bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of catheter-directed therapy for pulmonary embolism on pulmonary artery systolic pressure and PaO2/FiO2
Authors: Muzzio M , Rossini A , Costa D , Garcia Iturralde L , Gonzalez C , Sero B , Notrica M , Gregorietti V , Coronel R
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Pulmonary embolism (PE) is the third global cause of cardiovascular death. Treatment of high-risk cases and selected intermediate-risk cases is based on systemic thrombolysis, which can be inconvenient in patients with a contraindications for thrombolysis. Catheter-directed therapies are emerging as an alternative for treatment when there is an increased bleeding risk.

Methods

One-center retrospective study of patients with high or intermediate-high risk PE with contraindications for systemic thrombolysis. Catheter directed rheolytic thrombectomy or mechanical thrombectomy was performed, assessing its effect on clinical variables, pulmonary artery systolic pressure (PASP), PaO2/FiO2, and the occurrence of complications.

Results

In 12 patients with PE treated with catheter-directed therapy, we observed a mean increase of the PaO2/FiO2 of 62 mm Hg (p = 0.013), as well mean reduction in the PASP of 13 mm Hg (p < 0.001), as can be observed in the figure. As complications, there was one case of hemoptysis, and two of hemolysis, with an in-hospital mortality of 16.7%.

Conclusion

Catheter-directed therapy in patients with high or intermediate-high risk PE is a feasible option when there are contraindications for thrombolysis or there is a high bleeding risk. It has been shown to improve surrogate endpoints as PASP and right to left ventricle ratio in other studies, although data on mortality from a randomized trial is lacking. Abstract Figure. Gardner-Altman plots.
Outcome and predictors for mortality in cardiogenic shock: a Dutch nationwide registry-based study of 75,407 patients with acute coronary syndrome treated by PCI
Authors: Karami M , Lagrand WK , Houterman S , Den Uil CA , Engstrom AE , Otterspoor LC , Ottervanger JP , Montero-Cabezas JM , Sjauw K , Van Ramshorst J , Kraaijeveld AO , Verouden NJ , Lipsic E , Vlaar AP , Henriques JPS
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

OnBehalf

Netherlands Heart Registration

Background

It is important to gain more insight into cardiogenic shock (CS), as currently little is known on how to improve outcomes. The aim of this study was to assess the incidence, clinical outcome and predictors for mortality of CS in acute coronary syndrome (ACS) patients treated by percutaneous coronary intervention (PCI).

Methods

The Netherlands Heart Registration (NHR) is a nationwide registry on all cardiac interventions. We used NHR data of ACS patients treated with PCI between 2015 and 2019. CS was defined as shock present at admission. Cox regression analysis was used to calculate hazard ratios (HR) with 95% confidence intervals (CI).

Results

Among 75,407 ACS patients treated with PCI, 3,028 patients (4.1%) were identified with CS. The incidences of CS were respectively; 4.3%, 3.9%, 3.5% and 4.3% per year. Median follow-up duration was 9 months (IQR 0-26) for patients with CS and 22 months (IQR 12-36) for patients without CS. Thirty-day mortality was 36% for patient with CS and 3% for patients without CS (p < 0.001). Factors independently associated with mortality in CS were: age (HR 1.02, 95%CI 1.02-1.03), estimated glomerular filtration rate (eGFR) (HR 0.98, 95%CI 0.98-0.99), diabetes mellitus (DM) (HR 1.25, 95%CI 1.08-1.45), multivessel disease (HR 1.22, 95%CI 1.06-1.39), prior myocardial infarction (MI) (HR 1.24, 95%CI 1.06-1.45) and out-of-hospital cardiac arrest (OHCA) (HR 1.71, 95%CI 1.50-1.94) (Table 1).

Conclusion

In this Dutch nationwide registry-based study of ACS patients treated by PCI, the incidence of CS was 4.1% over the 4-year study period. Predictors for mortality in CS were higher age, renal insufficiency, presence of DM, multivessel disease, prior MI and OHCA. Multivariable Cox regression analysisHR95% CIp-valueAge (years)1.021.02-1.03<0.001MaleNSDiabetes mellitus1.251.08-1.45<0.01Multivessel disease1.221.06-1.39<0.01CTONSPrior MI1.241.06-1.45<0.01Prior CABGNSeGFR (ml/min/1.73 m2)0.980.98-0.99<0.001OHCA1.711.50-1.94<0.001STEMINSIntervention yearNS
Evaluation of basic life support education for high school students in a city in brazil
Authors: Coutinho Cordeiro J , Sousa Pinheiro S , Oliveira De Deus M , Aparecida De Sousa Pereira L , Souto Lucio De Oliveira MC
Published: April 2021

Funding Acknowledgements

Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): The researchers themselves.

Background

Cardiorespiratory Arrest (CRP) is a medical emergency that requires urgent aid as well as technical skills to initiate Cardiopulmonary Resuscitation (CPR) maneuvers, primarily among the lay population, seeing as the majority of CRP episodes take place in community environments.

Purpose

The purpose of this study is to compare the Basic Life Support (BLS) skills of high school students before and after a theoretical-practical approach.

Method

A quasi-experimental study was conducted, consisting of theoretical-practical training on BLS running 60 minutes total (20 minutes of theory and 40 minutes of practice), addressing various steps in layman’s out-of-hospital BLS. Evaluations were conducted before and after training. The instrument was developed by the researchers themselves and underwent a previous validation process. The statistical software employed for the purpose of analyzing the data was SPSS version 21.0 for Windows. At the outset, descriptive statistics were employed to present the data, as well as the Wilcoxon test to compare the results of questionnaires taken before and after the intervention.

Results

The sample consisted of 322 students from private institutions in Brazil. The median age was 16.0 years, with an interquartile interval (IQ) of 2 years, with 181 (56.2%) students being female and 141 (43.8%) male. The before and after results revealed statistically significant differences in performance: pre-training – median = 5 points, IQ = 2 points; post training – 9 points, IQ = 2 points; p < 0.0001. Conclusion: The conduction of theoretical-practical classes was followed by an increase in correct answers to the BLS questionnaire. The results suggest that simple educational strategies might aid in the training of lay young people to respond correctly to CRP scenarios.
Bullet-associated ventricular tachycardia: a case report
Authors: Doldi Florian , Reinke Florian , Yilmaz Ali , Eckardt Lars
Published: April 2021

Background

The majority of ventricular tachycardias (VTs) occurs in patients with structural heart disease and is associated with an increased risk of sudden cardiac death. These VT are scar-related and may develop in patients with ischaemic or non-ischaemic cardiomyopathies.

Case summary

We describe a 44-year-old patient without any pre-existing cardiovascular disease, presenting with the first documentation of a haemodynamically unstable sustained fast VT with a cycle length of 250 ms. He reported a suicidal attempt with a self-made handgun aged 16 when he had shot himself in the thorax and had injured the myocardium. After presenting with the VT coronary artery disease was excluded through cardiac catheterization. A cardiovascular magnetic resonance study showed a localized myocardial scar in the left ventricular free wall starting from the subepicardium and correlating to the scar described 28 years ago by the thoracic surgeons. In an electrophysiological study, non-sustained VT were easily inducible. Presuming a causal relationship between the fast VT and the epicardial scar, a single-chamber implantable cardioverter-defibrillator was implanted and beta-blocker therapy was initiated.

Discussion

Scar-related VT often occur many years after an acute event, e.g. an acute myocardial infarction. This case highlights, that any cardiac trauma, even a superficial epicardial projectile-related damage with subsequent scarring, may cause a VT after many years and to our knowledge for the first time describes the occurrence of a VT due to mechanical damage to the myocardium by a gunshot.
The Effect of Heterologous Insertions on Gene Conversion in Mitotically Dividing Cells in Drosophila melanogaster
Authors: Coveny Angela M , Dray Tammy , Gloor Gregory B
Published: April 2021

We examined the influence that heterologous sequences of different sizes have on the frequency of double-strand-break repair by gene conversion in Drosophila melanogaster. We induced a double-strand break on one X chromosome in female flies by P-element excision. These flies contained heterologous insertions of various sizes located 238 bp from the break site in cis or in trans to the break, or both. We observed a significant decrease in double-strand-break repair with large heterologous insertions located either in cis or in trans to the break. Reestablishing the homology by including the same heterologous sequence in cis and in trans to the double-strand break restored the frequency of gene conversion to wild-type levels. In one instance, an allelic nonhomologous insertion completely abolished repair by homologous recombination. The results show that the repair of a double-strand break by gene conversion requires chromosome pairing in the local region of the double-strand break.
The Saccharomyces cerevisiae RNase Mitochondrial RNA Processing Is Critical for Cell Cycle Progression at the End of Mitosis
Authors: Cai Ti , Aulds Jason , Gill Tina , Cerio Michael , Schmitt Mark E
Published: April 2021

We have identified a cell cycle delay in Saccharomyces cerevisiae RNase MRP mutants. Mutants delay with large budded cells, dumbbell-shaped nuclei, and extended spindles characteristic of “exit from mitosis” mutants. In accord with this, a RNase MRP mutation can be suppressed by overexpressing the polo-like kinase CDC5 or by deleting the B-type cyclin CLB1, without restoring the MRP-dependent rRNA-processing step. In addition, we identified a series of genetic interactions between RNase MRP mutations and mutations in CDC5, CDC14, CDC15, CLB2, and CLB5. As in most “exit from mitosis” mutants, levels of the Clb2 cyclin were increased. The buildup of Clb2 protein is not the result of a defect in the release of the Cdc14 phosphatase from the nucleolus, but rather the result of an increase in CLB2 mRNA levels. These results indicate a clear role of RNase MRP in cell cycle progression at the end of mitosis. Conservation of this function in humans may explain many of the pleiotropic phenotypes of cartilage hair hypoplasia.
Molecular Analysis of Nondisjunction in Mice Heterozygous for a Robertsonian Translocation
Authors: Underkoffler Lara A , Mitchell Laura E , Localio A Russell , Marchegiani Shannon M , Morabito Justin , Collins Joelle N , Oakey Rebecca J
Published: April 2021

A Robertsonian translocation results in a metacentric chromosome produced by the fusion of two acrocentric chromosomes. Rb heterozygous mice frequently generate aneuploid gametes and embryos, providing a good model for studying meiotic nondisjunction. We intercrossed mice heterozygous for a (7.18) Robertsonian translocation and performed molecular genotyping of 1812 embryos from 364 litters with known parental origin, strain, and age. Nondisjunction events were scored and factors influencing the frequency of nondisjunction involving chromosomes 7 and 18 were examined. We concluded the following: The frequency of nondisjunction among 1784 embryos (3568 meioses) was 15.9%.Nondisjunction events were distributed nonrandomly among progeny. This was inferred from the distribution of the frequency of trisomics and uniparental disomics (UPDs) among all litters.There was no evidence to show an effect of maternal or paternal age on the frequency of nondisjunction.Strain background did not play an appreciable role in nondisjunction frequency.The frequency of nondisjunction for chromosome 18 was significantly higher than that for chromosome 7 in males.The frequency of nondisjunction for chromosome 7 was significantly higher in females than in males.

These results show that molecular genotyping provides a valuable tool for understanding factors influencing meiotic nondisjunction in mammals.
Nuclear Import of Upf3p Is Mediated by Importin-α/-β and Export to the Cytoplasm Is Required for a Functional Nonsense-Mediated mRNA Decay Pathway in Yeast
Authors: Shirley Renee L , Ford Amanda S , Richards M Rachel , Albertini Markus , Culbertson Michael R
Published: April 2021

Upf3p, which is required for nonsense-mediated mRNA decay (NMD) in yeast, is primarily cytoplasmic but accumulates inside the nucleus when UPF3 is overexpressed or when upf3 mutations prevent nuclear export. Upf3p physically interacts with Srp1p (importin-α). Upf3p fails to be imported into the nucleus in a temperature-sensitive srp1-31 strain, indicating that nuclear import is mediated by the importin-α/β heterodimer. Nuclear export of Upf3p is mediated by a leucine-rich nuclear export sequence (NES-A), but export is not dependent on the Crm1p exportin. Mutations identified in NES-A prevent nuclear export and confer an Nmd– phenotype. The addition of a functional NES element to an export-defective upf  – allele restores export and partially restores an Nmd+ phenotype. Our findings support a model in which the movement of Upf3p between the nucleus and the cytoplasm is required for a fully functional NMD pathway. We also found that overexpression of Upf2p suppresses the Nmd– phenotype in mutant strains carrying nes-A alleles but has no effect on the localization of Upf3p. To explain these results, we suggest that the mutations in NES-A that impair nuclear export cause additional defects in the function of Upf3p that are not rectified by restoration of export alone.
A Genealogical Interpretation of Linkage Disequilibrium
Authors: McVean Gilean A T
Published: April 2021

The degree of association between alleles at different loci, or linkage disequilibrium, is widely used to infer details of evolutionary processes. Here I explore how associations between alleles relate to properties of the underlying genealogy of sequences. Under the neutral, infinite-sites assumption I show that there is a direct correspondence between the covariance in coalescence times at different parts of the genome and the degree of linkage disequilibrium. These covariances can be calculated exactly under the standard neutral model and by Monte Carlo simulation under different demographic models. I show that the effects of population growth, population bottlenecks, and population structure on linkage disequilibrium can be described through their effects on the covariance in coalescence times.
Mosaicism of Solid Gold Supports the Causality of a Noncoding A-to-G Transition in the Determinism of the Callipyge Phenotype
Authors: Smit Maria , Segers Karin , Carrascosa Laura Garcia , Shay Tracy , Baraldi Francesca , Gyapay Gabor , Snowder Gary , Georges Michel , Cockett Noelle , Charlier Carole
Published: April 2021

To identify the callipyge mutation, we have resequenced 184 kb spanning the DLK1-, GTL2-, PEG11-, and MEG8-imprinted domain and have identified an A-to-G transition in a highly conserved dodecamer motif between DLK1 and GTL2. This was the only difference found between the callipyge (CLPG) allele and a phylogenetically closely related wild-type allele. We report that this SNP is in perfect association with the callipyge genotype. The demonstration that Solid Gold—the alleged founder ram of the callipyge flock—is mosaic for this SNP virtually proves the causality of this SNP in the determinism of the callipyge phenotype.
Investigation of the Stability of Yeast rad52 Mutant Proteins Uncovers Post-translational and Transcriptional Regulation of Rad52p
Authors: Asleson Erin N , Livingston Dennis M
Published: April 2021

We investigated the stability of the Saccharomyces cerevisiae Rad52 protein to learn how a cell controls its quantity and longevity. We measured the cellular levels of wild-type and mutant forms of Rad52p when expressed from the RAD52 promoter and the half-lives of the various forms of Rad52p when expressed from the GAL1 promoter. The wild-type protein has a half-life of 15 min. rad52 mutations variably affect the cellular levels of the protein products, and these levels correlate with the measured half-lives. While missense mutations in the N terminus of the protein drastically reduce the cellular levels of the mutant proteins, two mutations—one a deletion of amino acids 210-327 and the other a missense mutation of residue 235—increase the cellular level and half-life more than twofold. These results suggest that Rad52p is subject to post-translational regulation. Proteasomal mutations have no effect on Rad52p half-life but increase the amount of RAD52 message. In contrast to Rad52p, the half-life of Rad51p is >2 hr, and RAD51 expression is unaffected by proteasomal mutations. These differences between Rad52p and Rad51p suggest differential regulation of two proteins that interact in recombinational repair.
Genetic Selection for Modulators of a Retinoic-Acid-Responsive Reporter in Human Cells
Authors: Richards Burt , Karpilow Jon , Dunn Christine , Peterson Isaac , Maxfield Andrew , Zharkikh Ludmilla , Abedi Majid , Hurlburt Anthony , Hardman Joshua , Hsu Forrest , Li Wenhua , Rebentisch Matthew , Sandrock Robert , Sandrock Tanya , Kamb Alexander , Teng David H-F
Published: April 2021

We used a genetic screening methodology, a human cell line bearing a retinoic-acid-responsive enhanced GFP reporter, and a flow sorter to recover dominant modulators of reporter expression. Four inducers and three suppressors that were fused to the C terminus of a protein scaffold for stability were isolated and their mechanisms of action studied. Mutagenesis experiments indicated that six of these dominant agents exerted their effects at the protein level. The single cDNA coding fragment that was isolated comprised the central 64-amino-acid section of human cyclophilin B, which contained its peptidyl-prolyl isomerase domain; this cyclophilin fragment repressed expression of the retinoic-acid-responsive reporter. The remaining clones encoded peptides shorter than 30 amino acids unrelated to known gene open reading frames. Genetic epistasis studies between the strongest inducer, R3, and a dominant-negative mutant of RARα suggest that the two factors function in the same pathway. Transcript microarray analyses suggest that R3 induced a subset of the retinoid-responsive genes in melanoma cells. Finally, yeast two-hybrid assays and co-immunoprecipitation studies of human cell extracts identified PAT1 as a protein that interacts with R3.
Mitochondria Are Inherited From theMATa Parent in Crosses of the Basidiomycete FungusCryptococcus neoformans
Authors: Yan Zhun , Xu Jianping
Published: April 2021

Previous studies demonstrated that mitochondrial DNA (mtDNA) was uniparentally transmitted in laboratory crosses of the pathogenic yeast Cryptococcus neoformans. To begin understanding the mechanisms, this study examined the potential role of the mating-type locus on mtDNA inheritance in C. neoformans. Using existing isogenic strains (JEC20 and JEC21) that differed only at the mating-type locus and a clinical strain (CDC46) that possessed a mitochondrial genotype different from JEC20 and JEC21, we constructed strains that differed only in mating type and mitochondrial genotype. These strains were then crossed to produce hyphae and sexual spores. Among the 206 single spores analyzed from six crosses, all but one inherited mtDNA from the MATa parents. Analyses of mating-type alleles and mtDNA genotypes of natural hybrids from clinical and natural samples were consistent with the hypothesis that mtDNA is inherited from the MATa parent in C. neoformans. To distinguish two potential mechanisms, we obtained a pair of isogenic strains with different mating-type alleles, mtDNA types, and auxotrophic markers. Diploid cells from mating between these two strains were selected and 29 independent colonies were genotyped. These cells did not go through the hyphal stage or the meiotic process. All 29 colonies contained mtDNA from the MATa parent. Because no filamentation, meiosis, or spore formation was involved in generating these diploid cells, our results suggest a selective elimination of mtDNA from the MATα parent soon after mating. To our knowledge, this is the first demonstration that mating type controls mtDNA inheritance in fungi.
Evidence for Diversifying Selection on Erythrocyte-Binding Antigens of Plasmodium falciparum and P. vivax
Authors: Baum Jake , Thomas Alan W , Conway David J
Published: April 2021

Malaria parasite antigens involved in erythrocyte invasion are primary vaccine candidates. The erythrocyte-binding antigen 175K (EBA-175) of Plasmodium falciparum binds to glycophorin A on the human erythrocyte surface via an N-terminal cysteine-rich region (termed region II) and is a target of antibody responses. A survey of polymorphism in a malaria-endemic population shows that nucleotide alleles in eba-175 region II occur at more intermediate frequencies than expected under neutrality, but polymorphisms in the homologous domains of two closely related genes, eba-140 (encoding a second erythrocyte-binding protein) and Ψeba-165 (a putative pseudogene), show an opposite trend. McDonald-Kreitman tests employing interspecific comparison with the orthologous genes in P. reichenowi (a closely related parasite of chimpanzees) reveal a significant excess of nonsynonymous polymorphism in P. falciparum eba-175 but not in eba-140. An analysis of the Duffy-binding protein gene, encoding a major erythrocyte-binding antigen in the other common human malaria parasite P. vivax, also reveals a significant excess of nonsynonymous polymorphisms when compared with divergence from its ortholog in P. knowlesi (a closely related parasite of macaques). The results suggest that EBA-175 in P. falciparum and DBP in P. vivax are both under diversifying selection from acquired human immune responses.
Selection in a Subdivided Population With Dominance or Local Frequency Dependence
Authors: Cherry Joshua L
Published: April 2021

The interplay between population structure and natural selection is an area of great interest. It is known that certain types of population subdivision do not alter fixation probabilities of selected alleles under genic, frequency-independent selection. In the presence of dominance for fitness or frequency-dependent selection these same types of subdivision can have large effects on fixation probabilities. For example, the barrier to fixation of a fitter allele due to underdominance is reduced by subdivision. Analytic results presented here relate a subdivided population that conforms to a finite island model to an approximately equivalent panmictic population. The size of this equivalent population is different from (larger than) the actual size of the subdivided population. Selection parameters are also different in the hypothetical equivalent population. As expected, the degree of dominance is lower in the equivalent population. The results are not limited to dominance but cover any form of polynomial frequency dependence.
Adaptive sequential Monte Carlo for posterior inference and model selection among complex geological priors
Authors: Amaya M , Linde N , Laloy E
Published: April 2021

Bayesian model selection enables comparison and ranking of conceptual subsurface models described by spatial prior models, according to the support provided by available geophysical data. Deep generative neural networks can efficiently encode such complex spatial priors, thereby, allowing for a strong model dimensionality reduction that comes at the price of enhanced non-linearity. In this setting, we explore a recent adaptive sequential Monte Carlo (ASMC) approach that builds on annealed importance sampling (AIS); a method that provides both the posterior probability density function (PDF) and the evidence (a central quantity for Bayesian model selection) through a particle approximation. Both techniques are well suited to parallel computation and rely on importance sampling over a sequence of intermediate distributions, linking the prior and the posterior PDF. Each subsequent distribution is approximated by updating the particle weights and states, compared with the previous approximation, using a small pre-defined number of Markov chain Monte Carlo (MCMC) proposal steps. Compared with AIS, the ASMC method adaptively tunes the tempering between neighboring distributions and performs resampling of particles when the variance of the particle weights becomes too large. We evaluate ASMC using two different conceptual models and associated synthetic cross-hole ground penetrating radar tomography data. For the most challenging test case, we find that the ASMC method is faster and more reliable in locating the posterior PDF than state-of-the-art adaptive MCMC. The evidence estimates are found to be robust with respect to the choice of ASMC algorithmic variables and much less sensitive to the model proposal type than MCMC. The variance of the evidence estimates are best estimated by replication of ASMC runs, while approximations based on single runs provide comparable estimates when using a sufficient number of proposal steps in approximating each intermediate distribution.
Association of Antiribosomal P Antibody with Neurological and Systemic Manifestations in Patients with Systemic Lupus Erythematosus in Southwestern Colombia
Authors: Marín Juan-David , Vargas Sthephany , Ruiz-Ordoñez Ingrid , Posso-Osorio Iván , Nieto-Aristizábal Ivana , Barrera María Claudia , Ríos-Serna Lady J , Tobón Gabriel J
Published: April 2021

Background

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by heterogeneous pathogenesis, various clinical manifestations, and a broad spectrum of autoantibodies which recognize different cellular components. This study examines the clinical significance and serological associations of serum antiribosomal P antibodies (anti-P) derived from SLE patients in a population from southwestern Colombia.

Methods

We performed a cross-sectional study of 66 SLE patients. Serum antiribosomal P0 autoantibodies were detected by line immunoassay using the ANA-LIA MAXX kit and processed on the automated HumaBlot 44FA system (Human Diagnostics, Germany).

Results

Of the 66 SLE patients included in the study, 17 patients (25.76%) showed anti-P positivity by line immunoassay (IA), 47 (71.21%) were negative, and results from 2 patients were indeterminate. We did not find an association with neuropsychiatric SLE (NPSLE), renal, or hepatic disorders (P > 0.05). Laboratory findings indicated that anti-P positivity was significantly associated to anti-Smith (P = 0.001), anti-Ro60/SSA (P = 0.046), and anti-dsDNA antibodies (P = 0.034), the latter being true only when performed using indirect immunofluorescence (IIF).

Conclusion

The anti-P antibodies are not associated with clinical manifestations such as NPSLE, lupus nephritis, or hepatic involvement in the southwest Colombian SLE population. Moreover, we confirmed previously reported association between anti-P antibody, serum anti-dsDNA, and anti-Smith.
Establishment and Development of a Quality Evaluation Method for Sangbaipi Decoction
Authors: Bao Huiwei , Yang Huailei , Li Jize , Xu Yang , Huang Xiaowei
Published: April 2021

Background

Sangbaipi decoction (SD), a traditional Chinese “Ancient Classical Prescription” consisting of eight medicinal materials, is usually used to treat asthma due to excess lung Qi and phlegm fire.

Objective

To establish a comprehensive quality evaluation method for SD.

Methods

HPLC fingerprint analysis, hierarchical cluster analysis (HCA), and principal component analysis (PCA) were applied for the quality control of SD prepared from different batches of medicinal materials. A total of 10 batches of SD samples were prepared and analyzed.

Results

A total of 24 common peaks and six active components (gardenoside, rutin, berberine, palmatine, baicalein, and wogonin) were identified in the HPLC fingerprint of SD. The ten batches of SD samples were divided into four groups via HCA and PCA. The HPLC fingerprint similarities of the 10 batch samples were 0.934 or higher. The precision, stability, repeatability, and other methodological indexes suggested that the developed method met the requirements for qualitative fingerprint research.

Conclusion

The results indicated that HPLC fingerprints combined with PCA and multicomponent determination can be successfully applied to SD quality control. This study also provides a basis for a more comprehensive quality evaluation method for SD.

Highlights

The fingerprint of SD, a TCM famous classical formula, was established by HPLC in this paper. Moreover, contents of six pharmacodynamic related components in SD were determined simultaneously in order to establish a comprehensive quality evaluation method of SD. This study can also provide a basis for raw material selection, quality evaluation, extraction process, preparation development and pharmacodynamic material basis research of SD.
Impact of Original and Artificially Improved Artificial Intelligence–based Computer-aided Diagnosis on Breast US Interpretation
Authors: Berg Wendie A , Gur David , Bandos Andriy I , Nair Bronwyn , Gizienski Terri-Ann , Tyma Cathy S , Abrams Gordon , Davis Katie M , Mehta Amar S , Rathfon Grace , Waheed Uzma X , Hakim Christiane M
Published: April 2021

Objective

For breast US interpretation, to assess impact of computer-aided diagnosis (CADx) in original mode or with improved sensitivity or specificity.

Methods

In this IRB approved protocol, orthogonal-paired US images of 319 lesions identified on screening, including 88 (27.6%) cancers (median 7 mm, range 1–34 mm), were reviewed by 9 breast imaging radiologists. Each observer provided BI-RADS assessments (2, 3, 4A, 4B, 4C, 5) before and after CADx in a mode-balanced design: mode 1, original CADx (outputs benign, probably benign, suspicious, or malignant); mode 2, artificially-high-sensitivity CADx (benign or malignant); and mode 3, artificially-high-specificity CADx (benign or malignant). Area under the receiver operating characteristic curve (AUC) was estimated under each modality and for standalone CADx outputs. Multi-reader analysis accounted for inter-reader variability and correlation between same-lesion assessments.

Results

AUC of standalone CADx was 0.77 (95% CI: 0.72–0.83). For mode 1, average reader AUC was 0.82 (range 0.76–0.84) without CADx and not significantly changed with CADx. In high-sensitivity mode, all observers’ AUCs increased: average AUC 0.83 (range 0.78–0.86) before CADx increased to 0.88 (range 0.84–0.90), P < 0.001. In high-specificity mode, all observers’ AUCs increased: average AUC 0.82 (range 0.76–0.84) before CADx increased to 0.89 (range 0.87–0.92), P < 0.0001. Radiologists responded more frequently to malignant CADx cues in high-specificity mode (42.7% vs 23.2% mode 1, and 27.0% mode 2, P = 0.008).

Conclusion

Original CADx did not substantially impact radiologists’ interpretations. Radiologists showed improved performance and were more responsive when CADx produced fewer false-positive malignant cues.
SPRINT, system parameters recurrent invasive tracking: a fast and least-cost online calibration strategy for adaptive optics
Authors: Heritier C T , Fusco T , Oberti S , Neichel B , Esposito S , Madec P-Y
Published: April 2021

Future large adaptive telescopes will trigger new constraints for the calibration of adaptive optics (AO) systems equipped with pre-focal deformable mirrors (DMs). The image of the DM actuator grid, as seen by the wavefront sensor (WFS), may evolve during the operations because of the flexures of the opto-mechanical components present in the optical path. This will result in a degraded AO performance that will affect the scientific operation. To overcome this challenge, it will be necessary to regularly monitor and compensate for these DM/WFS mis-registrations, either by physically realigning some optical components or by updating the control matrix of the system. In this paper, we present a new strategy to track mis-registrations using a pseudo-synthetic model of the AO system. The method is based on an invasive approach where signals are acquired on-sky, before or during the scientific operations, and fed to the model to extract the mis-registration parameters. We introduce a method to compute the most sensitive modes to these mis-registrations that allows us to reduce the number of degrees of freedom required by the algorithm and to minimize the effect on the scientific performance. We demonstrate that, by using only a few of these well-selected signals, the method provides very good accuracy for parameter estimation, well under the targeted accuracy, and has a negligible effect on the scientific path. In addition, the method appears to be very robust to varying operating conditions of noise and atmospheric turbulence and it performs equally for both pyramid and Shack–Hartmann WFSs.
Transgene codon usage drives viral fitness and therapeutic efficacy in oncolytic adenoviruses
Authors: Núñez-Manchón Estela , Farrera-Sal Martí , Otero-Mateo Marc , Castellano Giancarlo , Moreno Rafael , Medel David , Alemany Ramon , Villanueva Eneko , Fillat Cristina
Published: April 2021

Arming oncolytic adenoviruses with therapeutic transgenes is a well-established strategy for multimodal tumour attack. However, this strategy sometimes leads to unexpected attenuated viral replication and a loss of oncolytic effects, preventing these viruses from reaching the clinic. Previous work has shown that altering codon usage in viral genes can hamper viral fitness. Here, we have analysed how transgene codon usage impacts viral replication and oncolytic activity. We observe that, although transgenes with optimized codons show high expression levels at the first round of infection, they impair viral fitness and are therefore not expressed in a sustained manner. Conversely, transgenes encoded by suboptimal codons do not compromise viral replication and are thus stably expressed over time, allowing a greater oncolytic activity both in vitro and in vivo. Altogether, our work shows that fine-tuning codon usage leads to a concerted optimization of transgene expression and viral replication paving the way for the rational design of more efficacious oncolytic therapies.
The Modulatory Effect of Quantitative Sensory Testing in Shoulder Pain: A Systematic Review and Meta-Analysis
Authors: Lyng Kristian Damgaard , Thorsen Jens Bredbjerg Brock , Larsen Dennis Boye , Petersen Kristian Kjær
Published: April 2021

Background

The underlying mechanisms for shoulder pain (SP) are still widely unknown. Previous reviews have reported signs of altered pain processing in SP measured with quantitative sensory testing (QST). Evidence suggests that QST might hold predictive value for SP after an intervention, yet it is not known whether QST profiles can be modulated in response to different treatments. Therefore, this systematic review and meta-analysis aimed to assess whether QST parameters can be modified by interventions for patients with SP.

Methods

Three databases were searched to identify eligible studies. Eligible studies had a prospective design, with at least one QST variable as an outcome in conjunction with an intervention measured before and after the intervention. Studies that involved SP caused by spinal or brain injury and studies looking at combined chronic neck pain and SP were excluded.

Results

Nineteen studies investigating SP were eligible for inclusion in this review. Pressure pain threshold (PPT) was the most frequently used QST parameter to investigate local and widespread hyperalgesia. A meta-analysis was performed on data from 10 studies with a total of 16 interventions. Results demonstrated an overall acute effect (<24 hours after intervention) of interventions in favor of local decreased pain sensitivity and remote decreased pain sensitivity when PPTs before and after interventions were compared.

Conclusions

This study demonstrates that interventions such as exercise and manual therapy can modulate PPTs acutely, both locally and remotely, in patients with SP. Further research investigating the acute and long-term modulatory ability of these interventions on other QST parameters is needed in patients with SP.
O02 Low birthweight is associated with decreased grip strength and reduced leg muscle mass in middle age: findings from the UK Biobank imaging enhancement
Authors: Curtis Elizabeth M , D'Angelo Stefania , Ashai Shanze , Ward Kate , Raisi-Estbragh Zahra , Petersen Steffen , Cooper Cyrus , Harvey Nicholas C
Published: April 2021

Background/Aims 

Low birthweight has been shown to be associated with poorer musculoskeletal health in later life in a variety of epidemiological studies. We investigated relationships between birthweight and magnetic resonance imaging (MRI) measures of muscle volume, and between birthweight and measures of grip strength in UK Biobank.

Methods 

UK Biobank is a large prospective cohort of men and women aged 40-69 years, including a detailed baseline assessment in which birthweight was collected by self-report. A subset of participants underwent MRI examination with the dual-echo Dixon Vibe protocol, from neck to knees. Automated body composition analysis was performed using the AMRA ProfilerTM system, to segment and quantify total thigh muscle volume. Grip strength was assessed using a Jamar hydraulic hand dynamometer. Associations between birthweight, and thigh muscle volume or grip strength (expressed as Fisher-Yates z-scores) were investigated using multivariate linear regression analysis. This study was conducted under generic ethics approval (NRES:11/NW/0382).

Results 

13,048 participants [5,508 men, mean (SD) age 61.9 (7.6) years and 7,540 women, age 60.9 (7.2) years] were able to recall their birthweight and underwent MRI body composition analysis or had a measurement of grip strength. In both men and women, higher birthweight was associated with greater thigh muscle volume (adjusted for age and body mass index (BMI)): men, β (95% CI): 0.23 (0.16,0.30) SD/kg, p < 0.001; women, β (95% CI): 0.28 (0.22,0.35) SD/kg, p < 0.001. Higher birthweight was also associated with higher grip strength (adjusted for age and height); men, β (95% CI): 0.09 (0.06,0.13) SD/kg, p < 0.001; women, β (95% CI): 0.06 (0.02,0.09) SD/kg, p = 0.001. All associations were robust to additional adjustment for current smoking and physical activity.

Conclusion 

Birthweight was positively associated with MRI measures of thigh muscle volume and grip strength in a population of middle-aged UK adults. These findings provide novel evidence in support of the developmental programming hypothesis and suggest that interventions to optimise birthweight may help to prevent sarcopenia and reduce the risk of falls in future generations. (Project 3593)

Disclosure 

E.M. Curtis: None. S. D'Angelo: None. S. Ashai: None. K. Ward: None. Z. Raisi-Estbragh: None. S. Petersen: None. C. Cooper: None. N.C. Harvey: None.
O24 Risk of death during the 2020 UK COVID-19 epidemic and annual influenza seasons among people with vasculitis compared to the general population: a whole-population study using data from the NDRS and the RECORDER project
Authors: Rutter Megan , Lanyon Peter C , Grainge Matthew J , Hubbard Richard B , Peach Emily J , Bythell Mary , Aston Jeanette , Stevens Sarah , Pearce Fiona A
Published: April 2021

Background/Aims 

To quantify the risk of death among people with vasculitis during the UK 2020 COVID-19 epidemic compared with baseline risk, risk during annual influenza seasons and risk of death in the general population during COVID-19.

Methods 

We performed a cohort study using data from the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) under their legal permissions (CAG 10-02(d)/2015). Coded diagnoses for vasculitis (ANCA-associated vasculitis, Takayasu arteritis, Behçet's disease, and giant cell arteritis) were identified from Hospital Episode Statistics from 2003 onwards. Previous coding validation work demonstrated a positive predictive value >85%. The main outcome measure was age-standardised mortality rates (ASMRs) for all-cause death. ONS published data were used for general population mortality rates.

Results 

We identified 55,110 people with vasculitis (median age 74.9 (IQR 64.1-82.7) years, 68.0% female) alive 01 March 2020. During March-April 2020, 892 (1.6%) died of any cause. The crude mortality rate was 9773.0 (95% CI 9152.3-10,435.9) per 100,000 person-years. The ASMR was 2567.5 per 100,000 person-years, compared to 1361.1 (1353.6-1368.7) in the general population (see table).

The ASMR in March-April 2020 was 1.4 times higher than the mean ASMR for March-April 2015-2019 (1965.6). The increase in deaths during March-April 2020 occurred at a younger age than in the general population.

We went on to investige the effect of previous influenza seasons. The 2014/15 season saw the greatest excess all-cause mortality nationally in recent years, and there were 624 deaths in 38,888 people (6472.5 person-years) with vasculitis in our data (crude mortality rate 9640.8 (8913.3-10427.7); The ASMR was 2657.6, which was marginally higher than the ASMR among people with vasculitis recorded during March-April 2020 during the COVID-19 pandemic.

Conclusion 

People with vasculitis are at increased risk of death during circulating COVID-19 and influenza epidemics. The ASMR among people with vasculitis was high both during the 2014/15 influenza season and during the first wave of the COVID-19 epidemic. COVID-19 vaccination and annual influenza vaccination for people with vasculitis are both important, regardless of patient age.

Disclosure 

M. Rutter: None. P.C. Lanyon: Grants/research support; PCL has received funding for research from Vifor Pharma.. M.J. Grainge: None. R.B. Hubbard: None. E.J. Peach: Grants/research support; EJP has received funding for research from Vifor Pharma. M. Bythell: None. J. Aston: None. S. Stevens: None. F.A. Pearce: Grants/research support; FAP has received funding for research from Vifor Pharma..
P006 The potential of colour Doppler ultrasound in reducing temporal artery biopsies in suspected giant cell arteritis
Authors: Sidhu Arslan A , Nandagudi Anupama , Bharadwaj Anurag
Published: April 2021

Background/Aims 

Giant cell arteritis (GCA) is an emergency. The initial treatment with high dose glucocorticoids (GC) is often started on clinical suspicion without waiting for temporal artery biopsy (TAB) results. Colour Doppler ultrasound (CDUS) is a simple, non-invasive test which is readily available. However, like any other ultrasound, it is operator dependent. Non-compressible ‘halo sign’ is the most specific abnormality on CDUS. British society for Rheumatology (BSR) guidelines advises to avoid TAB in patients with low clinical probability and negative CDUS as well as in high clinical probability and positive CDUS.

Methods 

We adopted the quality improvement methodology for assessment. Retrospective data of suspected GCA patients was collected over the last two years. CDUS was introduced to investigative plan midway, after eleven months. Two rheumatology consultants were trained in CDUS. Results were compared before and after the introduction of ultrasound as a diagnostic tool. In collecting the data, our main focus for documentation was based on clinical symptoms, CDUS and TAB results. Patient were divided into high, medium and low probability groups based on clinical assessment by a rheumatologist. Final diagnosis was decided on the basis of clinical assessment at 6 months.

Results 

It was a retrospective review from January 2018 to November 2019, 101 patients were referred with suspected GCA. Median age was 72 years (50 - 91 years) with male to female ratio of 1:3. Thirty five patients were referred in the first 11 months and 28.6% were diagnosed with GCA. CDUS and TAB was done in 20% and 49% of patients respectively. Sixty six patients were referred in the next 12 months after CDUS was introduced and 21.2% were diagnosed as GCA. CDUS and TAB were done in 82% and 38% of the patients respectively. We reviewed all TABs in the second phase of QIP (38%). As per current BSR guideline, 8 TABs could have been avoided in patients with positive CDUS and high probability of GCA or negative CDUS and low probability of GCA. Even if we deduct these 8 TABs from total of 25, 26% of our suspected GCA referrals would still require TAB for diagnostic workup.

Conclusion 

After the routine introduction of CDUS, the percentage of patients requiring TAB has declined. Approximately one fourth patients would still require TAB as per BSR guidelines. To improve the clinical relevance of biopsies further we recommended; the routine use of GCA probability score, improve CDUS skills and arrange availability of urgent slots in clinic for CDUS. We also noticed that the number of patients referred has almost doubled. This might be due to better education and awareness at the primary and secondary care level which was done as part of the project.

Disclosure 

A.A. Sidhu: None. A. Nandagudi: None. A. Bharadwaj: None.
P024 The mighty mimic: intravascular large b-cell lymphoma masquerading as myositis: a case series
Authors: Mirza Maria A
Published: April 2021

Background/Aims 

Intravascular large b-cell lymphoma (IVLBCL) is a rare and aggressive form of extranodal diffuse lymphoma which due to its heterogeneous manifestations is often diagnosed at post mortem. The disease is typically contained within the small vessels thus sparing the surrounding tissue. Indeed, the presentation of the disease will depend on the organ involved with classical involvement of the central nervous system and skin.

Methods 

We herein report two compelling cases of patients presenting with features of myositis, only to find on muscle biopsy evidence of IVBCL. Biopsy of the affected area and indeed random skin biopsies (RSB) may be a fundamental tool in establishing this elusive diagnosis.

Results 

Features of the two cases are discussed, along with their various presentations, investigations, treatment and overall trajectory.

Conclusion 

IVBCL is a rare disease that can present in various ways and often a delay in reaching a diagnosis leads to patient deterioration and death. A multidisciplinary approach involving the microbiologists, rheumatologists and haematologists led to a timely identification of the disease and subsequent management in these two cases. As the disease is characteristically contained within the blood vessels, the diagnosis is normally not confirmed from peripheral blood tests or even bone marrow biopsy. Biopsy of the affected area is what revealed the diagnosis in our two cases. Random skin biopsies may be very useful in establishing the diagnosis when suspecting IVBCL. Treatment may be very effective in controlling the disease as demonstrated by these two cases.

Disclosure 

M.A. Mirza: None.