bluuebunny/crossref_metadata_2025 huggingface dataset:
Water hammer issues in refurbishment of a high-head hydropower plant equipped with Francis turbine
Authors: Bergant A , Ješe U , Mavrič R , Mazij J , Nikolić Z , Karadžić U
Published: October 2022

Refurbishment and upgrading of ageing hydropower plants contribute to increase of renewable energy share in modern electrical grid systems. The potential increase of discharge and flexibility of load variation may result in much higher dynamic loads on both refurbished and non-refurbished plant components during transient operating events. First, water hammer control strategies are outlined including operational scenarios, surge control devices, redesign of the pipeline components, or limitation of operating conditions. Water hammer models and solutions are briefly discussed in the light of their capability, availability and uncertainty. The core of the paper is devoted to investigations of water hammer effects in a high-head hydropower plant Piva, Montenegro which is currently in the final phase of refurbishment. The flow-passage system of the Piva HPP is comprised of the intake structure, followed by three parallel penstocks each with Francis type water turbine at the downstream end. The outlet part starts with three parallel draft tubes that are connected to a common lower orifice-type surge tank followed by tailrace tunnel and outlet structure. Computed and measured results for a selected emergency shut-down (ESD) of one turbine form full-load are compared and discussed. Then the validated computational model is used for simulation of ESDs for a wide operating range.
On the correlation between runner blade dynamic stresses and pressure fluctuations in a prototype Francis turbine
Authors: Favrel Arthur , Nicolle Jonathan , Morissette Jean-François , Giroux Anne-Marie
Published: October 2022

Francis turbines operating in off-design conditions are subject to pressure fluctuations resulting from the development of hydrodynamic instabilities in the draft tube. Depending on the nature of the flow-induced pressure fluctuations (synchronous or convective), this may induce dynamic stresses on the runner blades, increasing fatigue and the risk of crack propagation. This paper proposes to identify the impact of draft tube flow instabilities on the dynamic stresses of Francis turbine runners. Measurements are conducted on a prototype Hydro-Québec Francis turbine from low-load to full-load, including pressure and strain measurements on the stationary and rotating components, respectively. It is first noted that the convective component of the part-load vortex is the main source of excitation for the runner blades. The amplitude of the corresponding dynamic stresses is however reduced at locations closer to the leading edge, for which the dominant fluctuations result from the propagation of synchronous pressure fluctuations. Finally, correlations between runner dynamic stresses and pressure fluctuations measured in water passages are tentatively established for flow instabilities observed at both deep part-load and part-load conditions. This aims to evaluate the feasibility of estimating runner blade dynamic stresses based on signals measured in the stationary components for further investigation.
All-dielectric electromagnetically induced transparency-like metasurface with breaking symmetric
Authors: Shen Zhaoyang , Wang Chengwen , Lu Na
Published: October 2022

We investigate an all-dielectric metasurface to mimic the electromagnetically induced transparency-like phenomenon in the microwave. The unit cell is comprised of two hollow split ring resonators with different parameters, which form an asymmetric structure. The proposed metasurface acquires a high transmission efficiency at 17.17 GHz, which is caused by magnetic resonance. The corresponding physical mechanism is discussed and analyzed by the distributions of the electric and magnetic fields. The experiment result of the transmission spectra is well in agreement with the simulation data. The geometric parameter of hollow split ring resonators has deep influences on transmission spectra which leads to transparency peak variation. Concurrently, the imaginary parts of the effective permittivity and permeability for the proposed metasurface are presented to explain the low-loss property. Furthermore, the transparency peak is sensitive to the surrounding environment, which exhibits potential application in refractive index sensor.
Transportation emissions during pandemic: duality of impacts
Authors: Kontar Wissam , Ahn Soyoung , Hicks Andrea
Published: October 2022

Through the lens of an electric bicycle (E-bike) sharing program, this paper shows how the impact of the pandemic on transportation emissions can be multifaceted by impacting both (i) modal usage and (ii) trip generation. The pandemic led to a decrease in the number of trips by travelers, but it also induced a modal shift away from shared mobility into personalized modes. As a result, estimates of transportation emissions can present conflicting figures. In this work, we collect data on the travel behavior of users of an E-bike sharing program in Madison, Wisconsin, before and during the pandemic. Observations on trip choices and modal shifts of users provide means to estimate their relative and overall impact on transportation emissions. Results suggest that the influence of the pandemic on transportation behavior and environmental emissions is convoluted. Post-pandemic environmental implications would depend on the extent of recovery between modal shares and trip generations.
A framework for machine learning of model error in dynamical systems
Authors: Levine Matthew , Stuart Andrew
Published: October 2022

The development of data-informed predictive models for dynamical systems is of widespread interest in many disciplines. We present a unifying framework for blending mechanistic and machine-learning approaches to identify dynamical systems from noisily and partially observed data. We compare pure data-driven learning with hybrid models which incorporate imperfect domain knowledge, referring to the discrepancy between an assumed truth model and the imperfect mechanistic model asmodel error.Our formulation is agnostic to the chosen machine learning model, is presented in both continuous- and discrete-time settings, and is compatible both with model errors that exhibit substantial memory and errors that are memoryless.

First, we study memoryless linear (w.r.t. parametric-dependence) model error from a learning theory perspective, defining excess risk and generalization error. For ergodic continuous-time systems, we prove that both excess risk and generalization error are bounded above by terms that diminish with the square-root ofTT, the time-interval over which training data is specified.

Secondly, we study scenarios that benefit from modeling with memory, proving universal approximation theorems for two classes of continuous-time recurrent neural networks (RNNs): both can learn memory-dependent model error, assuming that it is governed by a finite-dimensional hidden variable and that, together, the observed and hidden variables form a continuous-time Markovian system. In addition, we connect one class of RNNs to reservoir computing, thereby relating learning of memory-dependent error to recent work on supervised learning between Banach spaces using random features.

Numerical results are presented (Lorenz ’63, Lorenz ’96 Multiscale systems) to compare purely data-driven and hybrid approaches, finding hybrid methods less datahungry and more parametrically efficient. We also find that, while a continuous-time framing allows for robustness to irregular sampling and desirable domain- interpretability, a discrete-time framing can provide similar or better predictive performance, especially when data are undersampled and the vector field defining the true dynamics cannot be identified. Finally, we demonstrate numerically how data assimilation can be leveraged to learn hidden dynamics from noisy, partially-observed data, and illustrate challenges in representing memory by this approach, and in the training of such models.
Ensemble classification based feature selection: a case of identification on plant pentatricopeptide repeat proteins
Authors: Zhao Xudong , Zhai Jingwen , Liu Tong , Wang Guohua
Published: October 2022

In order to identify plant pentatricopeptide repeat (PPR) proteins, a framework of variable selection has been proposed. In fact, it is an effective feature selection strategy that focuses on the performance of classification. Random forest has been used as the classifier with certain variables automatically selected for discrimination between PPR functional and non-functional proteins. However, it is found that samples regarded as PPR functional proteins are wrongly classified in a high rate. In this paper, we plan to improve the framework in order to achieve better classification results. Modifications are made on the framework for better identifying PPR functional proteins. Instead of random forest, a hybrid ensemble classifier is built with its base classifiers derived from six different classification methods. Besides, an incremental strategy and a clustering by search in descending order are alternatively used for feature selection, which can effectively select the most representative variables for identification on PPR proteins. In addition, it can be found that different base classifiers alternately play an important role in the ensemble classifier with feature dimension increasing. The experimental results demonstrate the effectiveness of our improvements.
binny: an automated binning algorithm to recover high-quality genomes from complex metagenomic datasets
Authors: Hickl Oskar , Queirós Pedro , Wilmes Paul , May Patrick , Heintz-Buschart Anna
Published: October 2022

The reconstruction of genomes is a critical step in genome-resolved metagenomics and for multi-omic data integration from microbial communities. Here, we present binny, a binning tool that produces high-quality metagenome-assembled genomes (MAG) from both contiguous and highly fragmented genomes. Based on established metrics, binny outperforms or is highly competitive with commonly used and state-of-the-art binning methods and finds unique genomes that could not be detected by other methods. binny uses k-mer-composition and coverage by metagenomic reads for iterative, nonlinear dimension reduction of genomic signatures as well as subsequent automated contig clustering with cluster assessment using lineage-specific marker gene sets. When compared with seven widely used binning algorithms, binny provides substantial amounts of uniquely identified MAGs and almost always recovers the most near-complete ($\gt 95\%$ pure, $\gt 90\%$ complete) and high-quality ($\gt 90\%$ pure, $\gt 70\%$ complete) genomes from simulated datasets from the Critical Assessment of Metagenome Interpretation initiative, as well as substantially more high-quality draft genomes, as defined by the Minimum Information about a Metagenome-Assembled Genome standard, from a real-world benchmark comprised of metagenomes from various environments than any other tested method.
A universal model of RNA.DNA:DNA triplex formation accurately predicts genome-wide RNA–DNA interactions
Authors: Warwick Timothy , Seredinski Sandra , Krause Nina M , Bains Jasleen Kaur , Althaus Lara , Oo James A , Bonetti Alessandro , Dueck Anne , Engelhardt Stefan , Schwalbe Harald , Leisegang Matthias S , Schulz Marcel H , Brandes Ralf P
Published: October 2022

RNA.DNA:DNA triple helix (triplex) formation is a form of RNA–DNA interaction which regulates gene expression but is difficult to study experimentally in vivo. This makes accurate computational prediction of such interactions highly important in the field of RNA research. Current predictive methods use canonical Hoogsteen base pairing rules, which whilst biophysically valid, may not reflect the plastic nature of cell biology. Here, we present the first optimization approach to learn a probabilistic model describing RNA–DNA interactions directly from motifs derived from triplex sequencing data. We find that there are several stable interaction codes, including Hoogsteen base pairing and novel RNA–DNA base pairings, which agree with in vitro measurements. We implemented these findings in TriplexAligner, a program that uses the determined interaction codes to predict triplex binding. TriplexAligner predicts RNA–DNA interactions identified in all-to-all sequencing data more accurately than all previously published tools in human and mouse and also predicts previously studied triplex interactions with known regulatory functions. We further validated a novel triplex interaction using biophysical experiments. Our work is an important step towards better understanding of triplex formation and allows genome-wide analyses of RNA–DNA interactions.
scGNN 2.0: a graph neural network tool for imputation and clustering of single-cell RNA-Seq data
Authors: Gu Haocheng , Cheng Hao , Ma Anjun , Li Yang , Wang Juexin , Xu Dong , Ma Qin
Published: October 2022

Motivation

Gene expression imputation has been an essential step of the single-cell RNA-Seq data analysis workflow. Among several deep-learning methods, the debut of scGNN gained substantial recognition in 2021 for its superior performance and the ability to produce a cell–cell graph. However, the implementation of scGNN was relatively time-consuming and its performance could still be optimized.

Results

The implementation of scGNN 2.0 is significantly faster than scGNN thanks to a simplified close-loop architecture. For all eight datasets, cell clustering performance was increased by 85.02% on average in terms of adjusted rand index, and the imputation Median L1 Error was reduced by 67.94% on average. With the built-in visualizations, users can quickly assess the imputation and cell clustering results, compare against benchmarks and interpret the cell–cell interaction. The expanded input and output formats also pave the way for custom workflows that integrate scGNN 2.0 with other scRNA-Seq toolkits on both Python and R platforms.

Availability and implementation

scGNN 2.0 is implemented in Python (as of version 3.8) with the source code available at https://github.com/OSU-BMBL/scGNN2.0.

Supplementary information

Supplementary data are available at Bioinformatics online.
An enChIP system for the analysis of genome functions in budding yeast
Authors: Fujii Hodaka , Fujita Toshitsugu
Published: October 2022

The identification of molecules associated with a specific genomic region is essential for elucidating the molecular mechanisms underlying genome functions such as transcription. Engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) is a technology that enables the purification of specific genomic regions and the subsequent identification of their associated molecules. In enChIP, the target genomic region is tagged with engineered DNA-binding molecules, such as variants of the clustered regularly interspaced short palindromic repeats (CRISPR) system consisting of a catalytically inactive form of Cas9 (dCas9) and a guide RNA. This article describes the generation of a plasmid expressing Streptococcus pyogenes dCas9 fused to a 3xFLAG-tag (3xFLAG-Sp-dCas9) and its successful expression in the budding yeast, Saccharomyces cerevisiae. Furthermore, we showed that this plasmid can be used for enChIP analysis in budding yeast. In addition, the plasmid may also be a useful tool for researchers analyzing genome functions such as transcription and for CRISPR interference experiments in budding yeasts.
Transcriptomic and connectomic correlates of differential spatial patterning among gliomas
Authors: Romero-Garcia Rafael , Mandal Ayan S , Bethlehem Richard A I , Crespo-Facorro Benedicto , Hart Michael G , Suckling John
Published: October 2022

Unravelling the complex events driving grade-specific spatial distribution of brain tumour occurrence requires rich datasets from both healthy individuals and patients. Here, we combined open-access data from The Cancer Genome Atlas, the UK Biobank and the Allen Brain Human Atlas to disentangle how the different spatial occurrences of glioblastoma multiforme and low-grade gliomas are linked to brain network features and the normative transcriptional profiles of brain regions.

From MRI of brain tumour patients, we first constructed a grade-related frequency map of the regional occurrence of low-grade gliomas and the more aggressive glioblastoma multiforme. Using associated mRNA transcription data, we derived a set of differential gene expressions from glioblastoma multiforme and low-grade gliomas tissues of the same patients. By combining the resulting values with normative gene expressions from post-mortem brain tissue, we constructed a grade-related expression map indicating which brain regions express genes dysregulated in aggressive gliomas. Additionally, we derived an expression map of genes previously associated with tumour subtypes in a genome-wide association study (tumour-related genes).

There were significant associations between grade-related frequency, grade-related expression and tumour-related expression maps, as well as functional brain network features (specifically, nodal strength and participation coefficient) that are implicated in neurological and psychiatric disorders.

These findings identify brain network dynamics and transcriptomic signatures as key factors in regional vulnerability for glioblastoma multiforme and low-grade glioma occurrence, placing primary brain tumours within a well established framework of neurological and psychiatric cortical alterations.
Age at menopause and risk of heart failure and atrial fibrillation: a nationwide cohort study
Authors: Shin Jean , Han Kyungdo , Jung Jin-Hyung , Park Hyo Jin , Kim Wonsock , Huh Youn , Kim Yang-Hyun , Kim Do-Hoon , Kim Seon Mee , Choi Youn Seon , Cho Kyung Hwan , Nam Ga Eun
Published: October 2022

Aims

This study aimed to examine the association of premature menopause and age at menopause with the risk of heart failure (HF) and atrial fibrillation (AF).

Methods and results

A total of 1 401 175 postmenopausal women, who had undergone health examination provided by the Korean National Health Insurance Service, were included, and their reproductive histories were collected. Multivariable Cox proportional hazard models were performed to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) of incident HF and AF, according to the history of premature menopause and age at menopause. At a mean follow-up of 9.1 years, there were 42 699 (3.0%) and 44 834 (3.2%) new cases of HF and AF, respectively. Women with history of premature menopause had an increased risk of HF (HR: 1.33, 95% CI: 1.26–1.40) and AF (HR: 1.09, 95% CI: 1.02–1.16), compared to women without the history. Compared with women aged ≥50 years at menopause, those aged 45−49, 40−44, and <40 years at menopause showed a significantly increased trend in HRs for the incident risk of both HF and AF (P for trend <0.001). The robustness of the results of a series of sensitivity analyses further strengthens the main findings.

Conclusion

Our findings suggest that postmenopausal women with a history of premature menopause or early menopausal age may have an increased risk of HF and AF. These reproductive factors need to be considered for preventing the future risk of HF and AF.
Impact of co-morbidities on survival after heart transplant in females of childbearing age: analysis of the International Society for Heart and Lung Transplantation (ISHLT) Registry
Authors: Bhagra C J , Cherikh W S , De Filippis E M , Ross H , Stehlik J , Macera F
Published: October 2022

Background

Data on life expectancy specific to female heart transplant (HT) recipients of reproductive age are lacking, but are needed to inform shared decision making at the time of pre-conception counseling. We analyzed the ISHLT registry for post-transplant survival and studied the impact of co-morbidities in women of childbearing age.

Methods

Female HT recipients reported to the ISHLT registry who were aged 15–45 yrs at time of HT were included in this retrospective analysis. Primary outcome was post-transplant survival. Secondary outcomes included the impact of co-morbidities on conditional survival at 5, 10 and 15 years.

Results

Of 121,501 HT recipients (Jan 1992–June 2018), 30,179 (24.8%) were women. 9,229 (7.6%) were 15–45 yrs at time of HT. Overall median post-transplant survival was 15.2 yrs. Diabetes mellitus (DM) and/or severe chronic kidney disease (CKD) at HT adversely impacted long-term survival (Figure 1). Co-morbidities including cardiac allograft vasculopathy (CAV), DM and CKD negatively impacted 5yr and 10yr conditional survival, individually as well as a combination (Figure 2). 15yr conditional survival confirmed the negative impact of DM and CKD, while CAV did not reach statistical significance.

Conclusion

Female HT recipients of childbearing age have favorable survival post-HT. Conditional survival at 5 and 10 yrs is negatively impacted by CAV, DM and CKD. The quantification of survival outcomes after heart transplant in women of childbearing age may improve counseling as part of pre-conception informed decision making.

Funding Acknowledgement

Type of funding sources: None.
Remnant cholesterol contributes to residual lipid risk after acute coronary syndromes
Authors: Wenzl F , Kraler S , Raeber L , Von Eckardstein A , Matter C , Gencer B , Nanchen D , Rodondi N , Mach F , Luescher T
Published: October 2022

Background

Increasing evidence indicates that cholesterol transported in triglyceride-rich lipoproteins (remnant cholesterol) is a causal risk factor for major adverse cardiovascular events (MACE) independent from other lipid fractions. To date, the relationship between remnant cholesterol (remnant-C) levels and cardiovascular (CV) outcomes after acute coronary syndromes (ACS) in patients with adequate low-density lipoprotein cholesterol (LDL-C) control is uncertain.

Purpose

This study evaluated the contribution of remnant-C to residual lipid risk after ACS.

Methods

Nested within 4'787 ACS patients in the prospective multicentre SPUM-ACS study (NCT0100070) we examined all patients presenting with LDL-C levels <100 mg/dl under lipid lowering therapy (n=756). Remnant-C was calculated as non-high-density lipoprotein cholesterol (non-HDL-C) minus calculated LDL-C using the Martin/Hopkins modified equation. The predefined primary outcome was a composite of CV death, myocardial infarction, and ischemia-driven revascularization at 12 months. Events were adjudicated by an independent external endpoint committee blinded to the lipid measurements. Multivariable-adjusted Cox models were fitted using smoothing splines for absolute remnant-C levels (continuous), log-transformed absolute remnant-C levels (continuous), remnant-C tertiles (categorical) and a prespecified cutoff (75th percentile) for high remnant-C (categorical). Bias-corrected bootstrapping was used for internal validation.

Results

Eighty-seven (11.5%) patients had an event, 14 (1.9%) patients withdrew consent, and 5 (0.7%) patients were lost to follow up at 12 months. In multivariable-adjusted analyses, remnant-C (hazard ratio [HR]: 1.63; 95% confidence interval [CI]: 1.04 to 2.74; per log2 increase; p=0.020), triglycerides (HR: 1.41; 95% CI: 1.04 to 1.96; per log2 increase; p=0.017), and low high-density lipoprotein (HDL)-C (HR: 0.56; 95% CI: 0.33 to 0.86; per log2 increase; p<0.040), but not LDL-C (HR: 1.41; 95% CI: 0.78 to 2.84; per log2 increase; p=0.272), were associated with MACE. High remnant-C was independently associated with elevated risk of MACE when adjusting for clinical and demographic factors including GRACE 2.0 risk estimates (HR: 2.43; 95% CI: 1.42 to 4.27; above vs. below 75th percentile; p<0.001; HR: 2.10; 95% CI: 1.09 to 4.70; tertile 3 vs. tertile 1; p=0.014).

Conclusion

In patients who develop ACS with LDL-C levels <100 mg/dl, levels of remnant-C and triglycerides, but not LDL-C, were associated with adverse CV outcomes independent of other risk factors.

Funding Acknowledgement

Type of funding sources: Public Institution(s). Main funding source(s): Swiss National Science FoundationSwiss Heart Foundation
Incidence of spontaneous coronary artery dissection during pregnancy in Swedish women between 1997 to 2019, a retrospective observational cohort study based on national Swedish health-registers
Authors: Nebeski D , Basic C , Svanvik T , Schaufelberger M , Ostgard Thunstrom E
Published: October 2022

Background/Introduction

Spontaneous coronary artery dissection (SCAD) is an acute myocardial event. Previous studies suggest female predominance. It is an unusual underlying cause of myocardial infarction. However, it is thought to be the most common cause of myocardial infarction associated with pregnancy.

Purpose

The aim of the study was to collect data on all women of reproductive age that had been diagnosed with SCAD in Sweden, including both pregnant and non-pregnant women, using the national Swedish health registers of the last two decades to describe the cohort and compare clinical characteristics.

Methods

Retrospective data on individuals with a diagnosis of SCAD (ICD-I25.4) occurring before fifty years of age were collected from four Swedish registers; the national patient register, the national medical birth register, the national cause of death register and the LISA register. Women diagnosed with SCAD between the years 1997 and 2019 and <50 years of age at diagnosis were included. SCAD during pregnancy or within 14 weeks post-partum was considered pregnancy-associated.

Results

A total of 75 women comprised the final cohort, seven of which met the criteria for pregnancy-associated SCAD. Nine percent of all women that had SCAD in Sweden before 50 years of age had it in association with pregnancy and in SCAD that occurred before 40 years of age, 28% arose in association with pregnancy. There were no clinically significant differences in height between women with pregnancy-associated SCAD and those with SCAD not associated with pregnancy. History of smoking, diabetes mellitus, hyperthyroidism, hypothyroidism and hyperlipidemia were not prominent in the cohort (9.3, 4, 1.3, 2.7 and 2.7% respectively). Seventeen percent of patients had had no pregnancies prior to first event of SCAD. Two patients (2.6%) were deceased due to ischemic heart disease, one had had SCAD associated with pregnancy.

Conclusion

Spontaneous coronary artery dissections are uncommon. However, when they do occur in women under forty years of age more than one in four (28%) is associated with pregnancy.

Funding Acknowledgement

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish heart lung foundation.
Administration of a human recombinant apyrase (AZD3366) limits myocardial tissue injury and improves cardiac function in a pig model of STEMI assessed by serial CMR
Authors: Vilahur G , Radike M , Sutelman P , Ben-Aicha S , Gutierrez M , Casani L , Mendieta G , Hidalgo A , Fjellstrom O , Carlsson L , Badimon L
Published: October 2022

Background

Mitigating myocardial tissue injury (MTI) remains an unmet clinical need in the reperfusion era. Stimulating adenosine synthesis through the breakdown of adenosine triphosphate (ATP) by apyrase (CD39), an endothelial ADPase, has emerged as a potential new avenue in the reduction of MTI.

Purpose

In this study we examined whether the intravenous administration of a recombinant soluble form of human apyrase (AZD3366) prior to reperfusion limits MTI and improves cardiac function in a pig model of STEMI as assessed by serial cardiac magnetic resonance (CMR) imaging.

Methods

Pigs (n=16) were subjected to STEMI induction (1.5h closed-chest complete LAD coronary balloon occlusion). Immediately prior to reperfusion, pigs were randomized to intravenously receive one single dose of 3 mg/kg AZD3366 (n=8) or vehicle (n=8). Serial-CMR imaging was performed at baseline, 3 days, and 42 days post-MI for the assessment of structural and functional readouts at rest and during dobutamine stress. Light transmittance aggregometry (LTA; challenged by 5, 10 and 20 μM ADP) and ear bleeding time were monitored pre-MI, post-MI and at day 3.

Results

AZD3366 significantly reduced MTI by limiting (around 60%) oedema formation (21.3±6.7 vs. 12.3±6.7 g LV) and infarct size (14.3±6.1 vs. 8.4±3.4 g LV) and preventing microvascular obstruction (2.3±0.9 vs. 0.5±0.5 g LV) at 3 days post-MI, compared to vehicle-administered STEMI pigs (p<0.05). At a functional level, LVEDV and LVESV showed less deterioration in AZD3366 treated animal as compared to vehicle 3 days post-MI (p<0.05) and less numerical decrease of LVEF. Furthermore, AZD3366-treated animals showed no deterioration in LVEF upon dobutamine stress in contrast to vehicle-infused animals, (p<0.05). AZD3366 treatment nearly abolished LTA at all tested ADP doses early post-STEMI, an effect that remained up to 3 days post-infusion but did not affect ear bleeding time at any of the tested time points. No additional effects were seen at 42 days.

Conclusion

Infusion of one single dose of the soluble recombinant apyrase AZD3366 prior to reperfusion exerts cardioprotection by reducing oedema formation, microvascular obstruction and necrosis and improving cardiac performance at rest and after dobutamine stress during the acute post-MI period. Administration of AZD3366 as an adjunctive therapy to standard of care for STEMI patients undergoing primary PCI may reduce myocardial tissue injury.

Funding Acknowledgement

Type of funding sources: Private company. Main funding source(s): AstraZeneca, Gothenburg, Sweden
Bed rest duration and complications after transfemoral cardiac catheterization: a network meta-analysis
Authors: Busca Erica , Airoldi Chiara , Bertoncini Fabio , Buratti Giulia , Casarotto Roberta , Gaboardi Samanta , Faggiano Fabrizio , Barisone Michela , White Ian R , Allara Elias , Dal Molin Alberto
Published: October 2022

Aims

To assess the effects of bed rest duration on short-term complications following transfemoral catheterization.

Methods and results

A systematic search was carried out in MEDLINE, Embase, CINAHL, Cochrane Database of Systematic Reviews, Scopus, SciELO and in five registries of grey literature. Randomized controlled trials and quasi-experimental studies comparing different durations of bed rest after transfemoral catheterization were included. Primary outcomes were haematoma and bleeding near the access site. Secondary outcomes were arteriovenous fistula, pseudoaneurysm, back pain, general patient discomfort and urinary discomfort. Study findings were summarized using a network meta-analysis (NMA). Twenty-eight studies and 9217 participants were included (mean age 60.4 years). In NMA, bed rest duration was not consistently associated with either primary outcome, and this was confirmed in sensitivity analyses. There was no evidence of associations with secondary outcomes, except for two effects related to back pain. A bed rest duration of 2–2.9 h was associated with lower risk of back pain [risk ratio (RR) 0.33, 95% confidence interval (CI) 0.17–0.62] and a duration over 12 h with greater risk of back pain (RR 1.94, 95% CI 1.16–3.24), when compared with the 4–5.9 h interval. Post hoc analysis revealed an increased risk of back pain per hour of bed rest (RR 1.08, 95% CI 1.04–1.11).

Conclusion

A short bed rest was not associated with complications in patients undergoing transfemoral catheterization; the greater the duration of bed rest, the more likely the patients were to experience back pain. Ambulation as early as 2 h after transfemoral catheterization can be safely implemented.

Registration

PROSPERO: CRD42014014222.
Phages, anti-CRISPR proteins, and drug-resistant bacteria: what do we know about this triad?
Authors: Ceballos-Garzon Andres , Muñoz Angela B , Plata Juan D , Sanchez-Quitian Zilpa A , Ramos-Vivas Jose
Published: October 2022

Phages are viruses that infect bacteria, relying on their genetic machinery to replicate. To survive the constant attack of phages, bacteria have developed diverse defense strategies to act against them. Nevertheless, phages rapidly co-evolve to overcome these barriers, resulting in a constant, and often surprising, molecular arms race. Thus, some phages have evolved protein inhibitors known as anti-CRISPRs (∼50–150 amino acids), which antagonize the bacterial CRISPR-Cas immune response. To date, around 45 anti-CRISPRs proteins with different mechanisms and structures have been discovered against the CRISPR-Cas type I and type II present in important animal and human pathogens such as Escherichia, Morganella, Klebsiella, Enterococcus, Pseudomonas, Staphylococcus, and Salmonella. Considering the alarming growth of antibiotic resistance, phage therapy, either alone or in combination with antibiotics, appears to be a promising alternative for the treatment of many bacterial infections. In this review, we illustrated the biological and clinical aspects of using phage therapy; furthermore, the CRISPR-Cas mechanism, and the interesting activity of anti-CRISPR proteins as a possible weapon to combat bacteria.
Ideology and the Red Button: How Ideology Shapes Nuclear Weapons’ Use Preferences in Europe
Authors: Onderco Michal , Etienne Tom W , Smetana Michal
Published: October 2022

Does partisan ideology influence whether Europeans are willing to use nuclear weapons, and if so, how? The US nuclear weapons stationed in Europe have been at the core of European security since the Cold War, but we have still yet to learn what would make Europeans be willing to support their use. In this paper, we present the results of a survey, in which we asked citizens in Germany and the Netherlands about their views on the use of the US nuclear weapons stationed on their territory in four distinct scenarios. Our results indicate that voters of right-wing parties are more likely to approve of the use of nuclear weapons in both countries. There are, however, important differences between the two countries in terms of the degree to which the participants oppose the use of nuclear weapons. These results have implications for NATO's nuclear deterrence posture.
Friendship in Later Life: A Pathway Between Volunteering Hours and Depressive Symptoms
Authors: Lim Emily , Peng Changmin , Burr Jeffrey A
Published: October 2022

Objectives

Friendships are essential in the face of social network changes in later life and friendships may be important for reducing depression risk. Social participation through volunteering is also associated with fewer depressive symptoms. What is less well-understood is whether friendships serve as a pathway in the link between volunteering and depression.

Methods

We used panel data from the Health and Retirement Study (2010, 2014, 2018). Negative binomial regression within the SEM modeling framework was employed to analyze the association between volunteering and friendship, focusing on the indirect effect of friendships for understanding the volunteering and depressive symptoms relationship.

Results

Volunteer hours were positively associated with friendship (1–99 hr: β = 0.17, p < .001, 100–199 hr: β = 0.15, p < .001, 200 hr and more: β = 0.23, p < .001) and negatively associated with number of depressive symptoms (1–99 hr: β = −0.07, p = .06, 100–199 hr: β = −0.14, p < .001, 200 hr and more: β = −0.17, p < .001). Friendship mediated the relationship between volunteer hours and depressive symptoms (indirect effects; 1–99 hr: β = −0.01, 95% confidence interval [CI] = [−0.02, −0.00], p = .03), 100–199 hr: β = −0.01, 95% CI = [−0.02, −0.00], p = .03), 200 hr and more: β = −0.02, 95% CI = [−0.03, −0.00], p = .03).

Discussion

Our findings underscored the role of volunteering in generating and maintaining friendships, as well as for friendships as a pathway between volunteer hours and depressive symptoms. Providing opportunities to maintain and grow friendships in later life may be a possible intervention strategy for older adults at risk of depression.
Assigning pathogenicity for TAB2 variants using a novel scalable functional assay and expanding TAB2 disease spectrum
Authors: Xu Weiyi , Graves Andrea , Weisz-Hubshman Monika , Hegazy Lamees , Magyar Christina , Liu Zian , Nasiotis Eleni , Samee Md Abul Hassan , Burris Thomas , Lalani Seema , Zhang Lilei
Published: October 2022

Haploinsufficiency of TGF-beta-activated kinase 1 (MAP3K7) binding protein 2 (TAB2) has been associated with congenital heart disease and more recently multiorgan structural abnormalities. Missense variant represents a major proportion of non-synonymous TAB2 variants reported in gnomAD (295/576) and Clinvar (16/73), most of which are variants of uncertain significance (VUSs). However, interpretation of TAB2 missense variants remains challenging because of lack of functional assays. To address this issue, we established a cell-based luciferase assay that enables high-throughput screening of TAB2 variants to assess the functional consequence for predicting variant pathogenicity. Using this platform, we screened 47 TAB2 variants including five pathogenic controls and one benign control, and the results showed that the transcriptional activity of activator protein 1 (AP-1) but not nuclear factor kappa B predicts the TAB2 variant pathogenicity. This assay provides accurate functional readout for both loss-of-function (LOF) and gain-of-function variants, which are associated with distinct phenotypes. In all, 22 out of 32 tested VUSs were reclassified. Genotype–Phenotype association showed that most patients with partial LOF variants do not exhibit congenital heart disease but high frequency of developmental delay, hypotonia and dysmorphic features, which suggests that genetic testing for TAB2 is needed for a broader spectrum of patients with more diverse phenotypes. Molecular modeling with Npl4 zinc finger (NZF) domain variants revealed that the stability of the NZF domain in TAB2 protein is crucial for AP-1 activation. In conclusion, we developed a highly effective functional assay for TAB2 variant prediction and interpretation.
The Translation Stage in LSP Lexicography: A Mixed Translation Model for LSP Bilingual Dictionary Terms
Authors: Katić Marina , Novakov Predrag
Published: October 2022

This paper focuses on the translation stage in LSP bilingual lexicography, where the condition of equivalence lies in the terminological/conceptual identity of the terms used in different linguistic systems. To this end, case study research was done on the corpus of the English-Serbian Dictionary of Waste Management. Seeking to provide a more extensive picture of the rendition of specialized terms, the authors propose a systematic translation framework by combining traditional Translation Theory with the modern Function Theory of Lexicography. Therefore, the LSP dictionary counterparts were analyzed from the perspectives of both theories, using a mixed translation model for both single and compound words. This paper aims to resolve the question of why the translation of the specialized dictionary terms produced the result it had, the explanation of which might help compile modern LSP bilingual dictionaries from English into Serbian, or into other languages of South-East Slavic origin.
Lower Insulin Sensitivity in Newborns With In Utero HIV and Antiretroviral Exposure Who Are Uninfected in Botswana
Authors: Jao Jennifer , Sun Shan , Bonner Lauren B , Legbedze Justine , Mmasa Keolebogile N , Makhema Joseph , Mmalane Mompati , Kgole Samuel , Masasa Gosego , Moyo Sikhulile , Gerschenson Mariana , Mohammed Terence , Abrams Elaine J , Kurland Irwin J , Geffner Mitchell E , Powis Kathleen M
Published: October 2022

Background

Few data exist on early-life metabolic perturbations in newborns with perinatal HIV and antiretroviral (ARV) exposure but uninfected (HEU) compared to those perinatally HIV unexposed and uninfected (HUU).

Methods

We enrolled pregnant persons with HIV (PWH) receiving tenofovir (TDF)/emtricitabine or lamivudine (XTC) plus dolutegravir (DTG) or efavirenz (EFV), and pregnant individuals without HIV, as well as their liveborn infants. Newborns were randomized to receive either zidovudine (AZT) or nevirapine (NVP) postnatal prophylaxis. Preprandial homeostasis model assessment for insulin resistance (HOMA-IR) was assessed at birth and 1 month. Linear mixed models were fit to assess the association between in utero HIV/ARV exposure and average HOMA-IR from birth to 1 month, adjusting for confounders.

Results

Of 450 newborns, 306 were HEU. HOMA-IR was higher in newborns HEU versus HUU after adjusting for confounders (mean difference of 0.068 in log HOMA-IR, P = .037). Among newborns HEU, HOMA-IR was not significantly different between TDF/XTC/DTG versus TDF/XTC/EFV in utero ARV exposure and between AZT versus NVP newborn postnatal prophylaxis arms.

Conclusions

Newborns HEU versus HUU had lower insulin sensitivity at birth and at 1 month of life, raising potential concern for obesity and other metabolic perturbations later in life for newborns HEU.

Clinical Trials Registration

NCT03088410.
Can medical students do anything useful to support the antimicrobial resistance agenda?
Authors: Launer David
Published: October 2022

The emergence of antimicrobial resistance (AMR) is a current and future challenge for patients and clinicians, but the role of medical students in combating AMR is not well established. The most important role for students would be supporting the agenda of antimicrobial stewardship (AMS), which is an effective and evidence-based set of actions that mitigate the emergence of resistance. Medical students can be seen as unlikely activists, who have a strong track record of becoming activists for other causes. If they could extend this activist role to AMR/AMS, they could have outsized impact. In order to achieve this, it is imperative that students begin to organize in their own institutions, in collaboration with those working in other disciplines.
Effects of limestone solubility on the efficacy of a novel consensus bacterial 6-phytase variant to improve mineral digestibility, retention, and bone ash in young broilers fed low-calcium diets containing no added inorganic phosphate
Authors: Bello Abiodun , Kwakernaak Cees , Dersjant-Li Yueming
Published: October 2022

This study evaluated the effect of limestone solubility on the capacity of a novel consensus bacterial 6-phytase variant (PhyG) to improve phosphorus (P) and calcium (Ca) digestibility, retention, and utilization in low-Ca broiler diets containing no added inorganic phosphate (Pi). Male Ross 308 broilers (n = 1,152) were fed one of 16 experimental diets from 11 to 21 d of age in a randomized complete design (12 birds/cage, 6 cages/treatment). Diets comprised three positive controls (PC3, PC2, and PC1) containing 1.8, 1.2, or 0.6 g/kg MCP-P and 7.7, 7.0, or 6.2 g/kg Ca, respectively, and a negative control (NC) containing no added Pi (4.4 g/kg P; 2.8 g/kg phytate-P) and 5.5 g/kg Ca from either low or high solubility limestone (LSL or HSL, respectively, [with 42% and 97% solubility after 5 min at pH 3.0]), supplemented with 0, 250, 500, 1,000, or 2,000 FTU/kg of PhyG. Fecal samples collected on days 18 to 20 and ileal digesta collected on day 21 were analyzed for titanium dioxide, Ca, P, and phytate (IP6, inositol hexakisphosphate). Tibias (day 21) were analyzed for ash content. Data were analyzed by factorial analysis (2 limestone solubilities × 4 MCP-P levels and 2 limestone solubilities × 5 phytase dose levels) and exponential regression. Increasing dose levels of PhyG resulted in an exponential increase (P < 0.01) in the apparent ileal digestibility (AID) of P, ileal digestible P content of the diet, ileal IP6 content, and IP6 disappearance in birds fed either HSL or LSL diets, but AID Ca and ileal digestible Ca were exponentially increased by the phytase only in HSL diets (P < 0.01). Relative to HSL, the LSL increased AID P, ileal digestible P, and IP6 disappearance (P < 0.05) but reduced AID Ca, ileal digestible Ca, and retainable Ca (P < 0.05), resulting in reduced retainable P and tibia ash. Phytase exponentially increased the apparent total tract digestibility of P, retainable P, and tibia ash in HSL and LSL diets, but at or above 500 FTU/kg values were higher in HSL than LSL (interaction P < 0.05). The findings highlight that phytase dose–response effects on mineral digestibility and utilization are different for high- and low-solubility limestones, and it is therefore recommended to use digestible rather than total Ca content during diet formulation to ensure an optimal balance of Ca and P, especially in low-Ca diets. In diets containing HSL, higher phytase dose levels may be needed to compensate for the low digestible P content of the basal diet.
Shifts in bacterial communities in the rumen, vagina, and uterus of beef heifers receiving different levels of concentrate
Authors: Pickett Autumn T , Cooke Reinaldo F , Mackey Shea J , Brandão Alice P , Colombo Eduardo A , Oliveira Filho Ramiro V , de Melo Gabriela Dalmaso , Pohler Ky G , Poole Rebecca K
Published: October 2022

This experiment investigated the effects of diet composition on rumen, vaginal, and uterine microbiota of beef heifers. Fifteen rumen-cannulated, pubertal Angus-influenced heifers were used in a replicated 3 × 3 Latin square design (28-d periods and 21-d washout intervals). Dietary treatments included diets based on (as-fed) 100% grass hay (HF), 60% grass hay + 40% corn-based concentrate (INT), or 25% grass hay + 75% corn-based concentrate (HG). Treatments were offered individually to heifers once daily at 2% body weight. Rumen, vaginal, and uterine samples were collected on days 0 and 28 of each period. Data were analyzed using orthogonal contrasts (linear and quadratic), using results from day 0 as independent covariates and heifer as the experimental unit. Ruminal pH on day 28 decreased linearly (P < 0.01) as concentrate inclusion increased. Uterine and vaginal pH on day 28 were not affected by treatments (P ≥ 0.35). Within the rumen samples, Bacteriodetes was the most abundant phylum and its relative abundance linearly decreased (P ≤ 0.01) with the inclusion of concentrate. Prevotella was the most abundant genus within the rumen but was not affected by treatments (P ≥ 0.44). Genera with relative abundance ≥1% (average across treatments) in the rumen that were impacted by treatments (P ≤ 0.01) included Bacteroides, Pedobacter, Dysgonomonas, Caloramator, and Ruminococcus. Firmicutes was the most abundant phylum in the vagina and uterus, but it was unaffected by treatments (P ≥ 0.16). Prevotella was the most abundant genus in the vagina, and its relative abundance increased (P < 0.01) with the inclusion of concentrate. Other genera with relative abundance ≥1% that were significantly affected (P ≤ 0.05) by treatments were Clostridium, Pedobacter, Roseburia, Oscillospira, Faecalibacterium, Caloramator, Paludibacter, Rhodothermus, and Porphyromonas. In uterine samples, Prevotella was the most abundant genus but was unaffected by treatments (P ≥ 0.29). Genera with relative abundance ≥1% in the uterus that were significantly affected (P < 0.01) by treatments were Caloramator, Paludibacter, and Thalassospira. Collectively, inclusion of concentrate in the diet altered the bacterial composition within the rumen as well as shifting bacterial populations within the vagina and uterus. Research is warranted to further understand the impacts of these diet-induced microbiota changes on reproductive function and performance of beef heifers.