bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matrix factorization-based data fusion for the prediction of RNA-binding proteins and alternative splicing event associations during epithelial–mesenchymal transition
Authors: Qiu Yushan , Ching Wai-Ki , Zou Quan 
Published: July 2021

AbstractMotivationThe epithelial-mesenchymal transition (EMT) is a cellular–developmental process activated during tumor metastasis. Transcriptional regulatory networks controlling EMT are well studied; however, alternative RNA splicing also plays a critical regulatory role during this process. Unfortunately, a comprehensive understanding of alternative splicing (AS) and the RNA-binding proteins (RBPs) that regulate it during EMT remains largely unknown. Therefore, a great need exists to develop effective computational methods for predicting associations of RBPs and AS events. Dramatically increasing data sources that have direct and indirect information associated with RBPs and AS events have provided an ideal platform for inferring these associations.ResultsIn this study, we propose a novel method for RBP–AS target prediction based on weighted data fusion with sparse matrix tri-factorization (WDFSMF in short) that simultaneously decomposes heterogeneous data source matrices into low-rank matrices to reveal hidden associations. WDFSMF can select and integrate data sources by assigning different weights to those sources, and these weights can be assigned automatically. In addition, WDFSMF can identify significant RBP complexes regulating AS events and eliminate noise and outliers from the data. Our proposed method achieves an area under the receiver operating characteristic curve (AUC) of $90.78\%$, which shows that WDFSMF can effectively predict RBP–AS event associations with higher accuracy compared with previous methods. Furthermore, this study identifies significant RBPs as complexes for AS events during EMT and provides solid ground for further investigation into RNA regulation during EMT and metastasis. WDFSMF is a general data fusion framework, and as such it can also be adapted to predict associations between other biological entities.
DNAgenie: accurate prediction of DNA-type-specific binding residues in protein sequences
Authors: Zhang Jian , Ghadermarzi Sina , Katuwawala Akila , Kurgan Lukasz 
Published: July 2021

AbstractEfforts to elucidate protein–DNA interactions at the molecular level rely in part on accurate predictions of DNA-binding residues in protein sequences. While there are over a dozen computational predictors of the DNA-binding residues, they are DNA-type agnostic and significantly cross-predict residues that interact with other ligands as DNA binding. We leverage a custom-designed machine learning architecture to introduce DNAgenie, first-of-its-kind predictor of residues that interact with A-DNA, B-DNA and single-stranded DNA. DNAgenie uses a comprehensive physiochemical profile extracted from an input protein sequence and implements a two-step refinement process to provide accurate predictions and to minimize the cross-predictions. Comparative tests on an independent test dataset demonstrate that DNAgenie outperforms the current methods that we adapt to predict residue-level interactions with the three DNA types. Further analysis finds that the use of the second (refinement) step leads to a substantial reduction in the cross predictions. Empirical tests show that DNAgenie’s outputs that are converted to coarse-grained protein-level predictions compare favorably against recent tools that predict which DNA-binding proteins interact with double-stranded versus single-stranded DNAs. Moreover, predictions from the sequences of the whole human proteome reveal that the results produced by DNAgenie substantially overlap with the known DNA-binding proteins while also including promising leads for several hundred previously unknown putative DNA binders. These results suggest that DNAgenie is a valuable tool for the sequence-based characterization of protein functions. The DNAgenie’s webserver is available at http://biomine.cs.vcu.edu/servers/DNAgenie/.
Comparison of approaches to transcriptomic analysis in multi-sampled tumors
Authors: Ku Anson T , Wilkinson Scott , Sowalsky Adam G 
Published: July 2021

Abstract
Intratumoral heterogeneity is a well-documented feature of human cancers and is associated with outcome and treatment resistance. However, a heterogeneous tumor transcriptome contributes an unknown level of variability to analyses of differentially expressed genes (DEGs) that may contribute to phenotypes of interest, including treatment response. Although current clinical practice and the vast majority of research studies use a single sample from each patient, decreasing costs of sequencing technologies and computing power have made repeated-measures analyses increasingly economical. Repeatedly sampling the same tumor increases the statistical power of DEG analysis, which is indispensable toward downstream analysis and also increases one’s understanding of within-tumor variance, which may affect conclusions. Here, we compared five different methods for analyzing gene expression profiles derived from repeated sampling of human prostate tumors in two separate cohorts of patients. We also benchmarked the sensitivity of generalized linear models to linear mixed models for identifying DEGs contributing to relevant prostate cancer pathways based on a ground-truth model.
PolyRound: polytope rounding for random sampling in metabolic networks
Authors: Theorell Axel , Jadebeck Johann F , Nöh Katharina , Stelling Jörg 
Published: July 2021

Abstract

Summary
Random flux sampling is a powerful tool for the constraint-based analysis of metabolic networks. The most efficient sampling method relies on a rounding transform of the constraint polytope, but no available rounding implementation can round all relevant models. By removing redundant polytope constraints on the go, PolyRound simplifies the numerical problem and rounds all the 108 models in the BiGG database without parameter tuning, compared to ∼50% for the state-of-the-art implementation.

Availability and implementation
The implementation is available on gitlab: https://gitlab.com/csb.ethz/PolyRound.

Supplementary information
Supplementary data are available at Bioinformatics online.
BioERP: biomedical heterogeneous network-based self-supervised representation learning approach for entity relationship predictions
Authors: Wang Xiaoqi , Yang Yaning , Li Kenli , Li Wentao , Li Fei , Peng Shaoliang 
Published: July 2021

Abstract

Motivation
Predicting entity relationship can greatly benefit important biomedical problems. Recently, a large amount of biomedical heterogeneous networks (BioHNs) are generated and offer opportunities for developing network-based learning approaches to predict relationships among entities. However, current researches slightly explored BioHNs-based self-supervised representation learning methods, and are hard to simultaneously capturing local- and global-level association information among entities.

Results
In this study, we propose a BioHN-based self-supervised representation learning approach for entity relationship predictions, termed BioERP. A self-supervised meta path detection mechanism is proposed to train a deep Transformer encoder model that can capture the global structure and semantic feature in BioHNs. Meanwhile, a biomedical entity mask learning strategy is designed to reflect local associations of vertices. Finally, the representations from different task models are concatenated to generate two-level representation vectors for predicting relationships among entities. The results on eight datasets show BioERP outperforms 30 state-of-the-art methods. In particular, BioERP reveals great performance with results close to 1 in terms of AUC and AUPR on the drug–target interaction predictions. In summary, BioERP is a promising bio-entity relationship prediction approach.

Availability and implementation
Source code and data can be downloaded from https://github.com/pengsl-lab/BioERP.git.

Supplementary information
Supplementary data are available at Bioinformatics online.
Retrospective Cohort Study Comparing Infliximab-dyyb and Infliximab in Biologic-Naive Patients With Inflammatory Bowel Disease in the United States
Authors: Smith Joshua T , Velayos Fernando S , Niu Fang , Liu Vincent , Delate Thomas , Pola Suresh , Le Kim , Hui Rita L 
Published: July 2021

Abstract

Background
Real-world assessments of biosimilars are needed to understand their effectiveness and safety in practice settings that may differ from those seen in clinical trials or healthcare systems in different countries. To assess the effectiveness and safety of a biosimilar (infliximab-dyyb) and its reference product (infliximab) in patients with inflammatory bowel disease (IBD) in the United States.

Methods
We conducted a retrospective cohort study of biologic-naive patients with IBD who started treatment with infliximab-dyyb or infliximab. The study included 3206 patients identified through electronic health records in a US integrated healthcare delivery system. The effectiveness outcome was a composite of IBD-related surgery, IBD-related emergency room visit, and IBD-related hospitalization within 12 months of initiation. Safety outcomes included incidence of any or serious infection, cancer, acute liver dysfunction, and tuberculosis. We used a non-inferiority test with an upper-limit margin of 10% to analyze effectiveness. Doubly robust methods incorporating Cox proportional hazard regression with standardized inverse probability of treatment weighting were used to analyze both effectiveness and safety outcomes.

Results
The composite effectiveness outcome occurred in 107 of 870 patients (12.3%) in the infliximab-dyyb and 379 of 2336 patients (16.2%) in the infliximab groups. Infliximab-dyyb was non-inferior (P &lt; .01) and was not different (hazard ratio [HR] 0.81; confidence interval [CI] 0.65–1.01; P = .06) to infliximab. Safety outcomes were not different between infliximab-dyyb and infliximab for any infections (HR 1.01; CI 0.86–1.17; P = .95), serious infections (HR 0.83; CI 0.54–1.26; P = .38), cancers (HR 0.83; CI 0.44–1.54; P = .55), and tuberculosis (HR 0.59; CI 0.10–3.55; P = .57).

Conclusions
Initiation of infliximab-dyyb was non-inferior to infliximab among biologic-naive patients with IBD in an US integrated healthcare delivery system.
Peritoneal dialysis improves quality-of-life in a left ventricular assist device destination therapy patient—a case report
Authors: Koppel Claire J , Jonker Jacqueline T , Michels Wieneke M , Beeres Saskia L M A 
Published: July 2021

Abstract

Background
Progressive renal insufficiency is frequent in heart failure patients with a left ventricular assist device (LVAD). The optimal strategy for long-term dialysis in LVAD patients and its effect on quality-of-life in these patients remain to be determined.

Case summary
Our 55-year-old patient with pre-existing renal insufficiency received an LVAD as destination therapy because of advanced ischaemic heart failure. Six years after implantation, he developed end-stage renal disease for which peritoneal dialysis (PD) was initiated. Left ventricular assist device flow alterations during ultrafiltration did not cause clinical or technical problems. The patient’s exercise capacity increased and quality-of-life improved. Over 7.5 years after LVAD implantation and 16 months after PD initiation, he died from encephalitis.

Discussion
Despite initial improvement, renal function often gradually decreases after LVAD implantation. Data on long-term renal replacement therapy in LVAD patients are limited. Haemodialysis is most commonly applied. Conceptually, however, PD has advantages over haemodialysis including less bloodstream infections, less haemodynamic shifts, and the comfort of the ambulant setting. This case illustrates that PD in an LVAD patient is feasible and improves quality-of-life. Key factors contributing to successful PD in LVAD patients may be a good right ventricular function and close cardiology–nephrology collaboration.
A case report of an interrupted inferior vena cava and azygos continuation: implications for preoperative screening in minimally invasive cardiac surgery
Authors: Knol Wiebe G , Oei Frans B , Budde Ricardo P J , ter Horst Maarten 
Published: July 2021

Abstract

Background
Femoral cannulation is commonly used in minimally invasive cardiac surgery to establish extracorporeal circulation. We present a case with a finding that should be evaluated when screening candidates for minimally invasive cardiac surgery.

Case summary
A 57-year-old male patient was scheduled for minimally invasive repair of the mitral and tricuspid valve and a MAZE procedure. During surgery there was difficulty advancing the venous cannula inserted in the right femoral vein. On transoesophageal echocardiography a guidewire advanced from the femoral vein was observed entering the right atrium from the superior vena cava. Despite inserting a second venous cannula in the jugular vein, venous drainage was insufficient for minimal invasive surgery. The approach was converted to a median sternotomy with bicaval cannulation. Re-examination of the preoperative computed tomography (CT) scan showed an interrupted inferior vena cava (IVC) with azygos continuation.

Discussion
In patients with major venous malformations such as the interrupted IVC with azygos continuation a full sternotomy is the preferred approach. The venous system should be evaluated when screening candidates for minimally invasive mitral valve surgery with preoperative CT. Additional cues to suspect interruption of the IVC are polysplenia and a broad superior mediastinal projection on the chest radiograph, mimicking a right paratracheal mass.
Double-blind randomized proof-of-concept trial of canakinumab in patients with COVID-19 associated cardiac injury and heightened inflammation
Authors: Cremer Paul C , Sheng Calvin C , Sahoo Debasis , Dugar Siddharth , Prada Robier Aguillon , Wang Tom Kai Ming , Hassan Ossama K Abou , Hernandez-Montfort Jamie , Wolinsky David A , Culver Daniel A , Rajendram Prabalini , Duggal Abhijit , Brennan Danielle M , Wolski Katherine E , Lincoff A Michael , Nissen Steven E , Menon Venu 
Published: July 2021

Abstract

Aims
In coronavirus disease 2019 (COVID-19), myocardial injury is associated with systemic inflammation and higher mortality. Our aim was to perform a proof of concept trial with canakinumab, a monoclonal antibody to interleukin-1β, in patients with COVID-19, myocardial injury, and heightened inflammation.

Methods and results
This trial required hospitalization due to COVID-19, elevated troponin, and a C-reactive protein concentration more than 50 mg/L. The primary endpoint was time to clinical improvement at Day 14, defined as either an improvement of two points on a seven-category ordinal scale or discharge from the hospital. The secondary endpoint was mortality at Day 28. Forty-five patients were randomly assigned to canakinumab 600 mg (n = 15), canakinumab 300 mg (n = 14), or placebo (n = 16). There was no difference in time to clinical improvement compared to placebo [recovery rate ratio (RRR) for canakinumab 600 mg 1.15, 95% confidence interval (CI) 0.46–2.91; RRR for canakinumab 300 mg 0.61, 95% CI 0.23–1.64]. At Day 28, 3 (18.8%) of 15 patients had died in the placebo group, compared with 3 (21.4%) of 14 patients with 300 mg canakinumab, and 1 (6.7%) of 15 patients with 600 mg canakinumab. There were no treatment-related deaths, and adverse events were similar between groups.

Conclusion
There was no difference in time to clinical improvement at Day 14 in patients treated with canakinumab, and no safety concerns were identified. Future studies could focus on high dose canakinumab in the treatment arm and assess efficacy outcomes at Day 28.
Content of Heart failure education by Health-care professionals in Noorder-Kempen, Belgium and Maastricht, the Netherlands: the INTERACT-in-HF study
Authors: Baldewijns K , Brunner-La-Rocca HP , Bektas S , Rhode C , De Maesschalck L , Deville A , Boyne JJJ 
Published: July 2021

Abstract

Funding Acknowledgements
INTERREG NWE IVb
Background
According to ESC-guidelines non-pharmacological interventions such as patient-education on lifestyle and self-care support are important to maintain quality of life (QOL) and to prevent (re)hospitalisation in Heart-Failure (HF). Additionally, these guidelines state that HF treatment should be organised in multidisciplinary programs. However, at this moment it remains unclear what kind of information and self-care support is provided by which health care (HC) professional in the regions Noorder-Kempen and Maastricht.
Purpose
The aim of this study is to describe which part of patient-education and self-care support is provided by different HC-providers in both regions
Methods
Semi-structured interviews with Cardiologists (CA), General Practitioners (GP’s) and Heart Failure Nurse (HFN) took place, followed by qualitative content analysis with a five-step approach, resulting in 2 main and 9 sub-themes.
Results
GP’s in both region express they spend very little time on life-style adjustments, symptom monitoring and self-care support. GP’s in Noorder-Kempen spend most consultation time on physical follow-up and pharmacological treatment of HF-patients, leaving no or little time for non-pharmacological interventions. GP’s in Maastricht notice that non-pharmacological treatment is someone else"s responsibility e.g. practice nurses, HFN, CA.
All interviewed HC-professionals inform patients considering their diagnosis. GP’s and CA in both regions educate patients considering pharmacological treatment and implanted devices. Moreover GP’s and CA in Noorder-Kempen emphasize the importance of compliance to therapy. HFN in both regions offer comprehensive advice regarding lifestyle adjustments. HFN in Maastricht explicitly mention self-care support as an important part of their interventions.

Conclusion
Little regional differences could be found in the non-pharmacological interventions offered by the different HC professions involved in HF-management, however each profession has its own focus. GP’s and CA mainly focus on pharmacological and device therapy and therefore educate patients considering these aspects of HF-treatment. HFN mainly focus on lifestyle adjustments and self-care support.
Stem cell therapy in patients with nonischemic heart failure
Authors: Tomsic Z , Androcec V 
Published: July 2021

Abstract

Funding Acknowledgements
None

Background
Advanced chronic heart failure, characterized by a functional NYHA class III/IV, low LVEF, elevated B-type natriuretic peptides and other criteria’s is a big epidemiological problem, and its prevalence is increasing every year. There are many treatment options for patients with chronic and advanced heart failure. Treatment options include optimal medical therapy, treatment with cardiac resynchronization devices, left ventricular assist devices, heart transplantation and from 2006 treatment with CD 34 + stem cells.

Method
Patient inclusion criteria for stem cell therapy include dilated cardiomyopathy with no valve disease, hypertension or substance abuse, with optimal medical management for 6 months and a decreased left ventricular ejection fraction of &lt;40%. Patients are treated with autologous pluripotent CD 34+ cells, which are mobilized in the blood stream with a bone marrow stimulant Filgrastim, administered subcutaneously for 5 days. The patients are educated by the nurses to do administer the injections at home, and have a contact number of our department in case of side effects. On the day of the procedure, stem cells are collected using the apheresis technique and then delivered transendocardialy in the catheterisation laboratory using the system for electromechanical mapping. If no complications develop, the patients can go home the next day.

Results
During follow-up visits patients treated with stem cells have an increased left ventricular ejection fraction, lower levels of NT-proBNP, increased distance of 6-minute walk test and increased survival compared with the control group. They also report better physical performance.

Conclusion
Stem cell therapy is thus a viable option and could become a mainstream therapy for the treatment of advanced heart failure in the future.
Implementation of shared decision-making for aortic stenosis: Development of a patient decision aid
Authors: Lauck S , Borregaard B , Lewis K , De Souza I 
Published: July 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
People living with aortic stenosis (AS) experience poor quality of life (QOL), repeat hospitalizations, and a poor prognosis in the absence of valve replacement. There is increasing equipoise in the evidence supporting the use of surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) in patients likely to derive survival and QOL benefit. A transition to a palliative approach may be a better option in the setting of excessive frailty and comorbid burden. Shared decision-making (SDM) is a bidirectional exchange between patients and health care providers that enables an information exchange about the best available evidence and decisions that consider patients" priorities. The goal is to inform and empower patients to participate in choosing the right decision. Patient decision aids (PDAs) are designed to support the process of SDM and help guide these conversation. To date, Canadians living with AS have not had access to a validated PDA.

Study Design
We will report on the design of the SharEd DEcision-MaKing for AS (SEEK-AS) study that aims to refine and comprehensively evaluate a set of PDAs and to build capacity for SDM through a unique partnership of patient and clinical knowledge users, multidisciplinary health care providers and researchers, and policy-makers. We will summarize the pilot work completed to obtain a debrief of patient resources used in all Canadian provinces, the draft development of a PDA in concert with a health policy initiative, and the design of an electronic platform to individualize risk in real time during a consultation. We will outline the components of SEEK-AS and the use of a cross-provincial comparative case study design to investigate how to establish an effective and sustainable approach for the implementation of the PDAs using the Knowledge-to-Action conceptual framework.

Implications
There is a pressing need for the development of evidence-based tools to strengthen the integration of patients" perspectives in the treatment of complex valvular heart disease given the rapid pace of change in technology, indications and practice. The study of the implementation of innovative strategies to achieve this goal is essential to accelerate the pace of change in clinical care.