bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Crossroads of Three Nations: Czechoslovak Ethnic Policy towards Railwaymen and Industrial Workers in Cieszyn Silesia, 1920–1938
Authors: GĄSIOR Grzegorz 
Published: October 2021

Abstract
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Cieszyn Silesia is a region which was divided between Czechoslovakia and Poland in 1920. Czechoslovakia obtained the industrially developed and strategically important part, which had a large Polish and German population. The purpose of this paper is to analyse the minority policy of the Czechoslovak state administration by focusing on the examples of state-run railway employees and workers in large, mostly private, industrial establishments. It discusses the mechanisms of an ethnic policy that functioned in a particular, distinctive region at the crossroads of three cultures—German, Polish and Czech. Policies towards minorities in Czechoslovakia in the period before the Munich Agreement of 1938 have often been regarded as democratic and tolerant. Nonetheless, the integration of Cieszyn Silesia was a significant challenge for Czechoslovak authorities and their actions were often in contradiction with liberal principles. This paper focuses not on the legislation, but on the practical approaches that contributed to the enhancement of the position of the Czech nation. In the case of both railwaymen and industrial workers, the state authorities took action that had a common goal—the Czechification of the region. The main difference in methods used against both groups depended on the direct dependence of the former (railwaymen) on the state as their employer. In the case of industrial workers, state policies had a less direct impact, but nonetheless created conditions conducive to discriminatory and assimilationist pressures.
Surgical management of failing Fontan circulation: results from 30 cases with 285 patient-years follow-up
Authors: Padalino Massimo A , Ponzoni Matteo , Castaldi Biagio , Leoni Loira , Chemello Liliana , Toscano Giuseppe , Gerosa Gino , Di Salvo Giovanni , Vida Vladimiro L 
Published: October 2021

Abstract

OBJECTIVES
Fontan patients are known to suffer from clinical attrition over the years, which has been characterized as Fontan failure. We sought to evaluate the clinical outcomes of such Fontan patients undergoing surgical management in a 25-year, single-centre experience.

METHODS
A retrospective single-centre analysis of patients undergoing surgical treatment for failing Fontan between 1995 and 2020, including any reoperations when ventricular function was preserved, or a heart transplant (HTx), when ventricular contractility was impaired. We analysed survival, indications for surgery and early and late complication rates.

RESULTS
We collected 30 patients (mean age 24.7 years) who required surgery after a mean time of 19.3 years from the original Fontan procedure: Fontan conversion in 21 (70%, extracardiac conduit in 19, lateral tunnel in 2), a HTx in 4 (13.3%) and other reoperations in 5 (16.7%). The most common indications for surgery were tachyarrhythmias (63.3%) and severe right atrial dilatation (63.3%). Overall survival at the 1-, 5-, 10- and 20-year follow-up examinations were 75.9% [95% confidence interval (CI): 91.4–60.4%], 75.9% (95% CI: 91.4–60.4%), 70% (95% CI: 78–52%) and 70% (95% CI: 78–52%), respectively. The most frequent complications were postoperative tachyarrhythmias (50%) and late Fontan-associated liver disease (56.5%). HTx and Fontan conversion provided comparably good outcomes compared to other reoperations (P = 0.022).

CONCLUSIONS
Surgery for failing Fontan can be performed effectively with overall good long-term survival. However, early and late morbidities are still a significant burden. Because other reoperations performed when patients presented with contraindications for a HTx have carried high mortality, close clinical follow-up is mandatory, and an earlier indication for Fontan conversion or a HTx is advisable to optimize outcomes.
Bleeding in patients with continuous-flow left ventricular assist devices: acquired von Willebrand disease or antithrombotics?
Authors: Consolo Filippo , Marasi Alessandra , Della Valle Patrizia , Bonora Marta , Pieri Marina , Scandroglio Anna Mara , Redaelli Alberto , Zangrillo Alberto , D’Angelo Armando , Pappalardo Federico 
Published: October 2021

Abstract

OBJECTIVES
To evaluate the competing pro-haemorrhagic contribution of acquired von Willebrand (vW) disease and antithrombotic therapy in patients implanted with continuous-flow left ventricular assist devices (LVADs).

METHODS
We compared the extent of vW factor (vWf) degradation [vWf antigen (vWf:Ag)] and a decrease of functional activity of large vWf multimers [vWf collagen binding (vWf:CB)] in LVAD patients who did and did not suffer from bleeding. Data were measured pre-implant, at short-term (t1: &lt;3 months) and long-term (t2: &gt;12 months) follow-up. The occurrence of primary bleeding events, as well as bleeding recurrence, was correlated with patient-specific vWf profile and antithrombotic regimen. Indeed, patients were discharged on warfarin (international normalized ratio: 2–2.5) and aspirin, with the latter withhold after a first bleeding episode.

RESULTS
Fifty-three patients were enrolled. The median follow-up was 324 (226–468) days. We recorded 25 primary bleeding events (47% of patients). All primary events occurred in patients on warfarin and aspirin. Both vWf:Ag and vWf:CB decreased significantly post-implant (P = 0.0003 and P &lt; 0.0001), and patients showing pathological vWf:CB/vWf:Ag ratio (&lt;0.7) increased progressively over the time of support (pre-implant = 26%, t1 = 58%, t2 = 74%; P &lt; 0.0001). Of note, activity of large vWf multimers of bleeders was significantly lower at t2 with respect to non-bleeders (vWf:CB: 61 (36–115) vs 100 (68–121), P = 0.04; vWf:CB/vWf:Ag ratio: 0.36 (0.26–0.61) vs 0.58 (0.33–0.96), P = 0.04). Despite these marked differences in the vWf profile, following aspirin discontinuation only 3 patients had bleeding recurrence.

CONCLUSIONS
Aspirin contributes significantly to haemorrhagic events in the background of acquired vW disease; its discontinuation significantly reduces bleeding recurrence.

Clinical trial registration
https://clinicaltrials.gov/ct2/show/NCT03255928; ClinicalTrials.gov Identifier: NCT03255928.
The Measurement Error Elephant in the Room: Challenges and Solutions to Measurement Error in Epidemiology
Authors: Innes Gabriel K , Bhondoekhan Fiona , Lau Bryan , Gross Alden L , Ng Derek K , Abraham Alison G 
Published: October 2021

AbstractMeasurement error, although ubiquitous, is uncommonly acknowledged and rarely assessed or corrected in epidemiologic studies. This review offers a straightforward guide to common problems caused by measurement error in research studies and a review of several accessible bias-correction methods for epidemiologists and data analysts. Although most correction methods require criterion validation including a gold standard, there are also ways to evaluate the impact of measurement error and potentially correct for it without such data. Technical difficulty ranges from simple algebra to more complex algorithms that require expertise, fine tuning, and computational power. However, at all skill levels, software packages and methods are available and can be used to understand the threat to inferences that arises from imperfect measurements.
Risk factors for left ventricular thrombus formation on transthoracic echocardiography in a propensity-matched case control study
Authors: Tang G H , Wang A , Markson L J , Manning W J , Strom J B 
Published: October 2021

Abstract

Introduction
The specific risk factors for left ventricular thrombus (LVT) formation on transthoracic echocardiography (TTE) independent of age, sex, and left ventricular ejection fraction (LVEF) remain uncertain.

Purpose
To conduct a propensity-matched case control study of LVT.

Methods
We queried structured TTE report data from 113,673 patients at our institution to identify individuals with LVT on TTE, 2000–2011. Cases were matched 1:1 with controls on age, sex, LVEF, inpatient/outpatient status, image quality, test year, blood pressure, heart rate, height, and weight. using propensity scores. Risk factors for LVT formation were determined using medical chart review.

Results
Over 12 years, we identified 132 patients with LVT and 132 matched controls (mean age 62.0±16.1 years, 73.1% male, mean LVEF 27.0% ± 16.0%). Cases were similar to controls across all matched variables except height (cases vs. controls, mean height 172.2±8.8 vs. 174.8±9.3 cm, p=0.03). Compared with controls, TTEs for cases were more frequently performed for the indications of myocardial infarction (MI; 28.0% vs. 9.9%, p&lt;0.001) and source of embolism (3.8% vs. 0.0%, p=0.008). Despite no differences between cases and controls in rates of hypertension, hyperlipidemia, diabetes, and thrombophilia (Table), a history of peripheral arterial disease was associated with a 3.4-fold increased odds of LVT formation (univariate odds ratio [OR], 3.35, 1.50–7.47, p=0.003). This association persisted despite adjustment for history of MI, stroke, height, history of recent major bleeding, and receipt of percutaneous coronary intervention (PCI) (adjusted OR, 4.33, 1.66–11.29, p=0.003). On presentation, 22.0% of cases were on anticoagulation including 20.5% on warfarin, none on a direct oral anticoagulant (DOAC), and 1.5% on heparin products. Additionally, 48.5% of cases were on antiplatelet medications. Of the 27 patients on warfarin on diagnosis of LVT, 25.9% had an International Normalized Range (INR) value &lt;2.0. All TTE parameters were similar across groups (p&gt;0.05 for all). Of those with LVT, 54 (40.9%) had LVT resolution over a median of 4.4 (0.9 to 13.6) months.

Conclusions
In this single center, propensity-matched case-control study of individuals with LVT on TTE, a history of peripheral arterial disease was associated with a 4.3-fold increased odds of LVT formation independent of age, sex, LVEF, history of MI, stroke, or PCI. Of those with LVT, anticoagulation was used on presentation in 22.0%. Nearly half had LVT resolution within 4.4 months.

Funding Acknowledgement
Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The project was funded by a grant from the National, Heart, Lung, and Blood Institute (1K23HL144907 - Strom).
Association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan: a cohort study
Authors: Kato T , Momose M , Uemura Y , Naya M , Matsumoto N , Hida S , Yamauchi T , Nakajima T , Suzuki E , Inoko M , Tamaki N 
Published: October 2021

Abstract

Background
There is an ongoing controversy regarding the necessity of single-photon emission computed tomography (SPECT) for patients with ischemic heart diseases after the publication of the results of the ISCHEMIA trial.

Purpose
We aimed to evaluate the association of the extent of myocardial ischemia with outcomes in patients with suspected coronary artery disease in Japan.

Methods
From the data of 2780 patients with stable angina who were enrolled prospectively between January 2006 and March 2008 in Japan and had undergone physician-referred non-invasive imaging tests, 1205 patients managed with SPECT were stratified by 10% myocardial ischemia. Major adverse cardiac events (MACEs), including death, myocardial infarction, hospitalization for heart failure, and late revascularization, were followed-up for 1 year.

Results
Patients with ≥10% myocardial ischemia (n=173) were older than patients with &lt;10% myocardial ischemia (n=1032) and had a significantly higher 1-year cumulative incidence of MACEs (9.1% vs. 1.2%, P&lt;0.0001). After adjusting for confounders, the risk of ≥10% myocardial ischemia relative to &lt;10% myocardial ischemia for MACEs remained significant (adjusted hazard ratio [95% confidence interval], 2.40 [1.09–5.26], P=0.029).

Conclusion
The presence of ≥10% myocardial ischemia was significantly associated with the 1-year risk for MACEs in Japanese patients with suspected coronary artery disease.

Funding Acknowledgement
Type of funding sources: None. Study flowchartOutcomes
The role of left atrial wall thickness and pulmonary vein anatomy in success of pulmonary vein isolation using the CLOSE protocol
Authors: Boussoussou M , Vattay B , Szilveszter B , Kolossvary M , Vecsey-Nagy M , Sallo Z , Geller L , Maurovich-Horvat P , Merkely B , Szegedi N ,   Cardiovascular Imaging Research Group
Published: October 2021

Abstract

Introduction
The CLOSE protocol is a novel contact-force guided technique for enclosing pulmonary veins in patients with atrial fibrillation (AF). Consistency and lesion contiguity are essential factors for procedural success. We sought to determine whether left atrial (LA) wall thickness (LAWT) and pulmonary vein (PV) dimensions as assessed by coronary CT angiography (CTA) could influence the efficacy of successful first-pass isolation using the CLOSE protocol.

Methods
In a single center, prospective study we enrolled 94 patients with symptomatic, drug-refractory AF who underwent pre-ablation left atrial CTA and initial radiofrequency catheter ablation between 2019.01–2020.09. The LA was divided into 11 regions when assessing LAWT. Additionally, the diameter and area of the PV orifices were obtained. First pass isolation was recorded separately for the right and left PVs. After the first pass ablation circles were ready, additional ablations were applied in those cases where first pass isolation was not achieved, to reach complete PV isolation. Predictors of successful first pass isolation were determined using logistic regression models that included anthropometrical, echocardiographic and CTA derived parameters.

Results
A total of 94 patients were included in the analysis with mean CHA2DS2-VASc score of 2.1±1.5 (mean age 62.4±12.6 years, 39.5% female). 61.7% were paroxysmal, 38.3 were persistent AF patients. Mean procedure times were 81.2±19.3 minutes.
Complete isolation of all four PVs was achieved in 100% of patients. First-pass isolation rate was 76%, 71% and 54%, for the right PVs, left PVs and all four PVs, respectively. No difference was found regarding comorbidities and imaging parameters between those with and without first pass isolation. LAWT (mean of all 11 regions or separately) had no effect on the procedural outcome (all p&gt;0.05). Out of all assessed parameters, only RSPV diameter was associated with right sided successful PVI on first pass isolation (p=0.04, OR 1.01).

Conclusion
The use of CLOSE protocol in AF patients resulted in high periprocedural success rate in terms of first pass isolation, independently from the thickness of the LA wall. RSPV diameter could influence the results of first pass isolation.

Funding Acknowledgement
Type of funding sources: None.
Cytokine storm induced coagulopathy in septic shock and critical Covid-19: head-to-head comparison
Authors: Dechamps M D M , De Poortere J , Laterre P F , Octave M , Ginion A , Robaux V , Bodart J , Gruson D , Van Dievoet M , Douxfils J , Derive M , Campion A , Martin M , Horman S , Beauloye C 
Published: October 2021

Abstract

Background
Septic shock generates an important inflammatory reaction, endothelial activation and a procoagulant state leading to microvascular thrombosis and subsequent organ impairment [1].
Similarly, a severe inflammatory reaction and a coagulopathy with pulmonary micro-thrombosis eventually leading to acute lung injury, is a typical feature of critical form of Coronavirus disease 2019 (Covid-19) [2].
Our aim was to compare coagulation, platelet activation and platelets-neutrophils interplay between control, septic shock and critical Covid-19 patients.

Methods/Materials
A total of 118 patients were included in our prospective, monocentric, observational study between February 2019 and June 2020. Septic shock (n=48) and Covid-19 (n=22) patients were consecutively included at admission in our ICU department. Control patients (n=48) with matched gender and co-morbidities were recruited at central lab consultation.

Results
Septic shock patients had worse severity scores due to multiple organ failure (assessed by APACHE II and SOFA score) whereas Covid-19 patients had more severe respiratory failure and a longer ICU length-of-stay (Table 1).
At the time of inclusion, CRP and lymphocyte count were comparable between septic shock and Covid-19 patients. White cell count ad neutrophil count was higher for septic shock patients.
Analysis of coagulation showed a prolonged INR, TT and aPTT in septic shock although only INR was prolonged in Covid-19. Thrombin antithrombin complex (TATc) formation was similar in both pathologies, whereas consumption of antithrombin III (ATIII) and D-dimers formation was more pronounced in septic shock.
Platelet count was lower in septic shock and platelet activation, assessed via plasmatic levels of soluble P-selectin (sCD62P) and Trem-like transcript 1 (sTLT-1), was more important in septic shock.
Neutrophil activation and NETosis, evaluated by levels of circulating myeloperoxidase (MPO) and citrullinated histone 3 (H3-Cit), was similarly increased in both groups (Figure 1).

Conclusions
This study confirmed an activation of coagulation cascade, platelet activation and NETosis in both septic shock and critical Covid-19, compared with control patients. Importantly, the extent of these changes was similar or less pronounced in critical COVID-19 compared with septic shock.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Fondation Saint Luc Figure 1
MMP-2 gene silencing attenuates age-dependent carotid stiffness via reduction of elastin degradation and increased eNOS activation
Authors: Puspitasari Y M , Diaz-Canestro C , Liberale L , Guzik T J , Flammer A J , Bonetti N R , Constantino S , Paneni F , Akhmedov A , Beer J H , Ruschitzka F , Hermann M , Luscher T F , Sudano I , Camici G G 
Published: October 2021

Abstract

Background and aims
Arterial stiffness is a hallmark of vascular aging. Being characterized by a loss of elasticity of large arterial walls, arterial stiffness is associated with an increased risk of cardiovascular disease (CVD). The age-dependent arterial stiffness is primarily attributed to alterations in the elastic and collagen deposition that is regulated by a number of enzymes, including matrix metalloproteinase-2 (MMP-2). Nevertheless, the mechanistic link between age-dependent arterial stiffness and MMP-2 remains unclear.
In this study, we investigated the effect and efficacy of therapeutic MMP-2 knockdown using small interfering RNA (siRNA) on age-dependent arterial stiffness.

Methods
Pulse wave velocity (PWV) was assessed in the right carotid artery of wild-type (WT) mice of different age groups. MMP-2 levels and activity in the carotid artery and plasma of young (3 months) and aged (20–25 months) WT mice were determined. Old WT mice (18–21 months) were treated for 4 weeks with either MMP-2 or scrambled siRNA, in which carotid PWV was assessed at baseline, 2 and 4 weeks after the start of the treatment. Elastin to collagen ratio, desmosin (DES) level, and endothelial nitric oxide synthase (eNOS) pathways were also evaluated and compared. Lastly, levels of circulating MMP-2 and DES, the breakdown product of elastin, were measured in a human cohort (23–86 years old), in whom carotid-femoral PWV was assessed.

Results
Carotid PWV, as well as both vascular and circulating MMP-2 levels, were elevated with increasing age in WT mice (Figure 1). Therapeutic MMP-2 knockdown in aged WT mice reduced the vascular MMP-2 expression and attenuated age-dependent carotid stiffness. Increased elastin to collagen ratio and a lower plasma DES level were observed on MMP-2 silenced treated animals (Figure 2). Moreover, siMMP-2 treated mice showed enhanced eNOS phosphorylation on Ser1177. A direct interaction between MMP-2 and eNOS was also observed, which, interestingly, is augmented with age. Finally, collected human data showed a higher level of circulating MMP-2 levels on the elderly subjects. In addition, plasma DES level is positively correlated with age and aortic PWV, indicating the involvement of vascular elastin catabolism on arterial stiffness.

Conclusions
Therapeutic MMP-2 gene silencing, specifically targeting vascular MMP-2, attenuates age-dependent carotid stiffness. This effect is mediated by augmenting eNOS activation and reducing elastin degradation. Thus, our findings indicate MMP-2 as a potential therapeutic target to mitigate age-dependent arterial stiffness and CVD.

Funding Acknowledgement
Type of funding sources: Foundation. Main funding source(s): Swiss National Science Foundation,Foundation for Cardiovascular Research–Zurich Heart House Figure 1
Metabolic reprogramming in pulmonary arterial hypertension: is it a cancer-like disease?
Authors: Ferreira C , Abreu M , Castro G , Goncalves L , Baptista R , Girao H 
Published: October 2021

Abstract

Background
Idiopathic pulmonary arterial hypertension (iPAH) is a rare and chronic disease associated with poor outcomes. Previously considered a disease restricted to the pulmonary circulation, PAH is now being recognized as a systemic disorder that is associated with metabolic dysfunction. The aim of this study is to analyze the metabolic reprogramming in the lung and peripheral blood mononuclear cell (PBMCs) of iPAH patients and explore their potential roles in PAH pathophysiology.

Methods
Five independent datasets, containing transcriptomic data of human PBMCs (GSE22356 and GSE33463) and lung (GSE48149 GSE113439 and GSE117261) samples, from 139 iPAH patients and 96 healthy controls, were downloaded at the GEO database. In each dataset, the samples were normalized and a pair-wise comparison between control and iPAH samples was performed using limma package, for the R programming language. Genes with a p-value lower than 0.05 were considered differentially expressed between the two groups. A subset of metabolism related genes was selected, and their expression was compared across the datasets.

Results
Among the 13 genes with differential expression identified, only 10 had a coherent expression across all datasets (Figure 1). Firstly, we report an association with insulin resistance through impairment of PI3K signaling in iPAH patients, by expressing lower levels of the heterodimer PIK3CD and regulatory PIK3IP1 and PIKR1 subunits in PBMCs, and by expressing higher levels of its downstream targets in the lung (TBC1D4). However, more extensive metabolic dysfunction was observed. A significant glycolytic shift in the lung and PBMCs was present, as a consequence of deregulation in genes involved in aerobic glycolysis and decreased fatty acid oxidation, namely increased expression of PD1K and lower levels of expression of LDHB. The findings of decreased SLC25A1 protein in both PBMCs and lung suggest impairment of the tricarboxylic acid (TCA) cycle flux in PAH. Additionally, SLC1A5 highlights the involvement of glutamine metabolism and glutaminolysis derangements in PAH. Conversely, SREBP1 is involved in sterol biosynthesis and lower levels in PMBCs results in impaired resolution of inflammatory responses. Finally, although the role of autophagy in iPAH is complex, higher levels of expression of ATG13 in PBMCs and lower levels in the lung confirm autophagy deregulation in iPAH. Interestingly, all the metabolic pathways identified (Figure 2) are hallmarks of the metabolic reprogramming seen in cancer cells, a finding already suggested by the clonal proliferation of pulmonary artery smooth muscle cells described in plexiform lesions.

Conclusion
Our results provide novel insights into the metabolic regulation in iPAH. Molecularly, these cells exhibit many features common to cancer cells, suggesting the opportunity to exploit therapeutic strategies used in cancer to treat iPAH.

Funding Acknowledgement
Type of funding sources: None.