bluuebunny/crossref_metadata_2025 huggingface dataset:
Crown defoliation decreases reproduction and wood growth in a marginal European beech population
Authors: Oddou-Muratorio Sylvie , Petit-Cailleux Cathleen , Journé Valentin , Lingrand Matthieu , Magdalou Jean-André , Hurson Christophe , Garrigue Joseph , Davi Hendrik , Magnanou Elodie
Published: April 2021

Background and Aims

Abiotic and biotic stresses related to climate change have been associated with increased crown defoliation, decreased growth and a higher risk of mortality in many forest tree species, but the impact of stresses on tree reproduction and forest regeneration remains understudied. At the dry, warm margin of species distributions, flowering, pollination and seed maturation are expected to be affected by drought, late frost and other stresses, eventually resulting in reproduction failure. Moreover, inter-individual variation in reproductive performance versus other performance traits (growth, survival) could have important consequences for population dynamics. This study investigated the relationships among individual crown defoliation, growth and reproduction in a drought-prone population of European beech, Fagus sylvatica.

Methods

We used a spatially explicit mating model and marker-based parentage analyses to estimate effective female and male fecundities of 432 reproductive trees, which were also monitored for basal area increment and crown defoliation over 9 years.

Key Results

Female and male fecundities varied markedly between individuals, more than did growth. Both female fecundity and growth decreased with increasing crown defoliation and competition, and increased with size. Moreover, the negative effect of defoliation on female fecundity was size-dependent, with a slower decline in female fecundity with increasing defoliation for the large individuals. Finally, a trade-off between growth and female fecundity was observed in response to defoliation: some large trees maintained significant female fecundity at the expense of reduced growth in response to defoliation, while some other defoliated trees maintained high growth at the expense of reduced female fecundity.

Conclusions

Our results suggest that, while decreasing their growth, some large defoliated trees still contribute to reproduction through seed production and pollination. This non-coordinated decline of growth and fecundity at individual level in response to stress may compromise the evolution of stress-resistance traits at population level, and increase forest tree vulnerability.
Strand Orientation Bias Detector to determine the probability of FFPE sequencing artifacts
Authors: Diossy Miklos , Sztupinszki Zsofia , Krzystanek Marcin , Borcsok Judit , Eklund Aron C , Csabai István , Pedersen Anders Gorm , Szallasi Zoltan
Published: April 2021

Formalin-fixed paraffin-embedded tissue, the most common tissue specimen stored in clinical practice, presents challenges in the analysis due to formalin-induced artifacts. Here, we present Strand Orientation Bias Detector (SOBDetector), a flexible computational platform compatible with all the common somatic SNV-calling pipelines, designed to assess the probability whether a given detected mutation is an artifact. The underlying predictor mechanism is based on the posterior distribution of a Bayesian logistic regression model trained on The Cancer Genome Atlas whole exomes. SOBDetector is a freely available cross-platform program, implemented in Java 1.8.
DECODE: a Deep-learning framework for Condensing enhancers and refining boundaries with large-scale functional assays
Authors: Chen Zhanlin , Zhang Jing , Liu Jason , Dai Yi , Lee Donghoon , Min Martin Renqiang , Xu Min , Gerstein Mark
Published: April 2021

Motivation

Mapping distal regulatory elements, such as enhancers, is a cornerstone for elucidating how genetic variations may influence diseases. Previous enhancer-prediction methods have used either unsupervised approaches or supervised methods with limited training data. Moreover, past approaches have implemented enhancer discovery as a binary classification problem without accurate boundary detection, producing low-resolution annotations with superfluous regions and reducing the statistical power for downstream analyses (e.g. causal variant mapping and functional validations). Here, we addressed these challenges via a two-step model called Deep-learning framework for Condensing enhancers and refining boundaries with large-scale functional assays (DECODE). First, we employed direct enhancer-activity readouts from novel functional characterization assays, such as STARR-seq, to train a deep neural network for accurate cell-type-specific enhancer prediction. Second, to improve the annotation resolution, we implemented a weakly supervised object detection framework for enhancer localization with precise boundary detection (to a 10 bp resolution) using Gradient-weighted Class Activation Mapping.

Results

Our DECODE binary classifier outperformed a state-of-the-art enhancer prediction method by 24% in transgenic mouse validation. Furthermore, the object detection framework can condense enhancer annotations to only 13% of their original size, and these compact annotations have significantly higher conservation scores and genome-wide association study variant enrichments than the original predictions. Overall, DECODE is an effective tool for enhancer classification and precise localization.

Availability and implementation

DECODE source code and pre-processing scripts are available at decode.gersteinlab.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
Graph transformation for enzymatic mechanisms
Authors: Andersen Jakob L , Fagerberg Rolf , Flamm Christoph , Fontana Walter , Kolčák Juri , Laurent Christophe V F P , Merkle Daniel , Nøjgaard Nikolai
Published: April 2021

Motivation

The design of enzymes is as challenging as it is consequential for making chemical synthesis in medical and industrial applications more efficient, cost-effective and environmentally friendly. While several aspects of this complex problem are computationally assisted, the drafting of catalytic mechanisms, i.e. the specification of the chemical steps—and hence intermediate states—that the enzyme is meant to implement, is largely left to human expertise. The ability to capture specific chemistries of multistep catalysis in a fashion that enables its computational construction and design is therefore highly desirable and would equally impact the elucidation of existing enzymatic reactions whose mechanisms are unknown.

Results

We use the mathematical framework of graph transformation to express the distinction between rules and reactions in chemistry. We derive about 1000 rules for amino acid side chain chemistry from the M-CSA database, a curated repository of enzymatic mechanisms. Using graph transformation, we are able to propose hundreds of hypothetical catalytic mechanisms for a large number of unrelated reactions in the Rhea database. We analyze these mechanisms to find that they combine in chemically sound fashion individual steps from a variety of known multistep mechanisms, showing that plausible novel mechanisms for catalysis can be constructed computationally.

Availability and implementation

The source code of the initial prototype of our approach is available at https://github.com/Nojgaard/mechsearch

Supplementary information

Supplementary data are available at Bioinformatics online.
Modeling drug combination effects via latent tensor reconstruction
Authors: Wang Tianduanyi , Szedmak Sandor , Wang Haishan , Aittokallio Tero , Pahikkala Tapio , Cichonska Anna , Rousu Juho
Published: April 2021

Motivation

Combination therapies have emerged as a powerful treatment modality to overcome drug resistance and improve treatment efficacy. However, the number of possible drug combinations increases very rapidly with the number of individual drugs in consideration, which makes the comprehensive experimental screening infeasible in practice. Machine-learning models offer time- and cost-efficient means to aid this process by prioritizing the most effective drug combinations for further pre-clinical and clinical validation. However, the complexity of the underlying interaction patterns across multiple drug doses and in different cellular contexts poses challenges to the predictive modeling of drug combination effects.

Results

We introduce comboLTR, highly time-efficient method for learning complex, non-linear target functions for describing the responses of therapeutic agent combinations in various doses and cancer cell-contexts. The method is based on a polynomial regression via powerful latent tensor reconstruction. It uses a combination of recommender system-style features indexing the data tensor of response values in different contexts, and chemical and multi-omics features as inputs. We demonstrate that comboLTR outperforms state-of-the-art methods in terms of predictive performance and running time, and produces highly accurate results even in the challenging and practical inference scenario where full dose–response matrices are predicted for completely new drug combinations with no available combination and monotherapy response measurements in any training cell line.

Availability and implementation

comboLTR code is available at https://github.com/aalto-ics-kepaco/ComboLTR.

Supplementary information

Supplementary data are available at Bioinformatics online.
On the feasibility of deep learning applications using raw mass spectrometry data
Authors: Cadow Joris , Manica Matteo , Mathis Roland , Reddel Roger R , Robinson Phillip J , Wild Peter J , Hains Peter G , Lucas Natasha , Zhong Qing , Guo Tiannan , Aebersold Ruedi , Rodríguez Martínez María
Published: April 2021

In recent years, SWATH-MS has become the proteomic method of choice for data-independent–acquisition, as it enables high proteome coverage, accuracy and reproducibility. However, data analysis is convoluted and requires prior information and expert curation. Furthermore, as quantification is limited to a small set of peptides, potentially important biological information may be discarded. Here we demonstrate that deep learning can be used to learn discriminative features directly from raw MS data, eliminating hence the need of elaborate data processing pipelines. Using transfer learning to overcome sample sparsity, we exploit a collection of publicly available deep learning models already trained for the task of natural image classification. These models are used to produce feature vectors from each mass spectrometry (MS) raw image, which are later used as input for a classifier trained to distinguish tumor from normal prostate biopsies. Although the deep learning models were originally trained for a completely different classification task and no additional fine-tuning is performed on them, we achieve a highly remarkable classification performance of 0.876 AUC. We investigate different types of image preprocessing and encoding. We also investigate whether the inclusion of the secondary MS2 spectra improves the classification performance. Throughout all tested models, we use standard protein expression vectors as gold standards. Even with our naïve implementation, our results suggest that the application of deep learning and transfer learning techniques might pave the way to the broader usage of raw mass spectrometry data in real-time diagnosis.

Availability and implementation

The open source code used to generate the results from MS images is available on GitHub: https://ibm.biz/mstransc. The data, including the MS images, their encodings, classification labels and results, can be accessed at the following link: https://ibm.ent.box.com/v/mstc-supplementary

Supplementary information

Supplementary data are available at Bioinformatics online.
SeRenDIP-CE: sequence-based interface prediction for conformational epitopes
Authors: Hou Qingzhen , Stringer Bas , Waury Katharina , Capel Henriette , Haydarlou Reza , Xue Fuzhong , Abeln Sanne , Heringa Jaap , Feenstra K Anton
Published: April 2021

Motivation

Antibodies play an important role in clinical research and biotechnology, with their specificity determined by the interaction with the antigen’s epitope region, as a special type of protein–protein interaction (PPI) interface. The ubiquitous availability of sequence data, allows us to predict epitopes from sequence in order to focus time-consuming wet-lab experiments toward the most promising epitope regions. Here, we extend our previously developed sequence-based predictors for homodimer and heterodimer PPI interfaces to predict epitope residues that have the potential to bind an antibody.

Results

We collected and curated a high quality epitope dataset from the SAbDab database. Our generic PPI heterodimer predictor obtained an AUC-ROC of 0.666 when evaluated on the epitope test set. We then trained a random forest model specifically on the epitope dataset, reaching AUC 0.694. Further training on the combined heterodimer and epitope datasets, improves our final predictor to AUC 0.703 on the epitope test set. This is better than the best state-of-the-art sequence-based epitope predictor BepiPred-2.0. On one solved antibody–antigen structure of the COVID19 virus spike receptor binding domain, our predictor reaches AUC 0.778. We added the SeRenDIP-CE Conformational Epitope predictors to our webserver, which is simple to use and only requires a single antigen sequence as input, which will help make the method immediately applicable in a wide range of biomedical and biomolecular research.

Availability and implementation

Webserver, source code and datasets at www.ibi.vu.nl/programs/serendipwww/.

Supplementary information

Supplementary data are available at Bioinformatics online.
Functional roles of the chromatin remodeler SMARCA5 in mouse and bovine preimplantation embryos†
Authors: Shi Yan , Zhao Panpan , Dang Yanna , Li Shuang , Luo Lei , Hu Bingjie , Wang Shaohua , Wang Huanan , Zhang Kun
Published: April 2021

Upon fertilization, extensive chromatin reprogramming occurs during preimplantation development. Growing evidence reveals species-dependent regulations of this process in mammals. ATP-dependent chromatin remodeling factor SMARCA5 (also known as SNF2H) is required for peri-implantation development in mice. However, the specific functional role of SMARCA5 in preimplantation development and if it is conserved among species remain unclear. Herein, comparative analysis of public RNA-seq datasets reveals that SMARCA5 is universally expressed during oocyte maturation and preimplantation development in mice, cattle, humans, and pigs with species-specific patterns. Immunostaining analysis further describes the temporal and spatial changes of SMARCA5 in both mouse and bovine models. siRNA-mediated SMARCA5 depletion reduces the developmental capability and compromises the specification and differentiation of inner cell mass in mouse preimplantation embryos. Indeed, OCT4 is not restricted into the inner cell mass and the formation of epiblast and primitive endoderm disturbed with reduced NANOG and SOX17 in SMARCA5-deficient blastocysts. RNA-seq analysis shows SMARCA5 depletion causes limited effects on the transcriptomics at the morula stage, however, dysregulates 402 genes, including genes involved in transcription regulation and cell proliferation at the blastocyst stage in mice. By comparison, SMARCA5 depletion does not affect the development through the blastocyst stage but significantly compromises the blastocyst quality in cattle. Primitive endoderm formation is greatly disrupted with reduced GATA6 in bovine blastocysts. Overall, our studies demonstrate the importance of SMARCA5 in fostering the preimplantation development in mice and cattle while there are species-specific effects.
On the power of Chatterjee’s rank correlation
Authors: Shi H , Drton M , Han F
Published: April 2021

Chatterjee (2021) introduced a simple new rank correlation coefficient that has attracted much attention recently. The coefficient has the unusual appeal that it not only estimates a population quantity first proposed by Dette et al. (2013) that is zero if and only if the underlying pair of random variables is independent, but also is asymptotically normal under independence. This paper compares Chatterjee’s new correlation coefficient with three established rank correlations that also facilitate consistent tests of independence, namely Hoeffding’s $D$, Blum–Kiefer–Rosenblatt’s $R$, and Bergsma–Dassios–Yanagimoto’s $\tau^*$. We compare the computational efficiency of these rank correlation coefficients in light of recent advances, and investigate their power against local rotation and mixture alternatives. Our main results show that Chatterjee’s coefficient is unfortunately rate-suboptimal compared to $D$, $R$ and $\tau^*$. The situation is more subtle for a related earlier estimator of Dette et al. (2013). These results favour $D$, $R$ and $\tau^*$ over Chatterjee’s new correlation coefficient for the purpose of testing independence.
PTEN somatic mutations contribute to spectrum of cerebral overgrowth
Authors: Koboldt Daniel C , Miller Katherine E , Miller Anthony R , Bush Jocelyn M , McGrath Sean , Leraas Kristen , Crist Erin , Fair Summer , Schwind Wesley , Wijeratne Saranga , Fitch James , Leonard Jeffrey , Shaikhouni Ammar , Hester Mark E , Magrini Vincent , Ho Mai-Lan , Pierson Christopher R , Wilson Richard K , Ostendorf Adam P , Mardis Elaine R , Bedrosian Tracy A
Published: April 2021

Phosphatase and tensin homologue (PTEN) regulates cell growth and survival through inhibition of the mammalian target of rapamycin (MTOR) signalling pathway. Germline genetic variation of PTEN is associated with autism, macrocephaly and PTEN hamartoma tumour syndromes. The effect of developmental PTEN somatic mutations on nervous system phenotypes is not well understood, although brain somatic mosaicism of MTOR pathway genes is an emerging cause of cortical dysplasia and epilepsy in the paediatric population.

Here we report two somatic variants of PTEN affecting a single patient presenting with intractable epilepsy and hemimegalencephaly that varied in clinical severity throughout the left cerebral hemisphere. High-throughput sequencing analysis of affected brain tissue identified two somatic variants in PTEN. The first variant was present in multiple cell lineages throughout the entire hemisphere and associated with mild cerebral overgrowth. The second variant was restricted to posterior brain regions and affected the opposite PTEN allele, resulting in a segmental region of more severe malformation, and the only neurons in which it was found by single-nuclei RNA-sequencing had a unique disease-related expression profile.

This study reveals brain mosaicism of PTEN as a disease mechanism of hemimegalencephaly and furthermore demonstrates the varying effects of single- or bi-allelic disruption of PTEN on cortical phenotypes.
Signs of congestion in patients with perioperative atrial fibrillation in major noncardiac surgery
Authors: Dzhioeva O , Shvartz VA , Drapkina OM
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Purpose

to evaluate the frequency of perioperative atrial fibrillation in patients with postoperative signs of systemic congestion.

Methods

we examined 102 patients who underwent cardiac monitoring in the perioperative period to detect episodes of atrial fibrillation and focused echocardiography to detect signs of systemic congestion. All patients underwent abdominal surgery lasting more than 180 minutes.Clinical, laboratory, and echocardiographic criteria were used to verify systemic stagnation in the postoperative period in patients after non-cardiac surgery.

Results

we determined the number of patients with perioperative AF who had acute decompensation of HF in the early postoperative period, determined by signs of systemic stagnation. When assessing the number of patients with preoperative anamnestic AF, which was initially 16 people, in 100% of cases in the postoperative period, decompensation of HF was noted. When evaluating the number of patients with intraoperative AF, which was detected in 24 patients, decompensation of HF in the first 24 hours after abdominal surgery was observed in 23 patients (95.8%) (OR: 25.4; 95% CI: 3.27-198.14; p <0.001). When assessing the number of patients with postoperative AF, which was detected in 36 patients, decompensation of HF in the first 24 hours after abdominal surgery was observed in 35 patients (97.2%) (OR:57.4;95% CI:7.39-435.45; p <0.001).

Conclusion

in major non-cardiac operations, most patients with perioperative atrial fibrillation show signs of systemic stagnation in the postoperative period with FOCUS.
Prognostic role of the Rockwood Clinical Frailty Scale in patients with acute heart failure:results from a single-centre retrospective cohort study
Authors: Todd F , Wong C , Hewitson L , Mohamed A , Doolub J , Gogola L , Skyrme-Jones A , Aziz S , Sammut E , Dastidar A
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Acute decompensated heart failure carries a poor prognosis and places a significant burden on healthcare resources. Our ability to predict patients at high risk of deterioration is limited. The Rockwood Clinical Frailty Scale (CFS) is an established frailty screening tool that stratifies patients on a nine-point scale ranging from 1 (very well) to 9 (terminally ill) providing a useful measure of physiological reserve. CFS is used extensively for general prognostication in geriatric populations, yet its impact on mortality specifically in patients admitted with acute heart failure remains sparsely investigated.

Purpose

We performed a retrospective cohort study to investigate the prognostic role for CFS for short term mortality in patients admitted with acute heart failure.

Methods

Over a period of 16 weeks (7th January – 27th April 2020), 283 consecutive patients presenting to our hospital with signs and symptoms of acute heart failure were identified. Discharge summaries, electronic notes and shared care networks were manually searched for each patient to determine frailty score, baseline demographics, admission bloods and co-morbidity indices. Short term mortality at 30 days was recorded from electronic hospital and GP records. Univariate and multivariate Cox regression analysis was performed to identify clinical and biochemical predictors of mortality.

Results

In total, 283 patients were admitted with acute heart failure over the study period (mean age 81+/-10 years, 46% female. The mean CFS score was 5+/-1 and mean Charlson Comorbidity Index score 8+/-3. 15% of patients died within 30 days. On univariate analysis age, creatinine, Charlson Comorbidity Index and CFS were associated with prognosis. On multivariate analysis, only CFS was found to be an independent predictor of mortality (hazard ratio 1.36, p = 0.029).

Conclusion

This study demonstrates a clear relationship between increasing frailty score and short-term mortality in acute heart failure. The CFS is a rapid and easily accessible screening tool used widely throughout the UK. This work highlights its potential for use alongside other parameters in prognostication of patients presenting with acute decompensated heart failure. Further work is needed to explore the impact on longer term mortality and to determine practical implementation in this setting. Abstract Figure.
Renin-angiotensin-aldosterone system blockers could contribute to the gender-related disparities in STEMI outcomes
Authors: Scridon A , Hadadi L , Sus I , Lakatos EK , Demjen Z , Ceamburu A , Fisca PC , Somkereki C , Serban RC
Published: April 2021

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Romanian Ministry of Education and Research, CNCS - UEFISCDI

BACKGROUND

Women with ST-segment elevation myocardial infarction (STEMI) have been shown to present higher in-hospital mortality compared to their male counterparts. However, most of these data were obtained in the pre-percutaneous coronary intervention (PCI) or even in the pre-thrombolytic era.

PURPOSE

We aimed to investigate the contribution of female gender to the occurrence of in-hospital complications in STEMI patients treated by primary PCI.

METHODS

Data regarding in-hospital outcomes (i.e., mortality, inotropic and diuretic drugs usage, occurrence of cardiogenic shock, cardiac arrest) were evaluated in 848 consecutive patients treated by primary PCI for STEMI. Occurrence of new-onset kidney dysfunction and length of hospital stay were also analysed. The relationship between gender and the occurrence of STEMI-related complications was evaluated.

RESULTS

Out of the 848 patients included in the study, 254 (29.9%) were women. Compared to their male counterparts, female STEMI patients were older (65.7 ± 11.3 vs. 60.1 ± 11.8 years; p< 0.0001), had more often pre-existing heart failure, hypertension, diabetes mellitus, and chronic kidney disease (all p< 0.05), longer symptom onset-to-cardiac catheterization laboratory time intervals (7.9 ± 6.7 vs. 6.4 ± 5.0 h; p< 0.001), and higher Killip class on admission (p = 0.02). Cardiogenic shock, inotropic and diuretic drugs usage, kidney dysfunction, and cardiac arrest occurred more often in female than in male patients (all p< 0.01). The length of hospital stay (p< 0.01) and in-hospital death (RR 1.89 [95%CI 1.43-2.50], p< 0.001) were also higher in female compared to male patients, whereas renin-angiotensin-aldosterone system (RAAS) blockers were used more rarely in female patients (p = 0.01). When corrected for potential confounders, female gender remained an independent predictor of in-hospital mortality (p = 0.01). However, when in-hospital RAAS blockers usage was included in the model, female gender was no longer associated with increased in-hospital mortality (p = 0.15).

CONCLUSIONS

Female patients with STEMI continue to display significantly higher in-hospital mortality rates compared to their male peers including in the primary PCI era. The difference in in-hospital mortality between female and male patients with STEMI could be at least partially due to the significantly lower usage of RAAS blockers in women. Increasing in-hospital RAAS blockers usage in female patients with STEMI may improve survival in this high-risk population.
Admission biomarkers among patients with acute myocardial-infarction related cardiogenic shock with or without out-of-hospital cardiac arrest
Authors: Thoegersen M , Frydland M , Helgestad O , Jensen LO , Josiassen J , Goetze JP , Moeller JE , Hassager C
Published: April 2021

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Lundbeck Foundation

OnBehalf

Critical Cardiac Care Research Group

Background

Approximately half of all patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) present with out-of-hospital cardiac arrest (OHCA). Cardiogenic shock due to OHCA is caused by abrupt cessation of circulation, whereas AMICS without OHCA is due to cardiac failure with low cardiac output. Thus, there may also be differences between the two conditions in terms of blood borne biomarkers.

Purpose

To explore the potential differences in the admission plasma concentrations of biomarkers reflecting tissue perfusion (lactate), neuroendocrine response (mid-regional proadrenomedullin [MRproADM], Copeptin, pro-atrial natriuretic peptide [proANP]), endothelial damage (Syndecan-1, soluble thrombomodulin [sTM]), inflammation (soluble suppression of tumorigenicity 2 [sST2]) and kidney injury (neutrophil gelatinase-associated lipocalin [NGAL]), in patients with AMICS presenting with or without OHCA.

Method

Consecutive patients admitted for acute coronary angiography due to suspected ST-elevation myocardial infarction (STEMI) were enrolled during a 1-year period. A total of 2,713 patients were screened. In the present study 86 patients with confirmed STEMI and CS at admission were included.

Results

Patients with OHCA (had significantly higher median admission concentrations of Lactate (6,9 mmol/L vs. 3.4 mmol/L p <0.001), NGAL (220 ng/ml  vs 150 ng/ml p = 0.046), sTM (10 ng/ml vs. 8.0  ng/ml p = 0.026) and Syndecan-1 (160 ng/ml vs. 120 ng/ml p= 0.015) and significantly lower concentrations of MR-proADM (0.85 nmol/L  vs. 1.6 nmol/L p <0.001) and sST2 (39 ng/ml vs. 62 ng/ml p < 0.001).  After adjusting for age, sex, and time from symptom onset to coronary angiography, lactate (p = 0.008), NGAL (p = 0.03) and sTM (p = 0.011) were still significantly higher in patients presenting with OHCA while sST2 was still significantly lower (p = 0.029). There was very little difference in 30-day mortality between the OHCA and non-OHCA groups (OHCA 37% vs. non-OHCA 38%).

Conclusion

Patients with STEMI and CS at admission with or without concomitant OHCA had similar 30-day mortality but differed in terms of Lactate, NGAL, sTM and sST2 levels at the time of admission to catheterization laboratory. These findings propose that non-OHCA and OHCA patients with CS could be considered as two individual clinical entities. Abstract Figure. Level of biomarkers OHCA vs. non-OHCA
Comparing doppler-echocardiography and thermodilution for cardiac output measurements in resuscitated out-of-hospital cardiac arrest patients undergoing targeted temperature management
Authors: Grand J , Hassager C , Kjaergaard J , Moller JE , Bro-Jeppesen J
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Cardiovascular dysfunction is common after out-of-hospital cardiac arrest (OHCA). Cardiac output measurements can be used to guide treatment during post-resuscitation care and echocardiography allows noninvasive cardiac output estimation.

Purpose

The aim of the present study was to compare Doppler echocardiography (doppler_CO) with thermodilution using pulmonary artery catheters (PAC_CO) for cardiac output estimation in a large and consecutively included cohort of comatose OHCA-patients undergoing targeted temperature management (TTM).

Methods

Single-center substudy of 171 patients included in the TTM-trial randomly assigned to 33 or 36 degrees C for 24 hours after OHCA. We measured PAC_CO and doppler_CO simultaneously shortly after admission and again after 24 hours.

Measurements and Main Results

We excluded 19 (11%) patients without PAC-measurement and 31 (18%) without doppler-measurements resulting in 120 paired measurements at admission. Patients were 61 (±11) years old, 86% were men and 91% had a witnessed OHCA. At ICU-admission, PAC_CO was 4.81 (±1.81) L/min. and doppler_CO was 3.74 (±1.38) L/min., with a mean bias of 1.07 (±1.65) L/min (with 95% limits of agreement of –2.16 to 4.04) L/min. Examining the Bland-Altman plot, precision fell with higher cardiac output  (figure). A statistically significant, but moderate correlation was found between doppler_CO and PAC_CO at admission (r = 0.49), p < 0.0001). After 24 hours, PAC_CO was 4.63 (±1.38) L/min. and doppler_CO was 3.61 (±1.14) L/min, with a mean bias of 0.96 L/min. Assessing the change from admission to 24 hours, PAC_CO decreased averagely -0.12 (±2.22) L/min. and doppler_CO decreased -0.19 (±1.91) L/min. The changes from admission to 24 hours correlated between doppler_CO and PAC_CO (r = 0.55), p < 0.0001) with a mean bias of the changes of 0.07 L/min, with 95% limits of agreement of –3.76 to 3.91 L/min.

Conclusions

Changes in cardiac output during TTM may be evaluated with Doppler echocardiography with little mean bias compared to changes in CO measured with thermodilution, but relatively large changes are needed in the individual patient before it can be considered as real. Abstract Figure. Comparing Doppler vs. thermodilution
The impact of percutaneous coronary intervention versus coronary artery bypass grafting surgery in left main coronary disease
Authors: Oliveira CC , Guerra A , Braga C
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Introduction

Although coronary artery bypass grafting (CABG) has been considered the gold-standard method for the treatment for left main stable ischemic coronary disease (s-LMCAD), percutaneous coronary intervention (PCI) has shown good results.

Objective

To evaluate patients with s-LMCAD who performed CABG or PCI and compare their outcomes.

Study design

Single center, retrospective study that included all s-LMCAD patients who performed LM PCI or CABG between January 2015 and November 2018 (n = 35 in the PCI group and 35 in the CABG group after propensity score and matches in a ratio of 1:1). Clinical and imaging information of patients was collected, relating to the pre- and post-procedure and with 3 years of follow-up (FUP).

Results

Overall, baseline clinical and angiographic characteristics were balanced between the groups. The PCI group had higher prevalence of previous coronary disease (54.3%% vs 28.6%, p = 0.029) and chronic obstructive pulmonary disease (22.9% vs 5.7%, p = 0.04). The anatomical complexity estimated through the calculation of the SYNTAX score showed no significant differences between groups (16 vs 19, p = 0.151). 50% of PCI group performed IVUS, 2.8% OCT and 2.8% FFR. All CABG grafts used were arterial. There were no registries of events during hospitalization. At 30 days, cardiovascular-mortality was higher in the PCI group than in CABG group (n = 2 (5.56%) vs 0, respectively), representing all cases of cardiovascular death in PCI group through the 3-years follow-up. In CABG group, cardiovascular-related death was more substantial at 3 years. At 3 years of FUP, no significant differences were found between the PCI and CABG groups in MACCE (hazard ratio (HR) of the PCI group, 2,786; confidence interval (CI) of 95%, 0.873 to 8,889; p = 0.084). However, patients submitted to PCI with a SYNTAX score≥23 had worse MACCE results (HR 9.022, 95% CI, 1,054 to 77.210; p = 0,045), though a large confidence interval was also registered. Though not significantly different, cardiac-related hospital admissions were more frequent in the CABG group (18 (25.00%) vs 6 (16.67%) in the PCI group), but occurred more acutely in the PCI group (< 30 days). Stroke events happened more frequently in the CABG group, with a total of 4 cases reported (5.56%) whereas in the PCI group none happened. Myocardial infarction rate was also higher in the PCI group (2, 5.71%) and 1 happened in the first 30 days which was related to a target lesion failure. Revascularization through PCI due to restenosis had only 1 (2.78%) case registered. Graft failure happened in only 1 patient.

Conclusion

In conclusion, for the treatment of patients with stable s-LMCAD and low anatomical complexity, PCI was noninferior to CABG. Our results suggest that PCI is an acceptable alternative to CABG for patients with stable left main coronary artery disease, except for the ones with high anatomical complexity.
Cardiovascular disease risk factors in the community of the western region of Saudi Arabia
Authors: Alsafrani T , Abukhodair A , Khojah O , Jastania E , Alamri R , Kinsara A
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Objectives

To estimate the prevalence of the risk factors for coronary artery disease (CAD) in the community of the Western Region, Saudi Arabia.

Background

CAD is a significant cause of mortality globally, particularly in developing countries, and predicted to increase significantly. The risk factors for CAD, such as hypertension, diabetes mellitus, hyperlipidemia, and smoking are increasingly prevalent, in addition to an increased prevalence of obesity.

Design/Methods:

A cross-sectional study was conducted in a mall, using a consecutive sampling technique. Individuals were interviewed in terms of clinical signs and symptoms as well as the risk factors. The anthropometric measurements were done on site to identify asymptomatic risk factors.

Results

In total, 193 individuals participated in this study. The mean age of the sample was 36.3 ± 12.4 years, with 53% male. Smoking was the most frequent risk factor (36.1%), followed by dyslipidemia (22.5%), hypertension (16.6%), and diabetes mellitus (14.5%). Less than half (40%) of the sample participated in sport for one to two hours per week. Almost all consumed fast food at least once a week, and 16.6% consumed fast food more than four times a week. The average systolic blood pressure was 129.41± 22.5 mmHg and the average body mass index (BMI) 28.6 ± 9.5 kg/m2.

Conclusion

Dyslipidemia was the most prevalent risk factor, followed by hypertension and diabetes mellitus. These three risk factors are first in the risk factor pyramid in commonality, and preventative interventions are pivotal to decrease the incidence of cardiovascular disease. The consumption of fast food is relatively high with a low level of physical activity. Educating the community regarding measures to reduce the modifiable risk factors is foundational to avoid catastrophic results.
Meta-analysis on the safety and efficacy of Lumbrokinase in peripheral arterial disease
Authors: Agoncillo A
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Background

Lumbrokinase, an oral anti-thrombotic and fibrinolytic agent, was not yet part of the recommendations of any recommendations but had shown in two studies that it could increase the Ankle Brachial Index (ABI). ABI was used to evaluate the drug efficacy for PAD.

Purpose

Peripheral Arterial Disease was one of the most neglected, under-screened, and undertreated high-risk groups among cardiovascular diseases like myocardial infarction and stroke. Few studies were done to evaluate the treatment of fibrinolytic such as Lumbrokinase for this population. 

Methods

We appraised two randomized control trials that evaluated the safety and efficacy of Lumbrokinase compared to placebo with the standard regimen and another study of Lumbrokinase compared to placebo with standard regimen versus Lumbrokinase with Prostaglandin E1 (PGE1) among adult patients for the reduction of symptoms of PAD and increase in ABI. Both trials treatment period lasted for 2 weeks.

Two independent reviewers assess the identified trials for inclusion by applying the selection criteria and quality was assessed using the JADAD scale. The data was analyzed using Meta analyst statistical software.

Main results

After weeks of treatment, the effect size is 0.90; this is an increase of at least +0.06 from the baseline that supports the trend in increasing the ankle-brachial index. The study did not show significant side effects by Lumbrokinase

Conclusions

Lumbrokinase at 460 to 490 mg three times a day for 2 weeks to 3 months has no significant relationship but has a trend in increasing the ankle-brachial index to a borderline level compared to placebo. Additional studies regarding the effect of Lumbrokinase in increasing ABI must be done with larger sample size.  Further research is needed to illuminate whether a longer duration of treatment with Lumbrokinase can increase the ankle-brachial index more.

Eligible Trials Table 1. Eligible trials, characteristics, and demographics.AuthorYearControlPatient enrolled (N)Patient Analysed (%)Age Mean SDMales %Diabetes %Dyslipidemia %1. NDRAHA2013PlaceboL = 10 C= 10L = 100 C = 100L = 55.8 C = 53.2L = 5 C = 5L = 35 C = 25L = 30 C = 302. LUL= 31 C = 31L = 100 C = 100L = 68 C = 68.4L = 74 C = 74NANASUM/RAW MEANSL= 41 C = 41L = 100 C = 100L = 61.9 C = 60.8L = 39.4 C = 39.4NANAL= Lumbrokinase groupC= Control groupNA = not availableAbstract Figure. Efficacy of Lumbrokinase
The efficacy and safety of prolonged dual antiplatelet therapy beyond 12 months in patients with high risk of ischemic or bleeding events after PCI
Authors: Wang HY , Ge JZ , Dou KF
Published: April 2021

Funding Acknowledgements

Type of funding sources: None.

Background

The relative benefit-risk profile of continuing DAPT beyond 1 year for patients undergoing PCI who are at high risk for ischemic or hemorrhagic complications in real-world practice remains to be determined. For this reason, we sought to evaluate the benefits and harms of DAPT beyond 1 year as compared with ≤1-year DAPT among high ischemic or bleeding risk patients undergoing PCI with DES from a prospective, real-world registry.

Methods

All consecutive patients undergoing PCI were prospectively included in the Fuwai PCI Registry from January 2013 to December 2013. We evaluated 7521 patients who were at high risk for thrombotic or hemorrhagic complications and were events free at 1 year after the index procedure. "TWILIGHT-like" patients with high risk of bleeding or ischemic events were defined by clinical and angiographic criteria. The clinical criteria chosen to enroll patients at high risk for either bleeding or ischemic complications after PCI were: ≥65 years, female sex, troponin-positive ACS, established vascular disease (previous myocardial infarction [MI], documented peripheral arterial disease [PAD] or CAD/PAD revascularization), diabetes mellitus treated with medication, and chronic kidney disease (CKD). Angiographic criteria included multivessel CAD, total stent length >30 mm, a bifurcation lesion treated with two stents, thrombotic target lesion, left main (≥50%) or proximal left anterior descending (LAD) (≥70%) lesion, and calcified target lesions requiring atherectomy. The primary ischemic outcome was major adverse cardiac and cerebrovascular events [MACCE] (a composite of all-cause death, myocardial infarction, or stroke).

Results

Median follow-up duration was 2.4 years. The risk of MACCE was significantly lower in DAPT > 12- group (n = 5252) than DAPT ≤ 1-year group (n = 2269) (1.5% vs. 3.8%; hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.27-0.50; P < 0.001). This difference was largely driven by a lower risk of all-cause death. In contrast, the risk of Bleeding Academic Research Consortium (BARC) type 2, 3 or 5 bleeding was statistically similar between the 2 groups (1.0% vs. 1.1%; HR: 0.80; 95% CI: 0.50-1.28; P = 0.346). Results were consistent after multivariable regression and propensity-score matching. Relative treatment effects were consistent for the outcomes of MACCE and clinically relevant bleeding independent of the number of clinical and angiographic high-risk features (1-3 [n = 310], 4-5 [n = 3560], or 6-9 [n = 854]).

Conclusions

Prolonged DAPT beyond 1 year after DES implantation resulted in a significantly lower rate of atherothrombotic events, including a mortality benefit, with no higher risk of clinically relevant bleeding in "TWILIGHT-like" patients who were at high-risk for ischemic or bleeding events. Abstract Figure.
Combined improvement of insulin resistance and hypertension using whole body digital twin technology in diabetic hypertensives- a real world study
Authors: Shamanna P , Joshi S , Shah L , Mohammed J , Mohammed M , Poon T , Mohamed T , Keshav A
Published: April 2021

Funding Acknowledgements

Type of funding sources: Private company. Main funding source(s): Twin Health

OnBehalf

TWIN Study Group

Introduction

Insulin resistance is multifaceted phenomenon that affects blood pressure homeostasis

Methods

207 patients (163 male), with T2DM and concomitant hypertension were evaluated for impact of the Twin Precision Nutrition (TPN) Program, which utilises a whole-body digital twin technology, powered by artificial intelligence and Internet of Things.  As part of the assessment, the change in, insulin resistance (HOMA2-IR) and systemic hypertension (Systolic BP, Diastolic BP), as measured by HBPM (Home Blood Pressure Monitoring) were evaluated longitudinally for three months. Student-t test and Pearson r was utilised for statistical analysis

Results

49.7% (n = 103) achieved HbA1c less than 7%, 37.1% (n = 77) achieved hypertension control (SBP < 130 mmHg, DBP <80 mmHg) and 20.2% (n = 42) achieved both hypertension and targeted glycemic control (SBP < 130 mmHg, DBP <80 mmHg, HbA1c <7%). Mean duration of diabetes was 8.9 years (±7.2, minimum 0, maximum 35, 95% CI 7.9 to 9.9). The reduction in the HbA1c (%), SBP (mmHg), DBP (mmHg) and HOMA2 IR was -1.8 ± 0.1, -10.67 ± 1.51, -6.28 ± 1.01 and -0.93 ± 0.16, was highly statistically significant, respectively (p < 0.0001) (Table). There was a positive correlation between insulin resistance (HOMA2-IR) and both SBP (r = 0.17, p = 0.0098) and DBP (r = 0.14, p = 0.0382). The association between the insulin resistance was relatively stronger for SBP than for DBP.  Of initial 69 patients who had high HOMA2-IR (≥2.9) reduced to just 6 patients

Conclusion

Our study is distinct to demonstrate the clinical utility of digital health intervention to utilise mutli-pronged approach provided by technology enabled precision nutrition, to address multiple pathways simultaneously. Our results provide insights into the acute benefits for hypertension and need corroboration with long term follow up to provide insights for end organ protection that directly mitigates the complications of diabetes and hypertension Change in the HbA1c, SBP, DBP and HOMA2-ParameterTime PointMean (±SD)MinimumMaximumRange95% CIp valueHba1cDay 08.8 ± 1.95.1159.88.5 to 9<0.0001 ****Day 906.9 ± 0.94.8105.36.8 to 7.1Systolic BPDay 0136 ± 179419096134 to 139<0.0001 ****Day 90126 ± 138716073124 to 127Diastolic BPDay 088 ± 12641437986 to 90<0.0001 ****Day 9082 ± 8.8561115581 to 83HOMA2-IRDay 02.6 ± 2.10.318182.3 to 2.9<0.0001 ****Day 901.6 ± 10.111111.5 to 1.8Abstract Figure. Correlation: Hypertension and HOMA2-IR
Canine exposure: open or closed?
Authors: Camilleri Simon
Published: April 2021

Evidence for open or closed exposure of palatally displaced canines is equivocal, but this study sheds light on new facets which may influence the method of choice. The aim of this article is to give a short perspective on this field, highlight the merits of a study published in this issue of the European Journal of Orthodontics by Björksved et al. the study, place the findings into context and show how it may influence clinical practice.
Informed proposal Monte Carlo
Authors: Khoshkholgh Sarouyeh , Zunino Andrea , Mosegaard Klaus
Published: April 2021

Any search or sampling algorithm for solution of inverse problems needs guidance to be efficient. Many algorithms collect and apply information about the problem on the fly, and much improvement has been made in this way. However, as a consequence of the No-Free-Lunch Theorem, the only way we can ensure a significantly better performance of search and sampling algorithms is to build in as much external information about the problem as possible. In the special case of Markov Chain Monte Carlo (MCMC) sampling we review how this is done through the choice of proposal distribution, and we show how this way of adding more information about the problem can be made particularly efficient when based on an approximate physics model of the problem. A highly non-linear inverse scattering problem with a high-dimensional model space serves as an illustration of the gain of efficiency through this approach.