bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of tumor-specific splicing from somatic mutations as a source of neoantigen candidates
Authors: Lang Franziska , Sorn Patrick , Suchan Martin , Henrich Alina , Albrecht Christian , Köhl Nina , Beicht Aline , Riesgo-Ferreiro Pablo , Holtsträter Christoph , Schrörs Barbara , Weber David , Löwer Martin , Sahin Ugur , Ibn-Salem Jonas
Published: May 2024

Motivation

Neoantigens are promising targets for cancer immunotherapies and might arise from alternative splicing. However, detecting tumor-specific splicing is challenging because many non-canonical splice junctions identified in tumors also appear in healthy tissues. To increase tumor-specificity, we focused on splicing caused by somatic mutations as a source for neoantigen candidates in individual patients.

Results

We developed the tool splice2neo with multiple functionalities to integrate predicted splice effects from somatic mutations with splice junctions detected in tumor RNA-seq and to annotate the resulting transcript and peptide sequences. Additionally, we provide the tool EasyQuant for targeted RNA-seq read mapping to candidate splice junctions. Using a stringent detection rule, we predicted 1.7 splice junctions per patient as splice targets with a false discovery rate below 5% in a melanoma cohort. We confirmed tumor-specificity using independent, healthy tissue samples. Furthermore, using tumor-derived RNA, we confirmed individual exon-skipping events experimentally. Most target splice junctions encoded neoepitope candidates with predicted major histocompatibility complex (MHC)-I or MHC-II binding. Compared to neoepitope candidates from non-synonymous point mutations, the splicing-derived MHC-I neoepitope candidates had lower self-similarity to corresponding wild-type peptides. In conclusion, we demonstrate that identifying mutation-derived, tumor-specific splice junctions can lead to additional neoantigen candidates to expand the target repertoire for cancer immunotherapies.

Availability and implementation

The R package splice2neo and the python package EasyQuant are available at https://github.com/TRON-Bioinformatics/splice2neo and https://github.com/TRON-Bioinformatics/easyquant, respectively.
High fat diet-induced obesity and gestational DMBA exposure alter folliculogenesis and the proteome of the maternal ovary
Authors: Novbatova Gulnara , Fox Isabelle , Timme Kelsey , Keating Aileen F
Published: May 2024

Obesity and ovotoxicant exposures impair female reproductive health with greater ovotoxicity reported in obese relative to lean females. The mother and developing fetus are vulnerable to both during gestation. 7,12-dimethylbenz[a]anthracene (DMBA) is released during carbon combustion including from cigarettes, coal, fossil fuels, and forest fires. This study investigated the hypothesis that diet-induced obesity would increase sensitivity of the ovaries to DMBA-induced ovotoxicity and determined impacts of both obesity and DMBA exposure during gestation on the maternal ovary. Female C57BL/6 J mice were fed a control or a High Sugar High Fat (45% kcal from fat; 20% kcal from sucrose) diet until ~30% weight gain was attained before mating with unexposed males. From gestation Day 7, mice were exposed intraperitoneally to either vehicle control (corn oil) or DMBA (1 mg/kg diluted in corn oil) for 7 d. Thus, there were four groups: lean control (LC); lean DMBA exposed; obese control; obese DMBA exposed. Gestational obesity and DMBA exposure decreased (P < 0.05) ovarian and increased liver weights relative to LC dams, but there was no treatment impact (P > 0.05) on spleen weight or progesterone. Also, obesity exacerbated the DMBA reduction (P < 0.05) in the number of primordial, secondary follicles, and corpora lutea. In lean mice, DMBA exposure altered abundance of 21 proteins; in obese dams, DMBA exposure affected 134 proteins while obesity alone altered 81 proteins in the maternal ovary. Thus, the maternal ovary is impacted by DMBA exposure and metabolic status influences the outcome.
Mapping adipocyte interactome networks by HaloTag-enrichment-mass spectrometry
Authors: Yazaki Junshi , Yamanashi Takashi , Nemoto Shino , Kobayashi Atsuo , Han Yong-Woon , Hasegawa Tomoko , Iwase Akira , Ishikawa Masaki , Konno Ryo , Imami Koshi , Kawashima Yusuke , Seita Jun
Published: May 2024

Mapping protein interaction complexes in their natural state in vivo is arguably the Holy Grail of protein network analysis. Detection of protein interaction stoichiometry has been an important technical challenge, as few studies have focused on this. This may, however, be solved by artificial intelligence (AI) and proteomics. Here, we describe the development of HaloTag-based affinity purification mass spectrometry (HaloMS), a high-throughput HaloMS assay for protein interaction discovery. The approach enables the rapid capture of newly expressed proteins, eliminating tedious conventional one-by-one assays. As a proof-of-principle, we used HaloMS to evaluate the protein complex interactions of 17 regulatory proteins in human adipocytes. The adipocyte interactome network was validated using an in vitro pull-down assay and AI-based prediction tools. Applying HaloMS to probe adipocyte differentiation facilitated the identification of previously unknown transcription factor (TF)–protein complexes, revealing proteome-wide human adipocyte TF networks and shedding light on how different pathways are integrated.
Establishing connectivity through microdissections of midbrain stimulation-related neural circuits
Authors: Skandalakis Georgios P , Neudorfer Clemens , Payne Caitlin A , Bond Evalina , Tavakkoli Armin D , Barrios-Martinez Jessica , Trutti Anne C , Koutsarnakis Christos , Coenen Volker A , Komaitis Spyridon , Hadjipanayis Constantinos G , Stranjalis George , Yeh Fang-Cheng , Banihashemi Layla , Hong Jennifer , Lozano Andres M , Kogan Michael , Horn Andreas , Evans Linton T , Kalyvas Aristotelis
Published: May 2024

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomofunctional mechanisms governing human behaviour, in addition to the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. Although the ventral tegmental area has been targeted successfully with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region is not fully understood.

Here, using fibre microdissections in human cadaveric hemispheres, population-based high-definition fibre tractography and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain and prefrontal cortex, which is implicated in the treatment of obsessive–compulsive disorder, major depressive disorder, Alzheimer’s disease, cluster headaches and aggressive behaviours.
Accelerated water stability test and lifetime prediction of metal-organic frameworks
Authors: Ohmura Tetsushi , Mukae Yusuke , Hosokawa Yoichi , Nakamura Hiroshi , Yamauchi Takafumi
Published: May 2024

To predict the lifetime of metal-organic frameworks (MOFs) with high water capacity/stability as water harvesters and adsorption heat pumps, a simple accelerated water stability test was developed using liquid water and water vapor in an autoclave. The function obtained from Bnlnauer-Emmett-Teller (BET) surface area loss analysis of MOF-801-P was applied to lifetime prediction, and a long-term stability test of MOF-801-P with liquid water at 65 °C agreed well with the values predicted using the developed test.
The interpretation of field and LEAP potentials recorded from cardiomyocyte monolayers
Authors: Boukens B , Ernault A C , Al-Shama R F M , Li J R , Devalla H D , De Groot J R , Coronel R F M , Vigmond E
Published: May 2024

Funding Acknowledgements 

None.

Multi-electrode arrays (MEA) are the method of choice for electrophysiological characterization of cardiomyocyte monolayers. The field potentials recorded using a MEA are like extracellular electrograms recorded from ventricular myocardium using conventional electrodes. Nevertheless, different criteria are often used to interpret field potential and extracellular electrogram, which hampers correct interpretation and translation to the patient.

To validate criteria for extracellular electrograms analysis applicable to field potentials,

we used neonatal rat cardiomyocytes to generate monolayers. We recorded field potentials using a MEA and simultaneously recorded action potentials using sharp micro-electrodes. In parallel we recreated our experimental setting in silico and performed simulations. We demonstrate that the amplitude of the local RS-complex of a field potential correlated with conduction velocity, but only in the lower ranges of conduction velocities. The time of the peak of the T-wave of the field potentials correlated well with APD90 and the time of the steepest upslope with APD50. By injecting current into the monolayer, we could record a local extracellular action potential (LEAP). The LEAP was of low amplitude and highly depolarized, and the shape differed markedly from the shape of the local action potential.

Criteria for interpreting extra cellular electrograms should also be applied to field potentials. This will provide a strong basis for analysis of heterogeneity in conduction velocity and repolarization in cultured monolayers of cardiomyocytes especially at low conduction velocities. A LEAP is not a recording of the local action potential but is generated by intracellular current provided by neighboring cardiomyocytes.
Gut microbiota alterations after acute coronary syndrome: a single center, case-control pilot study
Authors: Suntornlekha N , Leemasawat K , Suwannasom P , Apaijai N , Sriwichaiin S , Suparan K , Chattipakorn N , Chattipakorn S
Published: May 2024

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): National Research Council of Thailand

Background

Decreasing of gut microbiota diversity has been reported in coronary artery disease. However, the data of gut microbiota alterations after acute coronary syndrome (ACS) are still limited.

Objective

To determine the stool microbiota differences between ACS and controls. Also determine stool microbiota changes between ACS onset and 3 months apart.

Methods

We conducted a single-center, case-control pilot study. Ten ACS patients, aged between 18 to 80 years old, were consented. Echocardiogram, blood and fecal samples were obtained within 24 hours of hospitalization, then additionally 3 months apart. Ten of controls were also enrolled and collected the data. 16S ribosomal RNA gene was used to identify fecal bacteria.

Results

The mean age and gender were similar between both groups. The abundance of stool Clostridial was significantly decreased in ACS compared with controls (mean 8.476 ±0.570 vs. 9.254 ±0.829 Log10 copies/uL, p=0.025) and remained unchanged after 3 months (mean 8.256 ±0.787 Log10 copies/uL, p=0.483). The gut dysbiosis was not correlated with left ventricular function and medications.

Conclusion

Gut dysbiosis was observed in ACS patients and persisted afterward, regardless of LVEF and treatment. Gut dysbiosis might be an ACS risk marker in high cardiovascular risk patients. Further studies are warranted.Bacterial composition of fecal samples
Potential of [64Cu]Cu-RGD PET/CT for detection of cardiotoxicity in a rat model of doxorubicin induced heart failure
Authors: Hoeeg C , Follin B , Grandjean C , Sejersten Ripa R , Ekblond A , Kastrup J , Binderup T , Kjaer A
Published: May 2024

Funding Acknowledgements

Type of funding sources: Foundation. Main funding source(s): This work was supported by the European Union’s Horizon 2020 research and innovation program (ERC Advanced Grant) and the Novo Nordisk Foundation.

Background

Doxorubicin is a common and highly effective chemotherapeutic. However, its use is limited by cardiotoxic side effects, which occur in 5-23 % of patients treated, and the lack of methods to detect these conditions at early time points.

Purpose

In the present study, we evaluated if [64Cu]Cu-RGD positron emission tomography/computed tomography (PET/CT) could detect cardiotoxicity in a rat model of doxorubicin induced heart failure.

Methods

Male Lewis rats were divided into two groups and treated with either a cumulative dose of 15 mg/kg doxorubicin (n = 15) or left untreated (n = 10). Cardiac anatomy and function were assessed using magnetic resonance imaging at baseline and in week eight. [64Cu]Cu-RGD PET/CT scans were performed in week four. All animal experiments were approved by the Danish Animal Experiments Inspectorate (authorization number 2016-15-0201-00920) and study performed in accordance with the ARRIVA guidelines.

Results

Doxorubicin treatment led to a decline in left ventricular ejection fraction (66.5 ± 0.85 % to 46.67 ± 0.84 %, p < 0.001), as well as an increase in septal and thymic uptake of [64Cu]Cu-RGD (0.46 ± 0.02 vs. 0.29 ± 0.04, <0.001 and 0.87 ± 0.03 vs. 0.40 ± 0.07, p < 0.001, respectively). In addition, doxorubicin altered the cardiac gene expression, led to infiltration of macrophages (0.90 ± 0.12 % vs. 0.30 ± 0.04 %, p <0.001), reduced endothelial content (0.19 ± 0.02 % vs. 0.47 ± 0.07 %, p < 0.001), and increased interstitial fibrosis (13.6 ± 0.86 % vs. 10.5 ± 0.66 %, p = 0.014). Furthermore, concentrations of inflammatory plasma proteins were increased in the doxorubicin group.

Conclusion

Doxorubicin treatment resulted in the development of cardiotoxicity and heart failure, which could be detected using [64Cu]Cu-RGD PET/CT at early time points. [64Cu]Cu-RGD uptake in the myocardial septum and thymus predicted low left ventricular ejection fraction in week eight, thus it may serve as an early marker of cardiotoxicity.Experimental setup and timeline
Ectopic Pitx2 expression and sinoatrial node dysfunction in mice recapitulating a novel cardiac syndrome identified in unrelated families with deletions in a gene desert on chromosome 4q25
Authors: Van Der Maarel L , Bosada F , Mungroo M R , Tiel-Groenesteege F H T , Jensen B , Devalla H , Christoffels V M
Published: May 2024

Funding Acknowledgements

Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Dutch Research Councin/NWO

Introduction

Several unrelated families presenting with a complex, heterogeneous cardiac syndrome including sinoatrial node dysfunction and atrial fibrillation were found to share overlapping deletions in a 1.5 Megabase pair gene desert on chromosome 4q25. These overlapping regions contain evolutionarily conserved CTCF binding sites that modulate the separation of topologically associating domains containing the transcription factor-encoding gene PITX2 and noncoding RNA genes.

Aim

To understand mechanistically how the deletion in the gene desert causes sinoatrial node dysfunction and atrial arrhythmias.

Methods

Mice lacking the orthologue of the minimally overlapping genomic region deleted in affected patients were generated. Electrophysiology, morphology, tissue composition, and transcriptomes were analysed in this mouse model.

Results

These mice recapitulated major morpho-functional features of the syndrome, including sinoatrial node dysfunction and atrial arrhythmogenesis . Out of the 15 genes flanking the gene desert, only Pitx2 expression was deregulated in the sinoatrial node. During development, cardiac Pitx2c expression is normally restricted to the left side where it drives left sinus venosus and left atrial morphogenesis and prevents the formation of a left-sided sinoatrial node. The PITX2 locus has also been associated with atrial fibrillation in GWAS. Immunohistochemistry together with 3D volume analysis showed that Pitx2c was ectopically expressed in half of the pacemaker cardiomyocytes of the developing and postnatal sinoatrial node while its expression in the left atrium was maintained. Key transcription factors that drive pacemaker cell differentiation, Tbx3, Isl1 and Shox2, were lost where Pitx2c was ectopically expressed. Moreover, a conserved long non-coding RNA (Playrr) previously linked to Pitx2 regulation in the developing dorsal mesentery, was downregulated in the sinoatrial node of homozygous mutants. The downregulation of the pacemaker gene program additionally coincided with the activation of the atrial myocardial gene program in half of the pacemaker cardiomyocytes.

Conclusion

We generated a mouse model of a novel human cardiac syndrome including sinoatrial node dysfunction associated with the deletion of critical CTCF binding sites in a gene desert on chromosome 4q25. This deletion induced ectopic Pitx2c expression in the sinoatrial node alongside a substantial loss of pacemaker cardiomyocyte identity and a gain in a working atrial myocardium-like phenotype in the sinoatrial node of affected mice.Loss of pacemaker cardiomyocyte identitySinoatrial node dysfunction in mutants
Spatially resolved metabolomics revealed specific nucleotide alterations within the media and adventitia layers in idiopathic thoracic aortic aneurysms associated with tricuspid and bicuspid valves
Authors: Martin-Lorenzo M , Martin-Blazquez A , Donado A , Heredero A , Santiago-Hernandez A , Heeren R M A , Aldamiz-Echevarria G , Balluff B , Alvarez-Llamas G
Published: May 2024

Funding Acknowledgements

Type of funding sources: Public Institution(s). Main funding source(s): Instituto de Salud Carlos III co-supported by FEDER grants and co-funded by the European Union

Background

Thoracic aortic aneurysms (TAAs) curse silently and asymptomatic. The vast majority are idiopathic, representing 80-95% of the cases. Nevertheless, there is an association between TAA and the presence of bicuspid aortic valve (BAV) constituting BAV an independent risk factor of TAA. The presence of BAV accelerates the growth of the aneurysm affecting younger patients than those with tricuspid aortic valve (TAV). Evidence points to a profound remodeling of the media and adventitia layers, but the underlying mechanisms are unknown, especially the metabolic changes taking place and their in situ localization.

Purpose

Our aim was to identify, in a spatially resolved manner, the in situ metabolic alterations occurring in TAA human aortas while differentiating between BAV and TAV patients. In a further step, we sought to identify the changes happening particularly within the media and adventitia layers.

Methods

Mass spectrometry imaging (MSI) was applied to identify metabolic differences between human aortas with (TAA) and without (C) dilatation classified according to their aortic valve and obtained from cardiac surgeries. Clinical groups consisted on TAV-C (n=11), BAV-C (n=12), TAV-TAA (n=12) and BAV-TAA (n=12). Subsequent virtual microdissection histologically guided was applied to identify the specific metabolic changes located within media and/or adventitia. Changes were considered significant if FDR>2 and p-value <0.05.

Results

Purine metabolism resulted altered in BAV-TAA patients while no differences were found in TAV-TAA ones. Particularly, we detected a significant increase of aortic ATP (FC= 2.92; p-value= 0.030), ADP (FC= 2.04; p-value= 0.020), AMP (FC= 2.42; p-value= 0.011) and GDP (FC= 2.29; p-value= 0.046) in BAV-TAA vs. BAV-C subjects. In contrast, we found an in situ increment in pyrimidine metabolism resulting UDP and UMP increased in both, TAV and BAV associated TAAs. When comparing the arterial layers, media layer was found to be the major driver of BAV-TAA with no nucleotides changes in adventitia. However, TAV-TAA media and adventitia layer behave similarly with the exception of a massive increase of ATP (FC=50.23, p=0.046) in adventitia with no alteration in media of TAV-TAA vs. TAV-C patients.

Conclusions

Idiopathic TAAs course differently in subjects with bicuspid and tricuspid valves both in terms of mechanisms of action and arterial remodeling within the aortic layers. These findings suggest that TAA patients with bicuspid or tricuspid aortic valve should be treated as independent groups for optimal disease management.
Annual vascular and bleeding outcomes in East Asian poststenting patients with acute coronary syndrome: The BRIC-ACS II trial
Authors: Li D , Yu Y , Chen Y
Published: May 2024

Funding Acknowledgements

Type of funding sources: None. Main funding source(s): no

Objective

We aim to determine the incidence of events in the ‘real-world’ ACS Chinese patients over 1-year after PCI.

Methods and Results

From November 2017 till April 2020, we enrolled post-stenting ACS patients (n=5515) from 30 hospitals with the strict 1-year follow-up (n=5150). Only 153(3.0%) patients developed MACE (a composite of all-cause death, myocardial infarction, ischemic stroke, or urgent coronary revascularization). The cumulative incidence of annual bleeding (BARC≥2) was 5.8% (298/5150). The BARC≥2 bleeding was higher 298 (5.8%) and was not associated with worsened MACE (P =0.52). Patients treated with ticagrelor (n=1620, 6.0%) had a significantly increased risk of bleeding than those treated with clopidogrel (n=2331; 4.1%) (HR=1.486; 95% CI:1.12-1.97; P=0.006), but similar risk of vascular MACE (2.7% vs 2.8%; HR= 0.94; 95% CI:0.64-1.38; P=0.747).The factors independently associated with the comprehensive risk of BARC≥2 bleeding and MACE, including female gender, renal insufficiency, peptic ulcer, atrial fibrillation, continuous use of ticagrelor and non-continuous DAPT. The discrimination of the nomogram model was further tested by the ROC curve (AUC value:0.610 (95% CI, 0.577-0.642)).

Conclusions

The annual incidence of BARC≥2 bleeding in ACS patients treated with PCI in China was higher (5.8%) than MACE (3.0%). DAPT with ticagrelor increased the bleeding rates with no trend towards MACE reduction.
Aging promotes mast cell activation and antigen presenting capacity in atherosclerosis
Authors: Depuydt M A C , Smit V , Schaftenaar F H , Hemme E , Delfos L , Vlaswinkel F D , Simpson C , Kovanen P T , Slutter B , Kuiper J , Bot I , Foks A C
Published: May 2024

Funding Acknowledgements 

Type of funding sources: Foundation. Main funding source(s): Dutch Heart Foundation

Aging is an independent and dominant risk factor for atherosclerosis and is associated with a low-grade chronic inflammation termed inflammaging. This age-induced pro-inflammatory environment may have great impact on plaque-residing immune cells, including mast cells. Mast cells have been found to accumulate in the human atherosclerotic plaque upon disease progression and have been associated with plaque instability. However, it is currently unknown whether aging drives the pro-atherogenic effects of mast cells in atherosclerosis.

To assess the effects of aging on mast cell phenotype, we examined mast cell populations in young and old male Ldlr-/- mice fed either a chow (CD) or Western-type (WD) diet. We observed a 6-fold increase in the number of mast cells in the aged atherosclerotic aorta compared to young (Y-CD: 4.5±0.7 vs. O-CD: 279.4±9 cells, p<0.01; Y-WD: 45.3±15.2 vs. O-CD: 279.4±9 cells, p<0.01). Furthermore, we detected a marked increase in activation status with age as shown by the significantly augmented number of CD63+ mast cells in the atherosclerotic aorta (Y-CD: 1.8±0.6 vs. O-CD: 259.7±85.4 cells, p<0.01; Y-WD: 41.3±13.6 vs. O-CD: 259.7±85.4 cells, p<0.01). In line, we identified that aged bone-marrow derived mast cells displayed elevated basal CD63 expression compared to young cells, indicative of intrinsic low-grade activation. Moreover, we demonstrated that aging increases the amount of MHCII+ mast cells in atherosclerosis, allowing them to act as antigen-presenting cells, which correspondingly led to increased CD4+ T cell proliferation in vitro (young: 35.2±1.2% vs. old: 45.8±1.2%, p<0.001). Finally, single-cell RNA sequencing of human atherosclerotic plaques confirmed mast cell-specific expression of MHC-II orthologs.

To conclude, we established that aging induces phenotypic changes of mast cells in atherosclerosis, regarding both activation status and antigen presenting capacity, which can contribute to disease progression.
Targeted proteomic profiling of cardiogenic shock in the cardiac intensive care unit
Authors: Patel Siddharth M , Lopes Mathew S , Morrow David A , Bellavia Andrea , Bhatt Ankeet S , Butler Kayleigh K , D’Antonio Jessica , Dunn Michael , Fagundes Antonio A , Jarolim Petr , Marin Ethan P , Morton Lori , Olenchock Benjamin O , Senman Balimkiz , da Silva Danuzia S , Varshney Anubodh S , Bohula Erin A , Berg David D
Published: May 2024

Aims

We sought to characterize circulating protein biomarkers associated with cardiogenic shock (CS) using highly multiplex proteomic profiling.

Methods and results

This analysis employed a cross-sectional case–control study design using a biorepository of patients admitted to a cardiac intensive care unit between 2017 and 2020. Cases were patients adjudicated to have CS, and controls were those presenting for cardiac critical care without shock, including subsets of patients with isolated hypotension or heart failure (HF). The Olink platform was used to analyse 359 biomarkers with Bonferroni correction. The analysis included 239 patients presenting for cardiac critical care (69 cases with CS, 170 non-shock controls). A total of 63 biomarkers (17.7%) were significantly associated with CS after Bonferroni correction compared with all controls. Of these, nine biomarkers remained significantly associated with CS when separately cross-validated in subsets of controls presenting with isolated hypotension and HF: cathepsin D, fibroblast growth factor (FGF)-21 and -23, growth differentiation factor (GDF)-15, insulin-like growth factor-binding protein-1, N-terminal pro-B-type natriuretic peptide, osteopontin, oncostatin-M-specific receptor subunit beta (OSMR), and soluble ST2 protein (sST2). Four biomarkers were identified as providing complementary information for CS diagnosis with development of a multi-marker model: sST2, FGF-23, CTSD, and GDF-15.

Conclusion

In this pilot study of targeted proteomic profiling in CS, we identified nine biomarkers significantly associated with CS when cross-validated against non-shock controls including those with HF or isolated hypotension, illustrating the potential application of a targeted proteomic approach to identify novel candidates that may support the diagnosis of CS.
Association of left ventricular outflow tract size with arch morphology in interrupted aortic arch
Authors: Elbatarny Malak , Lee Grace , Howell Alison , Signorile Marisa , Honjo Osami , Barron David J
Published: May 2024

OBJECTIVES

Left ventricular outflow tract obstruction (LVOTO) is a major cause of morbidity and mortality in infants with interrupted aortic arch (IAA). Left Ventricular Outflow Tract (LVOT) development may be flow-mediated, thus IAA morphology may influence LVOT diameter and subsequent reintervention. We investigated the association of IAA morphology [type and presence of aortic arch aberrancy (AAb)] with LVOT diameter and reintervention.

METHODS

All surgical patients with IAA (2001–2022) were reviewed at a single institution. We compared IAA-A versus IAA-B; IAA with aortic AAb versus none; IAA-B with aberrant subclavian (AAbS) artery versus others. Primary outcomes included LVOT diameter (mm), LVOTO at discharge (≥50 mmHg), and LVOT reintervention.

RESULTS

Seventy-seven infants (mean age 10 ± 19 days) were followed for 7.6 (5.5–9.7) years. Perioperative mortality was 3.9% (3/77) and long-term mortality was 5.2% (4/77). Out of 51 IAA-B (66%) and 22 IAA-A (31%) patients, 30% (n = 22) had AAb. Smaller LVOT diameter was associated with IAA-B [IAA-A: 5.40 (4.68–5.80), IAA-B: 4.60 (3.92–5.50), P = 0.007], AAb [AAb: 4.00 (3.70–5.04) versus none: 5.15 (4.30–5.68), P = 0.006], and combined IAA-B + AAbS [IAA-B + AAbS: 4.00 (3.70–5.02) versus other: 5.00 (4.30–5.68), P = 0.002]. The likelihood of LVOTO was higher among AAb [N = 6 (25%) vs N = 1 (2%), P = 0.004] and IAA-B + AAbS [N = 1 (2%) vs N = 6 (30%), P = 0.002]. Time-to-event analysis showed a signal towards increased LVOT reintervention in IAA-B + AAbS (P = 0.11).

CONCLUSIONS

IAA-B and AAb are associated with small LVOT diameter and early LVOTO, especially in combination. This may reflect lower flow in the proximal arch during development. Most reinterventions occur in IAA-B + AAbS, hence these patients should be carefully considered for LVOT intervention at the time of initial repair.
Posterior crossbite corrections in the early mixed dentition with quad helix or rapid maxillary expander: a cost-effectiveness analysis of a randomized controlled trial
Authors: Hansson Stina , Johansson Naimi , Lindsten Rune , Petrén Sofia , Bazargani Farhan
Published: May 2024

Background

Unilateral posterior crossbite is a common malocclusion, and early treatment is recommended to enable normal growth. There are several possibilities regarding choice of appliances used for correcting this malocclusion; however, when treatment is financed by public funds the decision needs to be based not only on the effects but also on the effect in relation to the costs.

Objectives

The aim was to perform a cost-effectiveness analysis comparing quad helix (QH) and rapid maxillary expanders (RME; hyrax-type) in children in the early mixed dentition.

Material and methods

Seventy-two patients were randomized to treatment with either QH or RME, at two different centres. Data were collected from the patient’s medical records regarding success rate, number of visits, total treatment time, emergency visits, and so forth, together with answers from patient questionnaires concerning absence from school and use of analgesics. A cost-effectiveness analysis with both an intention-to-treat (ITT) and a per-protocol approach was performed, as well as a deterministic sensitivity analysis.

Results

The success rate, one year after the completion of the expansion, was equal between groups according to the ITT approach. From a healthcare perspective, the mean cost difference between RME and QH was €32.05 in favour of QH (P = 0.583; NS). From a societal perspective, the mean cost difference was €32.61 in favour of QH (P = 0.742; NS). The total appliance cost alone was higher in the RME group €202.67 resp. €155.58 in the QH group (P = 0.001). The probability of RME having a higher cost was 71% from a healthcare perspective and 62.7% from a societal perspective. The total treatment time was 97 days longer in the QH group. In the deterministic sensitivity analysis, when using a higher valuation of the children’s educational loss, the QH becomes €58 more costly than the RME. There was a statistically significant difference in chair time and visits between centres (P < 0.001).

Conclusion

The difference in costs between RME and QH is not statistically significant, however, there is a slightly higher probability that RME is more expensive than QH with a mean cost of an additional €32 per patient from a healthcare perspective. Different work procedures at different centres indicate that logistics around the patient’s treatment is a more important aspect than appliance used to decrease the number of visits and save chair time and thereby also costs.
Revisiting translation as a method in language teaching and learning
Authors: Ping Yuan
Published: May 2024

This article begins by defining translation and discussing its use in language education. It then presents a case study of an EFL listening and speaking course taught at a Chinese university that incorporates communicative translation activities, including vocabulary exercises, group presentations, and role-playing. The article concludes by reflecting on the experience of teaching the course and the lessons learnt. It aims to foster a deeper understanding of the relationship between translation and language teaching/learning and to suggest practical applications of this understanding for teachers in diverse educational settings.
The effect of information and beliefs on preferences for sustainably produced beef
Authors: Ishaq Mariam , Kolady Deepthi , Grebitus Carola
Published: May 2024

Beef production is a major contributor to greenhouse gas (GHG) emissions. We conducted a choice experiment to analyse consumers’ willingness to pay (WTP) for beef characterised as carbon-friendly. We included a treatment where respondents were informed about carbon-friendly production and surveyed beliefs regarding beef production’s contribution to GHG emissions. The results show that consumers have a positive WTP for carbon-friendly beef and providing information increases the premium that they are willing to pay for it. The findings also suggest that consumers who believe that beef production contributes to GHG emissions are willing to pay more for beef carrying a carbon-friendly label.
Health-related quality of life and healthcare costs of symptoms and cardiovascular disease events in patients with atrial fibrillation: a longitudinal analysis of 27 countries from the EURObservational Research Programme on Atrial Fibrillation general long-term registry
Authors: Walli-Attaei Marjan , Little Mathew , Luengo-Fernandez Ramon , Gray Alastair , Torbica Aleksandra , Maggioni Aldo P , Bairami Firoozeh , Huculeci Radu , Aboyans Victor , Timmis Adam D , Vardas Panos , Leal Jose
Published: May 2024

Aims

We examine the effects of symptoms and cardiovascular disease (CVD) events on health-related quality of life (HRQOL) and healthcare costs in a European population with atrial fibrillation (AF).

Methods and results

In the EURObservational Research Programme on AF long-term general registry, AF patients from 250 centres in 27 European countries were enrolled and followed for 2 years. We used fixed effects models to estimate the association of symptoms and CVD events on HRQOL and annual healthcare costs. We found significant decrements in HRQOL in AF patients in whom ST-segment elevation myocardial infarction (STEMI) [−0.075 (95% confidence interval −0.144, −0.006)], angina or non-ST-elevation myocardial infarction (NSTEMI) [−0.037 (−0.071, −0.003)], new-onset/worsening heart failure [−0.064 (−0.088, −0.039)], bleeding events [−0.031 (−0.059, −0.003)], thromboembolic events [−0.071 (−0.115, −0.027)], mild symptoms [0.037 (−0.048, −0.026)], or severe/disabling symptoms [−0.090 (−0.108, −0.072)] occurred during the follow-up. During follow-up, annual healthcare costs were associated with an increase of €11 718 (€8497, €14 939) in patients with STEMI, €5823 (€4757, €6889) in patients with angina/NSTEMI, €3689 (€3219, €4158) in patients with new-onset or worsening heart failure, €3792 (€3315, €4270) in patients with bleeding events, and €3182 (€2483, €3881) in patients with thromboembolic events, compared with AF patients without these events. Healthcare costs were primarily driven by inpatient costs. There were no significant differences in HRQOL or healthcare resource use between EU regions or by sex.

Conclusion

Symptoms and CVD events are associated with a high burden on AF patients and healthcare systems throughout Europe.
haploMAGIC: accurate phasing and detection of recombination in multiparental populations despite genotyping errors
Authors: Montero-Tena Jose A , Abdollahi Sisi Nayyer , Kox Tobias , Abbadi Amine , Snowdon Rod J , Golicz Agnieszka A
Published: May 2024

Recombination is a key mechanism in breeding for promoting genetic variability. Multiparental populations (MPPs) constitute an excellent platform for precise genotype phasing, identification of genome-wide crossovers (COs), estimation of recombination frequencies, and construction of recombination maps. Here, we introduce haploMAGIC, a pipeline to detect COs in MPPs with single-nucleotide polymorphism (SNP) data by exploiting the pedigree relationships for accurate genotype phasing and inference of grandparental haplotypes. haploMAGIC applies filtering to prevent false-positive COs due to genotyping errors (GEs), a common problem in high-throughput SNP analysis of complex plant genomes. Hence, it discards haploblocks not reaching a specified minimum number of informative alleles. A performance analysis using populations simulated with AlphaSimR revealed that haploMAGIC improves upon existing methods of CO detection in terms of recall and precision, most notably when GE rates are high. Furthermore, we constructed recombination maps using haploMAGIC with high-resolution genotype data from 2 large multiparental populations of winter rapeseed (Brassica napus). The results demonstrate the applicability of the pipeline in real-world scenarios and showed good correlations in recombination frequency compared with alternative software. Therefore, we propose haploMAGIC as an accurate tool at CO detection with MPPs that shows robustness against GEs.
Gene duplication and evolutionary plasticity of lin-12/Notch gene function in Caenorhabditis
Authors: Lyu Haimeng , Moya Nicolas D , Andersen Erik C , Chamberlin Helen M
Published: May 2024

Gene duplication is an important substrate for the evolution of new gene functions, but the impacts of gene duplicates on their own activities and on the developmental networks in which they act are poorly understood. Here, we use a natural experiment of lin-12/Notch gene duplication within the nematode genus Caenorhabditis, combined with characterization of loss- and gain-of-function mutations, to uncover functional distinctions between the duplicate genes in 1 species (Caenorhabditis briggsae) and their single-copy ortholog in Caenorhabditis elegans. First, using improved genomic sequence and gene model characterization, we confirm that the C. briggsae genome includes 2 complete lin-12 genes, whereas most other genes encoding proteins that participate in the LIN-12 signaling pathway retain a one-to-one orthology with C. elegans. We use CRISPR-mediated genome editing to introduce alleles predicted to cause gain-of-function (gf) or loss-of-function (lf) into each C. briggsae gene and find that the gf mutations uncover functional distinctions not apparent from the lf alleles. Specifically, Cbr-lin-12.1(gf), but not Cbr-lin-12.2(gf), causes developmental defects similar to those observed in Cel-lin-12(gf). In contrast to Cel-lin-12(gf), however, the Cbr-lin-12.1(gf) alleles do not cause dominant phenotypes as compared to the wild type, and the mutant phenotype is observed only when 2 gf alleles are present. Our results demonstrate that gene duplicates can exhibit differential capacities to compensate for each other and to interfere with normal development, and uncover coincident gene duplication and evolution of developmental sensitivity to LIN-12/Notch activity.
Does Social Support Moderate the Relationship Between Frailty and Functional Ability Trajectory Among Community-Dwelling Older Adults?
Authors: Yu Jiaqi , Si Huaxin , Liu Qinqin , Li Yanyan , Zhou Wendie , Wang Cuili
Published: May 2024

Background

Functional ability is the important prerequisite to live independently and achieve aging in place, which depends on the complex interaction of intrinsic and extrinsic factors. Identifying the trends and influencing factors of functional ability would contribute to the accurate assessment and intervention of geriatric health. This study aimed to disentangle the moderating effect of 3 types of social support, namely objective support, subjective support, and support utilization, on the relationship between frailty and functional ability trajectories.

Methods

This was a secondary analysis using data from a prospective 3-wave study with a sample of 777 Chinese community-dwelling older adults. Social support was assessed using the Social Support Rating scale. Frailty was assessed using the FRAIL scale. Functional ability was measured by the Lawton Instrumental Activities of Daily Living scale. Latent growth curve models were implemented to test their relationships.

Results

Objective support but not subjective support or support utilization moderated on the relationship between frailty and functional ability slope. Functional ability decline over time was buffered by objective support among robust individuals but exacerbated among (pre)frail individuals.

Conclusions

The moderating effect of social support on the relationship between frailty and functional ability trajectory varies by support types, which reminded that social support may be a promising intervention target to maintain functional independence for frail individuals, opening up a new perspective on social support in the field of disability prevention. Effective interventions should particularly address objective support in conjunction with empowering the frail older population to optimize the trajectory of functional ability.
A meta-analytical review of the relationship, antecedents, and consequences of information seeking and information scanning
Authors: Lewis Nehama , Andrews Emily A , Keefe Denali , Walter Nathan
Published: May 2024

Prior studies have examined correlates of health information seeking and scanning separately, focusing on distinct theoretical frameworks, antecedents, and outcomes. In this meta-analysis we synthesize this research (k = 21; N = 39,510) by examining the relationship between health information seeking and scanning, and their key antecedents and outcomes. Results show that seeking and scanning are moderately and positively correlated, supporting the claim that these are distinct, albeit related, and behaviors. Level of education and income are positive correlates of scanning (but not seeking) behaviors. Conversely, issue-relevance is positively associated with seeking (but not scanning). Results show substantial parity in associations between seeking and scanning with topic-relevant attitudes and behavioral intention. Information seeking (but not scanning), however, is a significant correlate of risk perceptions and perceived social norms. Thus, scanning and seeking are associated with distinct antecedents, but have similar effects. We offer theoretical implications and directions for future research.
A mixed-method analysis of the contribution of informal sport to public health in Australia
Authors: Jeanes Ruth , O’Connor Justen , Penney Dawn , Spaaij Ramon , Magee Jonathan , O’ Hara Eibhlish , Lymbery Lisa
Published: May 2024

Informal sport is a growth area of sport participation but there has been limited examination of how informal and unstructured forms of participation may contribute to health outcomes that are important for public health. This article aims to address the current lack of data examining the health outcomes associated with informal sport participation and consider the potential role of informal sport within efforts to promote healthier communities through sport. The article seeks to broaden understanding of how informal sport participation can contribute to health outcomes, particularly with regard to increasing physical activity and enhancing mental health and social connection. The article discusses the findings of an Australian mixed-method study that draws on observation, survey, interview and focus group data to examine the prospective health and social benefits of informal sport participation for adults. The findings demonstrate that informal sport participation can contribute to physical and mental health outcomes and facilitate social connection. Analysis of the observation data enabled an examination of the economic value of informal sport in relation to the health benefits it affords. The study provides valuable evidence of the value of informal sport for enhancing community health and broadens understanding of how sport can be utilized as a health promotion resource. The article concludes by suggesting that through leveraging existing infrastructure and the self-organizing aspects of informal sport, local government and health stakeholders can harness its potential to improve public health outcomes and address health inequities.
Extended-sleeve resection for endoluminal recurrence of B3 thymoma: does aerogenous spread really exist?
Authors: Tombelli Simone , Bongiolatti Stefano , Pasini Valeria , Voltolini Luca
Published: May 2024

Thymomas are a variant of thymic epithelial tumours. They are considered malignant due to their tendency to local invasion and they showed lower metastatic behaviour. Distal metastasis is rare and an endobronchial mass is a rare presentation. First-line treatment for early-stage thymomas is surgery; for Masaoka–Koga stage III, neoadjuvant or adjuvant chemoradiation therapy should be considered in association with surgery after Multidisciplinary Tumour Board evaluation. We report a rare case of radical resection with type A extended-sleeve lobectomy in a 63-year-old woman who was affected by endobronchial recurrence of B3 thymoma, 31 months after complete and radical thymectomy.
Experiences of community pharmacists in the United Kingdom on the provision of travel health services and associated educational requirements
Authors: Goodyer Larry , Evans Derek , Wilson Amanda , Palit Piali , Ma Christopher , Lister Helen R , Poletti Tiziano
Published: May 2024

Background

Travel health services play a critical role in public health. Previously, travel services were provided solely through GPs or private specialist clinics. In recent years, they have been available from community pharmacists in the UK. This study sought to understand the types of travel health services provided by community pharmacists and to establish the educational needs.

Method

Qualitative interviews and focus groups explored current practices and educational needs in travel medicine. Thematic analysis of transcribed interviews and focus groups was conducted to understand how travel services are provided and the training undertaken by community pharmacists in delivering these services.

Results

Nine individual interviews and one focus group of seven additional pharmacists was conducted. Pharmacists considered that they provided a comprehensive service and undertook the necessary training for safe delivery. Pharmacists described a ‘vaccine centric’ approach to travel services, with aspects, such as management of chronic conditions, fitness/preparedness for travel, prevention and self-management of travel-related conditions considered to be of lower priority. This was reflected in the travel medicine education that they had received and their perception of future requirements.

Conclusion

Whilst vaccination is a critical aspect of travel health medicine, taking a ‘vaccine centric’ approach represents a missed opportunity in public health. Future educational opportunities for pharmacists could include training that encourages a broader approach to travel health consultations, to include a co-created, structured, and holistic risk assessment for travellers and recommendations for appropriate prevention and management strategies for travellers prior to, during and after travel.
On a Theorem of Lafforgue
Authors: Baker Matthew , Lorscheid Oliver
Published: May 2024

We give a new proof, along with some generalizations, of a folklore theorem (attributed to Laurent Lafforgue) that a rigid matroid (i.e., a matroid with indecomposable basis polytope) has only finitely many projective equivalence classes of representations over any given field.