bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence, serovar, and antimicrobial resistance of Salmonella isolated from meat and minced meat used for production smoked sausage
Authors: Zaiko E V , Bataeva D S , Yushina Yu K , Grudistova M A , Velebit B
Published: November 2021

The objective of this study was to research the prevalence, serovars, and antimicrobial resistance profiles of Salmonella isolated from meat and minced meat used for the production of fermented sausage. A total of 116 samples were tested, and among them, 20 (17.2%) were positive. Salmonella was detected in 3 (10.3%) beef samples, 5 (19.2%) pork samples, and 6 (20.7%) poultry samples. In minced meat, the Salmonella prevalence was 18.8%. Salmonella enterica serovar Agama (5.2%) was the most commonly identified serovar, followed by S. Enteritidis (4.3%), S. Typhimurium (3.4%), S. Infantis (2.6%), and S. Lindenburg (1.7%). Most of the serovars identified in the present study are recognized as frequent causes of human salmonellosis. Thus, the presence of these serovars means foods with these meats are a likely source of human infections. We found the Salmonella isolates exhibited high rates of resistance to antimicrobials tetracycline, ampicillin, streptomycin, and ciprofloxacin. The highest level of resistance was to tetracycline (75%), followed by resistance to ampicillin (50%), streptomycin (30%), ciprofloxacin (20%), gentamicin (20%), and neomycin (10%). The high-level resistance observed for some of the serovars calls for concern. Salmonella with multidrug resistance in meat used to produce fermented sausages is considered a high additional risk for human health.
Five-Year Dynamic Prediction of Dementia Using Repeated Measures of Cognitive Tests and a Dependency Scale
Authors: Ben-Hassen Céline , Helmer Catherine , Berr Claudine , Jacqmin-Gadda Hélène
Published: November 2021

The progression of dementia prevalence over the years and the lack of efficient treatments to stop or reverse the cognitive decline make dementia a major public health challenge in the developed world. Identifying people at high risk of developing dementia could improve the treatment of these patients and help select the target population for preventive clinical trials. We used joint modeling to build a dynamic prediction tool of dementia based on the change over time of 2 neurocognitive tests (the Mini-Mental State Examination and the Isaacs Set Tests) as well as an autonomy scale (the Instrumental Activities of Daily Living). The model was estimated with data from the French cohort Personnes Agées QUID (1988–2015) and validated both by cross-validation and externally with data from the French Three City cohort (1999–2018). We evaluated its predictive abilities through area under the receiver operating characteristics curve and Brier score, accounting for right censoring and competing risk of death, and obtained an average area under the curve value of 0.95 for the risk of dementia in the next 5 or 10 years. This tool is able to discriminate a high-risk group of people from the rest of the population. This could be of help in clinical practice and research.
The Impact of Increasing the Minimum Legal Drinking Age from 18 to 20 Years in Lithuania on All-Cause Mortality in Young Adults—An Interrupted Time-Series Analysis
Authors: Tran Alexander , Jiang Huan , Lange Shannon , Livingston Michael , Manthey Jakob , Neufeld Maria , Room Robin , Štelemėkas Mindaugas , Telksnys Tadas , Petkevičienė Janina , Radišauskas Ričardas , Rehm Jürgen
Published: November 2021

Aims

To determine the effect of an alcohol policy change, which increased the minimum legal drinking age (MLDA) from 18 years of age to 20 years of age on all-cause mortality rates in young adults (18–19 years old) in Lithuania.

Methods

An interrupted time series analysis was conducted on a dataset from 2001 to 2019 (n = 228 months). The model tested the effects of the MLDA on all-cause mortality rates (deaths per 100,000 individuals) in three age categories (15–17 years old, 18–19 years old, 20–22 years old) in order to control for general mortality trends in young adults, and to isolate the effects of the MLDA from other alcohol control policies. Additional models that included GDP as a covariate and a taxation policy were tested as well.

Results

There was a significant effect of the MLDA on all-cause mortality rates in those 18–19 years old, when modelled alone. Additional analyses controlling for the mortality rate of other age groups showed similar findings. Inclusion of confounding factors (policies on alcohol taxation, GDP) eliminated the effects of MLDA.

Conclusions

Although there was a notable decline in all-cause mortality rates among young adults in Lithuania, a direct causal impact of MLDA on all-cause mortality rates in young adults was not definitively found.
iCRISEE: an integrative analysis of CRISPR screen by reducing false positive hits
Authors: Zhang Tengbo , Li Yaxu , Yang Yanrong , Weng Linjun , Wu Zhiqiang , Zhu Jiali , Qin Jieling , Liu Qi , Wang Ping
Published: November 2021

Clustered regularly interspaced short palindromic repeats associated protein 9 (CRISPR/Cas9) technology has become a popular tool for the study of genome function, and the use of this technology can achieve large-scale screening studies of specific phenotypes. Several analysis tools for CRISPR/Cas9 screening data have been developed, while high false positive rate remains a great challenge. To this end, we developed iCRISEE, an integrative analysis of CRISPR ScrEEn by reducing false positive hits. iCRISEE can dramatically reduce false positive hits and it is robust to different single guide RNA (sgRNA) library by introducing precise data filter and normalization, model selection and valid sgRNA number correction in data preprocessing, sgRNA ranking and gene ranking. Furthermore, a powerful web server has been presented to automatically complete the whole CRISPR/Cas9 screening analysis, where we integrated the main hypothesis in multiple algorithms as a full workflow, including quality control, sgRNA extracting, sgRNA alignment, sgRNA ranking, gene ranking and pathway enrichment. In addition, output of iCRISEE, including result mapping, sample clustering, sgRNA ranking and gene ranking, can be easily visualized and downloaded for publication. Taking together, iCRISEE presents to be the state-of-the-art and user-friendly tool for CRISPR screening data analysis. iCRISEE is available at https://www.icrisee.com.
FusionDTA: attention-based feature polymerizer and knowledge distillation for drug-target binding affinity prediction
Authors: Yuan Weining , Chen Guanxing , Chen Calvin Yu-Chian
Published: November 2021

The prediction of drug-target affinity (DTA) plays an increasingly important role in drug discovery. Nowadays, lots of prediction methods focus on feature encoding of drugs and proteins, but ignore the importance of feature aggregation. However, the increasingly complex encoder networks lead to the loss of implicit information and excessive model size. To this end, we propose a deep-learning-based approach namely FusionDTA. For the loss of implicit information, a novel muti-head linear attention mechanism was utilized to replace the rough pooling method. This allows FusionDTA aggregates global information based on attention weights, instead of selecting the largest one as max-pooling does. To solve the redundancy issue of parameters, we applied knowledge distillation in FusionDTA by transfering learnable information from teacher model to student. Results show that FusionDTA performs better than existing models for the test domain on all evaluation metrics. We obtained concordance index (CI) index of 0.913 and 0.906 in Davis and KIBA dataset respectively, compared with 0.893 and 0.891 of previous state-of-art model. Under the cold-start constrain, our model proved to be more robust and more effective with unseen inputs than baseline methods. In addition, the knowledge distillation did save half of the parameters of the model, with only 0.006 reduction in CI index. Even FusionDTA with half the parameters could easily exceed the baseline on all metrics. In general, our model has superior performance and improves the effect of drug–target interaction (DTI) prediction. The visualization of DTI can effectively help predict the binding region of proteins during structure-based drug design.
scIAE: an integrative autoencoder-based ensemble classification framework for single-cell RNA-seq data
Authors: Yin Qingyang , Wang Yang , Guan Jinting , Ji Guoli
Published: November 2021

Single-cell RNA sequencing (scRNA-seq) allows quantitative analysis of gene expression at the level of single cells, beneficial to study cell heterogeneity. The recognition of cell types facilitates the construction of cell atlas in complex tissues or organisms, which is the basis of almost all downstream scRNA-seq data analyses. Using disease-related scRNA-seq data to perform the prediction of disease status can facilitate the specific diagnosis and personalized treatment of disease. Since single-cell gene expression data are high-dimensional and sparse with dropouts, we propose scIAE, an integrative autoencoder-based ensemble classification framework, to firstly perform multiple random projections and apply integrative and devisable autoencoders (integrating stacked, denoising and sparse autoencoders) to obtain compressed representations. Then base classifiers are built on the lower-dimensional representations and the predictions from all base models are integrated. The comparison of scIAE and common feature extraction methods shows that scIAE is effective and robust, independent of the choice of dimension, which is beneficial to subsequent cell classification. By testing scIAE on different types of data and comparing it with existing general and single-cell–specific classification methods, it is proven that scIAE has a great classification power in cell type annotation intradataset, across batches, across platforms and across species, and also disease status prediction. The architecture of scIAE is flexible and devisable, and it is available at https://github.com/JGuan-lab/scIAE.
MatrixQCvis: shiny-based interactive data quality exploration for omics data
Authors: Naake Thomas , Huber Wolfgang
Published: November 2021

Motivation

First-line data quality assessment and exploratory data analysis are integral parts of any data analysis workflow. In high-throughput quantitative omics experiments (e.g. transcriptomics, proteomics and metabolomics), after initial processing, the data are typically presented as a matrix of numbers (feature IDs × samples). Efficient and standardized data quality metrics calculation and visualization are key to track the within-experiment quality of these rectangular data types and to guarantee for high-quality datasets and subsequent biological question-driven inference.

Results

We present MatrixQCvis, which provides interactive visualization of data quality metrics at the per-sample and per-feature level using R’s shiny framework. It provides efficient and standardized ways to analyze data quality of quantitative omics data types that come in a matrix-like format (features IDs × samples). MatrixQCvis builds upon the Bioconductor SummarizedExperiment S4 class and thus facilitates the integration into existing workflows.

Availability and implementation

MatrixQCVis is implemented in R. It is available via Bioconductor and released under the GPL v3.0 license.

Supplementary information

Supplementary data are available at Bioinformatics online.
GADGETS: a genetic algorithm for detecting epistasis using nuclear families
Authors: Nodzenski Michael , Shi Min , Krahn Juno M , Wise Alison S , Li Yuanyuan , Li Leping , Umbach David M , Weinberg Clarice R
Published: November 2021

Motivation

Epistasis may play an etiologic role in complex diseases, but research has been hindered because identification of interactions among sets of single nucleotide polymorphisms (SNPs) requires exploration of immense search spaces. Current approaches using nuclear families accommodate at most several hundred candidate SNPs.

Results

GADGETS detects epistatic SNP-sets by applying a genetic algorithm to case-parent or case-sibling data. To allow for multiple epistatic sets, island subpopulations of SNP-sets evolve separately under selection for evident joint relevance to disease risk. The software evaluates the identified SNP-sets via permutation testing and provides graphical visualization. GADGETS correctly identified epistatic SNP-sets in realistically simulated case-parent triads with 10 000 candidate SNPs, far more SNPs than competitors can handle, and it outperformed competitors in simulations with many fewer SNPs. Applying GADGETS to family-based oral-clefting data from dbGaP identified SNP-sets with possible epistatic effects on risk.

Availability and implementation

GADGETS is part of the epistasisGA package at https://github.com/mnodzenski/epistasisGA.

Supplementary information

Supplementary data are available at Bioinformatics online.
T2-DAG: a powerful test for differentially expressed gene pathways via graph-informed structural equation modeling
Authors: Jin Jin , Wang Yue
Published: November 2021

Motivation

A major task in genetic studies is to identify genes related to human diseases and traits to understand functional characteristics of genetic mutations and enhance patient diagnosis. Compared with marginal analyses of individual genes, identification of gene pathways, i.e. a set of genes with known interactions that collectively contribute to specific biological functions, can provide more biologically meaningful results. Such gene pathway analysis can be formulated into a high-dimensional two-sample testing problem. Given the typically limited sample size of gene expression datasets, most existing two-sample tests tend to have compromised powers because they ignore or only inefficiently incorporate the auxiliary pathway information on gene interactions.

Results

We propose T2-DAG, a Hotelling’s T2-type test for detecting differentially expressed gene pathways, which efficiently leverages the auxiliary pathway information on gene interactions from existing pathway databases through a linear structural equation model. We further establish its asymptotic distribution under pertinent assumptions. Simulation studies under various scenarios show that T2-DAG outperforms several representative existing methods with well-controlled type-I error rates and substantially improved powers, even with incomplete or inaccurate pathway information or unadjusted confounding effects. We also illustrate the performance of T2-DAG in an application to detect differentially expressed KEGG pathways between different stages of lung cancer.

Availability and implementation

The R (R Development Core Team, 2021) package T2DAG which implements the proposed T2-DAG test is available on Github at https://github.com/Jin93/T2DAG.

Supplementary information

Supplementary data are available at Bioinformatics online.
Genetic variation in the symbiont partners in the endangered macrolichenSeirophora villosa(Teloschistaceae: Ascomycota)
Authors: Garrido-Benavent Isaac , Molins Arántzazu , Barreno Eva
Published: November 2021

The decline observed in many populations of highly sensitive lichens has led to the inclusion of some species on regional Red Lists, but this has seldom been accompanied by an examination of the genetic variation of the fungal and algal symbiotic partners. Here, the red-listed epiphytic lichen Seirophora villosa was surveyed in 14 Mediterranean coastal populations to examine the genetic diversity of both partners. The geographical distribution of four-locus haplotypes followed the same trend in mycobiont and photobiont data sets, some being widespread and others restricted to single localities. The fungus showed a moderate selectivity in its photobiont choice, associating with two undescribed Trebouxia microalgae with a biased distribution across the western Mediterranean. One alga species occurred exclusively in the Italian Peninsula. This region also hosted the highest number of haplotypes for both symbionts. The use of 454-pyrosequencing revealed no clear signs of algal coexistence within selected thalli. The phylogenetic reconstruction for the mycobiont showed uncertain limits among Seirophora spp., stressing the need for further taxonomic evaluation. Additionally, we found that Ramalina lacera, a co-occurring epiphytic lichen in the studied area, shared photobiont genotypes with S. villosa. Our results thus suggest that the protection not only of the red-listed species S. villosa, but also of the whole epiphytic lichen community investigated here might be advisable.
The evolution of a bitter taste receptor gene in primates
Authors: Liang Qiufang , Shu Fanglan , Dong Xiaoyan , Feng Ping
Published: November 2021

Bitter taste perception is critical to prevent animals from ingesting potentially harmful substances. The aim of this study was to characterize the evolution of T2R4 and test the hypothesis that different regions of the T2R gene are subject to disparate selective pressures, with extracellular regions (ECs) being erratic while transmembrane (TMs) and intracellular regions (ICs) being constrained. Thus, we examined the selective pressures acting on T2R4 and its different regions in 37 primates, and discovered that T2R4 and ECs were subject to neutral evolution and purifying selection, respectively, whereas both TMs and ICs showed purifying selection, as suggested by the hypothesis. We attribute this result to the relatively conservative property of T2R4 gene and the limited number of bitter tastants that T2R4 can respond to. Furthermore, we found that positive selection had acted on the first loop of extracellular regions (EL1). In contrast, the second loop (EL2) and transmembrane region-3, -6, -7 (TM367) were subject to purifying selection, and the third loop (EL3) was subject to neutral evolution. This discovery is probably because EL2, EL3, and TMs play a crucial role in the ligand-binding process, and EL1 is involved in the tastant recognition process. We further tested whether the ω of T2R4 differs among species with different diets and found that a specialized diet affected the evolution of T2R4. Feeding habits, fewer T2Rs, and a dietary shift may account for the results. This study can help to uncover the evolution of T2Rs during the primate evolutionary course.
Association of cardiometabolic microRNAs with COVID-19 severity and mortality
Authors: Gutmann Clemens , Khamina Kseniya , Theofilatos Konstantinos , Diendorfer Andreas B , Burnap Sean A , Nabeebaccus Adam , Fish Matthew , McPhail Mark J W , O'Gallagher Kevin , Schmidt Lukas E , Cassel Christian , Auzinger Georg , Napoli Salvatore , Mujib Salma F , Trovato Francesca , Sanderson Barnaby , Merrick Blair , Roy Roman , Edgeworth Jonathan D , Shah Ajay M , Hayday Adrian C , Traby Ludwig , Hackl Matthias , Eichinger Sabine , Shankar-Hari Manu , Mayr Manuel
Published: November 2021

Aims

Coronavirus disease 2019 (COVID-19) can lead to multiorgan damage. MicroRNAs (miRNAs) in blood reflect cell activation and tissue injury. We aimed to determine the association of circulating miRNAs with COVID-19 severity and 28 day intensive care unit (ICU) mortality.

Methods and results

We performed RNA-Seq in plasma of healthy controls (n = 11), non-severe (n = 18), and severe (n = 18) COVID-19 patients and selected 14 miRNAs according to cell- and tissue origin for measurement by reverse transcription quantitative polymerase chain reaction (RT–qPCR) in a separate cohort of mild (n = 6), moderate (n = 39), and severe (n = 16) patients. Candidates were then measured by RT–qPCR in longitudinal samples of ICU COVID-19 patients (n = 240 samples from n = 65 patients). A total of 60 miRNAs, including platelet-, endothelial-, hepatocyte-, and cardiomyocyte-derived miRNAs, were differentially expressed depending on severity, with increased miR-133a and reduced miR-122 also being associated with 28 day mortality. We leveraged mass spectrometry-based proteomics data for corresponding protein trajectories. Myocyte-derived (myomiR) miR-133a was inversely associated with neutrophil counts and positively with proteins related to neutrophil degranulation, such as myeloperoxidase. In contrast, levels of hepatocyte-derived miR-122 correlated to liver parameters and to liver-derived positive (inverse association) and negative acute phase proteins (positive association). Finally, we compared miRNAs to established markers of COVID-19 severity and outcome, i.e. SARS-CoV-2 RNAemia, age, BMI, D-dimer, and troponin. Whilst RNAemia, age and troponin were better predictors of mortality, miR-133a and miR-122 showed superior classification performance for severity. In binary and triplet combinations, miRNAs improved classification performance of established markers for severity and mortality.

Conclusion

Circulating miRNAs of different tissue origin, including several known cardiometabolic biomarkers, rise with COVID-19 severity. MyomiR miR-133a and liver-derived miR-122 also relate to 28 day mortality. MiR-133a reflects inflammation-induced myocyte damage, whilst miR-122 reflects the hepatic acute phase response.
Into the Wild: Evidence for the Enemy Release Hypothesis in the Invasive Callery Pear (Pyrus calleryana) (Rosales: Rosaceae)
Authors: Hartshorn Jessica A , Palmer J Forest , Coyle David R
Published: November 2021

Wild Callery pear (Pyrus calleryana Decne.) results from a cross between various cultivars of P. calleryana and any other Pyrus individual. While many cultivars of this species are still commercially produced and sold for horticultural purposes in the United States, Callery pear is a detrimental invasive species that encroaches on many managed and natural areas, damages equipment and injures people, pets, and livestock with its thorny branches, and likely causes detrimental ecological impacts. Despite its importance as an invasive species, the mechanisms behind Callery pear’s invasion and spread are unclear. To identify potential drivers of invasion, we quantified feeding of generalist and specialist herbivores on Callery pear and four native tree species, based on insect host ranges, with choice and no-choice experiments followed by field surveys of herbivory on these same tree species. Feeding by all herbivores was lower on Callery pear than on native tree species in no-choice assays. Specifically, feeding on Callery pear was moderate by generalists and very low by specialists. Specialist feeding on Callery pear was comparable to native species in choice assays but was significantly reduced in no-choice assays. Reduced specialist feeding along with moderate generalist feeding on Callery pear in the field provides evidence for the Enemy Release Hypothesis as a potential driving mechanism behind its invasion success.
Incidence, clinical presentation, management, and outcome of acute pericarditis and myopericarditis
Authors: Prepoudis Alexandra , Koechlin Luca , Nestelberger Thomas , Boeddinghaus Jasper , Lopez-Ayala Pedro , Wussler Desiree , Zimmermann Tobias , Rubini Giménez Maria , Strebel Ivo , Puelacher Christian , Shrestha Samyut , Keller Dagmar I , Christ Michael , Gualandro Danielle M , Twerenbold Raphael , Martinez-Nadal Gemma , Lopez-Barbeito Beatriz , Miro Oscar , Mueller Christian ,   for the APACE investigators
Published: November 2021

Aims

Little is known about the epidemiology, clinical presentation, management, and outcome of acute pericarditis and myopericarditis.

Methods and results

The final diagnoses of acute pericarditis, myopericarditis, and non-ST-segment elevation myocardial infarction (NSTEMI) of patients presenting to seven emergency departments in Switzerland with acute chest pain were centrally adjudicated by two independent cardiologists using all information including serial measurements of high-sensitivity cardiac troponin T. The overall incidence of pericarditis and myopericarditis was estimated relative to the established incidence of NSTEMI. Current management and long-term outcome of both conditions were also assessed. Among 2533 chest pain patients, the incidence of pericarditis, myopericarditis, and NSTEMI were 1.9% (n = 48), 1.1% (n = 29), and 21.6% (n = 548), respectively. Accordingly, the estimated incidence of pericarditis and myopericarditis in Switzerland was 10.1 [95% confidence interval (95% CI) 9.3–10.9] and 6.1 (95% CI 5.6–6.7) cases per 100 000 population per year, respectively, vs. 115.0 (95% CI 112.3–117.6) cases per 100 000 population per year for NSTEMI. Pericarditis (85% male, median age 46 years) and myopericarditis (62% male, median age 56 years) had male predominance, and commonly (50% and 97%, respectively) resulted in hospitalization. No patient with pericarditis or myopericarditis died or had life-threatening arrhythmias within 30 days [incidence 0% (95% CI 0.0–4.8%)]. Compared with NSTEMI, the 2-year all-cause mortality adjusted hazard ratio of pericarditis and myopericarditis was 0.40 (95% CI 0.05–2.96), being 0.59 (95% CI 0.40–0.88) for non-cardiac causes of chest pain.

Conclusion

Pericarditis and myopericarditis are substantially less common than NSTEMI and have an excellent short- and long-term outcome.

Clinical trial registration

ClinicalTrial.gov, number NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587.
Referral decisions based on a pre-hospital HEART score in suspected non-ST-elevation acute coronary syndrome: final results of the FamouS Triage study
Authors: Tolsma Rudolf T , Fokkert Marion J , van Dongen Dominique N , Badings Erik A , van der Sluis Aize , Slingerland Robbert J , van ’t Riet Esther , Ottervanger Jan Paul , van ’t Hof Arnoud W J
Published: November 2021

Aims

Although pre-hospital risk stratification of patients with suspected non-ST-elevation acute coronary syndrome (NSTE-ACS) by ambulance paramedics is feasible, it has not been investigated in daily practice whether referral decisions based on this risk stratification is safe and does not increase major adverse cardiac events (MACE). In Phase III of the FamouS Triage study, it was investigated whether referral decisions by ambulance paramedics based on a pre-hospital HEART score, is non-inferior to routine management.

Methods and results

FamouS Triage Phase III is a non-inferiority study, comparing the occurrence of MACE before (Phase II) and after (Phase III) implementation of referral decisions based on a pre-hospital HEART score. In Phase II, all patients were risk-stratified and referred to the hospital; in Phase III, low-risk patients (HEART score ≤ 3) were not referred. Primary endpoint was MACE (acute coronary syndrome, revascularization, or death) within 45 days. A total of 1236 patients were included. Mean age was 63 years, 43% were female, 700 patients were included in the second phase and 536 in the third phase in which 149 low-risk patients (28%) were not transferred to the hospital. Occurrence of 45 days MACE was 16.6% in Phase II and 15.7% in Phase III (P = 0.67). Percentage MACE in low-risk patients was 2.9% in Phase II and 1.3% in Phase III. After adjustments for differences in baseline variables, the hazard ratio of 45 days MACE in Phase III was 0.88 (95% confidence interval 0.63–1.25) as compared to Phase II.

Conclusion

Pre-hospital risk stratification of patients with suspected NSTE-ACS, avoiding hospitalization of a substantial number of low-risk patients, seems feasible and non-inferior to transferring all patients to the hospital.
Are polygenic risk scores for systolic blood pressure and LDL-cholesterol associated with treatment effectiveness, and clinical outcomes among those on treatment?
Authors: Tapela Neo M , Collister Jennifer , Liu Xiaonan , Clifton Lei , Stiby Alexander , Murgia Federico , Hopewell Jemma C , Hunter David J
Published: November 2021

Aims 

Many studies have investigated associations between polygenic risk scores (PRS) and the incidence of cardiovascular disease (CVD); few have examined whether risk factor-related PRS predict CVD outcomes among adults treated with risk-modifying therapies. We assessed whether PRS for systolic blood pressure (PRSSBP) and for low-density lipoprotein cholesterol (PRSLDL-C) were associated with achieving SBP and LDL-C-related targets, and with major adverse cardiovascular events (MACE: non-fatal stroke or myocardial infarction, CVD death, and revascularization procedures).

Methods and results 

Using observational data from the UK Biobank (UKB), we calculated PRSSBP and PRSLDL-C and constructed two sub-cohorts of unrelated adults of White British ancestry aged 40–69 years and with no history of CVD, who reported taking medications used in the treatment of hypertension or hypercholesterolaemia. Treatment effectiveness in achieving adequate risk factor control was ascertained using on-treatment blood pressure (BP) or LDL-C levels measured at enrolment (uncontrolled hypertension: BP ≥ 140/90 mmHg; uncontrolled hypercholesterolaemia: LDL-C ≥ 3 mmol/L). We conducted multivariable logistic and Cox regression modelling for incident events, adjusting for socioeconomic characteristics, and CVD risk factors. There were 55 439 participants using BP lowering therapies (51.0% male, mean age 61.0 years, median follow-up 11.5 years) and 33 787 using LDL-C lowering therapies (58.5% male, mean age 61.7 years, median follow-up 11.4 years). PRSSBP was associated with uncontrolled hypertension (odds ratio 1.70; 95% confidence interval: 1.60–1.80) top vs. bottom quintile, equivalent to a 5.4 mmHg difference in SBP, and with MACE [hazard ratio (HR) 1.13; 1.04–1.23]. PRSLDL-C was associated with uncontrolled hypercholesterolaemia (HR 2.78; 2.58–3.00) but was not associated with subsequent MACE.

Conclusion 

We extend previous findings in the UKB cohort to examine PRSSBP and PRSLDL-C with treatment effectiveness. Our results indicate that both PRSSBP and PRSLDL-C can help identify individuals who, despite being on treatment, have inadequately controlled SBP and LDL-C, and for SBP are at higher risk for CVD events. This extends the potential role of PRS in clinical practice from identifying patients who may need these interventions to identifying patients who may need more intensive intervention.
A novel Trichoderma asperellum strain DQ-1 promotes tomato growth and induces resistance to gray mold caused by Botrytis cinerea
Authors: Wang Rui , Chen Di , Khan Raja Asad Ali , Cui Jia , Hou Jumei , Liu Tong
Published: November 2021

Gray mold caused by Botrytis cinerea is a major cause of economic losses during tomato production. In this study, we obtained 23 Trichoderma strains from tomato rhizosphere soil and their inhibitory effects on B. cinerea and the promoting effects on tomato growth were determined. Among them, the inhibition rate of strain DQ-1 on B. cinerea was 88.56%; compared with the control group, after treatment with strain DQ-1, the seeds germination rate and root length of tomato increased by 5.55 and 37.86%. The induced disease resistance of strain DQ-1 was evaluated by pot experiments. The disease incidence (DI) and disease severity index (DSI) of tomato pre-inoculated with strain DQ-1 and then inoculated with B. cinerea were reduced by 38 and 64% compared with the control. Furthermore, we detected the expression levels of tomato disease resistance related genes PR2 and TPX, ethylene pathway related genes ETR1 and CTR1 and jasmonic acid pathway related genes LOX1 and PAL in challenging and non-challenging inoculation treatments. The results showed that the tomato treated with strain DQ-1 triggered the system acquired resistance (SAR) and induced systemic resistance (ISR) pathway, thereby enhancing the disease resistance of tomato. Then the strain DQ-1 was identified as Trichoderma asperellum based on morphological characteristics and phylogenetic information. This study suggests that the novel T. asperellum strain DQ-1 can be a potential candidate for the biological control of gray mold in tomato.
Diversity of non-Saccharomycesyeasts of grape berry surfaces from representative Cabernet Sauvignon vineyards in Henan Province, China
Authors: Zhang Junjie , Shang Yimin , Chen Jinyong , Brunel Brigitte , Peng Shanshan , Li Shuo , Wang Entao
Published: November 2021

Non-Saccharomyces yeasts are important players during winemaking and may come from grapes grown in vineyards. To study the diversity of non-Saccharomyces yeasts on grape berry surfaces, 433 strains were isolated from different Cabernet Sauvignon vineyards grown in Henan Province. Our results demonstrated that these strains were classified into 16 morphotypes according to their growth morphology on Wallerstein Laboratory agar medium, and were identified as seven species from four genera—Hanseniaspora opuntiae, Hanseniaspora vineae, Hanseniaspora uvarum, Pichia occidentalis, Pichia kluyveri, Issatchenkia terricola and Saturnispora diversa—based on a series of molecular biological experiments. Hanseniaspora opuntiae was obtained from all sampling sites except Changyuan County, while Pichia kluyveri and Saturnispora diversa were only found in sites of Zhengzhou Grape Resource Garden and Minquan County, respectively. The site Minquan was home of the greatest species richness, while only one single species (Hanseniaspora opuntiae) was detected at NAPA winery from Zhengzhou or at Anyang County. Finally, this study suggested that the geographic distribution and diversity of non-Saccharomyces yeast populations on Cabernet Sauvignon grape berries were likely to be determined by a combination of grape varieties and environmental factors.
Keeping the host alive – lessons from obligate intracellular bacterial pathogens
Authors: Loterio Robson Kriiger , Zamboni Dario S , Newton Hayley J
Published: November 2021

Mammals have evolved sophisticated host cell death signaling pathways as an important immune mechanism to recognize and eliminate cell intruders before they establish their replicative niche. However, intracellular bacterial pathogens that have co-evolved with their host have developed a multitude of tactics to counteract this defense strategy to facilitate their survival and replication. This requires manipulation of pro-death and pro-survival host signaling pathways during infection. Obligate intracellular bacterial pathogens are organisms that absolutely require an eukaryotic host to survive and replicate, and therefore they have developed virulence factors to prevent diverse forms of host cell death and conserve their replicative niche. This review encapsulates our current understanding of these host–pathogen interactions by exploring the most relevant findings of Anaplasma spp., Chlamydia spp., Rickettsia spp. and Coxiella burnetii modulating host cell death pathways. A detailed comprehension of the molecular mechanisms through which these obligate intracellular pathogens manipulate regulated host cell death will not only increase the current understanding of these difficult-to-study pathogens but also provide insights into new tools to study regulated cell death and the development of new therapeutic approaches to control infection.
Covariance Generalized Linear Models: An Approach for Quantifying Uncertainty in Tree Stem Taper Modeling
Authors: Fiorentin Luan Demarco , Bonat Wagner Hugo , Pelissari Allan Libanio , Machado Sebastião do Amaral , Téo Saulo Jorge
Published: November 2021

A natural dependence among diameters measured within-tree is expected in taper data due to the hierarchical structure. The aim of this paper was to introduce the covariance generalized linear model (CGLM) framework in the context of forest biometrics for Pinus taeda stem form modeling. The CGLMs are based on marginal specification, which requires a definition of the mean and covariance components. The tree stem mean profiles were modeled by a nonlinear segmented model. The covariance matrix was built considering four strategies of linear combinations of known matrices, which expressed the variance or correlations among observations. The first strategy modeled only the variance of the diameters over the stem as a function of covariates, the second modeled correlation among observations, the third was defined based on a random walk model, the fourth was based on a structure similar to a mixed-effect model with a marginal specification, and the fourth was a traditional mixed-effect model. Mean squared error and bias showed that the approaches were similar for describing the mean profile for fitting and validation dataset. However, uncertainties expressed by confidence intervals of the relative diameters were significant and related to the matrix covariance structures of the CGLMs.
Adjoint envelope tomography for scattering and absorption using radiative transfer theory
Authors: Zhang Tuo , Sens-Schönfelder Christoph
Published: November 2021

To investigate the small-scale elastic structure of the subsurface at length scales below the resolution limits of waveform tomography, envelopes of high-frequency scattered seismic waveforms have been used with a variety of approaches. However, a rigorous framework for the iterative inversion of seismogram envelopes to image heterogeneity and high-frequency attenuation comparable to full waveform inversion (FWI) is missing. We present the mathematical framework for an iterative full envelope inversion using forward and adjoint simulations of the radiative transfer equations, in full analogy to FWI that is based on the wave equation. The forward and adjoint problems are solved by modelling 2-D multiple non-isotropic scattering in a random elastic medium with spatially variable heterogeneity and attenuation using the Monte Carlo method. Sensitivity kernels are derived for the squared difference between the full observed and modelled envelopes which is iteratively minimized with the L-BFGS method. We apply this algorithm in numerical tests in the acoustic approximation and show that it is possible to image the spatial distribution of small-scale heterogeneity and attenuation in iterative inversions. Our analysis shows that the relative importance of scattering and attenuation anomalies needs to be considered when the model resolution is assessed. The inversions confirm that the early coda is important for imaging the distribution of heterogeneity while later coda waves are more sensitive to intrinsic attenuation and we show that this dependency can be used to cope with the trade-off that exists between both material properties.
O-GlcNAcylation increases PYGL activity by promoting phosphorylation
Authors: Chen Yan-Fang , Zhu Jing-Jing , Li Jing , Ye Xin-Shan
Published: November 2021

O-GlcNAcylation is a post-translational modification that links metabolism with signal transduction. High O-GlcNAcylation appears to be a general characteristic of cancer cells. It promotes the invasion, metastasis, proliferation and survival of tumor cells, and alters many metabolic pathways. Glycogen metabolism increases in a wide variety of tumors, suggesting that it is an important aspect of cancer pathophysiology. Herein we focused on the O-GlcNAcylation of liver glycogen phosphorylase (PYGL)—an important catabolism enzyme in the glycogen metabolism pathway. PYGL expressed in both HEK 293T and HCT116 was modified by O-GlcNAc. And both PYGL O-GlcNAcylation and phosphorylation of Ser15 (pSer15) were decreased under glucose and insulin, whereas increased under glucagon and Na2S2O4 (hypoxia) conditions. Then, we identified the major O-GlcNAcylation site to be Ser430, and demonstrated that pSer15 and Ser430 O-GlcNAcylation were mutually reinforced. Lastly, we found that Ser430 O-GlcNAcylation was fundamental for PYGL activity. Thus, O-GlcNAcylation of PYGL positively regulated pSer15 and therefore its enzymatic activity. Our results provided another molecular insight into the intricate post-translational regulation network of PYGL.
Mini-thoracotomy and full-sternotomy approach for reoperative mitral valve surgery after a previous sternotomy
Authors: Kwon Yelee , Park Sung Jun , Kim Ho Jin , Kim Joon Bum , Jung Sung-Ho , Choo Suk Jung , Lee Jae Won
Published: November 2021

OBJECTIVES

Right mini-thoracotomy approach may enhance the visualization of mitral valve (MV) visualization during redo MV surgery, thereby minimizing the risk of reoperative median sternotomy. We described the clinical outcomes of redo MV surgery by mini-thoracotomy and full-sternotomy approach.

METHODS

Of 730 consecutive adult patients who underwent redo MV surgery between 2002 and 2018 at our institution, we identified 380 patients (age: 56.0 [14.8] years) after excluding those who underwent concomitant aortic valve or coronary artery surgeries.

RESULTS

The clinical outcomes in patients who underwent mini-thoracotomy (MINI group; n = 168) and full-sternotomy (STERN group; n = 218) were described. The early and overall mortality in the MINI group was 4.3% (7/162) and 17.3% (28/162), with the rates of early major complications as follows: low cardiac output syndrome, 5.6% (9/162); early stroke, 6.8% (11/162); new-onset dialysis, 6.2% (10/162); prolonged ventilation, 15.4% (25/162); and postoperative bleeding requiring exploration, 7.4% (12/162). In the STERN group, the early mortality was 11.0% (24/218), whereas the risk of low cardiac output syndrome, early stroke, new-onset dialysis, prolonged ventilation, and postoperative bleeding was 12.4% (27/218), 14.2% (31/218), 17.0% (37/218), 33.0% (72/218), and 10.1% (22/218), respectively. The duration of intensive care unit and hospital stay was 2.0 [range 1.0, 3.0] and 8.0 [6.0, 13.0], respectively, in the MINI group and 3.0 [2.0, 7.0] and 14.0 [8.0, 29.0], respectively, in the STERN group.

CONCLUSIONS

Mini-thoracotomy may be a viable alternative to conventional sternotomy for redo MV surgery.
A multi-scale/multi-physics model for the theoretical study of the vascular configuration of retinal capillary plexuses based on OCTA data
Authors: Chiaravalli Greta , Guidoboni Giovanna , Sacco Riccardo , Radell Jake , Harris Alon
Published: November 2021

The retinal tissue is highly metabolically active and is responsible for translating the visual stimuli into electrical signals to be delivered to the brain. A complex vascular structure ensures an adequate supply of blood and oxygen, which is essential for the function and survival of the retinal tissue. To date, a complete understanding of the configuration of the retinal vascular structures is still lacking. Optical coherence tomography angiography has made available a huge amount of imaging data regarding the main retinal capillary plexuses, namely the superficial capillary plexuses (SCP), intermediate capillary plexuses (ICP) and deep capillary plexuses (DCP). However, the interpretation of these data is still controversial. In particular, the question of whether the three capillary plexuses are connected in series or in parallel remains a matter of debate. In this work, we address this question by utilizing a multi-scale/multi-physics mathematical model to quantify the impact of the two hypothesized vascular configurations on retinal hemodynamics and oxygenation. The response to central retinal vein occlusion (CRVO) and intraocular pressure (IOP) elevation is also simulated depending on whether the capillary plexuses are connected in series or in parallel. The simulation results show the following: (i) in the in series configuration, the plexuses exhibit a differential response, with DCP and ICP experiencing larger pressure drops than SCP; and (ii) in the in parallel configuration, the blood flow redistributes uniformly in the three plexuses. The different vascular configurations show different responses also in terms of oxygen profiles: (i) in the in series configuration, the outer nuclear layer, outer plexiform layer and inner nuclear layer (INL) are those most affected by CRVO and IOP elevation; and (ii) in the in parallel configuration the INL and ganglion cell layer are those most affected. The in series results are consistent with studies on paracentral acute middle maculopathy, secondary to CRVO and with studies on IOP elevation, in which DCP and ICP and the retinal tissues surrounding them are those most affected by ischemia. These findings seem to suggest that the in series configuration better describes the physiology of the vascular retinal capillary network in health and disease.
A consistent quasi–second-order staggered scheme for the two-dimensional shallow water equations
Authors: Herbin Raphaèle , Latché Jean-Claude , Nasseri Youssouf , Therme Nicolas
Published: November 2021

A quasi–second-order scheme is developed to obtain approximate solutions of the two-dimensional shallow water equations (SWEs) with bathymetry. The scheme is based on a staggered finite volume space discretization: the scalar unknowns are located in the discretization cells while the vector unknowns are located on the edges of the mesh. A monotonic upwind-central scheme for conservation laws (MUSCL)-like interpolation for the discrete convection operators in the water height and momentum balance equations is performed in order to improve the accuracy of the scheme. The time discretization is performed either by a first-order segregated forward Euler scheme or by the second-order Heun scheme. Both schemes are shown to preserve the water height positivity under a Courants Friedrichs Lewy (CFL) condition and an important state equilibrium known as the lake at rest. Using some recent Lax–Wendroff type results for staggered grids, these schemes are shown to be LW-consistent with the weak formulation of the continuous equations, in the sense that if a sequence of approximate solutions is bounded and strongly converges to a limit, then this limit is a weak solution of the SWEs; besides, the forward Euler scheme is shown to be LW-consistent with a weak entropy inequality. Numerical results confirm the efficiency and accuracy of the schemes.
A New Family of Exceptional Rational Functions
Authors: Ding Zhiguo , Zieve Michael E
Published: November 2021

For each odd prime power $q$, we construct an infinite sequence of rational functions $f(X) \in{\mathbb{F}}_q(X)$, each of which is exceptional in the sense that for infinitely many $n$ the map $c \mapsto f(c)$ induces a bijection of ${\mathbb{P}}^1({\mathbb{F}}_{q^n})$. Moreover, each of our functions $f(X)$ is indecomposable in the sense that it cannot be written as the composition of lower-degree rational functions in ${\mathbb{F}}_q(X)$. These are the first known examples of wildly ramified indecomposable exceptional rational functions $f(X)$, other than linear changes of polynomials. In case $q$ is not a power of $3$, these are also the first known examples of indecomposable exceptional rational functions $f(X)$ over ${\mathbb{F}}_q$ which have non-solvable monodromy groups and have arbitrarily large degree.
Polarizations of Abelian Varieties Over Finite Fields via Canonical Liftings
Authors: Bergström Jonas , Karemaker Valentijn , Marseglia Stefano
Published: November 2021

We describe all polarizations for all abelian varieties over a finite field in a fixed isogeny class corresponding to a squarefree Weil polynomial, when one variety in the isogeny class admits a canonical lifting to characteristic zero, that is, a lifting for which the reduction morphism induces an isomorphism of endomorphism rings. Categorical equivalences between abelian varieties over finite fields and fractional ideals in étale algebras enable us to explicitly compute isomorphism classes of polarized abelian varieties satisfying some mild conditions. We also implement algorithms to perform these computations.
Complex Valued Analytic Torsion and Dynamical Zeta Function on Locally Symmetric Spaces
Authors: Shen Shu
Published: November 2021

We show that the Ruelle dynamical zeta function on a closed odd dimensional locally symmetric space twisted by an arbitrary flat vector bundle has a meromorphic extension to the whole complex plane and that its leading term in the Laurent series at the zero point is related to the regularised determinant of the flat Laplacian of Cappell–Miller. When the flat vector bundle is close to an acyclic and unitary one, we show that the dynamical zeta function is regular at the zero point and that its value is equal to the complex valued analytic torsion of Cappell–Miller. This generalises the author’s previous results for unitarily flat vector bundles as well as Müller and Spilioti’s results on hyperbolic manifolds.