bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural and dynamic assessment of a friction buffer stop
Authors: Megna G , Bracciali A
Published: May 2024

Under peculiar conditions railway braking system ca fail giving insufficient braking force during train ride or while standstill and buffer stops are used to avoid derailments at the end of railway tracks (dead tracks). Fixed stops are suitable only for quasi-static movements, while absorbing energy stops using hydraulic cylinders, friction shoes clamped on the rail head or a combination of both methods, are installed if crashes at higher speeds (about 25 km/h) are forecasted. Impact forces generated due to the interaction between train and buffer stops require a suitable design of the steel structure which is subjected to stress values depending on the braking performances of the buffer stop itself and a combined structural and dynamic analysis must be carried out to perform a proper design. Due to unavailability of detailed models and the uncertainties of the actual braking performances, the structure of currently available friction buffer stops is heavy and bulky, made of several steel profiles welded or bolted to each other. The paper describes an innovative and optimized design for friction buffer stops focusing on the dynamic analysis performed by Finite Element Method to assess the braking performances and structural strength of the buffer stop.
Stress mitigation of a thermal engine head block using the bioinspired BGM-FEM method
Authors: Groth C , Marra M , Porziani S , Schubert M , Biancolini M E
Published: May 2024

Structural optimization plays a pivotal role in the design and development of engine heads, as it directly affects the performance, efficiency, and durability of internal combustion engines. In this paper, we propose a novel approach for the thermo-structural optimization of the internal surfaces of the engine heads, using the Biological Growth Method (BGM). The BGM is a bio-inspired technique that mimics the growth patterns observed in some biological organisms, able to achieve superior structural efficiency thus generating optimal designs. The effectiveness of the BGM methodology, coupled with mesh morphing techniques based on Radial Basis Functions (RBF), is in this work demonstrated for several districts, effectively reducing material usage and enhancing structural performance.
Parametric Analysis on the Static and Modal Response of Folded Metamaterials
Authors: Santucci P.M. , Baldi A.
Published: May 2024

Metamaterials have been studied and analyzed in the past three decades because of their outstanding properties. Generally speaking, a metamaterial is a material that exhibits a mechanical behavior that does not depend only on the bulk material but also on the geometrical configuration in which it lies. This aspect leads to the possibility of tuning and engineering the structural response. One of the most interesting properties is the auxetic behavior of metamaterial. An auxetic material shows a global negative Poisson’s ratio. Shock absorption, acoustic dissipation, and shape morphing are some of the most popular employment for auxetic materials. In this article, we focus on the response of folded material under static and dynamic load conditions. Folded materials consist of folding a sheet under specific geometrical constraints. One of the most famous is the Miura-ori pattern, which comes from the origami-folding technique. The geometrical parameters, such as folding angles and edge lengths, play a fundamental role in achieving the desired auxetic behavior. These geometrical parameters define a unit cell that can be stacked into a periodic structure. This article proposes an experimental parametric study of the thickness impact on the auxetic behavior while edge dimensions and folding angles are fixed. The geometrical complexity of the pattern forced us to use additive manufacturing for the specimen fabrication. In particular, we choose Fused Filament Fabrication (FFF) using polymers like ABS and PLA. Digital Image Correlation (DIC) is used for monitoring the displacement and strain fields onto the Miura-ori surface under tensile load. Finally, Time Averaged Speckle Interferometry is employed for evaluating the modal response by using a quasi-full out-of-plane sensitivity setup.
Homogenized Stiffness Matrix of Two-Node Elements through Experimental Flexibility tests
Authors: Iandiorio C , Cafolla F , Marotta E , Salvini P
Published: May 2024

Homogenization is a numerical technique to obtain the equivalent mediated response of a complex material. However, there are some scenarios in which the complexity of the physical phenomena present in the real structure makes it difficult to generate a faithful Representative Volume Element (RVE). In these cases, it may turn easier and more reliable to perform a homogenization directly by experimental test results. For this reason, we present a procedure to build-up the whole stiffness matrix starting from experiments. This approach is here discussed to get a homogenised two-node beam element. The procedure requires some flexibility measurements, thus allowing fewer measurements if compared to stiffness-based approach. The method is verified with some experiments carried on a frame structure. The comparisons with a Finite Element model build up with stiffness matrix assembly demonstrates the validity and robustness of the proposed procedure.
Photoexcited charge carrier dynamics and electronic properties of two-dimensional MXene, Nb2CT
x
Authors: Fitzgerald Andrew M , Sutherland Emily , El-Melegy Tarek Ali , Hassig Mary Qin , Martin Julia L , Colin-Ulloa Erika , Ngo Ken , Grimm Ronald L , Uzarski Joshua R , Barsoum Michel W , Deskins N Aaron , Titova Lyubov V , Friedman Kateryna Kushnir
Published: May 2024

Two-dimensional, 2D, niobium carbide MXene, Nb2CT
x
, has attracted attention due to its extraordinarily high photothermal conversion efficiency that has applications ranging from medicine, for tumor ablation, to solar energy conversion. Here, we characterize its electronic properties and investigate the ultrafast dynamics of its photoexcitations with a goal of shedding light onto the origins of its unique properties. Through density functional theory, DFT, calculations, we find that Nb2CT
x
is metallic, with a small but finite DOS at the Fermi level for all experimentally relevant terminations that can be achieved using HF or molten salt etching of the parent MAX phase, including –OH, –O, –F, –Cl, –Br, –I. In agreement with this prediction, THz spectroscopy reveals an intrinsic long-range conductivity of ∼60 Ω−1 cm−1, with significant charge carrier localization and a charge carrier density (∼1020 cm−3) comparable to Mo-based MXenes. Excitation with 800 nm pulses results in a rapid enhancement in photoconductivity, which decays to less than 25% of its peak value within several picoseconds, underlying efficient photothermal conversion. At the same time, a small fraction of photoinjected excess carriers persists for hundreds of picoseconds, and can potentially be utilized in photocatalysis or other energy conversion applications.
Effect of adsorption interactions of Arabic gum with cement
Authors: B Sugumaran , Neme Ibsa
Published: May 2024

This study seeks to investigate the influence of cement and Arabic gum on the physico-mechanical and microstructural properties of cementitious composites. The influence of varying quantities of Arabic gum on the hydration, fluidity, mechanical performance and microstructure of cement paste was investigated. The influence of Arabic gum on slant shear performance and capillary water absorption was also investigated. The results indicate that the workability of cement was diminished as a result of the ability of Arabic gum to make the cement paste cohesive. It is evident that when the gum Arabic concentration increases from 147 to 174 mm, the resultant slump value for various w/b ratios drops. The adsorption characteristics showed that for a 15 mg g−1 dosage at 60, 45, 30, and 15 min, respectively, 1.43, 1.32, 1.25, and 1.03 mg g−1 are achieved. For 1% gum Arabic substitution, the highest flexural strength percentage growth is achieved at 38.46%, 23.74%, and 17.29% at 7, 14, and 28 days, respectively. In addition, the inclusion of Arabic gum improved the slant shear strength of cement composite, making it ideal for use as a building repair material with significant application potential. Experiments on the bonding behavior of the produced cementitious composite with the old mortar reveal that the shear bond strength was greatly increased, demonstrating the compatibility between the old and new cement composites. The microstructure and the porosity of the cement matrix also showed denser and compact matrix making them durable to attain better service life.
Additively manufactured microstrip patch antennas in flat, curved, and embedded configurations
Authors: Gurusekaran Arvind , Ahmad Mukhtar , Ciocca Manuela , Pompilio Michele , Nijkoops Annelot , Carrasco Pena Alejandro , Lugli Paolo , Petti Luisa
Published: May 2024

Microstrip patch antennas (MPAs) are compact and easy-to-fabricate antennas, widely used in long-distance communications. MPAs are commonly fabricated using subtractive methods such as photolithographic etching of metals previously deposited using sputtering or evaporation. Despite being an established technique, subtractive manufacturing requires various process steps and generates material waste. Additive manufacturing (AM) techniques instead allow optimal use of material, besides enabling rapid prototyping. AM methods are thus especially interesting for the fabrication of electronic components such as MPAs. AM methods include both 2D and 3D techniques, which can also be combined to embed components within 3D-printed enclosures, protecting them from hazards and/or developing haptic interfaces. In this work, we exploit the combination of 2D and 3D printing AM techniques to realize three MPA configurations: flat, curved (at 45∘), and embedded. First, the MPAs were designed and simulated at 2.3 GHz with a −16.25 dB S
11 value. Then, the MPA dielectric substrate was 3D-printed using polylactic acid via fused deposition modeling, while the antenna material (conductive silver ink) was deposited using three different AM methods: screen printing, water transfer, and syringe-based injection. The fabricated MPAs were fully operational between 2.2–2.4 GHz, with the flat MPA having a higher S
11 peak value compared to the curved and embedded MPAs. Development of such AM MPAs in various configurations demonstrated in this work can enable rapid development of long-range antennas for novel applications in e.g. aerospace and Internet of Things sectors.
Rationality of twist representation zeta functions of compact 𝑝-adic analytic groups
Authors: Stasinski Alexander , Zordan Michele
Published: May 2024

We prove that for any twist rigid compact

p
p

-adic analytic group

G
G

, its twist representation zeta function is a finite sum of terms

n

i

−
s

f

i

(

p

−
s

)

n_{i}^{-s}f_{i}(p^{-s})

, where

n

i

n_{i}

are natural numbers and

f

i

(
t
)
∈

Q

(
t
)

f_{i}(t)\in \mathbb {Q}(t)

are rational functions. Meromorphic continuation and rationality of the abscissa of the zeta function follow as corollaries. If

G
G

is moreover a pro-

p
p

group, we prove that its twist representation zeta function is rational in

p

−
s

p^{-s}

. To establish these results we develop a Clifford theory for twist isoclasses of representations, including a new cohomological invariant of a twist isoclass.
Fluorescent protein tags affect the condensation properties of a phase-separating viral protein
Authors: Barkley Russell J. R. , Crowley Jack C. , Brodrick Andrew J. , Zipfel Warren R. , Parker John S. L.
Published: May 2024

Fluorescent protein (FP) tags are extensively used to visualize and characterize the properties of biomolecular condensates despite a lack of investigation into the effects of these tags on phase separation. Here, we characterized the dynamic properties of µNS, a viral protein hypothesized to undergo phase separation and the main component of mammalian orthoreovirus viral factories. Our interest in the sequence determinants and nucleation process of µNS phase separation led us to compare the size and density of condensates formed by FP::µNS to the untagged protein. We found an FP-dependent increase in droplet size and density, which suggests that FP tags can promote µNS condensation. To further assess the effect of FP tags on µNS droplet formation, we fused FP tags to µNS mutants to show that the tags could variably induce phase separation of otherwise noncondensing proteins. By comparing fluorescent constructs with untagged µNS, we identified mNeonGreen as the least artifactual FP tag that minimally perturbed µNS condensation. These results show that FP tags can promote phase separation and that some tags are more suitable for visualizing and characterizing biomolecular condensates with minimal experimental artifacts.
Optimization of the fluorogen-activating protein tag for quantitative protein trafficking and colocalization studies in S. cerevisiae
Authors: Oppenheimer Katherine G. , Hager Natalie A. , McAtee Ceara K. , Filiztekin Elif , Shang Chaowei , Warnick Justina A. , Bruchez Marcel P. , Brodsky Jeffrey L. , Prosser Derek C. , Kwiatkowski Adam V. , O’Donnell Allyson F.
Published: May 2024

Spatial and temporal tracking of fluorescent proteins (FPs) in live cells permits visualization of proteome remodeling in response to extracellular cues. Historically, protein dynamics during trafficking have been visualized using constitutively active FPs fused to proteins of interest. While powerful, such FPs label all cellular pools of a protein, potentially masking the dynamics of select subpopulations. To help study protein subpopulations, bioconjugate tags, including the fluorogen activation proteins (FAPs), were developed. FAPs are comprised of two components: a single-chain antibody (SCA) fused to the protein of interest and a malachite-green (MG) derivative, which fluoresces only when bound to the SCA. Importantly, the MG derivatives can be either cell-permeant or -impermeant, thus permitting isolated detection of SCA-tagged proteins at the cell surface and facilitating quantitative endocytic measures. To expand FAP use in yeast, we optimized the SCA for yeast expression, created FAP-tagging plasmids, and generated FAP-tagged organelle markers. To demonstrate FAP efficacy, we coupled the SCA to the yeast G-protein coupled receptor Ste3. We measured Ste3 endocytic dynamics in response to pheromone and characterized cis- and trans-acting regulators of Ste3. Our work significantly expands FAP technology for varied applications in S. cerevisiae.
Male Occupations and Career Mobility
Authors: Brockliss Laurence , Smith Harry
Published: May 2024

Chapter 2 principally explores the extent to which sons entered the same careers as their fathers. Perhaps half the cohort did not come from a professional family but were the sons of merchants, tradesmen, and artisans. Whatever their background or wealth, there is little sign that the cohort viewed non-professional careers with disdain. Only a small minority of the cohort’s sons entered exactly the same profession as their fathers and many moved into business and trade. Some members of the cohort, moreover, lacked the means to put their sons in a profession even if they had wanted to: a handful of their sons ended up as factory workers and miners. There was the same limited evidence of occupational continuity in the case of the grandsons. What is particularly striking is that if a cohort son made a career outside the professions, there was virtually no chance that one of his sons would become a professional.
Male Family Members and Intergenerational Wealth
Authors: Brockliss Laurence , Smith Harry
Published: May 2024

Chapter 3 is a study of the intergenerational wealth of the male members of the families under review. It maps the spectrum of wealth left by members of the first generation, then compares and contrasts this with the wealth of their fathers and male descendants. It sets out to establish how far the professions were a passport to family fame and fortune and the factors affecting long-term success or failure. The chapter reveals that there was a huge disparity in wealth between the richest and poorest males in each generation and that a considerable percentage, not just those who ended up as artisans or labourers, had fallen out of respectable society. At the same time, the chapter shows that the large majority of sons and especially grandsons were much poorer than members of the cohort from whom they were descended. This was true even of the descendants of the richest cohort members.
Moving About
Authors: Brockliss Laurence , Smith Harry
Published: May 2024

Chapter 4 focuses on the geographical mobility of the 750 families. It considers how far cohort members and their male and female descendants moved around in the course of their lives locally, nationally, and internationally. Its aim is to establish to what extent the set of families surveyed in this study remained based in the same area in which they were located in 1851. The chapter explores in particular the extent to which families or branches of families were either lured to London or left Britain to build a new life in the United States or the Empire. The families dispersed slowly across time, especially those that in 1851 had already been resident in the cohort town or its surrounding county for a generation or more. Although there were differences between the town cohorts, emigration to the United States and the Empire was limited, and London had little appeal. Less than 10% of grandchildren died in the metropolis.
Male Leisure
Authors: Brockliss Laurence , Smith Harry
Published: May 2024

Chapter 5 is devoted to examining the wider social groups to which the cohort and their male descendants belonged and explores the associational life they cultivated in their leisure hours. Initial attention is paid to church membership. Membership of the Church of England is shown to be high, confessionally-mixed marriages common, and inter-confessional hostility rare. The rest of the chapter uncovers the degree of male involvement in local political, cultural, and recreational societies, and whether the level and direction of interest changed from one generation to the next. It demonstrates that among the better-off members of the cohort, there was widespread interest in local history and the local flora and fauna, and several undertook serious research. Other members threw themselves into local politics and served on improvement commissions. However, this enthusiasm for an active life outside home and work waned dramatically among their sons and was virtually non-existent among their grandsons, who showed some interest in sport but little else.
Nigerian Youth Engagement in Violent Electoral Environments: Political Apathy or ‘Constrained Optimism’?
Authors: Davis Justine , Turnbull Megan
Published: May 2024

How do young citizens engage with politicians and their political environment in contexts where elections are frequently affected by violence? We explore this question through focus group discussions (FGDs) in Nigeria, a country with high rates of election violence. We argue that young voters in violent electoral environments operate with ‘constrained optimism’, where they perceive low government responsiveness but possess high levels of self-efficacy. Participants condemned violence and expressed little faith in political institutions and leaders to curtail violence, but they also felt a determination to elect a better government and a strong sense of a civic duty to vote, participate in politics, and encourage others to do so as well. Many participants also shared that they would continue to support their preferred candidate if they were accused of violence. Some participants raised concerns about the veracity of such allegations while others explained that politicians sometimes use violence for defensive purposes. Still others stated that they would continue to support candidates who expressed remorse for engaging in violence and committed to peaceful campaigning in the future. Taken together, we argue that young voters in violent contexts operate with ‘constrained optimism’ where they remain committed to democracy, but face constraints on who they support and how they participate. Our findings nuance expectations of the effects of electoral violence on political participation and better help us understand the challenges facing voters in contexts where violence is rife.
Structural insights into starch-metabolizing enzymes and their applications
Authors: Tagami Takayoshi
Published: May 2024

Starch is a polysaccharide produced exclusively through photosynthesis in plants and algae; however, is utilized as an energy source by most organisms, from microorganisms to higher organisms. In mammals and the germinating seeds of plants, starch is metabolized by simple hydrolysis pathways. Moreover, starch metabolic pathways via unique oligosaccharides have been discovered in some bacteria. Each organism has evolved enzymes responsible for starch metabolism that are diverse in their enzymatic properties. This review, focusing on eukaryotic α-glucosidases and bacterial α-glucoside-hydrolyzing enzymes, summarizes the structural aspects of starch-metabolizing enzymes belonging to glycoside hydrolase families 15, 31, and 77 and their application for oligosaccharide production.
Exploring the impact of N4-acetylcytidine modification in RNA on non-neoplastic disease: unveiling its role in pathogenesis and therapeutic opportunities
Authors: Wan Keyu , Nie Tiantian , Ouyang Wenhao , Xiong Yunjing , Bian Jing , Huang Ying , Ling Li , Huang Zhenjun , Zhu Xianhua
Published: May 2024

RNA modifications include not only methylation modifications, such as m6A, but also acetylation modifications, which constitute a complex interaction involving “writers,” “readers,” and “erasers” that play crucial roles in growth, genetics, and disease. N4-acetylcytidine (ac4C) is an ancient and highly conserved RNA modification that plays a profound role in the pathogenesis of a wide range of diseases. This review provides insights into the functional impact of ac4C modifications in disease and introduces new perspectives for disease treatment. These studies provide important insights into the biological functions of post-transcriptional RNA modifications and their potential roles in disease mechanisms, offering new perspectives and strategies for disease treatment.
SPIN: sex-specific and pathway-based interpretable neural network for sexual dimorphism analysis
Authors: Ko Euiseong , Kim Youngsoon , Shokoohi Farhad , Mersha Tesfaye B , Kang Mingon
Published: May 2024

Sexual dimorphism in prevalence, severity and genetic susceptibility exists for most common diseases. However, most genetic and clinical outcome studies are designed in sex-combined framework considering sex as a covariate. Few sex-specific studies have analyzed males and females separately, which failed to identify gene-by-sex interaction. Here, we propose a novel unified biologically interpretable deep learning-based framework (named SPIN) for sexual dimorphism analysis. We demonstrate that SPIN significantly improved the C-index up to 23.6% in TCGA cancer datasets, and it was further validated using asthma datasets. In addition, SPIN identifies sex-specific and -shared risk loci that are often missed in previous sex-combined/-separate analysis. We also show that SPIN is interpretable for explaining how biological pathways contribute to sexual dimorphism and improve risk prediction in an individual level, which can result in the development of precision medicine tailored to a specific individual’s characteristics.
Chronic Q fever infective endocarditis: a case report
Authors: Al Suqri Badriya , Al Brashdi Azza
Published: May 2024

Q fever is an epidemic disease caused by the Coxiella burnetii infection. It can manifest clinically as an acute or chronic disease, with chronic infections being more common. Q fever endocarditis is the most common manifestation of chronic infection and usually occurs in patients with previous valvular heart disease like in our present study, a case of Q fever endocarditis that occurred in background of tetralogy of Fallot surgical repair. However, Q fever endocarditis is difficult to diagnose clinically and may lead to very serious or even life-threatening outcomes if not diagnosed promptly. In the present study, accurate diagnosis and treatment were achieved by 18F-FDG PET/CT combined with detection of the Q fever serological antibodies.
Moral Distress in Social Work: A Systematic Literature Review
Authors: Palma Contreras Andrea María , Pardo Adriasola María Angélica
Published: May 2024

The aim of this article is to present empirical evidence on the factors that facilitate the emergence of moral suffering and the consequences of the phenomenon in social workers published between 2018 and 2022. A systematic literature review was conducted in Scielo, Scopus and Web of Science, and eighteen articles were selected for analysis. Most of the articles are qualitative research reports and use interviews as data collection instruments. The studies primarily involve social workers working in the fields of healthcare and childhood, aiming to understand the factors influencing moral distress. Moral distress is conceptualised as arising from working conditions and organisational factors. The main consequences of the phenomenon are in the mental health of professionals and at the organisational level. Mental health issues such as depression, anxiety and burnout are reported, as well as organisational difficulties such as high turnover and the intention to quit the job. Despite the serious consequences of the phenomenon, evidence on this topic is scarce, particularly in Latin America, where no studies on the subject have been found. The precarious working conditions that social workers face in this geographical area show the need for further research.
Bloomington and Cambridge compared: varieties of ontological thinking, social positioning, and the self-governance of common-pool resources
Authors: Lewis Paul , Runde Jochen
Published: May 2024

This paper contributes to the literature on ontology and the history of economic thought by examining the ontological commitments of Nobel Laureate Elinor Ostrom from the vantage point of recent work on social positioning theory (SPT). The comparison highlights important features of Ostrom’s thought on common-pool resources (CPRs), most notably her emphasis on social positions and the correlative nature of the rights and duties and the role of power and authority associated with them. In addition to highlighting similarities between Ostrom and SPT, the paper also identifies differences and possible gains from trade. It is argued that Ostrom’s approach could potentially be enhanced by following SPT in allowing for the social positioning of objects as well as people and that SPT might benefit from Ostrom’s ideas about the epistemic challenges involved in deliberate attempts at social positioning and the possibility of failures in social positioning such challenges might entail.
Whole-blood transcriptome unveils altered immune response in acute myocardial infarction patients with aortic valve sclerosis
Authors: Poggio P , Piacentini L , Myasoedova V A , Chiesa M , Vavassori C , Moschetta D , Valerio V , Giovanetti G , Massaiu I , Cosentino N , Marenzi G , Colombo G I
Published: May 2024

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): Fondazione Umberto Veronesi (Research Grant 2011-12 to GIC)

Fondazione Gigi e Pupa Ferrari ONLUS (FPF-14 to PP)

Background

Aortic valve sclerosis (AVSc) presents similar pathogenetic mechanisms to coronary artery disease (CAD) and is associated with short- and long-term mortality in CAD patients. Evidence of AVSc-specific pathophysiological traits in acute myocardial infarction (AMI) is currently lacking.

Purpose

We aimed to identify a blood-based transcriptional signature that could differentiate AVSc from non-AVSc patients during AMI.

Methods

Whole-blood transcriptome of AVSc (n = 44) and no-AVSc (n = 66) patients with AMI was assessed by RNA-sequencing on hospital admission. Feature selection, differential expression, and enrichment analyses were performed to identify gene expression patterns discriminating AVSc from no-AVSc and infer functional associations. Multivariable Cox regression analysis was used to estimate the hazard ratios of cardiovascular events in AVSc versus no-AVSc patients.

Results

This cross-sectional study identified a panel of 100 informative genes capable of distinguishing

AVSc from no-AVSc patients with 94% accuracy. Further analysis revealed significant mean differences in 143 genes, of which 30 genes withstood correction for age and previous AMI or coronary interventions. Functional inference unveiled a significant association between AVSc and key biological processes, including acute inflammatory responses, type I interferons (IFN) response, platelet activation, and hemostasis. Notably, AMI patients with AVSc exhibited a significantly higher incidence of adverse cardiovascular events during a 10-year follow-up period, with a full adjusted hazard ratio of 2.4 (95% CI: 1.3–4.5).

Conclusions

Our findings shed light on the molecular mechanisms underlying AVSc and provide potential prognostic insights for AMI patients with AVSc. During AMI, AVSc patients showed increased type I IFN response and earlier adverse cardiovascular outcomes. Novel pharmacological therapies aiming at limiting type I IFN response during or immediately after AMI might improve poor cardiovascular outcomes of AMI patients with AVSc.
Bradycardia in a long QT type 2 family: coinciding KCNH2 and HCN4 variants
Authors: Copier J S , Andrzejczyk K , Amin A S , Van Der Crabben S N , Beekman L , Bezzina C R , Verkerk A O , Lodder E M
Published: May 2024

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): the Dutch Research Council: NWO Talent Scheme

Background

A large multigenerational family harboring a pathogenic KCNH2 variant (L69P) was identified. This gene encodes the hERG channel, responsible for the cardiac rapid delayed rectifier K+ current (IKr). Pathogenic variants in KCNH2 can cause Long QT syndrome type 2 (LQTS2). Interestingly, in addition to LQTS2 we observed a high incidence of bradycardia in this family. Bradycardia is a known feature of some types of LQTS. However, evidence of bradycardia in LQTS2 is limited to a few sporadic cases.

Purpose

This study aims to identify the genetic variants and biophysiological changes in ion channel function, explanatory of the phenotypes LQTS2 and bradycardia.

Methods

An overview of the phenotype and genetic information of the index and family members was generated , including symptoms and electrocardiogram (ECG) parameters. QTc was calculated using Bazetts’ correction. Segregation of the identified genetic variants with LQTS and bradycardia were determined by LOD score. Biophysiological properties of the encoded ion channels was measured by manual whole-cell patch-clamp experiments.

Results

On the basis of linkage analysis, the pathogenic variant KCNH2-p.L69P was found to be unrelated to the bradycardia. Therefore, Sanger sequencing of HCN4, encoding the channel responsible for the hyperpolarization-activated current (If), an important current for sinoatrial node automaticity, was performed. We identified the HCN4-p.R666W variant in multiple family members, which co-segregated with bradycardia (LOD-score 3.2). Patients carrying both variants had more severe phenotypes than carriers of a single variant. Patch-clamp experiments in HEK293A-cells expressing wild type, or KCNH2-p.L69P show a reduced current density, and an altered time component of the fast deactivation, explaining the observed LQTS2. Functional assays of HCN4-p.R666W will elucidate the biophysiological changes possibly underlying the bradycardia.

Conclusion

we present a large multigenerational family that harbors a likely pathogenic variant in HCN4 in conjunction with a pathogenic variant of KCNH2. Double carriers were more affected than single carriers, arguing for continued alertness and deep phenotyping even in families with known pathogenic variants. Furthermore, we identified functional changes in the kinetics of the hERG channel encoded by KCNH2-p.L69P, elucidating the molecular mechanism underlying LQTS2 in this family.
The impact of SLCO1B1 single nucleotide polymorphism and non-genetic factors on statin-induced myopathy
Authors: Alaryan T H , Youssef L
Published: May 2024

Funding Acknowledgements

None.

Background

Statins, also known as HMG CoA Reductase Inhibitors, are a class of drugs considered the drug of choice for treating hypercholesterolemia. Statins are well tolerated; however, they may cause severe myopathy in 20% to 30% of patients, due to the individual variation regarding its efficacy and related adverse effects. Of these, comes the Single Nucleotide Polymorphism (SNP) T521C of the SLCO1B1 gene that encodes the protein involved in the trafficking of statins from the blood to hepatocytes which is called Organic Anion Transport Protein 1B1 (OATP1B1). The T521C single nucleotide polymorphism (SNP) results in a substitute of valine with alanine resulting in a decreased or lack of functional protein.

Purpose

The aim is to determine the frequency of the high-risk C allele and to define its impact on statin-induced myopathy in Syrian patients on statins. In addition to the non-genetic factors that may affect the ability to develop statin-induced myopathy.

Methods

This was an observational case-control study that had ethical approval from Damascus University (No.433/ 2020). The case group included 44 patients on statins who experienced myopathy, 18 patients who had increased creatinine kinase levels (CK), and 26 patients with normal CK levels, while the control group encompassed 56 patients who were taking statins and had no muscular adverse events. The DNA was extracted from each sample and then genotyped using standard sequencing of specific PCR products using a specific pair of primers.

Results

The age of patients in the case arm ranged between 27 and 84 years with an average ± SD of (58.2 ± 12.7 years), 70% of them were males. In comparison with (53.34 ± 12.4 years) in the control arm, 66% of them were males without a statistically significant differences (p=0.672, 0.057) respectively. The statin type and dose have a statistically non-significant effect, the average statin dose in the case arm and the control arm was 26.02 mg and 31.27 mg respectively (p=0.072). While the statin type treatment varied as 59% used atorvastatin and 39% used rosuvastatin in the case group compared with 71% used atorvastatin and 27% used rosuvastatin in the control group, without a statistically significant difference (p=0.252). The frequency of the C allele reaches 19.3% and is distributed in three genotypes: wild-type TT (68%), heterozygote TC (25%), and homozygote CC (7%) in the case arm, while it does not exceed 8% in the control arm with the absence of the CC genotype. Only a statistically significant difference was found in the frequency of the CC genotype between these two groups (p=0.047).

Conclusion

Our study is the first to identify the frequency of the 521T>C SNP of the SLCO1B1 gene in Syrian patients taking statins. Our data reveals a high prevalence of risk allele C in the patients who suffer from statin-induced myopathy with a statically significant difference from the control arm (p=0.026).
The influence of different cheek and lip retractors and emissivity on intraoral infrared thermography
Authors: Moura Oliveira Lopes Layrlla Kateriny , Ramos Castelo Branco Rodolfo , Pequeno Reis Sousa Rafaela , Diniz de Lima Elisa , Bezerra Silva Diego Filipe , Pita de Melo Daniela
Published: May 2024

Objectives

To assess the influence of two conventional and one adapted cheek and lip retractors and three emissivity setting values on intraoral infrared thermography (IT) temperature values.

Methods

The sample was composed by 50 volunteers. Three cheek and lip retractors were tested: Group 1—flex retractor (FR); Group 2—FR adapted with Styrofoam; Group 3—U-type retractor (UR) for cheek and lip. All thermograms were acquired using FLIR T650 infrared camera. A set of three thermograms in frontal norm were acquired for each lip and cheek retractor at 0.91, 0.96, and 0.98ε, with an interval of 15 min between each set of images to avoid thermal interference. All images were assessed by two observers. The ROIs’ mean temperature of the four upper incisors was recorded. Two-way ANOVA and Sidak post-test were used for data assessment with a significance level of 5%.

Results

Group 3 showed higher mean temperature than Groups 1 and 2 at all emissivity settings for all assessed teeth (P < .05). 0.91ε showed higher temperature than 0.96ε and 0.98ε for all assessed variables (P < .01). Contralateral teeth assessed using Group 3 at 0.91ε showed statistical differences between each other (P < .05). No statistical difference was observed between contralateral teeth assessed using Groups 1 and 2 at 0.96ε and 0.98ε (P > .05).

Conclusions

The choice of cheek and lip retractor and emissivity setting can interfere on intraoral IT temperature values. U-type cheek and lip retractor and 0.91ε setting should not be used for IT image acquisition when assessing dental tissues.
Vertical and temporal flight patterns of coffee berry borer (Coleoptera: Curculionidae) in Hawaii
Authors: Johnson Melissa A , Maeda Colby T , Pulakkatu-Thodi Ishakh
Published: May 2024

Coffee berry borer (Hypothenemus hampei Ferrari) (Coleoptera: Curculionidae) is the most damaging insect pest of coffee worldwide, causing significant losses in coffee yields and quality. Knowledge of vertical and temporal flight patterns in coffee berry borer could be used to optimize spray timing and precision targeting of areas within the coffee tree, which may be more susceptible. In the present study, we estimated the vertical distribution of coffee berry borer females using traps set at 1-m intervals up to 5 m in height. We also quantified coffee berry borer infestation in the low, mid, and high canopy and documented fruit availability. Temporal flight patterns were estimated using timer traps, and correlation analyses were conducted to determine the relationship between the timing of daily flight and weather variables. Across the 4 study sites, we observed that 77%–84% of the trap catch was at 1 m, 11%–20% was at 2 m, and 1%–4% was at 3–5 m in height. Fruit infestation was significantly higher in the low branches (35%) relative to the high branches (17%). Flight height remained the same year-round, regardless of fruit availability. Coffee berry borer flew in low numbers during the day and night but peaked from 12 to 4 PM. Daily flight was positively correlated with an increase in air temperature and wind speed and negatively correlated with relative humidity. Findings from this study suggest that pesticide sprays should target low- to mid-level branches at 1–2 m in height and aim to be conducted in the early afternoon when coffee berry borer are actively flying and most vulnerable to chemical controls.
Does LDL-C determination method affect statin prescribing for primary prevention? A register-based study in Southern Denmark
Authors: Pottegård Anton , Gerdes Lars Ulrik , Wetche Jakob Langballe , Thompson Wade
Published: May 2024

Aims

Examine whether the low-density lipoprotein cholesterol (LDL -C) determination method influences the rate of statin initiation for primary prevention of cardiovascular disease.

Methods and results

We conducted a register-based retrospective study in the Region of Southern Denmark. Two hospital-based laboratories in the region directly measure LDL -C whereas four laboratories calculate LDL -C using Friedewald's formula. Physicians do not choose which method is used. We included all statin-naïve patients ≥40 years with no history of cardiovascular disease, diabetes, or chronic kidney disease, who had their LDL -C determined during 2018–2019. There were 202 807 people who had LDL -C determined during the study period (median age 59 years, 44% women) of which 37% had a direct LDL -C measurement. The median reported LDL -C was 3.40 mmol/L [interquartile range (IQR) 2.90–4.00] for those with a direct measurement vs. 3.00 mmol/L (IQR 2.40–3.50) for those with calculated LDL -C. For those with direct measurement, re-calculated LDL -C (using Friedewald's formula) was 0.35 mmol/L lower than the reported direct LDL -C measurement. Among those with directly measured LDL -C, 3.6% initiated statins compared with 2.7% of those with a calculated LDL -C. Direct LDL -C measurement led to higher odds of having a statin initiated compared with calculated LDL -C (adjusted odds ratio 1.23, 95% CI 1.17–1.30); for those with triglycerides >1.7 mmol/L the adjusted odds ratio was 1.41 (95% CI 1.30–1.52).

Conclusion

Differences in the reporting of LDL -C from laboratories using different methods have a substantial influence on physician's decisions to prescribe statins.
Heat and Observed Economic Activity in the Rich Urban Tropics
Authors: Fesselmeyer Eric , Liu Haoming , Salvo Alberto , Simorangkir Rhita P B
Published: May 2024

We use space- and time-resolved mobility data to assess how heat impacts Singapore, a rich city state and arguably a harbinger of what is to come in the urbanising tropics. Singapore’s offices, factories, malls, buses and trains are widely air conditioned, its public schools less so. We document increased attendance and commuting to workplaces, malls and the more air-conditioned schools on hotter relative to cooler days, particularly by low-income residents with limited use of adaptive technologies at home. Investment by rich cities may attenuate heat’s pervasive negative consequences on productive outcomes, yet this may worsen the climate emergency in the long run.
The patterns and risk factors for relapse in oesophageal squamous cell cancers that achieve pathological complete response to neoadjuvant chemoradiotherapy
Authors: Zhong Jian , Fang Shuogui , Chen Rui , Yuan Jianye , Xie Xiuying , Lin Ting , Liu Mengzhong , Liu Qianwen , Fu Jianhua
Published: May 2024

OBJECTIVES

The goal of this study was to investigate the patterns and risk factors for recurrence in patients with oesophageal squamous cell carcinoma with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT).

METHODS

Between January 2008 and December 2018, a total of 96 patients with pCR were enrolled in this study. Lymph nodes with a pCR [LN-ypCR response (+)] were defined as those lymph nodes without residual tumour but with the presence of treatment response to nCRT. Prognostic factors for recurrence-free survival (RFS) were analysed with Cox proportional hazards models and Fine-Gray competing risk models. Lymph node (LN) stations were counted according to the Japan Esophageal Society classification.

RESULTS

The median follow-up time was 51.5 months. Recurrence occurred in 15 cases (15.6%) with a 9.9-month median time to recurrence and a 15.6-month median survival after recurrence. The majority of recurrent diseases developed within the first 2 years postoperatively. Distant recurrences were detected in 14 cases (14.6%), in which the most common recurrence sites were no.104 LN and the lung, followed by no.16 LN. The mean RFS in the whole cohort was 116.6 months. The LN-ypCR response (+) was identified as the independent prognostic factor for worse RFS in both the multivariate Cox model and the Fine–Gray competing risk model (P = 0.001 and P = 0.002, respectively).

CONCLUSIONS

Relapse is not rare in oesophageal squamous cell carcinoma cases with pCR after nCRT. Distant recurrences, the predominant pattern of relapse, occur primarily within the first 2 years after oesophagectomy. Patients with pCR with an LN-ypCR response (+) have a higher risk for postoperative recurrence.
Mediastinal transposition of the greater omentum for treatment of infected prostheses of the ascending aorta and aortic arch
Authors: Pitts Leonard , Pasic Miralem , Wert Leonhard , Nersesian Gaik , Kaemmel Julius , Buz Semih , Knosalla Christoph , Düsterhöft Volker , Starck Christoph , Kempfert Jörg , Jacobs Stephan , Falk Volkmar
Published: May 2024

OBJECTIVES

The aim of this study was to evaluate the outcomes of transposition of the omentum into the mediastinum to support the replacement of infected aortic grafts or to cover infected aortic grafts that are not amenable for surgical replacement.

METHODS

All patients with thoracic aortic graft infections who underwent mediastinal transposition of the omentum at our institution between 2005 and 2023 were included in this study. Mediastinal transposition of the omentum was performed either after replacement of the infected graft (‘curative concept’) or solely as bailout procedure by wrapping the infected graft (‘palliative concept’). The diagnosis, including computed tomography scans during follow-up, was made according to the criteria of the Management of Aortic Graft Infection Collaboration.

RESULTS

The patient cohort consisted of 31 patients. Both in-hospital and 1-year mortality were 0% (n = 0) for the curative concept (n = 9) compared to 23% (n = 5) and 41% (n = 9) for the palliative concept (n = 22), respectively. There was no graft infection-associated death or recurrence of infection after 3 years in the curative group. Survival was 52% at 3 years in the palliative group, with freedom of infection in 59% of the patients (n = 13).

CONCLUSIONS

Transposition of the omentum and wrapping of the infected aortic prosthetic graft is a useful bailout strategy for patients who are ineligible for replacement of an infected aortic graft. However, mortality stays high. For radical treatment of aortic graft infections, it may prove an effective supportive therapy and represents an important tool in the armamentarium of cardiac surgeons.
Anticoagulation for post-operative atrial fibrillation after isolated coronary artery bypass grafting: a meta-analysis
Authors: van de Kar Mileen R D , van Brakel Thomas J , van’t Veer Marcel , van Steenbergen Gijs J , Daeter Edgar J , Crijns Harry J G M , van Veghel Dennis , Dekker Lukas R C , Otterspoor Luuk C
Published: May 2024

Background and Aims

This study aimed to evaluate clinical outcomes in patients developing post-operative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and characterize variations in oral anticoagulation (OAC) use, benefits, and complications.

Methods

A systematic search identified studies on new-onset POAF after CABG and OAC initiation. Outcomes included risks of thromboembolic events, bleeding, and mortality. Furthermore, a meta-analysis was conducted on these outcomes, stratified by the use or non-use of OAC.

Results

The identified studies were all non-randomized. Among 1 698 307 CABG patients, POAF incidence ranged from 7.9% to 37.6%. Of all POAF patients, 15.5% received OAC. Within 30 days, thromboembolic events occurred at rates of 1.0% (POAF: 0.3%; non-POAF: 0.8%) with 2.0% mortality (POAF: 1.0%; non-POAF: 0.5%). Bleeding rates were 1.1% for POAF patients and 2.7% for non-POAF patients. Over a median of 4.6 years, POAF patients had 1.73 thromboembolic events, 3.39 mortality, and 2.00 bleeding events per 100 person-years; non-POAF patients had 1.14, 2.19, and 1.60, respectively. No significant differences in thromboembolic risks [effect size −0.11 (−0.36 to 0.13)] and mortality [effect size −0.07 (−0.21 to 0.07)] were observed between OAC users and non-users. However, OAC use was associated with higher bleeding risk [effect size 0.32 (0.06–0.58)].

Conclusions

In multiple timeframes following CABG, the incidence of complications in patients who develop POAF is low. The use of OAC in patients with POAF after CABG is associated with increased bleeding risk.