bluuebunny/crossref_metadata_2025_split huggingface dataset:
Powerful and interpretable control of false discoveries in two-group differential expression studies
Authors: Enjalbert-Courrech Nicolas , Neuvial Pierre 
Published: October 2022

AbstractMotivationThe standard approach for statistical inference in differential expression (DE) analyses is to control the false discovery rate (FDR). However, controlling the FDR does not in fact imply that the proportion of false discoveries is upper bounded. Moreover, no statistical guarantee can be given on subsets of genes selected by FDR thresholding. These known limitations are overcome by post hoc inference, which provides guarantees of the number of proportion of false discoveries among arbitrary gene selections. However, post hoc inference methods are not yet widely used for DE studies.ResultsIn this article, we demonstrate the relevance and illustrate the performance of adaptive interpolation-based post hoc methods for two-group DE studies. First, we formalize the use of permutation-based methods to obtain sharp confidence bounds that are adaptive to the dependence between genes. Then, we introduce a generic linear time algorithm for computing post hoc bounds, making these bounds applicable to large-scale two-group DE studies. The use of the resulting Adaptive Simes bound is illustrated on a RNA sequencing study. Comprehensive numerical experiments based on real microarray and RNA sequencing data demonstrate the statistical performance of the method.Availability and implementationA cross-platform open source implementation within the R package sanssouci is available at https://sanssouci-org.github.io/sanssouci/.Supplementary informationSupplementary data are available at Bioinformatics online.
Update: Assessing the evolutionary trajectory of the Apaporis caiman (Caiman crocodilus apaporiensis, Medem 1955) via mitochondrial molecular markers
Authors: Balaguera-Reina Sergio A , Angulo-Bedoya Mónica , Moncada-Jimenez Juan F , Webster Mark , Roberto Igor J , Mazzotti Frank J 
Published: October 2022

Abstract
The spectacled caiman (Caiman crocodilus) is currently considered to be a species complex due to the relatively high morphological and molecular diversity expressed across its range. One of the populations of interest, inhabiting the Apaporis River (Colombia), was described based on skull features as an incipient species (C. c. apaporiensis) and has been treated by some authors as a full species. Recent molecular work challenged this hypothesis, because relatively low mitochondrial molecular differentiation was found between the morphologically described Apaporis caiman and C. crocodilus (s.s.) Amazonian populations. Here, we present an update on the topic based on a larger molecular sample size and on analysis of expanded geometric morphometric data that include six newly collected skulls. Morphometric data support the existence of previously recognized morphotypes within the complex in Colombia and demonstrate that the newly collected material can be assigned to the classic Apaporis caiman morphotype. However, our expanded genetic analysis fails to find appreciable mitochondrial molecular divergence of the Apaporis caiman population from the C. c. crocodilus population (COI-CytB: Amazon Peru 0.17 ± 0.06%, CytB-only: Caquetá River Colombia 0.08 ± 0.07%). The Apaporis caiman is interpreted to be a phenotypically distinct member of the cis-Andean C. crocodilus metapopulation that has not yet achieved (or may not be undergoing at all) appreciable genetic differentiation. Thus, it should not be considered a fully independent evolutionary lineage, nor given full species rank.
Biotic and abiotic factors in promoting the starting point of hybridization in the Neotropical flora: implications for conservation in a changing world
Authors: Turchetto Caroline , Segatto Ana Lúcia A , Turchetto-Zolet Andreia C 
Published: October 2022

AbstractCoevolution between floral traits and specific pollination behaviour is a significant evolutionary force in angiosperm diversification. However, hybridization is also reported to occur between plants with specialist pollination syndromes. Understanding the role of pollinators in plant diversification is crucial, especially in megadiverse regions, such as the Neotropics. In this review, we examine plant hybridization studies in the Neotropics with the aim of providing a perspective on biotic and abiotic factors starting hybrid zone formation. The Pleistocene was the most widely cited time for the occurrence of hybridization facilitated by geographical range shifts, but time-calibrated analyses are needed to recover a more realistic scenario. Our synthesis of hybridization and pollination systems suggested that specialist and generalist pollinators were associated with the starting point of hybridization in the Neotropical flora. Bees and hummingbirds are most likely to be the primary vectors of interspecific gene flow, and even sporadic visits by bees or other generalist pollinators could allow the formation of a new hybrid zone. We highlight that seed and pollen dispersal vectors should be included in an integrative discussion on hybridization in the Neotropical flora. We also provide a preliminary map of hybrid zones in the Neotropics, including Brazilian vegetation cover and losses in the last 30 years, with the aim of encouraging research into human-driven anthropogenic changes and formation and/or shift of hybrid zones through time.
Oral Presentation No. 32 The interplay between VWF, ADAMTS13 and TSP1, and their relation to clinical endpoints
Authors: Warlo Ellen Mathea Kirsch , Kalstad Are A , Myhre Peder L , Solheim Svein , Arnesen Harald , Tveit Arnljot , Seljeflot Ingebjørg , Bratseth Vibeke 
Published: October 2022

Abstract

Introduction
ADAMTS13 cleaves von Willebrand Factor (VWF) into less active fragments. TSP1 binds to VWFs cleavage-site, protecting it from degradation. Low ADAMTS13 and high VWF have been associated with cardiovascular disease (CVD) and atrial fibrillation (AF).
We aimed to investigate the interplay between VWF, ADAMTS13 and TSP1, and assess any relation to endpoints.

Materials and methods
1027 elderly with a recent myocardial infarction (MI) were followed for 2 years. ADAMTS13 antigen (ag) and activity (act), VWF ag and TSP1 were analyzed. The primary endpoint (MACE; n = 210) included MI, stroke, heart failure hospitalization, coronary revascularization and death. The secondary endpoint was new-onset AF (n = 43).

Results
ADAMTS13 ag and act were weakly correlated to VWF (r = 0.10, P = 0.002, both). TSP1 did not correlate to ADAMTS13 or VWF. Patients experiencing a MACE had higher VWF and lower ADAMTS13(ag) at baseline (P &lt; 0.012, both), however not significant after adjusting for covariates. The association with MACE was mainly driven by death (n = 40), with an adjusted OR 2.4 (P = 0.008) for VWF Q4 vs. Q1-3 and OR 0.4 (P = 0.012) for ADAMTS13(ag) Q1 vs. Q2-4. VWF was lower (1.25 vs. 1.39 IU/mL, P = 0.008) and VWF/ADAMTS13(ag)-ratio was lower (1.81 vs. 2.05 x10−3, P = 0.009) in patients with new-onset AF, and these associations persisted in adjusted models.

Conclusion
In elderly patients with a recent MI, levels of VWF, ADAMTS13 and TSP1 did not correlate. ADAMTS13 and VWF associated weakly with MACE, mainly driven by death. Low VWF and VWF/ADAMTS13-ratio were associated with new-onset AF in our population and needs further research.
Poster No. 031 Anti-inflammatory potential of cannabinoid extracts
Authors: Maly Martin , Viktorová Jitka , Ruml Tomáš , Stránská Milena 
Published: October 2022

Abstract
Inflammation plays a substantial role in the process of atherosclerosis. The key players are monocytes transformed to macrophages. Limited experience with anti-inflammatory drugs is described – antibodies for IL-1 (CANTOS) and colchicine (COLCOT, LoDoCo-2 trial). Cannabis extracts are known to have profound anti-inflammatory effect in diseases associated with chronic inflammation, e.g. rheumatoid arthritis. Human monocytic cell line THP-1 was differentiated into macrophages by incubation in the presence of phorbol-12-myristate-13-acetate, which leads to a macrophage-like phenotype characterized by changes in morphology and adhesion. Macrophages were polarized toward M1 pro-inflammatory phenotype responsible for production of several cytokines, esp. TNFα and IL-6.The ability of cannabinoids to decrease production of pro-inflammatory cytokines in polarized macrophages was measured by ELISA. The viability of macrophages after the treatment was verified by resazurin assay., Cannabigerol (CBG) and cannabidiol (CBD) significantly decreased the production of TNFα in dose-dependent manner. 7.5 mg/L of CBG and 1 mg/L of CBD decreased the production of TNFα by 32 and 34%, respectively. CBD, cannabidivarin (CBDV), cannabichromene (CBC), and cannabinol (CBN) significantly decreased also IL-6 production. 7.5 mg/L of CBDV and CBC decreased the production of IL-6 by 38 and 62%, respectively. 2 mg/L of CBD and CBN decreased the production of IL-6 by 33% (both).The concentration of the most potent cannabinoid (CBC) inhibiting IL-6 production by half (IC50) was determined to be 6.7 ± 0.1 mg/L, which is two-times better treatment potential than colchicine (13.4 ± 0.8 mg/L). Cannabinoids might be promising substance in the treatment of subclinical inflammation associated with atherosclerosis.
The project was funded by the Grant No 22–20860S of The Czech Science Foundation.
Oral Presentation No. 068 Plasma fibrinogen independently predicts hypofibrinolysis in severe COVID-19
Authors: Schrick Diana , Tokés-Füzesi Margit , Réger Barbara , Molnár Tihamér 
Published: October 2022

Abstract
High rates of thrombosis are present in patients with SARS-CoV-2 infection. Deeper insight into the prothrombotic state is essential to provide the best thromboprophylaxis care. We aimed to explore associations among platelet indices, conventional hemostasis parameters, and viscoelastometry data.
21 patients with severe COVID-19 and 21 age-matched controls were enrolled. Each patient received 100 mg aspirin therapy at the time of blood sampling. To monitor the aspirin therapy, a platelet function test from hirudin anticoagulated whole blood was performed using the ASPI test by Multiplate analyser. High on-aspirin platelet reactivity (n = 8) was defined with an AUC &gt; 40 cut-off value by ASPI tests. Furthermore, vitro viscoelastometric tests were carried out using a ClotPro analyser in COVID-associated thromboembolic events nor the survival rate showed significant associations with high on-aspirin platelet reactivity status.
Patients presented with higher levels of inflammatory markers, along with evidence of hypercoagulability by ClotPro. H-IPF (%) was significantly higher among non-survivors (n = 18) compared to survivors (P = 0.011), and a negative correlation (P = 0.002) was found between H-IPF and plasminogen level in the total population. The platelet count was significantly higher among patients with high on-aspirin platelet reactivity (P = 0.03). ECA-A10 (P = 0.008), and ECA-MCF (P = 0.016) were significantly higher, while the tPA-CFT (P &lt; 0.001) was significantly lower among patients with high on-aspirin platelet reactivity. However, only fibrinogen proved to be an independent predictor of hypofibrinolysis in severe COVID-19 patients.
Surprisingly, a faster developing, more solid clot formation was observed in aspirin taking COVID-19 patients. In conclusion, an individually tailored thromboprophylaxis is needed to prevent thrombotic complications, particularly in the hypofibrinolytic cluster.
Poster No. 103 Spontaneous coronary artery dissection: when pain and ST-segment elevation persist
Authors: Lopes Rafaela G , Cruz Isabel , Oliveira Inês Pereira , Bragança Bruno , Campos Inês G , Monteiro Joel Ponte , Almeida Carla , Castro Alexandra , Andrade Aurora 
Published: October 2022

Abstract
A 44-year-old female with nonrelevant medical history was admitted due to chest pain. She was hemodynamically stable. Normal physical examination. ECG with ST-segment depression in the inferior leads. Echocardiogram had no contractility abnormalities. High-sensitivity troponin I (hsTnI) of 164.4 pg/mL. Non-ST-segment elevation myocardial infarction (NSTEMI) diagnosis was made. 12 hours later she developed refractory chest pain. Emergent coronariography depicted independent ostia for the anterior descending and circumflex arteries and type 1 spontaneous coronary artery dissection (SCAD) of the circumflex artery. During angiography, pain subsided and a conservative approach was adopted. An hour later, she had recurrent pain refractory to medical treatment and new onset of persistent ST-segment elevation in leads V4-V6. It was decided to perform percutaneous coronary intervention and a drug eluting stent was placed in the proximal circumflex artery. There was distal propagation of the parietal hematoma, but TIMI 3 flow was restored. She was discharged on day 6. 5 days later she was readmitted due to NSTEMI. She had recurrent episodes of chest pain followed by reelevation of hsTnI. Coronary computer tomography depicted distal progression of the dissection with involvement of a first obtuse marginal and distal circumflex. After uptitration of anti-ischemic medication she was discharged. The case underlines the challenging and non-linear approach of SCAD in the setting persistent chest pain. Besides the technical difficulties of angioplasty, with higher risk of restenosis and stent failure, most recommendations support a conservative approach. However, persistent chest pain imply further action, as exemplified in this case report.
Poster No. 109 Prognostic value of white blood cell count variation during in-hospital stay in STEMI patients: Insights from SCALIM Registry
Authors: Boukhris Marouane , Molié Camille Dierx , Chenard Pierre , Gourceyrol Amandine , Gasnier Amandine , Virot Patrice , Aboyans Victor 
Published: October 2022

Abstract

Background
In patients with ST-elevation myocardial infarction (STEMI), white blood cell count (WBCC) is associated with infarct size and cardiovascular outcome. We sought to determine the impact of WBBC variation (?WBCC) during in-hospital stay on long-term outcome after STEMI.

Methods
From 2011 to 2019, consecutive patients with STEMI were enrolled. Those with at least two WBCC during hospitalization were included in this study. ?WBCC was calculated as: [WBCC (admission) – WBCC (before discharge)]. The population was divided into 3 groups according to ?WBCC tertiles. The primary outcome was total mortality.

Results
A total of 1778 patients (mean age 64.5 ± 14.1, 75.7% males), were included and divided in 3 groups: Group 1 (?WBCC &lt; 0.85 103/mm3); Group 2 (?WBCC 0.85–3.31 103/mm3); and Group 3 (?WBCC &gt; 3.31 103/mm3). Patients in Group 1 were the oldest (67.9 ± 13.8, vs. 65.1 ± 13.9 and 60.5 ± 13.7 years in Groups 2 and 3 respectively, P &lt; 0.001). Hypertension, prior coronary artery bypass and cancer were more prevalent in Groups 1 and 2. Troponin peak was the highest in Group 3 (3601 ± 563) than Group 2 and 3 (2810 ± 439 and 2451 ± 467 ng/ml, respectively; P &lt; 0.001).
Five-year survival was the lowest in Group 1 (78.6% vs. 87.2% and 87.5% in Group 2 and 3, respectively; P &lt; 0.001). Adjusted to age, gender, cardiovascular risk factors, MI territory and left ventricular ejection fraction, ?WBCC &lt; 0.85. 103/mm3 was independently associated with all-cause mortality [HR 1.46; 95%CI 1.12–1.91; P = 0.005].

Conclusion
?WBCC &lt; 850/mm3 Is associated with increased mortality. Low ?WBCC during hospitalization could represent an interesting prognostic tool in STEMI patients.
Oral Presentation No. 125 Relation of non-invasively measured ankle-brachial index and pulse-wave velocity towards all-cause mortality in unselected emergency department patients - a prospective cross-sectional study
Authors: Schnaubelt Sebastian , Eibensteiner Felix , Oppenauer Julia , Domanovits Hans , Schlager Oliver 
Published: October 2022

Abstract

Background
Increased pulse-wave velocity (PWV) and decreased ankle-brachial index (ABI) are related to an increased risk of all-cause- as well as cardiovascular mortality. Aim of this study was to assess the predictive value of PWV and ABI in an emergence department (ED) setting.

Methods
We assessed ABI-, brachial-ankle (ba) PWV-, and carotid-femoral (cf) PWV in patients presenting to a high-volume tertiary care ED. Primary outcome was all-cause mortality in the long-term follow-up of these patients, which was evaluated via Austria´s federal statistical office.

Results
We included 1,041 patients (60 ± 17 years; 56.6% males) with various chief complaints (e.g., chest pain, dyspnea, atrial fibrillation). ABI and cfPWV could be measured in 952 (91.5) and 910 (87.4%), respectively. Values of ABI (1.03 ± 0.13) and cfPWV (10.1 ± 2.9 m/s) were found to be pathological in 13.4% and 44.8%, respectively. Median follow-up time was 540 [344–877] days. During this observational period, 8.1% of patients had died; the majority of deaths was classified as cardiovascular events. Overall mortality differed significantly between patients with pathological ABI or elevated cfPWV (P &lt; 0.001) compared with those patients without pathological alterations. Even after multivariate cox-proportional hazard analysis (including age(-groups), sex, BMI and comorbidities), a pathological ABI (HR 0.07 [0.01–0.56], P = 0.01) and cfPWV (HR 1.13 [1.04–1.23], P = 0.003) were associated with overall mortality risk.

Conclusion
In unselected ED patients a pathological ABI or PWV are independent predictors for long-term mortality and may be used as an additional risk stratification tool in the emergency setting.
Poster No. 128 Association of platelet markers with occurrence of thromboembolic and bleeding events following left atrial appendage occlusion
Authors: Aarnink Errol , Rocca Domenico G Della , Cepas Pedro L , Polzin Amin , Branca Luca , Spoon Daniel , Freixa Xavier , Boersma Lucas V A 
Published: October 2022

Abstract

Background
Patients undergoing left atrial appendage occlusion (LAAO) often are at increased risk for bleeding or thromboembolic events. In most implanting centers, baseline blood is drawn as a pre-procedural check-up. However, it is unknown what laboratory parameters have added value in this specific population. Platelet count (PLC) and mean platelet volume (MPV) may identify which patients are at risk for thromboembolic events or bleeding.

Materials and methods
Five implanting centers retrospectively gathered data on pre-procedural platelet markers. Composite endpoints on thromboembolic events (stroke, transient ischemic attack, device-related thrombus and systemic embolism) and bleeding (minor, major, and intracranial hemorrhage) were collected.

Results and conclusions
A total of 1138 patients were included (73 ± 8 years, 63% male, CHA2DS2-VASc: 4.4 ± 1.5; HAS-BLED: 3.2 ± 1.1). Implanted devices consisted of Watchman 2.5/FLX (n = 778), Amplatzer Cardiac Plug/AMULET (n = 315), or another device (n = 45). Baseline PLC was present in 91% and MPV in 41%. PLC was significantly lower in the 97 patients developing a thromboembolic event (206 ± 73 vs. 225 ± 72*10*9/L, P = 0.028), but no difference in MPV was observed (9.7 ± 1.4 vs. 9.5 ± 1.5 fL, P = 0.40). In another 97 patients, significant bleeding was observed during follow-up. No difference in baseline PLC was found (216 ± 79 vs. 207 ± 72*10^9/L, P = 0.30) and a trend towards lower MPV could be observed (9.5 ± 1.3 vs. 9.8 ± 1.5 fL, P = 0.07). Patients developing bleeding more often were discharged with antiplatelet therapy, while patients developing a thromboembolic event more often received anticoagulation therapy. In conclusion, occurrence of a thromboembolic event was associated with lower baseline PLC, which may be explained by PLC being lower in more frail patients.
Poster No. 132 HTAD PATIENT PATHWAY: Strategy for diagnostic work-up of patients and families with (suspected) Heritable Thoracic Aortic Diseases (HTAD). A statement from the HTAD Working Group of VASCERN
Authors: de Backer Julie , Caruana Maryanne , Baars Marieke , Bashiardes Evi , Benke Kalman , Bjorck Erik , Codreanu Andrei , de Moya Rubio Elena , Dumfarth Julia , Evangelista Arturo , Groenink Maarten , Kallenbach Klaus , Kempers Marlies , Keravnu Anna , Loeys Bart , Mosquera Laura Muino , Nagi Edit , Nistri Stefano , Pepe Guglielmina , Hesselink Jolien Roos , Szabolcs Zoltan , Teixido Gisela , Timmermans Janneke , Van de Laar Ingrid , Van Kimmenade Roland , Verstraeten Aline , Von Kodolitsch Yskert , Jondeau Guillaume 
Published: October 2022

Abstract

Background
Timely diagnosis of patients with Heritable Thoracic Aortic Diseases (HTAD) is essential to avoid (often fatal) aortic dissection. Experts of the HTAD rare disease working group of the European Reference Network of Rare Vascular diseases (vascern) aimed to propose a pathway to: (1) improve patient care by diminishing time to diagnosis; (2) facilitate the establishment of a correct diagnosis, using molecular genetics when possible, which may lead to a more personalized treatment; (3) exclude the diagnosis in unaffected persons (family screening); (4) avoid overuse of financial and personnel resources.

Material and methods
This pathway is a consensus at expert level. It was generated based on available guidelines when possible. Discussion items were listed and, where necessary, items were included in a questionnaire sent out for voting and discussion over monthly teleconference calls.

Results and conclusions
Pathway Elements include Thoracic aortic aneurysm – and dissection, Bicuspid Aortic Valve, Medium-sized artery aneurysms/dissection, Extravascular features and Family History. Recommendations for the evaluation of patients and family members are provided.
This pathway is advised to implement standardisation of diagnostic workup and follow-up of patients with suspected HTAD and the screening of their relatives and it focuses on patients with heritable aortic diseases whether syndromic or not. It is subject to adjustment with better recognition of new entities, and with the technical progress and increased availability of genetic testing.
Poster No. 135 Stroke risk of patients with new AF during ACS may depend on onset and duration
Authors: Bor Wilbert , Azzahhafi J , di Maio N , Van Der Sangen N M R , Rayhi S , Peper J , Ten Berg J M 
Published: October 2022

Abstract

Background/rationale
Newly diagnosed atrial fibrillation(AF) during acute coronary syndrome(ACS) is associated with worse outcomes. In this study we evaluated the associated stroke risk of newly diagnosed AF in ACS patients according to the onset and duration of the episode.

Results
Amongst 4433 patients presenting with ACS, 439(9.9%) had newly diagnosed AF and 396(8.9%) had known AF. Of the new AF cases, 27.5% occurred post-CABG. The onset was within 24 hours of ACS presentation in 70.1% of non-CABG cases. The new AF episodes lasted longer than 24 hours in42.9% of the non-CABG cases. At discharge 54.0% of patients with new AF was treated with OAC, in contrast to 89.2% with known AF.
The incidence of ischemic stroke at one year was 1.2% in patients without AF, 1.0% with known AF, and 3.6% with new AF(P &lt; 0.001). Within patients developing AF post-CABG, the incidence was 4/120(3.3%). Within non-CABG patients, the incidence of ischemic stroke for patients with onset within 24 hours of presentation was 0/133(0.0%) for patients with an episode lasting &lt; 24 hours, and 6/109(5.5%) for patients with an episode lasting &gt; 24 hours. For patients with new AF onset after 24 hours the incidence was 5/120(5.5%) for patients with an episode lasting &lt; 24 hours, and 5/92(5.4%) for patients with an episode lasting &gt; 24 hours.

Conclusion
Patients with newly diagnosed AF during ACS seem undertreated with OAC. The associated risk of ischemic stroke with new AF during ACS may be lower in episodes that terminate within the first 24 hours of presentation.