bluuebunny/crossref_metadata_2025_split huggingface dataset:
PaIntDB: network-based omics integration and visualization using protein–protein interactions in Pseudomonas aeruginosa
Authors: Castillo-Arnemann Javier J , Solodova Olga , Dhillon Bhavjinder K , Hancock Robert E W 
Published: May 2021

Abstract

Summary
The Pseudomonas aeruginosa Interaction Database, PaIntDB, is an intuitive web-based tool for network-based systems biology analyses using protein–protein interactions (PPI) in this medically important pathogen. It enables the integration and visualization of omics analyses including RNA-Seq and Tn-Seq. High-throughput datasets can be mapped onto PPI networks, which can be explored visually and filtered to uncover novel putative molecular pathways related to the conditions of study. PaIntDB contains the most comprehensive P.aeruginosa interactome to date, collected from a variety of resources, including interactions predicted computationally to further expand analysis capabilities. The web server implementation makes it easily extendable to other bacterial species.

Availability and implementation
PaIntDB is freely available at https://www.paintdb.ca, the source code and database file are available at https://github.com/yavyx/PaIntDB.

Supplementary information
Supplementary data are available at Bioinformatics online.
Target–Decoy MineR for determining the biological relevance of variables in noisy datasets
Authors: Ovando-Vázquez Cesaré , Cázarez-García Daniel , Winkler Robert 
Published: May 2021

AbstractMotivationMachine learning algorithms excavate important variables from big data. However, deciding on the relevance of identified variables is challenging. The addition of artificial noise, ‘decoy’ variables, to raw data, ‘target’ variables, enables calculating a false-positive rate and a biological relevance probability for each variable rank. These scores allow the setting of a cut-off for informative variables, depending on the required sensitivity/specificity of a scientific question.ResultsWe tested the function of the Target–Decoy MineR (TDM) using synthetic data with different degrees of perturbation. Following, we applied the TDM to experimental Omics (metabolomics, transcriptomics and proteomics) results. The TDM graphs indicate the degree of difference between sample groups. Further, the TDM reports the contribution of each variable to correct classification, i.e. its biological relevance.Availabilityand implementationAn implementation of the algorithm in R is freely available from https://bitbucket.org/cesaremov/targetdecoy_mining/. The Target–Decoy MineR is applicable to different types of quantitative data in tabular format.Supplementary informationSupplementary data are available at Bioinformatics online.
CrossTalkeR: analysis and visualization of ligand–receptorne tworks
Authors: Nagai James S , Leimkühler Nils B , Schaub Michael T , Schneider Rebekka K , Costa Ivan G 
Published: May 2021

Abstract

Motivation
Ligand–receptor (LR) network analysis allows the characterization of cellular crosstalk based on single cell RNA-seq data. However, current methods typically provide a list of inferred LR interactions and do not allow the researcher to focus on specific cell types, ligands or receptors. In addition, most of these methods cannot quantify changes in crosstalk between two biological phenotypes.

Results
CrossTalkeR is a framework for network analysis and visualization of LR interactions. CrossTalkeR identifies relevant ligands, receptors and cell types contributing to changes in cell communication when contrasting two biological phenotypes, i.e. disease versus homeostasis. A case study on scRNA-seq of human myeloproliferative neoplasms reinforces the strengths of CrossTalkeR for characterization of changes in cellular crosstalk in disease.

Availability and implementation
CrosstalkeR is an R package available at: Github: https://github.com/CostaLab/CrossTalkeR.

Supplementary information
Supplementary data are available at Bioinformatics online.
Sex Differences in Lifespan Trajectories and Variability of Human Sulcal and Gyral Morphology
Authors: Díaz-Caneja Covadonga M , Alloza Clara , Gordaliza Pedro M , Fernández-Pena Alberto , de Hoyos Lucía , Santonja Javier , Buimer Elizabeth E L , van Haren Neeltje E M , Cahn Wiepke , Arango Celso , Kahn René S , Hulshoff Pol Hilleke E , Schnack Hugo G , Janssen Joost 
Published: May 2021

Abstract
Sex differences in the development and aging of human sulcal morphology have been understudied. We charted sex differences in trajectories and inter-individual variability of global sulcal depth, width, and length, pial surface area, exposed (hull) gyral surface area, unexposed sulcal surface area, cortical thickness, gyral span, and cortex volume across the lifespan in a longitudinal sample (700 scans, 194 participants 2 scans, 104 three scans, age range: 16–70 years) of neurotypical males and females. After adjusting for brain volume, females had thicker cortex and steeper thickness decline until age 40 years; trajectories converged thereafter. Across sexes, sulcal shortening was faster before age 40, while sulcal shallowing and widening were faster thereafter. Although hull area remained stable, sulcal surface area declined and was more strongly associated with sulcal shortening than with sulcal shallowing and widening. Males showed greater variability for cortex volume and lower variability for sulcal width. Our findings highlight the association between loss of sulcal area, notably through sulcal shortening, with cortex volume loss. Studying sex differences in lifespan trajectories may improve knowledge of individual differences in brain development and the pathophysiology of neuropsychiatric conditions.
Weight Change Following Antiretroviral Therapy Switch in People With Viral Suppression: Pooled Data from Randomized Clinical Trials
Authors: Erlandson Kristine M , Carter Christoph C , Melbourne Kathleen , Brown Todd T , Cohen Cal , Das Moupali , Esser Stefan , Huang Hailin , Koethe John R , Martin Hal , McComsey Grace A , Orkin Chloe , Post Frank A , Rockstroh Jürgen K , Sax Paul E , Stellbrink Hans-Jürgen , Waters Laura , Wei Xuelian , Lake Jordan E 
Published: May 2021

Abstract

Background
We sought to identify factors associated with weight gain in randomized clinical trials of antiretroviral therapy (ART) switch.

Methods
We explored the effects of demographic factors, clinical characteristics, and ART on weight gain in a pooled analysis of 12 prospective clinical trials, wherein virologically suppressed people living with human immunodeficiency virus (PWH) were randomized to switch or remain on a stable baseline regimen (SBR).

Results
Both PWH randomized to switch ART (n = 4166) and those remaining on SBR (n = 3150) gained weight. Median weight gain was greater in those who switched (1.6 kg, interquartile range [IQR], –.05 to 4.0 vs 0.4 kg, [IQR], –1.8 to 2.4 at 48 weeks, P &lt; .0001), with most weight gain occurring in the first 24 weeks after switch. Among baseline demographic and clinical characteristics, only younger age and lower baseline body mass index were associated with any or ≥10% weight gain. By week 48, 4.6% gained ≥10% weight (6.4% of switch and 2.2% of SBR), the greatest risk was with switch from efavirenz (EFV) to rilpivirine (RPV) or elvitegravir/cobicistat and switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Switch from abacavir to TAF was associated with less weight gain than switch from TDF to TAF and was not associated with increased risk for ≥10% weight gain.

Conclusions
Moderate weight gain after ART switch was common and usually plateaued by 48 weeks. Baseline ART was a predictor of post-switch weight gain; participants who switched off of EFV and TDF had the greatest weight gain. The biological mechanisms that underlie the differential effects of switching ART agents on weight and associated clinical implications require further study.
The Reliability ofk-Aryn-Cube Based on Component Connectivity
Authors: Lv Mengjie , Fan Jianxi , Zhou Jingya , Yu Jia , Jia Xiaohua 
Published: May 2021

AbstractConnectivity and diagnosability are two crucial subjects for a network’s ability to tolerate and diagnose faulty processors. The $r$-component connectivity $c\kappa _{r}(G)$ of a network $G$ is the minimum number of vertices whose deletion results in a graph with at least $r$ components. The $r$-component diagnosability $ct_{r}(G)$ of a network $G$ is the maximum number of faulty vertices that the system can guarantee to identify under the condition that there exist at least $r$ fault-free components. This paper first establishes that the $(r+1)$-component connectivity of $k$-ary $n$-cube $Q^{k}_{n}$ is $c\kappa _{r+1}(Q^{k}_{n})=-\frac{1}{2}r^{2}+\Big(2n-\frac{1}{2}\Big)r+1$ for $n\geq 2$, $k\geq 4$ and $1\leq r\leq n$. In view of $c\kappa _{r+1}(Q^{k}_{n})$, we prove that the $(r+1)$-component diagnosabilities of $k$-ary $n$-cube $Q^{k}_{n}$ under the PMC model and MM* model are $ct_{r+1}(Q^{k}_{n})=-\frac{1}{2}r^{2}+\Big(2n-\frac{3}{2}\Big)r+2n$ for $n\geq 4$, $k\geq 4$ and $1\leq r\leq n-1$.
The use of eculizumab as a bridge to retransplantation for chronic antibody-mediated rejection in a heart transplant recipient: a case report
Authors: Kearney Katherine , Macdonald Peter , Hayward Christopher , Muthiah Kavitha 
Published: May 2021

Abstract

Background
Antibody-mediated rejection (AMR) remains a major management challenge in heart transplantation given the complexity of pathological diagnosis and dearth of evidence for effective management. Eculizumab, an anti-C5 monoclonal antibody which inhibits terminal complement activation, has been reported to decrease early AMR in sensitized renal transplant recipients.

Case summary
We report a case of a 29-year-old gentleman with chronic AMR 8 years after heart transplantation, manifesting as significant graft dysfunction. Donor-specific antibodies to DQ7 were found to be causative. Antibody-mediated rejection was managed with quadruple oral immunosuppressive therapy (mycophenolate, prednisolone, everolimus, and tacrolimus) as well as a sequence of broad-spectrum immunological therapies; intravenous (IV) methylprednisolone, plasmapheresis, IV immunoglobulin, rituximab, bortezomib, tocilizumab, and splenic irradiation. No treatment had a sustained impact on donor-specific anti-HLA antibodies (DSAs) or graft function. After testing showed the DQ7 antibodies were complement-binding, a trial of eculizumab was started. This improved DSAs somewhat, and improved graft function and New York Heart Association functional class substantially. The patient was relisted for heart transplantation and successfully retransplanted in March 2018. Specifically, the new organ and recipient were matched at DQ7. After discontinuation of eculizumab, the patient has remained healthy and well, with normal graft function 28 months after retransplantation.

Discussion
To the best of our knowledge, this is the first case of chronic AMR in a heart transplant patient, successfully stabilized with eculizumab and bridged to retransplantation.
The role of some additional risk factors in the occurrence of paroxysmal / persistent atrial fibrillation in patients with arterial hypertension
Authors: Grigoryan S , Hazarapetyan LG , Ter-Markaryan AA , Stepanyan AA 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Arterial hypertension (AH) and atrial fibrillation (AF) are two important public health problems and often coexist in the same patient. AH ultimately increases the risk of AF and several pathogenetic mechanisms underlying the higher risk of AF in hypertensive patients are still incompletely known. AH is one of the main reasons for the remodeling process in these patients and makes a significant contribution to the development of structural changes. The aim of this study is to identify predictors of paroxysmal/persistent AF occurrence and progression in hypertensive patients

Methods
In this study where enrolled 109 hypertensive patients with non-valvular paroxysmal/persistent AF (mean age 61.6 ±6.4) who were hospitalized at Institute of Cardiology between 2008 and 2016 year. As a control group, 44 hypertensive patients without AF were also examined. The study lasted 8 years. After the enrollment the echocardiography examination and 24-hour ambulatory Holter monitoring ECG were registered in each patient. We measured plasma indexes of inflammation (hsCRP, IL-6) and fibrosis marker - transforming growth factor (TGF-β1). The database consisting of 33 indicators that characterize the clinical, hemodynamic and structural-functional state of the heart, as well as markers of inflammation and fibrosis was created. .All data were analyzed by SPSS 13 and EXCEL - 2013 programs using logistic analysis by odds ratio (OR).

Results
The comparative results of clinical, hemodynamic, inflammation and fibrosis markers OR with AF in hypertensive patients relative to the control group showed that in hypertensive patients with AF there was a significant increase in diastolic pressure (OR 1.09, р=0.017) , the number of hypertensive crises episodes ( OR 1.56 р=0.001) and patients of older age groups (OR 1.18, р= 0.001) There was a significant deterioration in electrical remodeling (Pmax 3.92, р=0.001, P dispersion 4.90, р=0.001), LV diastolic function (isometric ventricular contraction time 1.69, р=0.042) and of left atrial volume (OR 3.69, р=0.001). There were significant increases in levels of inflammatory and fibrosis markers concentrations in comported with hypertensive patients without AF (OR of hsСRP 5.57, р=0.01; IL-6 4.80, р=0.001 and TGF-β1 3.84, р=0.005).

Conclusions
The multifactorial analysis revealed that increased diastolic pressure, frequency of hypertensive crises, age, deterioration of diastolic function, as well as an increase in markers of inflammation and fibrosis concentration are additional risk factors for AF in patients with hypertension.
Importance of medication compliance and lifestyle modification in heart failure readmission: single centre cohort study
Authors: Tun H 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Medication poor adherence is a common problem among heart failure (HF) patients. Inadequate compliance of drugs lead to increased HF exacerbations, higher risk for hospital admission and death. Despite this recent attention to HF readmission, we know relatively little about its actual causes despite the fact that patients are in many ways best positioned to identify the underlying factors that contribute to their readmissions.

Objective
To systematically investigate the patients" perspectives about the reasons for their hospital readmission related to drug compliance in chronic heart failure patients .
Method and Materials
Patients were recruited for this study was admitted to national institute of cardiovascular diseases, through emergency department. Patients discharged with a primary discharge diagnosis for HF who were then readmitted for any cause in the subsequent 6 month were eligible for the study. Eligible patients were approached, consented, and interviewed within the next 24 hours while they were still in hospital.

Result
For the readmission, median length of stay was 6 days. Total 500 patient included, out of which 375 (75%) were male and most important cause of heart failure is ischaemic cardiomyopathy 400 (80%). No death recorded. Common reasons for readmission are lack of counselling 200(40%), noncompliance medication ; under dose 75(15%), non-compliance 60(12%), volume over load 50(10%), hypertension 50(10%), secondary infection 35(7%).

Conclusion
We concluded that patient compliance of medication, appropriate fluid intake, self-care and life style modification are the important elements to care off according to this study which can be improve with psychotherapies and proper counselling session. For physician side proper information and detail discussion should be done with patient at the time of diagnosis.
HFrEF patient activity levels during COVID-19 lockdown: A comparison between physical activity questionnaires and implantable devices data
Authors: Tsarouchas A , Bakogiannis C , Mouselimis D , Lazaridis C , Kelemanis I , Theofillogiannakos EK , Pagourelias ED , Papadopoulos CE , Fragakis N , Vassilikos VP 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
The ongoing COVID-19 pandemic is a major public health crisis of great risk to patients with cardiovascular comorbidities. Heart failure (HF) is a deadly chronic disease, a leading cause of hospitalizations worldwide and a great detriment to patients’ quality of life. HF therapy guidelines suggest prescribing physical activity to improve long-term outcomes. Self- or government- imposed behavioral modifications in response to COVID-19 ranging from avoiding social interactions to outright restrictions of movement (lockdowns) could compromise regular PA in HF patients, who constitute an extremely high-risk group.

Purpose
Investigate the effect of the national lockdown in Greece 23rd March – 4th May 2020) on the PA levels of patients suffering from HF with reduced ejection fraction (HFrEF) and cardiac implantable electronic devices (CIEDs).

Methods
HFrEF patients with CIEDs were included in the study. Participants answered the Physical Activity Questionnaire (PAQ) regarding the period before, during and after the 42-day national lockdown. CIED-derived daily activity levels for the corresponding periods were recorded through CIED telemetry. The differences in PAQ- and CIED-derived PA levels and sedentary time before, during and after the lockdown period were investigated.

Results
67 HFrEF patients participated in the study (mean age 69 ± 10.2y, 85% male). Activity levels fell in 55 (82%) of patients. The median PAQ-derived PA level decreased by 28% during lockdown, from 840.5 (944) METmin/week to 602 (1054) METmin/week during the lockdown (p = 0.01). A 53% increase was observed after the lockdown, to 924 (1214) METmin/week (p = 0.004). The CIED-derived activity level was 2.38 (1.3) hours/day pre-lockdown, 1.78 (1.1) hours/day during the lockdown (25% decrease, p &lt; 0.001) and 2.69 (1.5) hours/day post-lockdown (51% increase, p &lt; 0.001). Time spent on sedentary activities also increased to 9 (3) hours per day during the lockdown, up from 6.5 (4) hours before lockdown (p = 0.001).

Conclusions
All measures examined in this study indicate that the COVID-19 lockdown period was associated with a significant decrease in HFrEF patients’ PA. All efforts must be made on the part of clinicians and public health organizations to promote safe exercise in this subgroup of the population that is particularly vulnerable to the effects of a sedentary lifestyle.
Abstract Figure. Patient activity around COVID lockdown
Impact of age and sex on subclinical coronary atherosclerosis in a healthy asian population
Authors: Wong M , Yap J , Yeo KK 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background and Aims
The influence of age and gender on clinical atherosclerotic cardiovascular disease is well reported, but literature remains sparse on whether these extend to the disease in its preclinical stage. We aim to report the prevalence, risk-factors and impact of age and gender on the burden of subclinical coronary atherosclerosis in a healthy Asian population.

Methods
Healthy subjects aged 30-69 years old, with no history of cardiovascular disease or diabetes were recruited from the general population. Subclinical coronary atherosclerosis was quantified via the Coronary Artery Calcium Score (CACS) with CACS of 0 indicating the absence of calcified plaque, 1 to 10 minimal plaque, 11 to 100 mild plaque, and &gt;100 moderate to severe plaque.

Results
A total of 663 individuals (mean age 49.4 ± 9.2 years, 44.8% male) were included. The prevalence of any CAC was 29.3% with 9% having CAC &gt; 100. The prevalence was significantly higher in males than females (43.1 vs 18.0%, p &lt; 0.001). These gender differences became increasingly pronounced with increasing age, especially in those with moderate-severe CAC. Multivariable analysis revealed significant associations between increasing age, male, higher blood pressure, increased glucose levels and higher LDL cholesterol levels with the presence of any CAC. LDL cholesterol was more significantly associated with CAC in females compared to males (Pinteraction = 0.022).

Conclusions
The prevalence of preclinical atherosclerosis increased with age, and was higher in males than females, with gender-specific differences in associated risk factors. These results will better inform individualised future risk management strategies to prevent the development and progression of coronary artery disease within healthy individuals.
Implementation and clinical outcomes of pharmacogenetic CYP2C19 testing for clopidogrel therapy in real-world clinical practice.
Authors: O"drisceoil POD , Kiernan TK , Arnous SA 
Published: May 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.
BACKGROUNDCYP2C19 loss-of-function (LOF) polymorphisms are associated with adverse ischaemic events after PCI. The use of a point-of-care assay (POC) to routinely genotype patients immediately post PCI could rapidly identify patients at risk of adverse cardiac outcomes. PURPOSE To investigate the incidence of CYP2C19 polymorphisms (*2, *17) and 30-day MACE in patients presenting to catheter laboratory for PCI (See table 1).METHODS We performed a single centre prospective analysis of patients presenting to a cardiac catheterisation laboratory for percutaneous coronary intervention. Participants underwent prospective rapid point-of-care genotyping of CYP2C19 major alleles (2*,17*), using the SpartanRx PCR device via buccal swab sample. All patients provided written consent. RESULTS:A total of 120 tests were performed, 51 patients were normal allele carriers (*1), 31 patients were carriers of LOF alleles (*2) and 38 patients were carriers of gain of function alleles (*17). All tests results returned in one hour. Rate of dyslipidaemia was significantly different between three groups (55% vs. 63% vs. 36%; p = 0.050). A numerically higher proportion of LOF allele carriers received clopidogrel prior to undergoing pharmacogenetic testing but this was not statistically significant (52% vs. 35% vs. 34%; p = 0.09). Two cases of MACE at 30 day follow up occurred in the loss-of-function group. Both cases received clopidogrel.CONCLUSIONSWe have demonstrated that a rapid POC of CYP2C19 testing can take place in a real-world setting. Our incidence rate of LOF carriers is concordant with international published literature. We found 52% of LOF carriers were commenced on clopidogrel therapy prior to genetic analysis.
Comparison of CPY2C19 Metabolisers genotype Loss of function normal Gain of function p values baseline characteristics age in years, median (range) 65 (43-82) 64 (43-85) 65 (42-89) 0.717 Male, N (%) 21 (68%) 43 (64%) 27 (71%) 0.198 Hypertensive, N (%) 16 (52%) 29 (57%) 24 (50%) 0.623 Dyslipidaemia. N (%) 17 (55%) 32 (63%) 14 (36%) 0.050 Indication, N (%) St-Elevation MI 12 (39%) 18 (35%) 11 (29%) 0.558 NSTEMI 5 (16%) 15 (29%) 14 (37%) 0.142 Unstable Angina 5 (16%) 7 (14%) 3 (8%) 0.518 Stable CAD 9 (29%) 11 (22%) 10 (26%) 0.731 Antiplatelet, N (%) Ticagrelor 15 (48%) 33 (65%) 25 (66%) 0.09 Clopidogrel 16 (52%) 18 (35%) 13 (34%) Complication, N (%) 30-day MACE 2 (6.5%) 0 0 0.01