bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine learning methods for prediction of cancer driver genes: a survey paper
Authors: Andrades Renan , Recamonde-Mendoza Mariana 
Published: February 2022

AbstractIdentifying the genes and mutations that drive the emergence of tumors is a critical step to improving our understanding of cancer and identifying new directions for disease diagnosis and treatment. Despite the large volume of genomics data, the precise detection of driver mutations and their carrying genes, known as cancer driver genes, from the millions of possible somatic mutations remains a challenge. Computational methods play an increasingly important role in discovering genomic patterns associated with cancer drivers and developing predictive models to identify these elements. Machine learning (ML), including deep learning, has been the engine behind many of these efforts and provides excellent opportunities for tackling remaining gaps in the field. Thus, this survey aims to perform a comprehensive analysis of ML-based computational approaches to identify cancer driver mutations and genes, providing an integrated, panoramic view of the broad data and algorithmic landscape within this scientific problem. We discuss how the interactions among data types and ML algorithms have been explored in previous solutions and outline current analytical limitations that deserve further attention from the scientific community. We hope that by helping readers become more familiar with significant developments in the field brought by ML, we may inspire new researchers to address open problems and advance our knowledge towards cancer driver discovery.
Isolation and characterization mesenchymal stem cells from red panda (Ailurus fulgens styani) endometrium
Authors: Wang Dong-Hui , Wu Xue-Mei , Chen Jia-Song , Cai Zhi-Gang , An Jun-Hui , Zhang Ming-Yue , Li Yuan , Li Fei-Ping , Hou Rong , Liu Yu-Liang 
Published: February 2022

AbstractEndometrial mesenchymal stem cells (eMSCs) are undifferentiated endometrial cells with self-renewal, multidirectional differentiation and high proliferation potential. Nowadays, eMSCs have been found in a few species, but it has never been reported in endangered wild animals, especially the red panda. In this study, we successfully isolated and characterized the eMSCs derived from red panda. Red panda eMSCs were fibroblast-like, had a strong proliferative potential and a stable chromosome number. Pluripotency genes including Klf4, Sox2 and Thy1 were highly expressed in eMSCs. Besides, cultured eMSCs were positive for MSC markers CD44, CD49f and CD105 and negative for endothelial cell marker CD31 and haematopoietic cell marker CD34. Moreover, no reference RNA-seq was used to analyse the eMSCs transcriptional expression profile and key pathways. Compared with skin fibroblast cell group, 9104 differentially expressed genes (DEGs) were identified, among which are 5034 genes upregulated, 4070 genes downregulated and the top 20 enrichment pathways of DEGs in Gene Ontology (GO) and the Kyoto Encyclopedia of Genes Genomes (KEGG) mainly associated with G-protein coupled receptor signalling pathway, carbohydrate derivative binding, nucleoside binding, ribosome biogenesis, cell cycle, DNA replication, Ras signalling pathway and purine metabolism. Among the DEGs, some representative genes about promoting MSCs differentiation and proliferation were upregulated and promoting fibroblasts proliferation were downregulated in eMSCs group. Red panda eMSCs also had multiple differentiation ability and could differentiate into adipocytes, chondrocytes and hepatocytes. In conclusion, we, for the first time, isolated and characterized the red panda eMSCs with ability of multiplication and multilineage differentiation in vitro. The new multipotential stem cell could be beneficial not only for the germ plasm resources conservation of red panda, but also for basic or pre-clinical studies in the future.
David Edwards and the Later Stuart Underground Press
Authors: Hone Joseph 
Published: February 2022

Abstract
This article investigates the English underground press in the later Stuart period. Following the end of pre-publication licensing in 1695, the ongoing threat of government reprisals meant that controversial political and religious tracts continued to be printed in secret; yet the survival of the underground press into this period has been neglected in recent works of political, religious, social, cultural and literary history. The dominant view, established by some of the most influential book historians of the past century, is that the materials necessary for a study of secret printing do not survive. This article argues otherwise. Through a detailed case-tudy of the career of one such printer, David Edwards, it illustrates how the clandestine activities of a subset of printers helped shape contemporary debate. Combining historical and bibliographical modes of investigation, this article explores the fundamental mechanics of how controversial tracts, written and printed in secret, reached the public. It examines Edwards’s training under the Whig printer Thomas Braddyll, his subsequent links to the exiled Jacobite court, the clandestine techniques he used to disguise his activities, and the authorship of books he printed. These included the use of indentures and tokens to ensure against imposters and tweaking copy texts to mask distinctive stylistic tics. The article concludes by arguing that the vibrant culture of partisan print associated with the later Stuart public sphere was enabled not solely by the demise of pre-publication licensing in 1695, but also by the persistence of the underground press.
Prospective validation and extension of the Multimodality Prognostic Score for the treatment allocation of pleural mesothelioma patients
Authors: Greb Daria , Hebeisen Monika , Matter Alessandra , Opitz Isabelle , Lauk Olivia 
Published: February 2022

Abstract

OBJECTIVES
Patient allocation to multimodality treatment in patients with malignant pleural mesothelioma remains a challenge. The aim of this study was to validate our previously established Multimodality Prognostic Score (MMPS) (tumour volume before chemotherapy, histological subtype, C-reactive protein before chemotherapy and tumour progression after chemotherapy) and to extend the score with additional blood parameters for better patient outcome.

METHODS
Patients with histologically proven malignant pleural mesothelioma and curative intended therapy with clinical stage T1–T3 N0–N2 M0 were eligible. The existing MMPS was validated and further additional blood markers (erythrocytes, neutrophils, monocytes, albumin, gamma-glutamyl transferase and alkaline phosphatase) were evaluated for potential incorporation.

RESULTS
For the validation of the existing MMPS, as the first part of this analysis, 117 patients treated as of September 2011 were included. A total of 88 patients were treated with macroscopic complete resection, whereas 29 patients were treated with palliative or no surgery. Patients treated with macroscopic complete resection and a high MMPS showed statistically significant lower overall survival. In the second part, the extension of the MMPS with additional blood parameters was analysed. Albumin, the only parameter showing evidence for having influence on overall survival, was further added to the extended MMPS. When comparing the performance measures Area under the curve (AUC) and Brier score, the extended score performed better (higher AUC, lower Brier score) than the original MMPS.

CONCLUSIONS
The extended score with albumin showed improved performance in comparison to the original score. The extended MMPS also may help allocating patients to surgery.
The paradox of “Malthusian urbanization”: urbanization without growth in the Republic of Genoa, 1300–1800
Authors: Oddo Luigi , Zanini Andrea 
Published: February 2022

AbstractThis paper investigates the relationships between urbanization and long-term economic growth in the pre-industrial world. To this end, we compiled a novel dataset collecting all currently available data on urban and rural populations in an Italian pre-unification state, the Republic of Genoa. Data show the paradoxical coexistence of high urbanization levels with cyclical Malthusian stagnations. Putting together empirical results and historical evidence, we interpreted this puzzle, highlighting how a high degree of urbanization could be the consequence of widespread poverty, rather than a measure of rising standards of living. To describe this phenomenon, we coined the term “Malthusian urbanization”.
The association between neutrophil to lymphocyte ratio and echocardiographic parameters in hospitalised adults with COVID-19 - a retrospective analysis
Authors: Agarwal R , Priyonugroho G , Hertine S , Wicaksono S H , Almazini P , Zamroni D , Muliawan H S 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
The neutrophil to lymphocyte ratio (NLR) is an inflammatory biomarker with prognostic value in several cardiovascular conditions. Hyperinflammation contributes to severe coronavirus disease 2019 (COVID-19), which is characterized by a multi-organ dysfunction. Cardiovascular complications of COVID-19 include arrhythmias, myocardial damage, acute heart failure, and acute coronary syndrome. Transthoracic echocardiography (TTE) can be used to assess cardiovascular structure and function non-invasively.

Purpose
To investigate the association between NLR at admission and TTE abnormalities in hospitalised adults with COVID-19.

Methods
This single-centre retrospective study was conducted at a COVID-19 referral hospital in Indonesia. All consecutive hospitalised adults with confirmed COVID-19 who underwent TTE assessments between 3 April 2020 to 6 April 2021 were included. Comprehensive data including NLR at admission, demographics, co-morbidities, peak severity of COVID-19, and TTE parameters were extracted from electronic medical records. A receiver operating characteristic (ROC) curve analysis was conducted to determine the optimal NLR cut-off for prediction of severe-critical COVID-19. Patients with high and low NLR were compared using the chi-square test and odds ratios (OR), with a confidence level of 95%.

Results
A total of 487 patients were included in this study. From ROC curve analysis, the area under curve was 0.80 (95% CI: 0.76 – 0.84). The optimal NLR cut-off was determined as 4.42, which predicted severe-critical COVID-19 with a sensitivity of 74.5% and a specificity of 74.6%. Based on this, the low NLR and high NLR groups had 223 and 264 patients, respectively. Male sex, diabetes, and chronic kidney disease occurred more frequently in the high NLR group (P &lt; 0.05). On TTE assessment, the high NLR group had higher odds of left ventricular (LV) systolic dysfunction (OR: 2.49; 95% CI: 1.14 – 5.45), LV wall motion abnormalities (OR: 2.62; 95% CI: 1.41 – 4.87), valve abnormalities (OR: 2.04; 95% CI: 1.35 – 3.07), and right ventricular (RV) dysfunction (OR: 10.55; 95% CI: 2.46 – 45.25).

Conclusions
COVID-19 patients with a high NLR at admission had higher odds of abnormal TTE findings, including LV systolic dysfunction, LV wall motion abnormalities, valve abnormalities, and RV dysfunction. This indicates a possible link between inflammation and cardiovascular dysfunction in COVID-19, which must be confirmed in larger prospective studies. Abstract Figure. ROC Curve Analysis Abstract Figure. Odds Ratios for TTE Abnormalities
Evaluation of subclinical LV systolic dysfunction by global longitudinal strain using 2D-speckle tracking echocardiography in patients having angina with normal epicardial coronary arteries
Authors: Hoque MD S , Ahmed C M , Osmany DMM F , Banerjee S K 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: Other. Main funding source(s): Self

Background
Global longitudinal strain (GLS), assessed by 2D speckle tracking echocardiography would be a trustworthy noninvasive tool to detect subclinical LV systolic dysfunction in patients having angina with normal epicardial coronary arteries.

Objective
The primary objective of the study to detect subclinical LV systolic dysfunction by GLS using 2D-STE in patient having angina with normal coronary arteries and also by conventional echocardiogram at baseline.

Materials and Methods
This was a comparative case control study that was conducted during the period of March 2018 to August 2018. The study included 60 patients who have been suffering from angina like syndrome despite normal coronary arteries along with 60 normal healthy individuals . All subjects were assessed by transthoracic echocardiography (TTE ) and GLS using 2D speckle-tracking analysis to assess resting LV systolic function . The results of all three planes in GLS (the apical four-chamber , two-chamber , and three-chamber views) were combined in a single bull’s eye summary (agreeing with the standard 17-segment model), which presented the analysis of each segment along with a global peak systolic strain value for the LV.

Results
This study identified normal reference value of the mean GLS in healthy control group was −19.7 ± 1.84%. GLS assessed by 2D STE was significantly impaired in patients having angina like syndrome with normal epicardial coronary arteries (-18.78 ± 1.87 vs -19.7 ± 1.84%; p &lt; 0.007) than healthy control group despite preserved LVEF. In case group, 8 out of 60 patients (13.3 %) had more negative global longitudinal strain than control subject.

Conclusions
Patients having angina with normal epicardial coronary arteries are likely to have microvascular disease. GLS assessed by 2D STE has the potential to improve the value of conventional echocardiography in the detection of the coronary microvascular disease. Despite normal LVEF, significant impairment of LV global longitudinal systolic function can differentiate microvascular group of patients from others who have angina with normal coronaries.
When type 2 diabetes coexists with atrial fibrillation in Middle Eastern patients: Clinical profiles and utilization of oral anticoagulant agents
Authors: Hammoudeh A , Alzyoud W , Ja"ara D , Bahour M , Nasereddin R , Al-Mousa E , Badaineh Y 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

OnBehalf
The Jordan Atrial Fibrillation (JoFib) Study
Background. Studies from different regions in the world have shown that patients with atrial fibrillation (AF) who have type 2 diabetes mellitus (T2D) have unfavorable baseline clinical profile, higher prevalence of comorbidities and higher risk scores compared with those who do not have T2D. It is largely unknown if this applies to Middle Eastern (ME) patients.
Purpose. To evaluate baseline clinical features, prevalence of comorbid diseases, CHA2DS2-VASc scores in AF patients with T2D, and the utilization of oral anticoagulant agents (OACs) compared with those who do not have T2D in a large ME cohort.
Methods. Of 2163 AF patients enrolled in the Jordan AF study (May 2019 - January 2021), 953 (44.1%) had T2D and 1210 (55.9%) did not have T2D. Nonvalvular AF (NVAF) was diagnosed in 94% and 89% of both groups, respectively. Compared with AF patients who did not have T2D, those with T2D were older (mean age 70.3 ± 9.7 years vs. 65.9 ± 15.1 years, p &lt; 0.001), more likely to be women (56.3% vs. 51.9%, p = 0.05), and had higher prevalence of hypertension (88.6% vs. 63.7%, p &lt; 0.001) and obesity (71.9% vs. 43.6%, p &lt; 0.001). More AF patients with T2D had high risk CHA2DS2-VASc score (&gt;3 in women and &gt;2 in men) than those with no T2D (96.9% vs. 72.3%, p &lt; 0.001). Furthermore, they had higher prevalence of past stroke/systemic embolization (19.2% vs. 15.0%, p = 0.01), heart failure (29.3% vs. 19.7%, p &lt; 0.001) and coronary artery disease (14.0% vs. 8.2%, p = 0.001). OACs utilization was not different in AF patients with or without T2D (83.4% vs. 85.9%, p = 0.19, respectively). Multivariate analysis showed that high CHA2DS2-Vasc and low HAS-BLED scores, age 50-75 years, history of stroke, and non-paroxysmal AF, but not T2D, were associated with higher rates of OACs utilization among patients with NVAF.
Conclusions. The coexistence of AF and T2D in a large Middle Eastern cohort was associated with unfavorable baseline clinical profile and risk scores. The great majority of AF patients were prescribed OACs, independent of the presence or absence of T2D.
A single-centre analysis of in-stent restenosis after left main stenting
Authors: Jariwala P , Jadhav KARTIK 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
Percutaneous coronary interventions (PCI) can be the standard of care for left main (LM) coronary artery disease. In-stent restenosis (ISR) is a rare complication and is associated with patient- and procedure-specific aspects. The aim of our analysis is to evaluate the incidence and the predictors of ISR after left main PCI.

Methods
From June 2018 till June 2019, 156 LM procedures were performed in our centre with second-generation drug-eluting stents (DES). Our registry includes a wide spectrum of patients, with stable coronary artery disease and with acute coronary syndrome, including STEMI, unprotected and protected LM, high and low SYNTAX scores, with or without true bifurcation disease (engagement).

Results
In 22.3 percent of the patients, previous percutaneous or surgical revascularization was found. In 78 percent of cases, the recommended care method was provisional stenting, and in 68 percent, IVUS support was used. In hospital discharge the 1st, 6th, 12th month, and each year afterwards, patients were prospectively followed up for MACE (defined as death, stroke, symptom triggered repeat revascularization).
According to our data, the only predictor of ISR at multivariate analysis turned out to be type II diabetes mellitus (OR = 3.84; 95% CI: 1.18-13.65, p = 0.007), while sex, age, prior revascularisation and the clinical presentation at admission (stable or acute), stent technique and complex anatomy were not. All patients with significant ISR were retreated successfully; 38 (24%) of them interventionally and in 3 (1.92%) of the cases, surgically.

Conclusions
According to the results from our registry, composed of all-comer patients, restenosis after PCI of LM with second-generation DES is an infrequent event. The most common location of IRS is at the ostium of the circumflex artery and distal left main. Type II diabetes mellitus is the only predictor of ISR at multivariate analysis.
P2Y12 pre-treatment for NSTE-ACS in a tertiary hospital centre: real world compliance experience with ESC 2020 guidelines
Authors: Kaul R , Khoo J , Pender P , Hopkins A , Lo S 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: None.

Background
The 2020 ESC guidelines for managing NSTE-ACS recommend against routine pre-treatment with a P2Y12 receptor inhibitor if coronary anatomy is not known and an early (&lt;24h) invasive management is planned. With delayed (&gt;24h) invasive management, pre-treatment may be considered in selected cases.

Purpose
Evaluate antiplatelet pre-treatment practices for NSTE-ACS in a tertiary cardiology centre in Australia.

Methods
Retrospective analysis of NSTE-ACS cases from January to August 2021 were obtained from the cardiac laboratory database. Patients on a P2Y12 inhibitor prior to presentation were excluded. Clinical, demographic, angiographic and medication data were obtained from the electronic database.

Results
85 cases were included. Mean age was 62 ± 11.5 and 81% were male. The prevalence of hypertension, hypercholesterolaemia, type 2 diabetes and active smoking was 54.8%, 51.2%, 38.1% and 34.5% respectively. Mean time to angiography was 1.7 ± 1.4 days and the median peak pre-procedural troponin T was 191.5 (80 to 852). Access was predominantly radial (84.5%) with the remainder femoral (15.5%).
Angiographic findings included, obstructive disease amenable to percutaneous coronary intervention (50.0%), obstructive disease for surgical revascularisation (22.6%), and non-obstructive disease (27.4%). The mean time from angiography to surgical revascularisation was 6.4 ± 4.4 days. Three patients (3.6%) had bleeding [managed conservatively], specifically upper limb haematoma, groin haematoma, and haemoptysis.
The majority of patients (79.8%) received P2Y12 inhibitors (40.5% clopidogrel and 39.3% ticagrelor) prior to angiography. Of these, 49.3% had percutaneous angioplasty, 17.9% had surgical revascularisation and 32.8% had non-obstructive disease (managed with single antithrombotic agent). Of those who did not receive P2Y12 inhibitors [n = 17, 20.2%]. Of these, 53% had percutaneous angioplasty, 40% had surgical revascularisation, and 5% had non-obstructive disease.

Conclusions
Overall, pre-treatment with a P2Y12 inhibitor was still very common, risking delays to bypass surgery and increasing bleeding. Practice did not generally align with contemporary ESC 2020 guidelines. Understanding the reasons for guideline non-compliance would be important for optimising treatments. Education for emergency and cardiology staff as well as creation of local practice policies may help increase compliance with evidence-based guidelines.
The impact of blood pressure variation on mortality and symptomatic intracerebral hemorrhage in stroke patients after thrombolytic therapy
Authors: Kotruchin P , Kliangsa-Ard H , Mitsungnern T , Imoun S , Kongbunkiat K 
Published: February 2022

Abstract

Funding Acknowledgements
Type of funding sources: Public Institution(s). Main funding source(s): Faculty of Medicine, Khon Kaen University
Introduction Blood pressure variation (BPV) was one of the risk factors for unfavorable stokes outcomes. However, the association between BPV and short-term outcomes in stroke patients after received thrombolysis (recombinant tissue plasminogen activator; rt-PA) was limited.
Objectives We aimed to determine the association between BPV and mortality and symptomatic intracerebral hemorrhage (s-ICH) in stroke patients after rt-PA administration.
Methods This was a cross-sectional study in a specialized stroke unit of our university hospital, during 2015-2019. Adult ischemic-stroke patients who were eligible for receiving rt-PA were enrolled. Supine BP was measured just before starting rt-PA and at 0, 4, 8, 12, 16, 20, and 24 hours after completing rt-PA administration. The standard deviation (SD), coefficient of variation (CV), and successive variation (SV) of both systolic blood pressure (SBP) and diastolic blood pressure (DBP) were calculated. Final outcomes were in-hospital mortality, or s-ICH.
Results There were 278 patients enrolled, 138 men (49.6%), and mean age 65 ± 13 years old. Ten patients died (3.6%) and 27 patients had s-ICH (9.7%). There were 86 (30.9%) patients who received IV nicardipine before and after rt-PA. All BPV profiles of SBP were associated with mortality and s-ICH. Odds ratio (OR) for mortality were as follows; SD, 1.10 (1.02-1.19); CV, 1.13 (1.02-1.25); and SV, 1.07 (1.01-1.13), and OR for s-ICH were as follows; SD, 1.07 (1.02-1.14); CV, 1.11 (1.03-1.19); and SV, 1.05 (1.01-1.10). The BPV profiles of DBP also showed significant positive association with mortality and s-ICH. However, mean SBP and DBP, and time to rt-PA were not associated with both outcomes.
Conclusions BPV profiles of both SBP and DPB were positively associated with mortality and s-ICH in stroke patients after receiving rt-PA, independent of BP levels. Further study on the optimal BPV and the treatment towards it is crucial.