bluuebunny/crossref_metadata_2025 huggingface dataset:
Oral Presentation No. 090 Pleiotropic effect of antiplatelet ticagrelor: expression of CYP4F2 in HUVEC and HepG2
Authors: Ciapiene Ieva , Meskauskaite Ugne , Andruskeviciute Silvija , Lesauskaite Vaiva , Tatarunas Vacis
Published: October 2022

Background

Ticagrelor is a first drug of a new chemical class cyclopentyltriazolopyrimidines and a third-generation P2Y12 inhibitor that targets and directly binds platelet P2Y12 receptors. It is recommended to be given as a dual antiplatelet therapy (DAPT) with aspirin for the prevention of thrombotic events and the following ischemic heart disease. Ticagrelor is also known to have pleiotropic effects of unknown mechanisms. It is questioned whether ticagrelor could influence the expression of cytochrome P450 4F2 (CYP4F2) enzyme involved in the resolution of inflammation and biosynthesis of pro-inflammatory eicosanoids. This study aimed to investigate if ticagrelor could alter the expression of CYP4F2 and its encoded protein concentration in both endothelial cells (human umbilical vein endothelial cells, HUVEC) and the metabolism of various xenobiotics performing, CYPs-rich liver cells (HepG2).

Material and methods

The expression of CYP4F2 was determined in HUVEC and HepG2 cell lines by qPCR on real time thermal cycler ABI 7900HT (Applied Biosystems, USA). CYP4F2 protein concentration was determined with sandwich enzyme immunoassay kit for CYP4F2 (Cloud-Clone Corp., USA).

Results and conclusions

Ticagrelor was observed to reduce the expression of CYP4F2 in HUVEC and HepG2 cell lines. It also reduced CYP4F2 protein levels in HUVEC cells. Thus, ticagrelor may have a protective role in endothelial cells and reduce vascular inflammation.

Funding sources

This work was supported by the Research Council of Lithuania under Grant 09.3.3.-LMT-K-712-16-0187.
Poster No. 094 Age-dependent decline in common femoral artery flow-mediated dilation and wall shear stress in healthy subjects
Authors: Bapir Mariam , Skene Simon S , Campagnolo Paola , Heiss Christian
Published: October 2022

Background

Femoral artery (FA) endothelial function is a promising biomarker for peripheral artery disease (PAD) prevention. We assessed FA flow-mediated dilation (FMD) in healthy adults of various ages.

Material and methods

Repeated common FA and brachial artery (BA) FMD measurements were performed with ultrasound induced by5 minutes distal cuff occlusion (thigh, calf, forearm) to assess intra- and interindividual variability and acceptability (n = 10). We then performeda cross-sectional study with FA- and BA-FMD measurements in healthy participants aged 18–80 (n = 53).

Results and conclusions

All FMD protocols had good reproducibility with average deviation of −0.1% (SD 0.6%, 0.9%, 0.6%) but thigh occlusion was less well tolerated. BA- and FA-FMD with thigh occlusion did not significantly differ while FA-FMD with calf occlusion was significantly lower (−1.0 ± 0.9%).

Both FA-FMD and BA-FMD inversely correlated with age and baseline diameter and positively with wall shear stress (WSS). FA-FMD and BA-FMD correlated significantly (r = 0.57, P < 0.001). The baseline diameter was significantly greater in the FA as compared to the BA while the WSS was significantly lower. At the onset of reactive hyperaemia, the mean flow velocity, WSS and flow reserve were lower in the FA as compared to the BA. A large proportion of FA WSS values in older participants were below 5 dyne/ cm2 which is regarded as pro-atherogenic.

FA endothelial function declines with age in parallel with the BA. FAs exhibits stronger age-dependent enlargement as compared to the BA leading to a critical decrease in WSS that may explain part of the age-dependent predisposition for PAD.
Oral Presentation No. 105 Endothelial dysfunction and alterations in erythrocyte function in a murine model of chronic heart failure
Authors: Mohaissen Tasnim
Published: October 2022

Endothelial dysfunction (ED) and red blood cell distribution width (RDW) are both prognostic factors in heart failure (HF), but the relationship between them is not clear. In this study, we used a unique mouse model of HF to characterize the relationship between the development of peripheral ED and the occurrence of structural nanomechanical and biochemical changes in red blood cells (RBCs).

Methods and results

Systemic ED was detected in vivo in 8-month-old Tgαq*44 mice, as evidenced by impaired acetylcholine-induced vasodilation in the aorta. ED in the aorta was associated with impaired nitric oxide (NO) production in the aorta and diminished systemic NO bioavailability (characterized by increased superoxide and eicosanoid production). In 4- to 6-month-old Tgαq*44 mice, RBC size and membrane composition displayed alterations that did't result in significant changes in their nanomechanical and functional properties. However, 8-month- old Tgαq*44 mice presented accentuated structural, size changes and increased RBC stiffness. In 12-month-old Tgαq*44 mice, the erythropathy was featured by altered RBC shape and elasticity, increased RDW, impaired RBC deformability. Moreover, RBCs taken from 12-month-old Tgαq*44 mice, coincubated with aortic rings from FVB mice, induced impaired endothelium-dependent vasodilation and this effect was partially reversed by arginase inhibitor.

Conclusion

In the Tgαq*44 murine model of HF, systemic ED accelerates erythropathy and, conversely, erythropathy may contribute to ED. These results suggest that erythropathy may be regarded as a marker and a mediator of systemic ED in HF. RBC arginase and possibly other RBC-mediated mechanisms may represent novel therapeutic targets for systemic ED in HF.
Poster No. 110 History of venous thromboembolic disease: a prognostic risk marker following STEMI? Insights of the French SCALIM registry
Authors: Chenard Pierre , Dousset Benjamin , Boukhris Marouane , Virot Patrice , Aboyans Victor
Published: October 2022

Background

Venous and arterial thrombosis are two different entities. However, they share common risk factors and a continuum between arterial and venous thrombosis has been suggested. The purpose of our study was to determine whether a history venous thromboembolic disease (VTE) is associated with poorer outcome in patients with ST-elevation myocardial infarction (STEMI).

Methods

All consecutive STEMI patients between 2011 and 2019 were included in our regional SCALIM registry. Clinical history of VTE was collected at baseline. The primary outcome was cardiovascular mortality and recurrent non-fatal arterial events (including non-fatal-myocardial infarction, ischemic stroke and peripheral ischemic event) at 5-year follow-up. The secondary outcome was total mortality.

Results

A total of 1924 patients (64.7 ± 14.1 years; 75.1% men) were included, among whom 2.8% with history of VTE. The latter were older than those without VTE (respectively 72.8 ± 14.1 vs. 64.4 ± 14.0 years; P < 0.001) and had more often hypertension, history of stroke and cancer. We found no statistical difference between the two groups regarding the 5-year cardiovascular mortality (11.3% vs. 7.1%, P = 0.231) and recurrent non-fatal arterial events (17.0% vs. 14.9%, P = 0.754). Five-year all-cause mortality was significantly higher in patients with history of VTE (33.3% vs. 14.6%, P = 0.001).

In a nested case-control study adjusted for age, no difference was found in primary and secondary outcomes according to VTE history.

Conclusion

We found no impact of history of VTE on 5-year cardiovascular outcome in who had STEMI patients. Higher mortality in these patients are related to older age and comorbidities.
Oral Presentation No. 121 Aortic stiffness descriptors by cardiac magnetic resonance are correlated with mechanical testing of ex-vivo aortic aneurysms specimens
Authors: Muñoz Aroa Ruiz , Guala Andrea , Cilla Myriam , Martínez Miguel , Dux-Santoy Lydia , Teixidó-Turà Gisela , Garrido-Oliver Juan , Galian Laura , Sao-Aviles Augusto , Evangelista Arturo , Ferreira-Gonzalez Ignacio , Peña Estefania , Rodriguez-Palomares Jose
Published: October 2022

Background

Aortic stiffness independently predicts mayor adverse cardiovascular events and mortality in the general population. Cardiovascular magnetic resonance (CMR) permits the assessment of a number of parameters theoretically linked to aortic stiffness, such as distensibility (AD), pulse wave velocity (PWV) and proximal aorta longitudinal strain. However, no previous study validates these parameters as descriptors of aortic wall stiffness against ex-vivo mechanical testing.

Materials and methods

Ascending aorta (AAo) specimens were collected from 20 patients undergoing AAo replacement for aneurysms. Patients underwent a CMR protocol in the days leading to the surgery, including 4D flow CMR. Two 15×5 mm specimens (one oriented in the circumferential and the other in the longitudinal aortic direction) were extracted during surgery, and later tested controlling for extension force. Elongation was measured by laser video extensometer and the tangent of the stress-strain curve at diastolic pressure was extracted. AAo PWV and the Eh product (E being Young modulus and h wall thickness) were measured from 4D flow CMR while AD and AAo longitudinal were quantified from cine images.

Results and conclusions

Marked correlations were found between circumferential elastic modulus and AAo AD (R = −0.502), PWV(R = 0.652) and Eh (R = 0.602). Similarly, strong correlation was identified between AAo longitudinal strain and longitudinal elastic modulus(R = −0.513). In conclusion, PWV and the Eh product are positively related to aortic wall stiffness while aortic distensibility and strain show negative relationships. Thus, these biomarkers are a reliable expression of aortic wall stiffness.

Funding

PI17/00381,SEC/FEC-INV-CLI20/015,LCF/BQ/PR22/11920008.
Oral Presentation No. 126 NOACs safety and efficacy in Adult Congenital Heart Disease
Authors: Pinto Ricardo Jorge Reis Alves , Carvalho Miguel Martins , Proença Tânia , Costa Catarina , Amador Ana Filipa , Calvão João , Marques Catarina , Cabrita André , Santos Luís , Oliveira Cátia , Pinho Ana , Cruz Cristina , Macedo Filipe
Published: October 2022

Introduction

Adult Congenital Heart Disease(ACHD) patients are an increasing population with known high risk for thromboembolic events.Validated scores are uncertain in this population. Although apparently safe, data is scarce about the use of NOAC.

Purpose

To evaluate all patients on-NOAC followed in an ACHD outpatients clinic and observe its safety and efficacy during a median follow-up of 34 months (IQR 7–60 months). Major bleeding was defined according to types 3 to 5 in BARC scale. Adverse event was defined as ≥ 1 of the follows: death, stroke, myocardial infarction, systemic embolism or major bleeding.

Results

A total of 65 patients were included, with a mean age of 52 ± 14 year-old, 66% female. Most frequent ACHD were atrial septal defect (22%) and tetralogy of Fallot (22%), followed by atrioventricular septal defect (17%) and transposition of great arteries (9%). Most patients had preserved biventricular function, 20% presented systemic ventricle systolic dysfunction and 12% subpulmonic ventricle systolic dysfunction. Atrial fibrillation or atrial flutter (AF/AFL) were the major reasons for anticoagulation (94%); the remaining were on NOAC due to previous ischaemic stroke, intra-cardiac thrombus or deep venous thrombosis. At the time of NOAC initiation, 49% had a CHA2DS2-VASc score ≥ 2 (median 1, IQR 1-3) and median HAS-BLED score was 0 (IQR 0-2);43% were medicated with apixaban, 29% with rivaroxaban,22% with edoxaban and 6% with dabigatran.During a median follow-up of 34 months, none had ischaemic complications or major bleeding and one patient died after pulmonic prothesis dysfunction surgery. Concerning time-to- adverse-event analysis, all patients kept uneventful after 2 years and more than 95% continued event-free after 8 years on-NOAC.
Poster No. 127 Intravenous statin administration during myocardial infarction mitigates cardiac damage and preserves cardiac function in diabetic cardiomyopathy rats
Authors: Alcover Sebastian , López Sergi , Badimon Lina , Vilahur Gemma
Published: October 2022

Introduction

Diabetic patients may develop diabetic cardiomyopathy (DCM) and are at increased risk of myocardial infarction (MI). Yet, cardioprotection remains a challenge in the presence of comorbidities.

Objectives

We examined whether intravenous administration of atorvastatin during ongoing myocardial ischemia prevents against the deleterious effects of MI in DCM rats.

Methods

DCM was induced by streptozotocin (65 mg/kg) in Sprague Dawley rats (n = 14). 5 weeks thereafter animals exhibited a DCM phenotype associated with a significant diastolic (IVRT + 15.64 ± 5.49ms P < 0.05 vs. baseline) and systolic (LVEF, −8.63 ± 6.71% P < 0.05 vs. baseline) ventricular dysfunction. AMI was then induced by coronary ligation of the LAD for 45minutes. Early after ischemia (15minutes) DCM-rats received either i.v atorvastatin or vehicle. Animals were reperfused and sacrificed at 24h for infarct size assessment and molecular analysis. Cardiac function was monitored by echocardiography.

Results

No differences were detected as per the area-at-risk between both animal groups. Atorvastatin significantly reduced infarct size expansion (35% relative reduction) as compared to vehicle (15.3 ± 1.03% vs. 23.7 ± 4.3% IS/AAR; P < 0.05). LVEF, shortening fraction, and stroke volume were better preserved in atorvastatin-treated DCM rats as compared to vehicle (4.62 ± 2.55% vs. 12.4 ± 3.16%; 5.77 ± 3.74% vs. 15.9 ± 4.9%; and 58.93 ± 28.79μl vs. 101.73 ± 31.58 μl, respectively; P < 0.05). At a molecular level, atorvastatin administration was associated with a lower expression of Phosphorylated-p53 (apoptosis) and higher P-AMPK/AMP ratio (cardiac metabolism); P < 0.05 vs. vehicle).

Conclusion

Intravenous administration of atorvastatin during MI limits infarct size and preserves cardiac function post-MI in rats with manifest DCM supporting the cardioprotective potential of this therapeutic approach despite comorbid conditions.
Clinical Case 01—Cardioembolic stroke with a twist: a case of left ventricular thrombus
Authors: Vazão Adriana , Gonçalves Carolina Miguel , Ribeiro Rui Filipe , Domingues Ana Catarina , Cerqueira Margarida , Carvalho João Filipe , de Jesus Banz Maria , Morais João
Published: October 2022

Presentation and diagnosis

A 62-years old male was brought to the emergency department after being found unconscious, lying on his left side. He was last seen 1 week before. Past medical history revealed ischemic cardiomyopathy with reduced ejection fraction of 35% after ST-segment elevation myocardial infarction 3 months before, subject to coronary angioplasty of 2 vessels (left anterior descending artery with drug-eluting stent and circumflex artery with balloon angioplasty). He had poor therapeutic compliance with missing cardiology appointments. On examination, he was hypothermic and hemodynamically unstable with signs of hypoperfusion. He was admitted for septic shock with origin in a decubitus ulcer on his left-hand dorsum. Head CT-scan revealed sub-acute ischemic stroke in the right middle cerebral artery territory. He started fluid therapy, vasopressors and large spectrum antibiotics with favorable clinical evolution and no heart failure symptoms but remained febrile. Meanwhile, Proteus hauseri had grown in blood cultures. An echocardiography was performed excluding infectious endocarditis and revealing a large apical thrombus on the left ventricle.

Management

Therapeutic anticoagulation with enoxaparin was initiated and antibiotic was de-escalated according to the antibiogram. Later on, anticoagulation was switched to warfarin (target INR∼2.0–3.0). When clinically stable, was discharged home with anticoagulation and clopidogrel, with an echocardiography scheduled after 3 months.

Learning points

Left ventricular thrombus is a rare complication of ischemic cardiomyopathy with high risk of adverse outcomes, including ischemic stroke and death. Vitamin K antagonists are usually preferred to direct oral anticoagulants in the management of these patients, but further research is needed.
Clinical Case 10—An unusual case of thrombocytopenia following transfemoral aortic valve implantation
Authors: Câmara de Sá Ana Débora , Antunes André , Santos M Raquel , Temtem Margarida , Sousa João Adriano , Silva Bruno
Published: October 2022

Clinical Case: An 85-year-old female patient with diabetes, hypertension, obesity, chronic kidney disease and severe aortic stenosis was submitted to transcatheter aortic valve implantation (TAVI). During procedure unfractionated heparin was administered. Intervention was performed without complications and she was discharged with platelet count of 116,000/μL.

Fifteen days after (day 0), she was readmitted with dyspnea. Arterial blood gas showed hypoxemia and lactate levels of 5,8mmol/L. The ECG showed new-onset atrial fibrillation (AFib) with a rapid ventricular rate. Blood tests showed platelet count of 45,000/μL, D-dimers 2790ng/mL, worsening kidney function and high inflammation markers. An echocardiogram showed normofunctioning transcatheter aortic valve.

Pulmonary embolism (PE) or respiratory infection with new-onset AFib were admitted. The patient started enoxaparin and an antibiotic.

On day 4 the patient was oliguric needing dialysis. A CT Angiography was performed that excluded PE but showed several thrombus on the right atrium and appendix, right ventricle and on the abdominal aorta. Blood results showed hemolytic anemia. On day 8, the platelet count reached the nadir of 11 000/μL.

At that time, differential diagnoses included thrombotic thrombocytopenic purpura (TTP), heparin-induced thrombocytopenia and sepsis-induced disseminated intravascular coagulation (DIC). Laboratory evaluation showed a near-normal coagulation profile and a PF4+ antibody. Enoxaparin was stopped; fondaparinux and plasma therapy were started.

Platelet count took weeks to reach previous levels. The patient was discharged with a DOAC.

It is usual to have some degree of thrombocytopenia after TAVI. In this case we have a complex and challenging scenario, properly handled, and with a good outcome.
Clinical Case 12—Thrombus on apical left ventricle: when the clinical suspicion is high
Authors: Duarte Fabiana Silva , dos Santos Inês Coutinho , Barradas Maria Inês , Oliveira Luís , Machado Carina , Dourado Raquel , Martins Dinis
Published: October 2022

Introduction

Left ventricular thrombi may develop as a complication of myocardial infarction. Transthoracic echocardiography (TTE) has a low sensitivity for thrombus detection and other imaging methods are usually required.

Case report

A 32-years-old man with a past medical history of smoking habits, obesity and a ST-segment elevation myocardial infarction (STEMI) diagnosed on December 2017. Primary angioplasty was performed with stent implantation in the anterior descending coronary artery. TTE revealed severe systolic dysfunction (SD) and an apical aneurysm with thrombus formation. Six months after anticoagulation with warfarin, a cardiac magnetic resonance revealed thrombus resolution and it was decided to stop warfarin. On September 2021, the patient presented to the Emergency Department referring sudden chest pain. The electrocardiogram showed an anterior STEMI and in the Cath Lab a late stent thrombosis was evident. TTE revealed a severe SD and akinesia of apical segments (poor acoustic window).

On the 3rd day of hospital stay, the patient developed backache and Murphy´s punch sign.

Imaging workup was suggestive of right renal infarction. At this time, the suspicion of embolic source arises, and the patient underwent contrast echocardiography demonstrating a filling defect suggestive of an apical thrombus. Therapy with warfin was reinitiated concomitantly with dual antiplatelet therapy.

Conclusion

This is a particular case of an apical thrombus formation occurring twice in a young patient. There is a lack of evidence about the adequate screening methods and therapeutic approach. More cases need to be reported to understand the best approach in each case to minimize complications.
Clinical Case 21—An unusual cause for hypoxemia and breathlessness
Authors: de Figueiredo Margarida Gancho , Paula Sofia , Almeida Samuel , Gomes Francisco , Ferreira Filipa , Luz João , Cunha Diogo , Baltazar Oliveira , Almeida Lurdes
Published: October 2022

75-year-old woman with past medical history of ischemic stroke in 2019, when complementary diagnostic tests were performed and it was found that the patient had a patent foramen ovale (PFO). Current hospitalization due to COVID-19 pneumonia, which was complicated by bacterial co-infection and intermediate-low risk right main pulmonary artery thromboembolism. The patient was successfully treated, with improvement of the clinical condition and evident imaging resolution of pulmonary cavitations and recanalization of the right pulmonary artery. However, something intriguing was observed: the patient presented dyspnea in the upright position and a decline in transcutaneous oxygen saturation from 96% in the supine position to 85% in orthostatism, with reversal of these findings with the recumbency. This led to the suspicion of platypnea-orthodeoxia syndrome. A transesophageal echocardiogram with bubble test was then performed, revealing an atrial shunt in the supine position without Valsalva maneuver. With these evidences, the diagnosis of platypnea-orthodeoxia syndrome was made. Even though the patient was >60 years, due to important right-to-left shunt, the history of stroke and the current platypnea-orthodeoxia, it was decided to close the PFO. The day after the procedure, the patient was placed in the upright position, maintaining an oxygen saturation of 96%.

This case is an example that the decision of closing PFO must be individualized, not focusing only on patient's age, but also on his medical history and current situation, as indicated in the 2022 Guidelines for the Management of Patent Foramen Ovale. Figure 1Transesophageal echocardiogram showing interatrial communication.
Clinical Case 23—Adult-onset recurrent Kawasaki disease complicated by coronary aneurysms and recurrent acute myocardial infarction
Authors: Carvalho Mariana Margarida Ferreira , Gonçalves Carolina , Cabral Margarida , Fernandes Sara Lopes , Carvalho Rita Ribeiro , Guardado Jorge , Morais João
Published: October 2022

Summary of case: A 67-year-old man presented to the emergency department (ED) with acute chest pain. He had the previous diagnosis of Kawasaki disease (KD) made when he was 51 years-old in a event of a acute myocardial infarction. Upon admission, his blood pressure was 100/70 mm Hg, heart rate was 55 beats/min, apyretic. Clinical examination was unremarkable. Electrocardiogram showed a synus rhythm without any ST-T alterations. An echocardiogram showed mildly decreased left ventricular function (LVEF) of 44% by the biplane Simpson method, with hypokinesia of anterolateral and inferolateral wall, and enlargement of the ascendent aorta and aorta root. Cardiac enzymes were elevated, troponin-I 10.5 ng/mL and NTproBNP of 832 ng/mL. The diagnosis of acute myocardial infarction without ST segment elevation was made. Cardiac catheterization revealed diffuse aneurysmal dilation of the left anterior descendent artery and right coronary artery. Circunflex artery was occluded in the mid segment. Thrombotic aspiration was made and a drug-eluting stent was implanted. The patient showed clinical improvement and was discharged 4 days later with ticagrelor and aspirin.

This case illustrates the importance to recognize adult-onset KD as part of the differential diagnosis of chest pain with ST-segment elevation in a adult, even if uncommon. Early recognition is fundamental, permitting correct treatment and prevention of potentially fatal coronary complications.
Retracted: Clinical Case 28—Hyperacute synchronous cardiocerebral infarction in a patient with new-onset atrial fibrillation	a rare case of MINOCA
Authors: Papakonstantinou Panteleimon E , Manousiadis Konstantinos , Bei Ilianna , Lentza Malamati-Eleni , Panourgia Maria , Tachmetzidi-Papoutsi Dimitra , Sideris Antonios
Published: October 2022

This abstract has been withdrawn. Please see: https://doi.org/10.1093/cvr/cvac183
Shared Patterns of Gene Expression and Protein Evolution Associated with Adaptation to Desert Environments in Rodents
Authors: Bittner Noëlle K J , Mack Katya L , Nachman Michael W
Published: October 2022

Desert specialization has arisen multiple times across rodents and is often associated with a suite of convergent phenotypes, including modification of the kidneys to mitigate water loss. However, the extent to which phenotypic convergence in desert rodents is mirrored at the molecular level is unknown. Here, we sequenced kidney mRNA and assembled transcriptomes for three pairs of rodent species to search for shared differences in gene expression and amino acid sequence associated with adaptation to deserts. We conducted phylogenetically independent comparisons between a desert specialist and a non-desert relative in three families representing ∼70 million years of evolution. Overall, patterns of gene expression faithfully recapitulated the phylogeny of these six taxa providing a strong evolutionary signal in levels of mRNA abundance. We also found that 8.6% of all genes showed shared patterns of expression divergence between desert and non-desert taxa, much of which likely reflects convergent evolution, and representing more than expected by chance under a model of independent gene evolution. In addition to these shared changes, we observed many species-pair-specific changes in gene expression indicating that instances of adaptation to deserts include a combination of unique and shared changes. Patterns of protein evolution revealed a small number of genes showing evidence of positive selection, the majority of which did not show shared changes in gene expression. Overall, our results suggest that convergent changes in gene regulation play an important role in the complex trait of desert adaptation in rodents.
10. Moral Rights
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter focuses on moral rights conferred by the Copyright, Designs and Patents Act 1988 on the authors of certain works to protect their non-pecuniary or non-economic interests. It begins by describing the nature of and rationales for grant of moral rights as well as a number of criticisms made about such rights. This is followed by a detailed consideration of the moral right of attribution or right of paternity, the right to object to false attribution, and the right of integrity. This discussion identifies when such rights arise (including the requirement of assertion of the attribution right), when the moral rights are infringed, and exceptions to such rights. The chapter also considers how far such rights can be waived.
13. Rights Associated with Copyright
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter deals with regimes that are related to, but fall outside of, the remit of copyright law: performers’ rights in their performances (recognized internationally and often designated as a ‘neighbouring right’ or, in the EU, a ‘related right’); database right, sometimes referred to as the sui generis database right; public lending right (that is, an author’s right to claim remuneration from a public fund, the remuneration being calculated by reference to the frequency with which a given author’s book is loaned by public libraries); rights relating to technological protection measures (‘TPMs’); rights management information (which, along with TPMs, are sometimes designated ‘para-copyright’); and the so-called droit de suite (artist’s resale royalty right, that is, the right to claim a proportion of the sale price when an artwork is publicly resold). The chapter discusses each regime in turn, considering relevant factors such as the subsistence, types of rights available, duration, infringement, exceptions, defences, and remedies.
18. Novelty
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter considers novelty as a prerequisite for an invention to be patentable under both the Patents Act 1977 and the European Patents Convention. More specifically, it tackles three questions to help decide whether an invention is novel: what the invention is; what information is disclosed by the prior art; and whether the invention is novel (part of the state of the art). It also looks at the so-called ‘right to work’ argument, whereby novelty helps to ensure that patents are not used to prevent people from doing what they had already done before the patent was granted, and its modification as a result of changes in the way in which novelty is determined. The chapter concludes by discussing three specific types of inventions and the problems that have arisen when evaluating their novelty: inventions relating to medical uses and non-medical uses, and so-called selection inventions.
34. Damage
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter examines one element that a claimant must prove to sustain a passing off action: the requirement that they have suffered, or are likely to suffer, damage as a result of the defendant’s misrepresentation. It first considers four types of damage that have been recognized by the courts in connection with misrepresentation: loss of existing trade and profits; loss of potential trade and profits; damage to reputation; and dilution. It then discusses the notion of extended passing off and its three elements: goodwill, misrepresentation, and damage. It also looks at the principles of unfair competition.
39. Revocation
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter examines revocation as a reason for removing a mark from the register and the grounds for revocation as set out in section 46 of the Trade Marks Act 1994. It begins by discussing the first ground on which a mark may be revoked: ‘non-use’ (the trade mark has not been used for five years following the date of completion of the registration). It considers the relevant period of non-use and proper reasons for non-use, along with the issue of rewriting the specification with respect to goods and services. The chapter then looks at the second ground for the revocation of trade marks: if the mark has become the ‘common name in the trade’ (that is, generic marks). The final reason for revocation is if the mark has been used in a way that misleads the public (that is, deception is involved).
40. Infringement
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter deals with trade mark infringement, as set out in sections 10(1)-(3) of the Trade Marks Act 1994. It first outlines a non-exhaustive list of the situations in which a person uses a sign, such as affixing the sign to the goods or to the packaging; importing or exporting goods under the sign; or using the sign on business papers or in advertising. It then discusses how the claimant’s and defendant’s marks may be identified for comparison purposes, and the range of situations in which an infringement claim is viable, including when a mark is used in a relevant manner, in the course of trade, within the territory of the UK, and in relation to goods and services. Finally, it examines the functions of a trade mark, commencing with the ‘origin’ function. It concludes by considering secondary or accessory liability for trade mark infringement, especially relevant for Internet platforms.
43. Geographical Indications of Origin
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter examines the sui generis protection of geographical indications (GIs) in the UK. It describes the historical origins of and justifications for such regimes, which developed around wine protection. It then describes the major international treaties in this area, while indicating the importance of bilateral agreements. Drawing on the Quality Schemes Regulation for agricultural products and foodstuffs, the chapter outlines the basic features of registration-based protection for wines, spirits, aromatised wines, and agricultural products and foodstuffs. It describes the two forms of protected signs: protected designations of origin (PDOs) and protected geographical indications (PGIs). The chapter concludes by looking at situations in which a registered name will be infringed (or misused), together with the scope of protection against infringement.
47. Misuse of Private Information
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter examines the tort of misuse of private information. It begins by considering the sort of information that can be considered private. It then moves on to examining the test for whether there is a reasonable expectation of privacy over such information. The chapter looks at the ‘ultimate balancing test’ that is the balancing of rights under Articles 8 and 10 of the European Convention of Human Rights and concludes by touching on reform.
48. Litigation
Authors: Bently L. , Sherman B. , Gangjee D. , Johnson P.
Published: October 2022

This chapter introduces some of the more important aspects of intellectual property litigation. It begins by considering who can bring proceedings and who can be sued with respect to infringement before discussing how evidence is obtained and preserved, with particular reference to disclosure orders and search orders. In addition, the chapter looks at presumptions that alter the normal burden of proof; unjustified threats of infringement; special courts and tribunals that deal with the technical nature of intellectual property litigation; parallel proceedings and the problems that they raise; the use of experts in litigation; and jurisdictional issues and conflicts of law. Finally, it examines alternative dispute resolution as an approach to resolving disputes concerning intellectual property.
Extensions of the d’Alembert formulae to the half line and the finite interval obtained via the unified transform
Authors: Fokas A S , Kalimeris K
Published: October 2022

We derive the solution of the one-dimensional wave equation for the Dirichlet and Robin initial-boundary value problems (IBVPs) formulated on the half line and the finite interval, with non-homogeneous boundary conditions. Although explicit formulas already exist for these problems, the unified transform method provides a convenient framework for deriving different representations of the solutions for these and other types of IBVPs. Specifically, it provides solution formulas in the Fourier space or solutions which constitute the extension of the classical formula of d’Alembert of the initial value problem on the full line. We also derive the solution of the forced wave equation on the half line.
Fallacies of Democratic State-Building
Authors: Trantidis Aris
Published: October 2022

This paper criticizes the epistemic foundations of democratic state-building, which are derived from a model of political transitions according to which liberal democratic institutions will transform a hitherto authoritarian and troubled country into a more prosperous and stable society and, therefore, foreign interventions to establish these institutions are realistic and worthy investments, provided they are properly planned based on knowledge of what has worked elsewhere. This expectation is based upon two epistemological premises. The first premise, linearity, is that social and institutional change exhibits identifiable input–output relations connecting socioeconomic conditions and outcomes. The second premise, ergodicity, is that these relations, inferred from past samples, provide reliable probabilistic projections about future outcomes, which can guide the focus of policy interventions. Drawing from the study of complex systems, the paper indicates why these two premises offer a flawed conception of political transitions and why radical and large-scale interventions, such as state-building, will tend to generate unintended consequences rather than the planned effect.
nudt7 gene depletion causes transcriptomic change in early development of zebrafish
Authors: Bhandari Sushil , Hong KwangHeum , Miyawaki-Kuwakado Atsuko , Tomimatsu Kosuke , Kim Yong-Il , Nam In-Koo , Sagerström Charles G , Nakamura Mako , Choe Seong-Kyu
Published: October 2022

The Nudt family has been identified as enzymes performing Coenzyme A to 3′5′-ADP + 4′-phospho pantetheine catalysis. The members of this family have been shown to be particularly involved in lipid metabolism, while their involvement in gene regulation through regulating transcription or mRNA metabolism has also been suggested. Here, we focused on peroxisomal NUDT7, possessing enzymatic activity similar to that of its paralog, peroxisomal NUDT19, which is involved in mRNA degradation. No reports have been published about the Nudt family in zebrafish.

Our transcriptomic data showed that the Nudt family members are highly expressed around zygotic gene activation (ZGA) in developing zebrafish embryos. Therefore, we confirmed the computational prediction that the products of the nudt7 gene in zebrafish were localized in the peroxisome and highly expressed in early embryogenesis. The depletion of nudt7 genes by the CRISPR/Cas9 system did not affect development; however, it decreased the rate of transcription in ZGA. In addition, H3K27ac ChIP-seq analysis demonstrated that this decrease in transcription was correlated with the genome-wide decrease of H3K27ac level. This study suggests that peroxisomal Nudt7 functions in regulating transcription in ZGA via formation of the H3K27ac domain in active chromatin.
Islam in the defence of the Anglican Church: John Gregory (1607–1646)
Authors: Matar Nabil
Published: October 2022

This article examines the writings of John Gregory (d. 1646), who used the Qurʾān in resolving inter-denominational conflicts in the England of the 1640s. Living during the British Civil Wars, Gregory witnessed the assault on the Anglican Church by Presbyterians and Independents, on the one hand, and by Catholics, on the other. To defend the church of the via media in which he was ordained, Gregory took the unprecedented step of consulting the Qurʾān and the Arabic legacy, both Islamic and Christian, to find support for the theological and ecclesiastical positions of Anglicanism. He was an accomplished Arabist, and his unique treatment of the Qurʾān and of Islam influenced writers well into the eighteenth century, including Henry Stubbe (d. 1676) and Charles Hornby (d. 1739).
Attosecond electron-beam technology: a review of recent progress
Authors: Morimoto Yuya
Published: October 2022

Electron microscopy and diffraction with ultrashort pulsed electron beams are capable of imaging transient phenomena with the combined ultrafast temporal and atomic-scale spatial resolutions. The emerging field of optical electron beam control allowed the manipulation of relativistic and sub-relativistic electron beams at the level of optical cycles. Specifically, it enabled the generation of electron beams in the form of attosecond pulse trains and individual attosecond pulses. In this review, we describe the basics of the attosecond electron beam control and overview the recent experimental progress. High-energy electron pulses of attosecond sub-optical cycle duration open up novel opportunities for space-time-resolved imaging of ultrafast chemical and physical processes, coherent photon generation, free electron quantum optics, electron–atom scattering with shaped wave packets and laser-driven particle acceleration.

Graphical Abstract
Impact of Transcript (p16/p14ARF) Alteration on Cancer Risk in CDKN2A Germline Pathogenic Variant Carriers
Authors: Sargen Michael R , Helgadottir Hildur , Yang Xiaohong R , Harland Mark , Hatton Jessica N , Jones Kristine , Hicks Belynda D , Hutchinson Amy , Curry Michael , Tucker Margaret A , Goldstein Alisa M , Pfeiffer Ruth M
Published: October 2022

Background

Few studies have evaluated the relationship between CDKN2A germline pathogenic variants (GPV), transcript (p16/p14ARF) alteration, and cancer risk.

Methods

Standardized incidence ratios (SIRs) comparing cancer risk with the general population were calculated for 385 CDKN2A GPV carriers from 2 large cohorts (259 United States and 126 Swedish individuals) using Poisson regression; statistical significance was defined as P less than .002 (Bonferroni correction). Cumulative incidence is reported for melanoma and nonmelanoma cancer.

Results

Incidence was increased for melanoma (SIR = 159.8, 95% confidence interval [CI] = 132.1 to 193.2), pancreatic cancer (SIR = 24.1, 95% CI = 14.7 to 39.4), head and neck squamous cell carcinoma (SIR = 16.2, 95% CI = 9.5 to 27.6), and lung cancer (SIR = 5.6, 95% CI = 3.4 to 9.1) in GPV carriers. Similar associations were observed with p16 alteration. Combined p16 and p14ARF alteration was associated with increased incidence of esophageal cancer (SIR = 16.7, 95% CI = 5.7 to 48.9) and malignant peripheral nerve sheath tumor (SIR = 113.0, 95% CI = 16.4 to 780.9), although cancer events were limited (n < 5 for each malignancy). Cumulative incidence at age 70 years for melanoma and nonmelanoma cancer was 68.3% (95% CI = 68.0% to 68.6%) and 35.2% (95% CI = 34.9% to 35.6%), respectively. A total 89% of smoking-related cancers (lung, head and neck squamous cell carcinoma, pancreatic, esophageal) occurred in ever smokers.

Conclusion

These findings highlight the impact of p16 and p14ARF alteration on cancer risk. Smoking was an important risk factor for smoking-related cancers in our study.
Divergent leaf nutrient-use strategies of coexistent evergreen and deciduous trees in a subtropical forest
Authors: Chen Xiaoping , Le Xingui , Niklas Karl J , Hu Dandan , Zhong Quanlin , Cheng Dongliang
Published: October 2022

Evergreen and deciduous species coexist in the subtropical forests in southeastern China. It has been suggested that phosphorus (P) is the main limiting nutrient in subtropical forests, and that evergreen and deciduous species adopt different carbon capture strategies to deal with this limitation. However, these hypotheses have not been examined empirically to a sufficient degree. In order to fill this knowledge gap, we measured leaf photosynthetic and respiration rates, and nutrient traits related to P-, nitrogen (N)- and carbon (C)-use efficiencies and resorption using 75 woody species (44 evergreen and 31 deciduous species) sampled in a subtropical forest. The photosynthetic N-use efficiency (PNUE), respiration rate per unit N and P (Rd,N and Rd,P, respectively) of the deciduous species were all significantly higher than those of evergreen species, but not in the case of photosynthetic P-use efficiency. These results indicate that, for any given leaf P, evergreen species manifest higher carbon-use efficiency (CUE) than deciduous species, a speculation that is empirically confirmed. In addition, no significant differences were observed between deciduous and evergreen species for nitrogen resorption efficiency, phosphorus resorption efficiency or N:P ratios. These results indicate that evergreen species coexist with deciduous species and maintain dominance in P-limited subtropical forests by maintaining CUE. Our results also indicate that it is important to compare the PNUE of deciduous species with evergreen species in other biomes. These observations provide insights into modeling community dynamics in subtropical forests, particularly in light of future climate change.
Opportunities and Obstacles for Achieving Language Equity among Adolescents Resettled from the Middle East and North Africa
Authors: Gillespie Alli , Brumbaum Hannah , Salama Mariam , Bennouna Cyril , Allaf Carine , Hassan Wafa , Aldrich Jeremy , Meyer Sarah R , Stark Lindsay
Published: October 2022

Adolescents resettled to the US from conflict-affected countries in the Middle East and North Africa region face a range of acculturative challenges, including language barriers, that may affect their wellbeing. This qualitative study aims to understand the variety of approaches US schools use to support the education of Arabic-speaking students. Utilizing Ruíz’s influential typology of language orientations, our analysis reveals a range of school approaches aligning most closely with the ‘language-as-problem’ and ‘language-as-resource’ orientations. Participants identified several perceived effects of these orientations on academic achievement and acculturation, and providers highlighted promising directions and potential barriers for bolstered language supports. Findings indicate that Arabic-speaking newcomer students experience persistent language inequity but also locate promising pathways towards reducing these inequities. We discuss structural shifts schools can implement to bolster language as a resource and move towards larger systems change in which heritage language is a right.
Delayed axial flaps for coverage of a fourth degree scalp burn
Authors: Moltaji S , El Khatib A , Rogers A D
Published: October 2022

Although free tissue transfers may be required to cover wounds of the head and neck with bone involvement and exposure, options lower on the reconstructive ladder should still be considered during the planning process. We present a case of an elderly gentleman with a history of cardiovascular comorbidity and neck radiotherapy, who sustained a deep flame burn injury to his scalp. Two delayed axial flaps, based on the superficial temporal and supraorbital arteries respectively, were used to obtain durable coverage of this complex wound.
Unifying Epistemic and Practical Rationality
Authors: Skipper Mattias
Published: October 2022

Many theories of rational action are predicated on the idea that what it is rational to do in a given situation depends, in part, on what it is rational to believe in that situation. In short: they treat epistemic rationality as explanatorily prior to practical rationality. If they are right in doing so, it follows, on pain of explanatory circularity, that epistemic rationality cannot itself be a form of practical rationality. Yet, many epistemologists have defended just such a view of epistemic rationality. According to them, there is no such thing as a distinctively epistemic form of rationality which could be explanatorily prior to practical rationality. Rather, they maintain, there is just one form of rationality—practical rationality—of which epistemic rationality is a species. What to make of this conflict? The aim of this paper is to motivate a view about the relationship between epistemic and practical rationality which resolves the conflict in a way that should be attractive to both sides. The central idea is to ground both epistemic and practical rationality in an independently motivated notion of evidential probability which is itself to be understood in non-normative terms. Doing so, I argue, allows us to unify epistemic and practical rationality in a way that does justice to the idea that what it is rational to do depends, in part, on what it is rational to believe; and to do so in a way that avoids explanatory circularity.