminant analysis (LDA) was conducted that discriminated the tested samples at 100%. This LDA was then used to evaluate samples of unknown quality. Finally, 90% of them were classified with a probability of correct classification (posterior probability) >95%. The present study proves that mesozooplankton diversity indices can discriminate different levels of anthropogenic impacts. In this sense, it can be used as a reliable indicator for environmental assessment in the pelagic habitats of the Mediterranean Sea.
The PRK/Rubisco shunt strongly influences Arabidopsis seed metabolism and oil accumulation, affecting more than carbon recycling
Authors: Deslandes-Hérold Gabriel , Zanella Martina , Solhaug Erik , Fischer-Stettler Michaela , Sharma Mayank , Buergy Léo , Herrfurth Cornelia , Colinas Maite , Feussner Ivo , Abt Melanie R , Zeeman Samuel C
Published: December 2022

The carbon efficiency of storage lipid biosynthesis from imported sucrose in green Brassicaceae seeds is proposed to be enhanced by the PRK/Rubisco shunt, in which ribulose 1,5-bisphosphate carboxylase/oxygenase (Rubisco) acts outside the context of the Calvin–Benson–Bassham cycle to recycle CO2 molecules released during fatty acid synthesis. This pathway utilizes metabolites generated by the nonoxidative steps of the pentose phosphate pathway. Photosynthesis provides energy for reactions such as the phosphorylation of ribulose 5-phosphate by phosphoribulokinase (PRK). Here, we show that loss of PRK in Arabidopsis thaliana (Arabidopsis) blocks photoautotrophic growth and is seedling-lethal. However, seeds containing prk embryos develop normally, allowing us to use genetics to assess the importance of the PRK/Rubisco shunt. Compared with nonmutant siblings, prk embryos produce one-third less lipids—a greater reduction than expected from simply blocking the proposed PRK/Rubisco shunt. However, developing prk seeds are also chlorotic and have elevated starch contents compared with their siblings, indicative of secondary effects. Overexpressing PRK did not increase embryo lipid content, but metabolite profiling suggested that Rubisco activity becomes limiting. Overall, our findings show that the PRK/Rubisco shunt is tightly integrated into the carbon metabolism of green Arabidopsis seeds, and that its manipulation affects seed glycolysis, starch metabolism, and photosynthesis.
Examining the safety of relaxed drug monitoring for methotrexate in response to the COVID-19 pandemic
Authors: Shadeed Abdulrahman , Kattach Leila , Sam Sharlene , Flora Kalveer , Farah Ziad
Published: December 2022

Objectives

This is a retrospective study that set out to assess the safety, feasibility and cost savings of temporary relaxed blood test monitoring for patients on MTX under the rheumatology service that was rolled out during the coronavirus pandemic.

Methods

This is a single-centre study that reviewed the blood tests of all patients who received an MTX prescription from the trust between December 2019 and November 2020. After the application of inclusion and exclusion criteria, the blood testing intervals and findings were analysed and collated. The cost of the blood tests was obtained from the laboratory.

Results

A total of 1194 patients were identified as having received an MTX prescription. After applying inclusion and exclusion criteria, 462 patients were included. Of these, 395 (85%) patients had a blood test within the standard 3-month schedule and 67 had blood tests within the relaxed blood monitoring schedule. Six patients had an abnormality identified on their blood tests, but no harm was caused by any of these abnormalities. The intervention resulted in a cost savings of at least £1187 from the blood test costs alone.

Conclusion

MTX is a widely used steroid-sparing agent that requires regular blood test monitoring to reduce adverse outcomes for patients. During extraordinary circumstances such as a pandemic, relaxing the interval between monitoring blood tests in stable patients is a feasible intervention. A relaxed monitoring blood test interval for a set period is safe, achievable and cost effective.
Labor Force Demographics and Corporate Innovation
Authors: Derrien François , Kecskés Ambrus , Nguyen Phuong-Anh
Published: December 2022

Firms in younger labor markets produce more innovation. We establish this by instrumenting the current labor force with historical births in each local labor market in the United States. Analyses of firms and inventors allow us to rule out unobservable heterogeneity across local labor markets and firms, life cycles, and other effects. Corporate innovation in younger labor markets reflects the innovative characteristics of younger labor forces, and its market value is higher. Younger workers as a group, not merely inventors by themselves, produce more innovation for firms through the labor force channel rather than through a financing or consumption channel.

Authors have furnished an Internet Appendix, which is available on the Oxford University Press Web site next to the link to the final published paper online.
Crystalline silica exposure in patients with rheumatoid arthritis and systemic sclerosis: a nationwide cross-sectional survey
Authors: Cavalin Catherine , Lescoat Alain , Sigaux Johanna , Macchi Odile , Ballerie Alice , Catinon Mickaël , Vincent Michel , Semerano Luca , Boissier Marie-Christophe , Rosental Paul-André
Published: December 2022

Objectives

Develop and validate a thorough exposure questionnaire to comprehensively explore crystalline silica (SiO2) exposure in the general population (gender-specific, occupational and non-occupational) and in patients with autoimmune diseases (rheumatoid arthritis (RA), systemic sclerosis (SSc)).

Methods

Lifetime exposures to SiO2 in occupational and non-occupational settings were assessed using a thorough exposure questionnaire. The questionnaire was applied to a general population panel (n = 2911) sampled from the French rolling census, and to unselected patients with SSc (n = 100) and RA (n = 97). Global (GES), occupational (OES) and non-occupational (NOES) exposure scores were assessed in SSc and RA patients, and compared with up to four controls from the general population, matched by age group, sex and tobacco consumption.

Results

Patients had higher GES than their matched controls (SSc: P = 0.001; RA: P < 0.0001) due to higher OES (P < 0.0001 for SSc and RA). Men had higher GES than women (SSc: P < 0.0001; RA: P = 0.002) due to higher OES (P < 0.0001 for SSc and RA). The NOES did not differ between men and women. In SSc patients: Men had higher GES than controls (P < 0.0001). Men and women with SSc had higher OES than controls (P < 0.0001). In RA patients: GES and OES were higher in both men (P = 0.00521; P < 0.0001) and women (P < 0.0001; P < 0.0001) than in their respective controls. Women had higher NOES than controls (P = 0.045).

Conclusion

The lifetime SiO2 exposure gap between RA and SSc patients and controls was substantially due to occupational exposure. In both diseases, men had higher exposure scores than women.
Combined use of monensin and virginiamycin to improve rumen and liver health and performance of feedlot-finished steers
Authors: Ceconi Irene , Viano Sergio A , Méndez Daniel G , González Lucas , Davies Patricio , Elizalde Juan C , Bressan Elbio , Grandini Danilo , Nagaraja T G , Tedeschi Luis O
Published: December 2022

Monensin and virginiamycin are included in beef cattle finishing diets as prophylaxis to minimize the incidence of ruminal acidosis and liver abscesses. Due to different and probably complementary modes of action, this study aimed to determine the effects of a combination of monensin and virginiamycin, both included in the diet at recommended doses, on ruminal health, the occurrence of liver abscesses, and growth performance of feedlot-finished cattle. One hundred and forty-four steers (6 animals/pen) were fed 1 of 3 corn-based finishing diets containing 30 mg of monensin (MN), 25 mg of virginiamycin (VM), or 30 and 25 mg of monensin and virginiamycin (MN + VM), respectively, per kilogram of dry matter. Ruminal pH probes were inserted into two animals per pen and set to record pH every 10 min. On d 100, animals were slaughtered, and rumens and livers were recovered, on which occurrence and degree of ruminal damage, prevalence and number of liver abscesses, and liver scores (A−: livers with no more than two small abscesses; A+: livers with at least one large abscess or more than four medium abscesses; A: any other abscessed liver) were determined. Simultaneous inclusion of monensin and virginiamycin resulted in a 4.3% decrease (P < 0.04) in dry matter intake (DMI; 8.8, 9.2, and 9.2 ± 0.19 kg/d for MN + VM, MN, and VM-fed animals, respectively) and similar (P > 0.13) average daily body weight gain (ADG; 1.49 ± 0.021 kg/d) and hot carcass weight (HCW; 269 ± 1.7 kg), compared with feeding diets containing one additive or the other. Therefore, in terms of ADG, a 9.4% improvement (P < 0.01) in feed efficiency was observed in MN + VM-fed animals. Backfat thickness (5.6 ± 0.08 mm) and ribeye area (69.9 ± 0.53 cm2) remained unaffected (P ≥ 0.74), as well as the minimum (4.98 ± 0.047), mean (6.11 ± 0.037), and maximum ruminal pH (7.23 ± 0.033) values and the time (125 ± 22.3 min/d), area (57.67 ± 12.383 pH × h), and episodes (22 ± 3.8 bouts) of pH below 5.6 (P ≥ 0.12). Overall, prevalence (24 ± 3.4%) and the number of liver abscesses (1.6 ± 0.14 abscesses/abscessed liver), liver scores (20 ± 3.1% of A− and 4 ± 1.8% of A livers), and prevalence (67 ± 3.5%) and degree of damage to the ruminal epithelium (2.5 ± 0.22% affected surface) were similar (P ≥ 0.18) across treatments; however, the occurrence of ruminal lesions tended (P ≤ 0.07) to be associated with that of liver abscesses and reduced ADG when feeding monensin alone.
Traffic signal control in mixed traffic environment based on advance decision and reinforcement learning
Authors: Du Yu , ShangGuan Wei , Chai Linguo
Published: December 2022

Reinforcement learning-based traffic signal control systems (RLTSC) can enhance dynamic adaptability, save vehicle travelling time and promote intersection capacity. However, the existing RLTSC methods do not consider the driver's response time requirement, so the systems often face efficiency limitations and implementation difficulties. We propose the advance decision-making reinforcement learning traffic signal control (AD-RLTSC) algorithm to improve traffic efficiency while ensuring safety in mixed traffic environment. First, the relationship between the intersection perception range and the signal control period is established and the trust region state (TRS) is proposed. Then, the scalable state matrix is dynamically adjusted to decide the future signal light status. The decision will be displayed to the human-driven vehicles (HDVs) through the bi-countdown timer mechanism and sent to the nearby connected automated vehicles (CAVs) using the wireless network rather than be executed immediately. HDVs and CAVs optimize the driving speed based on the remaining green (or red) time. Besides, the Double Dueling Deep Q-learning Network algorithm is used for reinforcement learning training; a standardized reward is proposed to enhance the performance of intersection control and prioritized experience replay is adopted to improve sample utilization. The experimental results on vehicle micro-behaviour and traffic macro-efficiency showed that the proposed AD-RLTSC algorithm can simultaneously improve both traffic efficiency and traffic flow stability.
Genome Evolution and Early Introductions of the SARS-CoV-2 Omicron Variant in Mexico
Authors: Castelán-Sánchez Hugo G , Martínez-Castilla León P , Sganzerla-Martínez Gustavo , Torres-Flores Jesús , López-Leal Gamaliel
Published: December 2022

A new variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), named Omicron (Pango lineage designation B.1.1.529), was first reported to the World Health Organization by South African health authorities on 24 November 2021. The Omicron variant possesses numerous mutations associated with increased transmissibility and immune escape properties. In November 2021, Mexican authorities reported Omicron’s presence in the country. In this study, we infer the first introductory events of Omicron and the impact that human mobility has had on the spread of the virus. We also evaluated the adaptive evolutionary processes in Mexican SARS-CoV-2 genomes during the first month of the circulation of Omicron. We inferred 160 introduction events of Omicron in Mexico since its first detection in South Africa; subsequently, after the first introductions there was an evident increase in the prevalence of SARS-CoV-2 during January. This higher prevalence of the novel variant resulted in a peak of reported cases; on average 6 weeks after, a higher mobility trend was reported. During the peak of cases in the country from January to February 2022, the Omicron BA.1.1 sub-lineage dominated, followed by the BA.1 and BA.15 sub-lineages. Additionally, we identified the presence of diversifying natural selection in the genomes of Omicron and found six non-synonymous mutations in the receptor binding domain of the spike protein, all of them related to evasion of the immune response. In contrast, the other proteins in the genome are highly conserved; however, we identified homoplasic mutations in non-structural proteins, indicating a parallel evolution.
Isolation and Characterization of Bacteria Associated with Onion and First Report of Onion Diseases Caused by Five Bacterial Pathogens in Texas, U.S.A.
Authors: Khanal Manzeal , Bhatta Bed Prakash , Malla Subas
Published: December 2022

Bacterial diseases pose a severe challenge to growers and cause significant loss to the billion-dollar onion industry in the United States. Texas is the sixth largest onion producing state, yet the bacterial communities associated with short-day onion crops grown in Texas have not been studied. This study was conducted to identify, characterize, and understand the diversity of bacteria associated with onion production in Texas. In 2020, 190 foliar and 210 bulb samples were collected from onion crops in the Rio Grande Valley and Winter Garden regions of Texas. Sequencing of the 16s rRNA gene was used to identify each bacterial strains to a genus. The pathogenicity to onion of each bacterial strain was tested using three assays: a red onion scale assay, a yellow onion bulb assay, and a foliar assay. Whole genome sequencing was done to identify the onion-pathogenic strains to species. Collectively, isolates of 24 genera belonging to three phyla were detected, including 19 genera from foliar samples and nine genera from bulb samples. Isolates in the Phylum Proteobacteria, including 15 genera of Gram-negative bacteria, were the most abundant of the taxa, comprising 90.0% of the strains isolated. The diversity of foliar isolates was evenly distributed between Gram-positive and Gram-negative bacteria, while Gram-negative bacteria dominated the isolates from bulb samples. In total, 83.9% of the bacterial isolates were not pathogenic on onion, with only isolates of Pantoea, Pseudomonas, Burkholderia, Erwinia, Enterobacter, and Curtobacterium proving pathogenic. Strains of Burkholderia gladioli, Pseudomonas alliivorans, Pantoea agglomerans, P. ananatis, and P. allii are the first documented cases of these pathogens of onion in Texas. Identifying and characterizing the nature of onion microflora, including pathogens of onion, is vital to developing rapid disease detection techniques via pathogenomics and minimizing losses through the application of effective disease management measures.
Targeting Pain Science Education in Youth With Chronic Pain
Authors: Pate Joshua W. , Harrison Lauren E. , Hess Courtney W. , Moseley G. Lorimer , Rush Gillian , Heathcote Lauren C. , Simons Laura E.
Published: December 2022

Objectives:

An important part of providing pain science education is to first assess baseline knowledge and beliefs about pain, thereby identifying misconceptions and establishing individually-tailored learning objectives. The Concept of Pain Inventory (COPI) was developed to support this need. This study aimed to characterize the concept of pain in care-seeking youth and their parents, to examine its clinical and demographic correlates, and to identify conceptual gaps.

Materials and Methods:

Following an initial interdisciplinary evaluation, a cohort of 127 youth aged 8 to 18 years, and their parents, completed a series of questionnaires.

Results:

Parents had slightly higher COPI scores than youth did, reflecting parents’ greater alignment with contemporary pain science. The moderate positive association with older age among youth (r=.32) suggests that COPI is sensitive to cognitive development and life experiences. Youth and parent COPI responses were weakly associated (r=0.24), highlighting the importance of targeting the concept of pain in both groups. For both parents and youth, ‘Learning about pain can help you feel less pain’ was the least endorsed concept. This conceptual ‘gap’ is a key point of intervention that could potentially lead to greater engagement with multidisciplinary pain treatment.

Discussion:

The COPI appears useful for identifying conceptual gaps or ‘sticking points’; this may be an important step to pre-emptively address misconceptions about pain through pain science education. Future research should determine the utility of COPI in assessing and treating youth seeking care for pain. The COPI may be a useful tool for tailoring pain science education to youth and their parents.
Exploring the Use of an Electronic Competency Assessment Document Using iPad Minis to Assess Clinical Practice Competency in a Preregistration Nursing Program
Authors: Caples Maria , McCarthy Vera , Wills Teresa , Goodwin John , McCloskey Sean , Burton Aileen , Forde Mary , Erlandsson Tomas , Ryan Eoin , Noonan Brendan
Published: December 2022

The aim of this study was to explore the feasibility of using iPad minis as a method of completing competency assessment in clinical practice. Digital technology helps to revolutionize all aspects of our lives. The use of digital technologies in clinical practice can facilitate a move toward a more flexible learning environment and enable students to adapt in a rapidly changing, interconnected world. The introduction of electronic clinical booklets in practice placements could facilitate the sharing of clinical information through connected healthcare systems, thus improving the student experience. A cross-sectional design was used in this study. A sample of BSc nursing students (n = 53) and clinically based healthcare professionals (n = 27) (preceptors and clinical placement coordinators) participated in this study. Data were collected using a modified version of Garrett and colleagues' instrument, the System Usability Scale, a demographics questionnaire, and three open-ended questions. There was a significant difference between the students and preceptors/clinical placement coordinators across all items with higher proportions of students (ranging from 66% to 75.5%), indicating that they agreed or strongly agreed with the reliability, ease of use, and effectiveness of the device in assessing their clinical competency (ranging from 11.1% to 40.7%). In addition, the iPad minis were found to be smaller, lighter, and easier to carry than paper-based booklets and encouraged students to access timely online learning resources during placement to help augment their learning. The use of iPad mini to complete the electronic competency assessment document as a replacement for a paper-based system to assess clinical practice is feasible. The introduction of electronic assessment documents should incorporate a robust training plan and standard operating procedures.
Aortic dissection: global epidemiology
Authors: Yin Jianhan , Liu Feng , Wang Jiabin , Yuan Pengfei , Wang Shuangjing , Guo Wei
Published: December 2022

Aortic dissection is a highly fatal disease with limited predictability requiring emergency response. It remains a challenging clinical problem and has a reported lower 5-year survival rate, especially in acute cases. Studying the epidemiology of aortic dissection can be important for targeting key populations and developing public health policies. Past studies have focused more on the in-hospital and follow-up mortality associated with aortic dissection but the global epidemiology review is still lacking. Incidence data have rarely been generated or provided. We estimated and analyzed the incidence of aortic dissection in all 195 countries and 54 regions worldwide and in the population structures of 15 selected countries. We further reviewed risk factors and baseline characteristics related to aortic dissection. We outlined the topic in terms of the biological, social, environmental, and psychosocial factors. Public health departments should screen target groups and key regions and introduce policies for disease prevention and relieve the high medical burdens.
Accounting for Misclassification and Selection Bias in Estimating Effectiveness of Self-managed Medication Abortion
Authors: Jayaweera Ruvani T. , Bradshaw Patrick T. , Gerdts Caitlin , Egwuatu Ijeoma , Grosso Bélen , Kristianingrum Ika , Nmezi Sybil , Zurbriggen Ruth , Ahern Jennifer , Moseson Heidi
Published: December 2022

Background:

Studies on the effectiveness of self-managed medication abortion may suffer from misclassification and selection bias due to self-reported outcomes and loss of follow-up. Monte Carlo sensitivity analysis can estimate self-managed abortion effectiveness accounting for these potential biases.

Methods:

We conducted a Monte Carlo sensitivity analysis based on data from the Studying Accompaniment model Feasibility and Effectiveness Study (the SAFE Study), to generate bias-adjusted estimates of the effectiveness of self-managed abortion with accompaniment group support. Between July 2019 and April 2020, we enrolled a total of 1051 callers who contacted accompaniment groups in Argentina and Nigeria for self-managed abortion information; 961 took abortion medications and completed at least one follow-up. Using these data, we calculated measures of effectiveness adjusted for ineligibility, misclassification, and selection bias across 50,000 simulations with bias parameters drawn from pre-specified Beta distributions in R.

Results:

After accounting for the potential influence of various sources of bias, bias-adjusted estimates of effectiveness were similar to observed estimates, conditional on chosen bias parameters: 92.68% (95% simulation interval: 87.80%, 95.74%) for mifepristone in combination with misoprostol (versus 93.7% in the observed data) and 98.47% (95% simulation interval: 96.79%, 99.39%) for misoprostol alone (versus 99.3% in the observed data).

Conclusions:

After adjustment for multiple potential sources of bias, estimates of self-managed medication abortion effectiveness remain high. Monte Carlo sensitivity analysis may be useful in studies measuring an epidemiologic proportion (i.e., effectiveness, prevalence, cumulative incidence) while accounting for possible selection or misclassification bias.
Development and Validation of Algorithms to Estimate Live Birth Gestational Age in Medicaid Analytic eXtract Data
Authors: Zhu Yanmin , Thai Thuy N. , Hernandez-Diaz Sonia , Bateman Brian T. , Winterstein Almut G. , Straub Loreen , Franklin Jessica M. , Gray Kathryn J. , Wyss Richard , Mogun Helen , Vine Seanna , Taylor Lockwood G. , Ouellet-Hellstrom Rita , Ma Yong , Qiang Yandong , Hua Wei , Huybrechts Krista F.
Published: December 2022

Background:

While healthcare utilization data are useful for postmarketing surveillance of drug safety in pregnancy, the start of pregnancy and gestational age at birth are often incompletely recorded or missing. Our objective was to develop and validate a claims-based live birth gestational age algorithm.

Methods:

Using the Medicaid Analytic eXtract (MAX) linked to birth certificates in three states, we developed four candidate algorithms based on: preterm codes; preterm or postterm codes; timing of prenatal care; and prediction models – using conventional regression and machine-learning approaches with a broad range of prespecified and empirically selected predictors. We assessed algorithm performance based on mean squared error (MSE) and proportion of pregnancies with estimated gestational age within 1 and 2 weeks of the gold standard, defined as the clinical or obstetric estimate of gestation on the birth certificate. We validated the best-performing algorithms against medical records in a nationwide sample. We quantified misclassification of select drug exposure scenarios due to estimated gestational age as positive predictive value (PPV), sensitivity, and specificity.

Results:

Among 114,117 eligible pregnancies, the random forest model with all predictors emerged as the best performing algorithm: MSE 1.5; 84.8% within 1 week and 96.3% within 2 weeks, with similar performance in the nationwide validation cohort. For all exposure scenarios, PPVs were >93.8%, sensitivities >94.3%, and specificities >99.4%.

Conclusions:

We developed a highly accurate algorithm for estimating gestational age among live births in the nationwide MAX data, further supporting the value of these data for drug safety surveillance in pregnancy. See video abstract at, http://links.lww.com/EDE/B989.
The use of loop diuretics in the context of hypertensive disorders of pregnancy: a systematic review and meta-analysis
Authors: Malhamé Isabelle , Dong Susan , Syeda Ambreen , Ashraf Rizwana , Zipursky Jonathan , Horn Daphne , Daskalopoulou Stella S. , D'Souza Rohan
Published: December 2022

Aims:

Addressing volume expansion may improve the management of hypertension across the pregnancy continuum. We conducted a systematic review to summarize the evidence on the use of loop diuretics in the context of hypertensive disorders during pregnancy and the postpartum period.

Methods and results:

Medline, Embase, Cochrane library, ClinicalTrials.gov, and Google Scholar were searched for original research articles published up to 29 June 2021. Of the 2801 results screened, 15 studies were included: eight randomized controlled trials, six before–after studies, and one cohort study. Based on random effects meta-analysis of before–after studies, antepartum use of loop diuretics was associated with lower DBP [mean difference −17.73 mmHg, (95% confidence intervals −34.50 to −0.96); I
2 = 94%] and lower cardiac output [mean difference −0.75 l/min, (−1.11 to −0.39); I
2 = 0%], with no difference in SBP, mean arterial pressure, heart rate, or total peripheral resistance. Meta-analysis of randomized controlled trials revealed that postpartum use of loop diuretics was associated with decreased need for additional antihypertensive patients [relative risk 0.69, (0.50–0.97); I
2 = 14%], and an increased duration of hospitalization [mean difference 8.80 h, (4.46–13.14); I
2 = 83%], with no difference in the need for antihypertensive therapy at hospital discharge, or persistent postpartum hypertension.

Conclusion:

Antepartum use of loop diuretics lowered DBP and cardiac output, while their postpartum use reduced the need for additional antihypertensive medications. There was insufficient evidence to suggest a clear benefit. Future studies focusing on women with hypertensive pregnancy disorders who may most likely benefit from loop diuretics are required.
Disparities in Access to Hepatitis C Treatment Among Arizona Medicaid Beneficiaries With Chronic Hepatitis C
Authors: Jiang Xinyi , Song Hyun Jin , Chang Ching-Yuan , Wilson Debbie , Guo Jingchuan , Lo-Ciganic Wei-Hsuan , Park Haesuk
Published: December 2022

Background:

High costs of direct-acting antivirals (DAAs) have led to their restricted access for patients with hepatitis C virus (HCV).

Objective:

The aim was to assess how HCV treatment access and predictors of HCV treatment changed in the post-DAA period compared with pre-DAA period.

Methods:

A retrospective cohort study using Arizona Medicaid data was conducted for patients with HCV to compare treatment initiation rates between pre-DAA (January 2008–October 2013) and post-DAA (November 2013–December 2018) periods. Multivariable logistic regression was used, controlling for demographic and clinical variables.

Results:

Twenty-four thousand and ninety and 28,756 patients during the pre-DAA and post-DAA periods were identified. Overall, 12.6% were treated in the post-DAA period compared with 7.8% in the pre-DAA period (P<0.001). The relative increase in the HCV treatment initiation rate from the pre-DAA to the post-DAA period was significant greater for Black beneficiaries compared with White beneficiaries (P=0.002). Hispanic beneficiaries were less likely to be treated in the post-DAA period [adjusted odds ratios (aOR): 0.88; CI: 0.79–0.98] compared with White beneficiaries. Those with mental illness (aOR: 0.71; 95% CI: 0.63–0.80) and substance use disorders (aOR: 0.63; 95% CI: 0.58–0.68) were less likely to be treated in the post-DAA period.

Conclusions:

Although treatment initiation increased and disparities for Black beneficiaries compared with White beneficiaries attenuated in the post-DAA period, only 13% of Arizona Medicaid patients with HCV received DAA treatment. Disparities in DAA access remained among Hispanic patients and those with mental illness and substance use disorders.
Update on combined heart and liver transplantation: evolving patient selection, improving outcomes, and outstanding questions
Authors: Tracy Kaitlyn M. , Matsuoka Lea K. , Alexopoulos Sophoclis P.
Published: December 2022

Purpose of review

Combined heart and liver transplantation (CHLT) is an uncommon but increasingly performed procedure with rising need as the population who has undergone Fontan palliation for single ventricle physiology grows. This article reviews the current literature to summarize what is known about patient selection and outcomes and highlights the questions that remain.

Recent findings

Congenital heart disease (CHD) with Fontan-associated liver disease (FALD) has surpassed noncongenital heart disease as the most common indication for CHLT. In patients with failing Fontan physiology, accurate assessment of recoverability of liver injury remains challenging and requires multifaceted evaluation to determine who would benefit from isolated versus dual organ transplantation. Patient survival has improved over time without significant differences between those with and without a diagnosis of CHD. En bloc surgical technique and best use of intraoperative mechanical circulatory support are topics of interest as the field continues to evolve.

A more refined understanding of appropriate patient selection and indication-specific outcomes will develop as we gain more experience with this complex operation and perform prospective, randomized studies.
Creating a Safe Space for Simulation
Authors: Preiksaitis Carl M. , Lee Moon O. , Schertzer Kimberly
Published: December 2022

Summary Statement

Use of the term “confederate” is often used in research literature to describe an individual allied with the research team. Confederate is used in simulation research to describe participants allied with the simulation facilitator. Confederate can also refer to the Confederate States of America and has connotations of racial injustice and slavery. Use of this term in simulation may adversely affect psychological safety of learners. Use of the term within the literature is a potential driver of use during simulation sessions. We completed a rapid review of the health care simulation literature to determine the frequency of the term confederate. From 2000 to 2021, 2635 uses of confederate were identified in 765 articles. There seems to be an increased trend in use of this word. We argue that alternative terms exist and should be used to maximize psychological safety of learners.