bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nano-RNases: oligo- or dinucleases?
Authors: Lee Vincent T , Sondermann Holger , Winkler Wade C 
Published: August 2022

Abstract
Diribonucleotides arise from two sources: turnover of RNA transcripts (rRNA, tRNA, mRNA, and others) and linearization of cyclic-di-nucleotide signaling molecules. In both cases, there appears to be a requirement for a dedicated set of enzymes that will cleave these diribonucleotides into mononucleotides. The first enzyme discovered to mediate this activity is oligoribonuclease (Orn) from Escherichia coli. In addition to being the enzyme that cleaves dinucleotides and potentially other short oligoribonucleotides, Orn is also the only known exoribonuclease enzyme that is essential for E. coli, suggesting that removal of the shortest RNAs is an essential cellular function. Organisms naturally lacking the orn gene encode other nanoRNases (nrn) that can complement the conditional E. coli orn mutant. This review covers the history and recent advances in our understanding of these enzymes and their substrates. In particular, we focus on (i) the sources of diribonucleotides; (ii) the discovery of exoribonucleases; (iii) the structural features of Orn, NrnA/NrnB, and NrnC; (iv) the enzymatic activity of these enzymes against diribonucleotides versus other substrates; (v) the known physiological consequences of accumulation of linear dinucleotides; and (vi) outstanding biological questions for diribonucleotides and diribonucleases.
Genome-wide polymorphism and genic selection in feral and domesticated lineages of Cannabis sativa
Authors: Woods Patrick , Price Nicholas , Matthews Paul , McKay John K 
Published: August 2022

Abstract
A comprehensive understanding of the degree to which genomic variation is maintained by selection vs. drift and gene flow is lacking in many important species such as Cannabis sativa, one of the oldest known crops to be cultivated by humans worldwide. We generated whole genome resequencing data across diverse samples of feralized (escaped domesticated lineages) and domesticated lineages of C. sativa. We performed analyses to examine population structure, and genome-wide scans for FST, balancing selection, and positive selection. Our analyses identified evidence for subpopulation structure and further supported the Asian origin hypothesis of this species. Feral plants sourced from the United States exhibited broad regions on chromosomes 4 and 10 with high F¯ST, which may indicate chromosomal inversions maintained at high frequency in this subpopulation. Both our balancing and positive selection analyses identified loci that may reflect differential selection for traits favored by natural selection and artificial selection in feral vs. domesticated subpopulations. In the US feral subpopulation, we found 6 loci related to stress response under balancing selection and 1 gene involved in disease resistance under positive selection, suggesting local adaptation to new climates and biotic interactions. In the marijuana subpopulation, we identified the gene SMALLER TRICHOMES WITH VARIABLE BRANCHES 2 to be under positive selection, which suggests artificial selection for increased tetrahydrocannabinol yield. Overall, the data generated and results obtained from our study help to form a better understanding of the evolutionary history in C. sativa.
Functional genomic assays to annotate enhancer–promoter interactions genome wide
Authors: Leung Alden King-Yung , Yao Li , Yu Haiyuan 
Published: August 2022

Abstract
Enhancers are pivotal for regulating gene transcription that occurs at promoters. Identification of the interacting enhancer–promoter pairs and understanding the mechanisms behind how they interact and how enhancers modulate transcription can provide fundamental insight into gene regulatory networks. Recently, advances in high-throughput methods in three major areas—chromosome conformation capture assay, such as Hi-C to study basic chromatin architecture, ectopic reporter experiments such as self-transcribing active regulatory region sequencing (STARR-seq) to quantify promoter and enhancer activity, and endogenous perturbations such as clustered regularly interspaced short palindromic repeat interference (CRISPRi) to identify enhancer–promoter compatibility—have further our knowledge about transcription. In this review, we will discuss the major method developments and key findings from these assays.
Basic principles of cardiothoracic surgery training: a position paper by the European Association for Cardiothoracic Surgery Residents Committee
Authors: Zientara Alicja , Hussein Nabil , Bond Chris , Jacob Kirolos A , Naruka Vinci , Doerr Fabian , Nägele Felix , Pölzl Leo , Eid Maroua , Jarral Omar , Cerqueira Rui , Haunschild Josephina , Sádaba J Rafael , Gollmann-Tepeköylü Can 
Published: August 2022

Abstract

OBJECTIVES
Across Europe there are significant variations in the fundamental structure and content of cardiothoracic surgery (CTS) training programmes. Previous efforts have been made to introduce a Unified European Training System, which outlined the fundamentals of the ideal programme and supported a paradigm shift from an apprenticeship to a competency-based model. This article’s goal was to define key structural, administrative and executive details of such a programme to lay the foundations for the standardization of cardiothoracic surgical training across Europe.

METHODS
The European Association for Cardiothoracic Surgery Residents Committee had previously conducted a residents’ training survey across Europe in 2020. Training curricula from the twelve most represented countries across Europe were either searched online or obtained from the countries’ national trainee representative and reviewed by the committee. Information was collated and placed into one of the following categories to develop the position paper: (i) selection of eligible candidates, (ii) guidance for an outcome-based syllabus, (iii) documentation and evaluation of training progress, (iv) mandatory rotations and training courses, (v) number of independent or assisted cases and (vi) requirements and quality assurance of teachers.

RESULTS
An independent professional body should promote an outcome-based syllabus and take responsibility for the training programme’s quality assurance. Trainees should be selected on merit by an open and transparent process. Training should be delivered within a defined period and supervised by an appointed training committee to ensure its implementation. This committee should review the trainees progression regularly, provide feedback and offer trainees the opportunity to experience various training environments and trainers. A common electronic portal be used by trainees to record their agreed objectives and to evidence their completion. Trainees should regularly attend specialty-relevant courses and conferences to promote professional and academic development. The end of training is reached when the formal requirements of the training programme are met and the trainee is able to perform at the level expected of a day-1 independent surgeon.

CONCLUSIONS
This article defines the key structural, administrative, and executive principles for CTS training. Programmes are encouraged to review and modify their training curricula, if necessary, to ensure the delivery of high-quality, standardized, outcome-orientated CTS training across Europe.
Trimethoprim-associated hyperkalaemia: a systematic review and meta-analysis
Authors: Faré Pietro B , Memoli Erica , Treglia Giorgio , Bianchetti Mario G , Milani Gregorio P , Marchisio Paola , Lava Sebastiano A G , Janett Simone 
Published: August 2022

Abstract

Introduction
Trimethoprim is structurally similar to potassium-sparing diuretics and may induce hyperkalaemia. The prevalence and the factors that predispose to trimethoprim-associated hyperkalaemia have never been extensively addressed.

Methods
A literature search with no date or language limits was carried out using the National Library of Medicine, Embase and Web of Science in March and repeated during August 2021. The principles underlying the Economic and Social Research Council guidance on the conduct of synthesis and the PRISMA guidelines were employed. For the analysis, we retained reports including ≥10 subjects on treatment with trimethoprim, which addressed the possible occurrence of hyperkalaemia.

Results
Eighteen reports were retained for the final analysis. The pooled prevalence of potassium value &gt;5.0 mmol/L, &gt;5.5 mmol/L and &gt;6.0 mmol/L or symptomatic, was, respectively, 22%, 10% and 0.2%. The analysis disclosed that the risk of trimethoprim-associated hyperkalaemia is dose-related and enhanced by drugs with known hyperkalaemic potential including potassium-sparing diuretics, renin–angiotensin–aldosterone system inhibitors, β-blockers and non-steroidal anti-inflammatory agents. Poor kidney function also increased the tendency towards hyperkalaemia. The time to onset of hyperkalaemia was generally 1 week or less after starting trimethoprim.

Conclusions
The present analysis documents the hyperkalaemic potential of trimethoprim, a widely prescribed drug that was introduced more than 50 years ago. Clinicians must recognize patients at risk of trimethoprim-associated hyperkalaemia.
Binding of temocillin to plasma proteins in vitro and in vivo: the importance of plasma protein levels in different populations and of co-medications
Authors: Ngougni Pokem Perrin , Matzneller Peter , Vervaeke Steven , Wittebole Xavier , Goeman Lieven , Coessens Marie , Cottone Eleonora , Capron Arnaud , Wulkersdorfer Beatrix , Wallemacq Pierre , Mouton Johan W , Muller Anouk E , Zeitlinger Markus , Laterre Pierre François , Tulkens Paul M , Van Bambeke Françoise 
Published: August 2022

Abstract

Background
Temocillin plasma protein binding (PPB) in healthy individuals is reported to be ∼85% but had not been studied in patients.

Objectives
To obtain normative data on temocillin PPB in patients in relation to infection and impact of co-medications widely used in ICU.

Methods
Plasma was obtained from healthy individuals (Group #1), non-ICU patients with UTI (Group #2), ICU patients with suspected/confirmed ventriculitis (Group #3) or with sepsis/septic shock (Group #4). Total and unbound temocillin concentrations were measured in spiked samples from temocillin-naive donors (in vitro) or in plasma from temocillin-treated subjects (in vivo). The impact of diluting plasma, using pharmaceutical albumin, or adding drugs potentially competing for PPB was tested in spiked samples. Data were analysed using a modified Hill–Langmuir equation taking ligand depletion into account.

Results
Temocillin PPB was saturable in all groups, both in vitro and in vivo. Maximal binding capacity (Bmax) was 1.2–2-fold lower in patients. At 20 and 200 mg/L (total concentrations), the unbound fraction reached 12%–29%, 23%–42% and 32%–52% in Groups #2, #3, #4. The unbound fraction was inversely correlated with albumin and C-reactive protein concentrations. Binding to albumin was 2–3-fold lower than in plasma and non-saturable. Drugs with high PPB but active at lower molar concentrations than temocillin caused minimal displacement, while fluconazole (low PPB but similar plasma concentrations to temocillin) increased up to 2-fold its unbound fraction.

Conclusions
Temocillin PPB is saturable, 2–4-fold lowered in infected patients in relation to disease severity (ICU admission, hypoalbuminaemia, inflammation) and only partially reproducible with albumin. Competition with other drugs must be considered for therapeutic concentrations to be meaningful.
Interruptive Electronic Alerts for Choosing Wisely Recommendations: A Cluster Randomized Controlled Trial
Authors: Ho Vy T , Aikens Rachael C , Tso Geoffrey , Heidenreich Paul A , Sharp Christopher , Asch Steven M , Chen Jonathan H , Shah Neil K 
Published: August 2022

Abstract

Objective
To assess the efficacy of interruptive electronic alerts in improving adherence to the American Board of Internal Medicine’s Choosing Wisely recommendations to reduce unnecessary laboratory testing.

Materials and methods
We administered 5 cluster randomized controlled trials simultaneously, using electronic medical record alerts regarding prostate-specific antigen (PSA) testing, acute sinusitis treatment, vitamin D testing, carotid artery ultrasound screening, and human papillomavirus testing. For each alert, we assigned 5 outpatient clinics to an interruptive alert and 5 were observed as a control. Primary and secondary outcomes were the number of postalert orders per 100 patients at each clinic and number of triggered alerts divided by orders, respectively. Post hoc analysis evaluated whether physicians experiencing interruptive alerts reduced their alert-triggering behaviors.

Results
Median postalert orders per 100 patients did not differ significantly between treatment and control groups; absolute median differences ranging from 0.04 to 0.40 for PSA testing. Median alerts per 100 orders did not differ significantly between treatment and control groups; absolute median differences ranged from 0.004 to 0.03. In post hoc analysis, providers receiving alerts regarding PSA testing in men were significantly less likely to trigger additional PSA alerts than those in the control sites (Incidence Rate Ratio 0.12, 95% CI [0.03–0.52]).

Discussion
Interruptive point-of-care alerts did not yield detectable changes in the overall rate of undesired orders or the order-to-alert ratio between active and silent sites. Complementary behavioral or educational interventions are likely needed to improve efforts to curb medical overuse.

Conclusion
Implementation of interruptive alerts at the time of ordering was not associated with improved adherence to 5 Choosing Wisely guidelines.

Trial Registration
NCT02709772
Accuracy of ICD-10-CM encounter diagnoses from health records for identifying self-harm events
Authors: Simon Gregory E , Shortreed Susan M , Boggs Jennifer M , Clarke Gregory N , Rossom Rebecca C , Richards Julie E , Beck Arne , Ahmedani Brian K , Coleman Karen J , Bhakta Bhumi , Stewart Christine C , Sterling Stacy , Schoenbaum Michael , Coley R Yates , Stone Marc , Mosholder Andrew D , Yaseen Zimri S 
Published: August 2022

Abstract

Objective
Assess the accuracy of ICD-10-CM coding of self-harm injuries and poisonings to identify self-harm events.

Materials and Methods
In 7 integrated health systems, records data identified patients reporting frequent suicidal ideation. Records then identified subsequent ICD-10-CM injury and poisoning codes indicating self-harm as well as selected codes in 3 categories where uncoded self-harm events might be found: injuries and poisonings coded as undetermined intent, those coded accidental, and injuries with no coding of intent. For injury and poisoning encounters with diagnoses in those 4 groups, relevant clinical text was extracted from records and assessed by a blinded panel regarding documentation of self-harm intent.

Results
Diagnostic codes selected for review include all codes for self-harm, 43 codes for undetermined intent, 26 codes for accidental intent, and 46 codes for injuries without coding of intent. Clinical text was available for review for 285 events originally coded as self-harm, 85 coded as undetermined intent, 302 coded as accidents, and 438 injury events with no coding of intent. Blinded review of full-text clinical records found documentation of self-harm intent in 254 (89.1%) of those originally coded as self-harm, 24 (28.2%) of those coded as undetermined, 24 (7.9%) of those coded as accidental, and 48 (11.0%) of those without coding of intent.

Conclusions
Among patients at high risk, nearly 90% of injuries and poisonings with ICD-10-CM coding of self-harm have documentation of self-harm intent. Reliance on ICD-10-CM coding of intent to identify self-harm would fail to include a small proportion of true self-harm events.
Incidence of invasive fungal infections in patients with hematological malignancies receiving ibrutinib therapy in south-east Austria
Authors: Egger Matthias , Gornicec Max , Wölfler Albert , Lembeck Anna Lena , Tinchon Christoph , Maderdonner Manuela , Prattes Juergen 
Published: August 2022

Abstract
Since the broad implementation of ibrutinib therapy, an increasing number of studies have been reported on invasive fungal infections (IFI) associated with ibrutinib administration. We conducted a retrospective cohort study in three hospitals in south-east Austria in order to assess the local epidemiology of ibrutinib associated IFIs. A total of 113 patients with underlying hematological malignancy were included in the study. During the study period, a single IFI episode was observed, which corresponds to an IFI incidence of 2.3 cases per 100 person years (95% CI: 0.12–11.47). IFIs during ibrutinib therapy seem to be a rare event in case of absent additional risk factors for IFIs.
The short ionizing photon mean free path at z = 6 in Cosmic Dawn III, a new fully coupled radiation-hydrodynamical simulation of the Epoch of Reionization
Authors: Lewis Joseph S W , Ocvirk Pierre , Sorce Jenny G , Dubois Yohan , Aubert Dominique , Conaboy Luke , Shapiro Paul R , Dawoodbhoy Taha , Teyssier Romain , Yepes Gustavo , Gottlöber Stefan , Rasera Yann , Ahn Kyungjin , Iliev Ilian T , Park Hyunbae , Thélie Émilie 
Published: August 2022

ABSTRACT
Recent determinations of the mean free path of ionizing photons (mfp) in the intergalactic medium (IGM) at z = 6 are lower than many theoretical predictions. In order to gain insight, we investigate the evolution of the mfp in our new massive fully coupled radiation-hydrodynamics cosmological simulation of reionization: Cosmic Dawn III (CoDa III). CoDa III’s scale ($\rm 94^3 \, cMpc^3$) and resolution ($\rm 8192^3$ grid) make it particularly suitable to study the IGM during reionization. The simulation was performed with ramses-cudaton on Summit, and used 13 1072 processors coupled to 24 576 GPUs, making it the largest reionization simulation, and largest ever ramses simulation. A superior agreement with global constraints on reionization is obtained in CoDa III over Cosmic Dawn II (CoDa II), especially for the evolution of the neutral hydrogen fraction and the cosmic photoionization rate, thanks to an improved calibration, later end of reionization (z = 5.6), and higher spatial resolution. Analysing the mfp, we find that CoDa III reproduces the most recent observations very well, from z = 6 to z = 4.6. We show that the distribution of the mfp in CoDa III is bimodal, with short (neutral) and long (ionized) mfp modes, due to the patchiness of reionization and the coexistence of neutral versus ionized regions during reionization. The neutral mode peaks at sub-kpc to kpc scales of mfp, while the ionized mode peak evolves from 0.1 Mpc h−1 at z = 7 to ∼10 Mpc h−1 at z = 5.2. Computing the mfp as the average of the ionized mode provides the best match to the recent observational determinations. The distribution reduces to a single neutral (ionized) mode at z &gt; 13 (z &lt; 5).
Modelling the host galaxies of binary compact object mergers with observational scaling relations
Authors: Santoliquido Filippo , Mapelli Michela , Artale M Celeste , Boco Lumen 
Published: August 2022

ABSTRACT
The merger rate density evolution of binary compact objects and the properties of their host galaxies carry crucial information to understand the sources of gravitational waves. Here, we present galaxy$\mathcal {R}$ate, a new code that estimates the merger rate density of binary compact objects and the properties of their host galaxies, based on observational scaling relations. We generate our synthetic galaxies according to the galaxy stellar mass function. We estimate the metallicity according to both the mass–metallicity relation (MZR) and the fundamental metallicity relation (FMR). Also, we take into account galaxy–galaxy mergers and the evolution of the galaxy properties from the formation to the merger of the binary compact object. We find that the merger rate density changes dramatically depending on the choice of the star-forming galaxy main sequence, especially in the case of binary black holes (BBHs) and black hole neutron star systems (BHNSs). The slope of the merger rate density of BBHs and BHNSs is steeper if we assume the MZR with respect to the FMR, because the latter predicts a shallower decrease of metallicity with redshift. In contrast, binary neutron stars (BNSs) are only mildly affected by both the galaxy main sequence and metallicity relation. Overall, BBHs and BHNSs tend to form in low-mass metal-poor galaxies and merge in high-mass metal-rich galaxies, while BNSs form and merge in massive galaxies. We predict that passive galaxies host at least ∼5–10 per cent, ∼15–25 per cent, and ∼15–35 per cent of all BNS, BHNS, and BBH mergers in the local Universe.
A deep, multi-epoch Chandra HETG study of the ionized outflow from NGC 4051
Authors: Ogorzalek A , King A L , Allen S W , Raymond J C , Wilkins D R 
Published: August 2022

ABSTRACT
Actively accreting supermassive black holes significantly impact the evolution of their host galaxies, truncating further star formation by expelling large fractions of gas with wide-angle outflows. The X-ray band is key to understanding how these black hole winds affect their environment, as the outflows have high temperatures (∼105–8 K). We have developed a Bayesian framework for characterizing active galactic nucleus outflows with an improved ability to explore parameter space and perform robust model selection. We applied this framework to a new 700 ks and an archival 315 ks Chandra High Energy Transmission Gratings observation of the Seyfert galaxy NGC 4051. We have detected six absorbers intrinsic to NGC 4051. These wind components span velocities from 400 to 30 000 km s−1. We have determined that the most statistically significant wind component is purely collisionally ionized, which is the first detection of such an absorber. This wind has T ≈ 107 K and v ≈ 880 km s−1 and remains remarkably stable between the two epochs. Other slow components also remain stable across time. Fast outflow components change their properties between 2008 and 2016, suggesting either physical changes or clouds moving in and out of the line of sight. For one of the fast components, we obtain one of the tightest wind density measurements to date, log n/(cm−3) = 13.0$^{+0.01}_{-0.02}$, and determine that it is located at ∼240 gravitational radii. The estimated total outflow power surpasses 5 per cent of the bolometric luminosity (albeit with large uncertainties) making it important in the context of galaxy–black hole interactions.