bluuebunny/crossref_metadata_2025_split huggingface dataset:
RegulomePA: a database of transcriptional regulatory interactions in Pseudomonas aeruginosa PAO1
Authors: Galán-Vásquez Edgardo , Luna-Olivera Beatriz Carely , Ramírez-Ibáñez Marcelino , Martínez-Antonio Agustino 
Published: November 2020

Abstract
We present RegulomePA, a database that contains biological information on regulatory interactions between transcription factors (TFs), sigma factor (SFs) and target genes in Pseudomonas aeruginosa PAO1. RegulomePA consists of 4827 regulatory interactions between 2831 nodes, which represent the interactions of TFs and SFs with their target genes, from the total of predicted RegulomePA including 27.27% of the TFs, 54.16% of SFs and 50.8% of the total genes. Each entry in the database corresponds to one node in the network and provides comprehensive details about the gene and its regulatory interactions such as gene description, nucleotide sequence, genome-strand position and links to other databases as well as the type of regulation it exerts or to which it is being subject (repression or activation), the associated experimental evidence and references, and topological information. Additionally, RegulomePA provides a way to recover information on the regulatory circuits of the network to which a gene pertains and also makes available the source codes to analyze the topology of any other regulatory network. The database will be updated yearly, by our team, with the contributions from ourselves and users, since the users are provided with an interactive platform where they can add interactions to the regulatory network feeding it with their respective references.
Database URL: www.regulome.pcyt.unam.mx.
Ileal Transcriptomic Analysis in Paediatric Crohn’s Disease RevealsIL17-andNOD-signalling Expression Signatures in Treatment-naïve Patients and Identifies Epithelial Cells Driving Differentially Expressed Genes
Authors: Ashton James J , Boukas Konstantinos , Davies James , Stafford Imogen S , Vallejo Andres F , Haggarty Rachel , Coelho Tracy A F , Batra Akshay , Afzal Nadeem A , Vadgama Bhumita , Williams Anthony P , Beattie R Mark , Polak Marta E , Ennis Sarah 
Published: November 2020

AbstractBackground and AimsCrohn’s disease [CD] arises through host-environment interaction. Abnormal gene expression results from disturbed pathway activation or response to bacteria. We aimed to determine activated pathways and driving cell types in paediatric CD.MethodsWe employed contemporary targeted autoimmune RNA sequencing, in parallel to single-cell sequencing, to ileal tissue derived from paediatric CD and controls. Weighted gene co-expression network analysis [WGCNA] was performed and differentially expressed genes [DEGs] were determined. We integrated clinical data to determine co-expression modules associated with outcomes.ResultsIn all, 27 treatment-naive CD [TN-CD], 26 established CD patients and 17 controls were included. WGCNA revealed a 31-gene signature characterising TN-CD patients, but not established CD, nor controls. The CSF3R gene is a hub within this module and is key in neutrophil expansion and differentiation. Antimicrobial genes, including S100A12 and the calprotectin subunit S100A9, were significantly upregulated in TN CD compared with controls [p = 2.61 x 10-15 and p = 9.13 x 10-14, respectively] and established CD [both p = 0.0055]. Gene-enrichment analysis confirmed upregulation of the IL17-, NOD- and Oncostatin-M-signalling pathways in TN-CD patients, identified in both WGCNA and DEG analyses. An upregulated gene signature was enriched for transcripts promoting Th17-cell differentiation and correlated with prolonged time to relapse [correlation-coefficient-0.36, p = 0.07]. Single-cell sequencing of TN-CD patients identified specialised epithelial cells driving differential expression of S100A9. Cell groups, determined by single-cell gene expression, demonstrated enrichment of IL17-signalling in monocytes and epithelial cells.ConclusionsIleal tissue from treatment-naïve paediatric patients is significantly upregulated for genes driving IL17-, NOD- and Oncostatin-M-signalling. This signal is driven by a distinct subset of epithelial cells expressing antimicrobial gene transcripts.
Tissue Exposure does not Explain Non-Response in Ulcerative Colitis Patients with Adequate Serum Vedolizumab Concentrations
Authors: Van den Berghe Nathalie , Verstockt Bram , Gils Ann , Sabino João , Ferrante Marc , Vermeire Séverine , Declerck Paul , Thomas Debby 
Published: November 2020

AbstractBackground and AimsSome patients with ulcerative colitis [UC] do not respond to vedolizumab treatment despite adequate drug exposure in serum. This study aimed to investigate vedolizumab in tissue and questioned whether insufficient tissue exposure could explain non-response in UC patients with adequate serum vedolizumab concentrations.MethodsA paired serum sample and colonic mucosal biopsy was collected from 40 UC patients [20 endoscopic responders, 20 non-responders] at week 14 of vedolizumab treatment. Vedolizumab, soluble [s]-mucosal addressin cell adhesion molecule-1 [MAdCAM-1], s-vascular cell adhesion molecule-1 [VCAM-1] and s-intercellular adhesion molecule-1 [ICAM-1] were measured in serum and/or tissue. Endoscopic response was defined as Mayo endoscopic sub-score ≤1.ResultsA significant positive correlation was observed between vedolizumab serum and colonic tissue concentrations [ρ = 0.84, p &lt; 0.0001], regardless of the macroscopic inflammatory state of the tissue. Vedolizumab tissue concentrations were lower in non-responders than in responders [0.07 vs 0.11 µg/mg, p = 0.04]. In the subgroup of patients with adequate vedolizumab serum concentrations [&gt;14.6 µg/mL], tissue vedolizumab was not significantly different between responders and non-responders [0.15 vs 0.13 µg/mg; p = 0.92]. Serum sMAdCAM-1 concentrations, but not serum sICAM-1 or sVCAM-1 concentrations, were significantly higher in responders than in non-responders with adequate vedolizumab serum concentrations [1.04 vs 0.83 ng/mL, p = 0.03].ConclusionsVedolizumab concentrations in colonic mucosal tissue of UC patients reflect the concentration in serum regardless of the macroscopic inflammatory state of the tissue. Our data show that insufficient tissue exposure does not explain non-response in UC patients with adequate serum vedolizumab concentrations.
Watch out for ST-elevation myocardial infarction: a case report of ST-elevation in single-lead electrocardiogram tracing of a smartwatch
Authors: Stark Konstantin , Czermak Thomas , Massberg Steffen , Orban Martin 
Published: November 2020

AbstractBackgroundIt was recently demonstrated that the detection of atrial fibrillation based on heart rate tracking by optical sensors is feasible and reliable using the Apple Watch and the corresponding application. There are already a number of smartwatches and other wearable devices alongside the Apple Watch that can additionally record a single-lead electrocardiogram (ECG) and it is reasonable to expect this technology to become a standard feature, as is already the case with automated heart rate tracking. This could potentially have enormous impact regarding the early diagnosis of several cardiac diseases.Case summaryA 61-year-old male patient without previously known coronary artery disease was admitted with subacute ST-elevation myocardial infarction (STEMI) caused by occlusion of left anterior descending artery. Due to mildness of symptoms, the patient did only seek medical attention due to morphological changes in the single-lead ECG tracing acquired on his Apple Watch 5. The ECG recording of his smartwatch clearly showed ST-elevation, QRS widening, R-wave loss, and T-wave inversion. Coronary angiography revealed occlusion of the left anterior descending and recanalization was performed. The patient recovered without any complications and was discharged from the hospital 4 days after admission.DiscussionWhile the potential of ECG recordings by smartwatches to detect atrial fibrillation is currently under scientific investigation, this case highlights the possible potential of these devices to detect STEMI.
Reporting of the methodological quality of search strategies in orthodontic quantitative systematic reviews
Authors: AlMubarak Danah , Pandis Nikolaos , Cobourne Martyn T , Seehra Jadbinder 
Published: November 2020

Summary

Background
This study aimed to assess the reporting of the methodological quality of search strategies undertaken in orthodontic quantitative systematic reviews (SRs) and hence their reproducibility.

Materials and methods
A search of a single electronic database (Medline via PubMed) was undertaken to identify interventional orthodontic SRs with meta-analysis published within a 10-year period. The Cochrane Library of Systematic Reviews was also sourced. Full articles were reviewed by two assessors against the eligibility criteria. The reporting quality of each search strategy was assessed using a previously validated checklist with a score of 1 or 2 given for each of the eight items. Cumulative totals were calculated. Guided by previous research, the authors agreed the following cut-offs to categorize the overall level of quality: 8–10 (poor), 10–12 (fair), and greater than 13 (good).

Results
A total of 127 SRs were analysed. The overall median quality score for the reporting of the search strategy was 14 [interquartile range (IQR): 13–15]. Cochrane SRs and those originating in Europe received higher aggregate scores, whereas no difference was evident based on Prospero registration. The continent of the corresponding author predicated the overall score. Non-Cochrane reviews achieved lower overall scores compared to Cochrane reviews (−1.0, 95% confidence interval: −1.65, −0.34, P = 0.003). The most frequently searched database was EMBASE (N = 93) and the median number of authors was 5 (IQR 4–6). Authors of 26.8% of SRs searched the grey literature. Language restrictions were applied to the search strategies of 88 (69.3%) SRs.

Conclusions
The reporting quality of search strategies undertaken in orthodontic SRs is at a good level but differences between Cochrane and non-Cochrane reviews currently exist. The reporting of searching of the grey literature and application of no language restrictions can be improved.
The natural history of hypertrophic cardiomyopathy
Authors: Autore Camillo , Musumeci Maria Beatrice 
Published: November 2020

Abstract
In the early years of the disease recognition, hypertrophic cardiomyopathy (HCM) was viewed as an ominous disease with unfavourable prognosis and with an annual mortality between 4% and 6%. At that time, 73% of the patients reported in the literature came from only two referral centres. With the introduction of echocardiography, our understanding of HCM has improved and non-selected patient populations were assembled in several centres. A more benign prognostic profile was documented with an annual mortality rate of 1.5% or less. In the 2000s, important therapeutic interventions further improved the prognosis of patients with HCM: implantable-cardioverter defibrillator for prevention of sudden death, heart transplantation for treatment of severe refractory heart failure, and an extensive treatment with myectomy for relief of left ventricular outflow tract gradient. The natural history of HCM has changed substantially with contemporary treatment achieving an annual mortality rate less than 1% with extended longevity and a greatly improved quality of life.
The new type 2 diabetes mellitus therapy: comparison between the two classes of drugs GLPR (glucagon-like peptide receptor) agonists and SGLT2 (sodium–glucose cotransporter 2) inhibitors
Authors: Borghi Claudio , Bragagni Alessio 
Published: November 2020

Abstract
Type 2 diabetes mellitus represents one of the most common chronic-degenerative diseases in modern society and is the cause of innumerable micro- and macrovascular complications that weigh on the national health system. Until a few years ago, there was no anti-diabetic drug that, in addition to lowering blood sugar, had an impact on cardiovascular risk in these patients. In this report, we will analyse the characteristics, contraindications, and evidence in favour of the use of two innovative categories of molecules that aim, for the first time in history, at controlling blood sugar levels and simultaneously lower cardiovascular risk in diabetics individuals: the glucagon-like peptide receptor agonists and the sodium–glucose cotransporter 2 inhibitors.
The PARAGON-HF trial: the sacubitril/valsartan in heart failure with preserved ejection fraction
Authors: Gronda Edoardo , Vanoli Emilio , Iacoviello Massimo 
Published: November 2020

Abstract
Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical condition characterized by large pathophysiology heterogeneity with lack of effective therapies as proven by the disappointing results generated by randomized controlled trials. The innovative therapeutic concept provided by sacubitril–valsartan, a molecule combining angiotensin receptor blocking agent and neprilysin inhibitor has suggested the hypothesis it would have led to a reduced risk of hospitalization for HF or death from cardiovascular causes among patients with HF and preserved ejection fraction. The PARAGON-HF (ClinicalTrials.gov number, NCT01920711) investigated HF subjects class II to IV HF, ejection fraction of 45% or higher, elevated level of natriuretic peptides, and structural heart disease to receive sacubitril–valsartan (target dose, 97 mg of sacubitril with 103 mg of valsartan twice daily) or valsartan (target dose, 160 mg twice daily). The trial missed the primary outcome of cardiovascular death and HF hospitalization (HFH) in the overall study population. A subgroup analysis addressed significant decrease of HFH in subjects with left ventricular ejection fraction below the median 57% value in the study. The data were consistent with previous post hoc analysis performed in studies where candesartan and spironolactone were investigated in HFpEF. Those results open the door to investigate angiotensin aldosterone and peptidases inhibition efficacy in the unexplored HF middle range ejection fraction, currently lacking of valid evidence.
Procedures for chronic total occlusion: when are they recommended and when not
Authors: Menozzi Mila , Piovaccari Giancarlo 
Published: November 2020

Abstract
Coronary chronic total occlusion (CTO) produces an important clinical problem, often treated with medical therapy or coronary artery bypass grafting. Recent clinical studies, both registries and randomized trials, demonstrated that percutaneous coronary interventions (PCI), could provide a valid therapeutic option. Nonetheless, significant reduction in all-cause mortality, cardiac mortality, myocardial infarction, MACE, and MACCE has not been demonstrated in the subgroups analysis of randomized trials. These analyses suggest that PCI for CTO should be reserved for patients with angina or with large areas of the myocardium with reversible ischaemia. Large randomized studies should search for a personalized approach, considering the risks and complexity of PCI in CTO, which should mainly consider the extension of the ischaemia and the viability of the myocardium.
Clinical application of personalized medicine: heart failure with preserved left ventricular ejection fraction
Authors: Gori Mauro , D’Elia Emilia , Iorio Anita , Iacovoni Attilio , Senni Michele 
Published: November 2020

Abstract
Heart failure (HF) with preserved left ventricular (LV) ejection fraction (HFpEF) represent today the largest ‘unmet medical need’, because none of the drugs presently available improved survival in this consistent proportion of patients with HF, ∼50% of the total, who have an LV ejection fraction ≥50%. Heart failure with preserved left ventricular ejection fraction is a clinical syndrome that in its classical form, is associated to typical risk factors and comorbidities. The comorbidities represent one of the element contributing to the extreme heterogeneity which characterizes HFpEF. The pathophysiological mechanisms, as well as the clinical presentation, are multifaceted. These factors explain, by and large, the failure of a generalized therapeutic strategy, while build the argument for personalized medicine, designed to address the specific phenotypes, with therapies proven in specific subgroups of patients with HFpEF to reduce mortality and improve ‘surrogate’ outcomes, such as quality of life.
Focus on arrhythmogenic right ventricular cardiomyopathy
Authors: Sinagra Gianfranco , Cappelletto Chiara , DE Luca Antonio , Romani Simona , Paldino Alessia , Korcova Renata , Ferro Matteo Dal , Vitrella Giancarlo , Pagnan Lorenzo , Pinamonti Bruno 
Published: November 2020

Abstract
Arrhythmogenic right ventricular cardiomyopathy is a myocardial disease generally caused by desmosomal mutations and characterized by progressive replacement of cardiomyocites with fibro-adipose tissue. In the classic form of the disease right ventricle is predominantly affected. However, biventricular and left-dominant variants have been recently recognized, leading to the new nosological definition of arrhythmogenic cardiomyopathy. The condition affects mostly young adults and athletes and is clinically characterized by ventricular arrhythmias, heart failure and sudden cardiac death. The diagnosis is based on clinical-instrumental criteria, including family history, morpho-functional and electrocardiographic abnormalities, ventricular arrhythmias and genetic defects (Task Force Criteria, 2010). The main goal in the management of patients is the prevention of sudden cardiac death, where implantable cardioverter-defibrillator is the only effective therapeutic strategy. Many arrhythmic risk factors have been described. Recently, an on-line calculator has been proposed, but it needs further validation.
Time is brain: timing of revascularization of brain arteries in stroke
Authors: Risitano Angela , Toni Danilo 
Published: November 2020

Abstract
Ischaemic stroke is the second leading cause of mortality and disability in the western world. Revascularization interventions are the cornerstone of the acute treatment of this pathology and must be administered as soon as possible after the patient’s arrival. They consist of intravenous thrombolysis (IVT) with alteplase, recommended by the guidelines within 4.5 h of the onset of symptoms, and endovascular treatment, recommended within 6 h of the onset of symptoms. The individualized patient selection based on the extent of the mismatch between the penumbra and the ischaemic core allowed to overcome the limits imposed by the rigid time windows, defining a benefit of mechanical revascularization therapies up to 24 h from the theoretical onset of symptoms (last time the patient was known to be well) and up to 9 h for IVT since the theoretical onset of symptoms (last time the patient was known to be well). Advanced neuroimaging methods with perfusion studies are a fundamental tool in patient selection. Their spread in the territory, together with a greater availability of neurovascular treatment units are desirable to ensure a fair delivery of treatment to all patients with ischaemic stroke.
Advancing health literacy measurement in old age
Authors: Konopik Nadine , Kaspar Roman , Penger Susanne , Oswald Frank , Himmelsbach Ines 
Published: November 2020

Summary
Health literacy is described as a domain of competence across the life-span, gaining particular prominence in light of age-associated health restrictions. However, no specific measurement approach has been proposed for old age. The aim of this study is to augment the existing HLS-EU-Q16 scale (16 items) by items sensitive to age-specific aspects of health literacy to ensure validity and reliability for use in old age. In a first step, the HLS-EU-Q16 was administered in a sample of 463 individuals aged 72 − 92 years. Psychometric properties were evaluated using confirmatory factor analysis and item-response-theory item fit statistics. Scale reliability was found to be poor in this population segment. In a second step, age-specific items were developed based on qualitative in-depth interviews with older persons. In a third step, we tested if the additional set of age-specific items was able to enhance a valid and reliable measurement of health literacy in a second sample of older adults (N = 107, 49 − 91 years). With the inclusion of an eight-item add-on, it was possible to measure health literacy in old and very old age with both high validity and satisfying precision (reliability = 0.80). The study contributes to a population-specific measurement of health literacy.
Catch-up and the entry strategies of latecomers: Chinese firms in the mobile phone sector
Authors: Capone Gianluca , Li Daitian , Malerba Franco 
Published: November 2020

AbstractAs interfaces between human beings and the digital world, mobile phones have evolved from relatively simple devices (e.g., feature phones) to complex products (e.g., smartphones). Many firms in emerging countries such as China have successfully entered the mobile phone sector. A research question that emerges from the evidence on China is whether the entry strategies of these catching up firms have been affected by the introduction of smartphones. In order to investigate this question, the article follows the methodology of evolutionary theory and history-friendly models. It first examines historically the various strategies of the Chinese entrants in the mobile phone sector. On the basis of this empirical analysis, it then develops appreciative theorizing on the factors that have affected the catch-up entry strategies. Our results show that the successful catch-up entry strategies differ depending on the sectoral environment. A technology-driven strategy is more appropriate when there is a market sheltered from competition, so that technological capabilities can be accumulated; on the contrary a marketing-driven strategy is more appropriate when standardized technological solutions become widely available. The article contributes to the catch-up literature by identifying a new entry strategy and by pointing at the role of the sectoral environment, and to the sectoral innovation system literature by addressing the catch-up strategies of latecomer firms under different technological, industrial structure, and market conditions.