bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative evaluation of coronary artery calcium and vascular function by hybrid rubidium-82 PET/CT imaging in heart transplanted patients
Authors: Mannarino T , Assante R , Zampella E , D'antonio A , Cacciatore F , Amarelli C , Falzarano M , Mattucci I , Chiappetti R , Gaudieri V , Buongiorno P , Panico M , Maiello C , Cuocolo A , Acampa W
Published: June 2024

Aim/Introduction

Cardiac myocardial perfusion imaging (MPI) by positron emission tomography (PET)/ computed tomography (CT) represents a noninvasive method used for an integrated measurement of myocardial blood flow (MBF), myocardial flow reserve (MFR) and coronary artery calcium (CAC) content. No study has investigated the relationship between coronary atherosclerotic burden and vascular function in heart transplanted patients. Thus, we assessed the relationship between CAC score, MBF and MFR in heart transplant patients undergoing hybrid 82Rb positron emission tomography (PET)/computed tomography (CT) imaging.

Materials and Methods

We enrolled a total of 100 (mean age 60±13 years) consecutive patients referred to hybrid 82Rb PET/CT myocardial perfusion imaging for evaluation of myocardial ischemia. CAC score was measured according to the Agatston method and patients were categorized into 4 groups (0, 0.01-99.9, 100-399.9, and ≥400). Baseline and hyperemic MBF were automatically quantified. MFR was calculated as the ratio of hyperemic to baseline MBF and it was considered reduced when <2. The Spearman correlation coefficient was assessed between continuous CAC score and MBF or MFR values. Univariable and multivariable logistic regression analyses were used to determine the variables associated with reduced MFR.

Results

Global CAC score showed a significant inverse correlation with hyperemic MBF (r=-0.28, P < .05) and MFR (r=-0.40, P < .001), while no correlation between CAC score and baseline MBF was found (P = 0.9). CAC score was zero in 71 (71%) patients, 0.1-99.9 in 8 (8%), 100-399.9 in 12 (12%), and ≥400 in 9 (9%). Global baseline MBF was comparable among the four groups of patients at different levels of CAC score (F = 0.040, P = 0.989). Whereas hyperemic MBF (F = 2.897) and MFR (F = 4.344) progressively decreased with increasing CAC levels (P for trend <0.05). Univariable analysis demonstrated that age, diabetes, and CAC score (all P < .05) were associated with reduced MFR. At multivariable logistic regression analysis only age and CAC score (both P < .05) were independently associated with reduced MFR. The addition of CAC score to clinical data, increased the global chi-square value for predicting reduced MFR from 18.79 to 25.66 (P < .01).

Conclusion

In heart transplanted patients there was an inverse relationship between CAC score and MFR. The evaluation of calcium content might be helpful for identifying patients with a reduced MFR, at high risk to develop cardiac allograft vasculopathy.MBF across CAC score categories  MFR across CAC score categories
Ischaemic burden reduction and impact on absolute perfusion in remote myocardium after chronic total occlusion percutaneous coronary intervention
Authors: Carlos T , Leite L , Campos G , Rocha L , Silva R , Abrunhosa A , Gomes A , Castelo-Branco M , Goncalves L , Ferreira M J
Published: June 2024

Background

Chronic total coronary occlusion (CTO) poses a complex challenge in angiographic hemodynamics. Blood supply to the affected myocardium is dependent on the formation of collateral network from adjacent vessels. However, this coronary steal phenomenon reduces myocardial blood flow (MBF) to the remote myocardium, particularly under stress conditions. Limited data exist on myocardial quantitative perfusion alterations in both these regions following intervention.

Purpose

To assess the effect of percutaneous coronary intervention (PCI) on MBF (measured in mL.min-1.g-1) in both CTO territory and remote myocardium, using [13N]NH3 positron emission tomography computed tomography (PET-CT).

Methods

We conducted a single-centre prospective study on patients with CTO, who had myocardial quantitative perfusion evaluation by [13N]NH3 PET-CT both pre- and post- PCI. Patients with no indication for PCI according to prevailing guidelines, inadequate follow-up, insufficient data or absence of either pre- or post- procedure [13N]NH3 PET-CT were excluded.

Results

Within our cohort of 19 patients with CTO, 13 individuals underwent PCI and pre- and post- procedural assessment using [13N]NH3 PET-CT. The mean age was 68 years (± 4.3) and 76.9% were male. Following PCI, hMBF demonstrated significant improvement in the CTO territory (Δ 0.36 ± 0.34, p=0.003), whereas no statistically significant differences were observed in the remote myocardium (Δ 0.05 ± 0.21, p=0.423). At rest, MBF did not significantly change after PCI in either CTO territory (Δ 0.06 ± 0.21, p=0.351) or remote myocardium (Δ 0.04 ± 0.16, p=0.444). Myocardial flow reserve also showed no statistically significant differences between the two groups. Notably, alterations in MBF in the CTO territory exhibited a strong linear correlation with the corresponding changes in the remote myocardium (hMBF: r=0.732, p=0.004; rMBF: r=0.958, p<0.001).

Conclusion

PCI enhanced myocardial perfusion, mainly in stress conditions and in the CTO dependent territory. Restoring blood flow through the CTO vessel normally results in regression of the collateral network and subtly improves perfusion of the remote myocardium. In our study, this effect was more pronounced when there was a greater improvement in the CTO territory perfusion, likely due to a previously larger coronary steal phenomenon, that diminished after PCI.  Figure 1
Myocardial ischemic burden and angiographic assessment of collateral network in patients with chronic total coronary occlusion
Authors: Carlos T , Bahadoran A , Leite L , Campos G , Rocha L , Silva R , Gomes A , Abrunhosa A , Castelo-Branco M , Goncalves L , Ferreira M J
Published: June 2024

Background

Chronic total coronary occlusion (CTO) myocardial territories maintain perfusion via collateral circulation from adjacent vessels, thereby preventing transmural myocardial infarction and partially preserving ventricular function. The collateral network may be categorized based on its angiographic characteristics, using either Rentrop or Werner classification, which may be used to evaluate the need for revascularization. Nevertheless, their relationship with myocardial ischemic burden is not entirely established.

Purpose

To assess whether collateral angiographic characteristics of patients with CTO have an impact on quantitative myocardial ischemic burden, evaluated by [13N]NH3 positron emission tomography computed tomography (PET-CT).

Methods

We conducted a single-centre observational prospective study on patients with CTO who had angiographic characteristics assessed by coronariography and quantitative myocardial perfusion in CTO territory measurements assessed by [13N]NH3 PET-CT, using the quantification software PCARDP (PMOD Cardiac PET Analysis Tool). Patients with insufficient data were excluded. Well developed (WD) collaterals were defined as a concomitant angiographic Rentrop grade 3 and Werner collateral connection score 2 or 3, whereas the remaining were categorized as poorly developed (PD).

Results

A total of 15 patients, with a mean age of 66.8 years (±4.2) and a male prevalence (80%) were included. The most affected artery was the right main coronary artery (60%). Regarding collateral evaluation, 9 patients (60%) had WD collateral circulation. When comparing myocardial ischemic burden using quantitative parameters, no statistically significant differences were observed between patients exhibiting WD and PD collateral circulation (hyperaemic myocardial blood flow, measured in mL.min-1.g-1: WD 1.24±0.53 vs. PD 1.25±0.38, p=0.971; rest myocardial blood flow, measured in mL.min-1.g-1: WD 0.66±0.17 vs. PD 0.74±0.32, p=0.513; myocardial flow reserve: WD 1.91±0.59 vs. PD 1.91±0.81, p=0.893).

Conclusion

The angiographic evaluation of collateral network and subsequent categorization in WD and PD collaterals in patients with CTO revealed no significant association with the observed myocardial ischemic burden in these patients. Therefore, its utility to guide decisions concerning percutaneous intervention benefit should be used cautiously.
Physical performance can be improved by revascularization if treatment decision is guided by quantitative assessment of myocardial perfusion using cardiac positron emission tomography
Authors: Akil S , Szekely A S , Mosen H , Hedeer F , Arheden H , Engblom H
Published: June 2024

Background

Revascularization in patients with chronic coronary syndrome (CCS) is performed to improve patient prognosis and/or to alleviate ischemic symptoms and thereby possibly improve patient physical capacity. To select patients with suspected CCS that would benefit from revascularization, current guidelines (1) recommend assessment of myocardial perfusion prior to treatment decision. However, revascularization decisions are still often only guided by presence of coronary stenoses on coronary angiography.

Purpose

The aim of this study was to investigate how patient physical performance is affected by revascularization of vessel territories which prior to treatment show reduced myocardial perfusion reserve (MPR) in relation to territories with normal MPR as assessed by quantitative cardiac positron emission tomography (PET).

Methods

Twenty-eight patients (11 females) with suspected CCS, referred for a clinical coronary angiography (CA), were included. All patients performed a baseline cardiopulmonary exercise test (CPET) for assessment of physical performance and stress/rest cardiac 13NH3-PET 4±4 weeks before CA. A follow-up CPET examination was performed 7±2 months after the CA. By study design, the angiographer making the decision to perform a revascularization was blinded to the CPET and PET data. MPR was calculated from stress/rest dynamic cardiac PET images according to the 17-segment model (excluding apex) (2) for each vessel territory separately (LAD, RCA and LCx), and MPR <2.0 was considered reduced. Physical performance was assessed from the CPET by calculating peak oxygen uptake (VO2peak) expressed as percentage of predicted maximum.

Results

A revascularization was performed in 21/28 patients (32 vessel territories). Figure 1 shows that a higher proportion of patients with vessel territories showing MPR<2.0 at baseline improved in VO2peak compared to those with an MPR>2.0 (79% [11/14] vs 14% [1/7], p=0.02). In 3/7 patients that were not revascularized, MPR was <2.0 at baseline. All three of them had decreased VO2peak at follow-up compared to baseline.

Conclusion

Patient physical performance improves when vessel territories with reduced MPR are revascularized but not if MPR is normal. Thus, quantitative assessment of myocardial perfusion by cardiac PET prior to coronary intervention may enable appropriate selection of patients that will benefit from revascularization.
Fibroblast activation following myocardial infarction and left ventricular remodelling
Authors: Barton A K , Tzolos E , Craig N , Loganath K , Joshi S , Fletcher A , Van Beek E , Slomka P , Newby D , Dweck M
Published: June 2024

Background

Novel molecular positron emission tomography (PET) assessments of fibrosis are now available but have not been compared directly to cardiovascular magnetic resonance (CMR), the current reference standard for myocardial scar assessment. Using 68Gallium-fibroblast activation protein inhibitor (FAPI), a radiotracer that binds to activated fibroblasts, we compared CMR and PET assessments of myocardial scar following ST-elevation myocardial infarction.

Methods

Hybrid 68Ga-FAPI-46 PET/MR with gadolinium-based contrast agent was performed in 40 patients within 4 weeks of acute ST-elevation myocardial infarction (acute STEMI) with 19 returning at 12 weeks for repeat PET/MR (subacute STEMI). Scar burden (%LGE) was measured on late enhancement short axis CMR images (Circle Cardiovascular Imaging software, Canada). Volume and intensity of global myocardial 68Ga-FAPI uptake was quantified (QPET, Cedars Sinai, Los Angeles) to determine the volume myocardium with tracer uptake (%68Ga-FAPI) and intensity of PET signal (target-to-background ratio, TBRmax) after correcting for right atrial blood-pool activity.

Results

In acute STEMI, high intensity uptake of 68Ga-FAPI was observed localized to the infarct. The area of fibroblast activation greatly exceeded the area of scar detected by late gadolinium enhancement (LGE) (%68Ga-FAPI 26.6+-15.4% vs 14.5+-11.4%, p<0.001). 68Ga-FAPI volume and intensity declined between acute and subacute STEMI (%68Ga-FAPI 26.6+-15.4% vs 12.8+-8.1%, p<0.001, TBRmax 3.9+-1.1 vs 2.7+-0.7, p<0.001). By week 12, there was no difference between the area of fibroblast activation detected by 68Ga-FAPI uptake and area of scar detected by LGE (%68Ga-FAPI 12.8+-8.1% vs %LGE 10.3+-6.1%, ns).

Conclusion

Molecular PET assessments of myocardial scar formation provide different but complementary information to structural assessments of myocardial scar. Fibroblast activation following myocardial infarction is a dynamic process that can be non-invasively measured for the first time by 68Ga-FAPI PET.
Left bundle branch block predicts inadequate glucose metabolism suppression in [18F]-FDG PET/CT
Authors: Hartikainen S , Tompuri T , Laitinen T M , Hedman M , Laitinen T
Published: June 2024

Introduction

Inadequate glucose metabolism suppression (GMS) may hamper diagnostics of inflammatory cardiac diseases in cardiac [18F]-FDG PET/CT. Even with successful one-day ketogenic diet with elongated fasting with or without heparin premedication, studies show inadequate GMS in 20-30 % of cases. Patient-to-patient variation of GMS is not well understood. Left bundle branch block (LBBB) is associated with altered myocardial perfusion and heterogenous myocardial glucose metabolism in viability imaging.(1,2) However, there are no reports on LBBB associated inadequate GMS in inflammation imaging with [18F]-FDG PET/CT.

Purpose

The aim of our study was to recognize variables that lead to inadequate GMS.

Methods

60 patients (31 male) with known or suspected inflammatory cardiac disease were recruited for this study. Cohort included twelve patients with LBBB. All patients had followed the ketogenic diet for one day and fasted for at least 12 hours before imaging. Blood β-hydroxybutyrate (BHB) level was measured both with a point-of-care device and in laboratory. Blood glucose, cholesterol, high- and low-density lipoproteins (HDL and LDL), triglyceride and free fatty acid (FFA) levels were measured in laboratory. HOMA-IR was calculated from glucose and insulin levels. Those whose point-of-care measured BHB was less than 0.35 mmol/l, received unfractionated heparin 50 IU/kg 15-20 min before FDG-injection. FDG uptake was measured from PET imaging data as maximal standardized uptake values (SUVmax) from eight 1 cm diameter regions of interest in the left ventricle lateral wall and septum, and mean of those was calculated (SUVlv), and one region of interest in the left ventricle blood pool background (SUVbackground). Adequate GMS was defined as SUVlv/SUVbackground (SUVratio) ≤ 1. Spearmans ρ was used to evaluate bivariate correlations between SUVratio and other variables. Continuous variables were tested using the Mann-Whitney U test and categorical variables using the chi-square test.

Results

Median SUVratio was 0.84 (min-max 0.45-12.98), with adequate GMS in 40 patients (67 %). Median BHB was 0.4 mmol/l (0.1-3.0 mmol/l) with point-of-care device and 0.30 mmol/l (0.0-2.49 mmol/l) with laboratory analysis. Median HOMA-IR was 1.96 (0.28-13.22, and triglyceride level 0.99 mmol/l (0.44-7.33 mmol/l). Variables that correlated with SUVratio were BHB level (r=-0.310, p=0.017 for point-of-care, r=-0.378, p=0.01 for laboratory analyzed), triglyceride level (r=-0.367, p=0.004), FFA (r=-0.386, p=0.003). Median SUVratio was 1.17 (0.66-4.88) in those with LBBB and 0.80 (0.45-12.98) in those without LBBB (p=0.044). There was no difference between LBBB and no-LBBB groups in variables that correlated with adequate GMS.

Conclusion

Patients with LBBB seem to have poorer GMS response to the ketogenic diet and a longer diet with these individuals should be considered. Studies with larger cohort to analyze underlying pathophysiology is needed.
FDG PET/CT of AtriClip left atrial appendage closure device: always active, infected or not
Authors: Scholtens A
Published: June 2024

Introduction

FDG PET/CT is used increasingly for the diagnosis of cardiac implant infection, with the newly revised ESC guidelines further cementing its role. Data show the accuracy of FDG PET/CT in diagnosing infection varies between different types of implants. The AtriClip, a left atrial appendage closure device, is becoming more common in clinical practice, but there is little knowledge regarding the normal variation of FDG uptake surrounding these devices.

Purpose

To describe and better understand the appearance of AtriClip devices on FDG PET/CT.

Methods

We retrospectively searched FDG PET/CT reports for the terms "AtriClip" or "Atrial closure device". Scans with AtriClips in situ were re-evaluated and SUVmax and SUVratio (compared to aortic blood pool) were measured on EARL 1.0 reconstructions. We compared the findings in scans performed for a suspicion of infection with scans performed for other indications. SUV findings were compared with students' T-test.

Results

We retrieved 13 scans in 8 patients. 9 were performed for suspicion of infection, 3 for cancer (1 lungcarcinoma, 2 coloncarcinoma) and 1 for sarcoidosis. There was increased FDG uptake surrounding the AtriClip on all FDG PET/CT scans, with no obvious visual differences between scans performed for infection and scans performed for other indications (Figure 1). There were no statistical differences between SUVmax or SUVratio (Figure 2), with SUVmax (mean ± SD) 5.4 ± 0.8 versus 4.8 ± 0.4 (p=0.118) and SUVratio 2.63 ± 0.45 versus 2.88 ± 0.38 (p=0.204), for infection and other indications respectively.

Conclusions

FDG uptake occurs commonly around AtriClip devices, and does not imply or differentiate infection.Scans for infection (A) and cancer (B).  SUV measurements surrounding AtriClips.
Molecular imaging of the immune-fibrosis axis to guide therapeutic intervention after myocardial infarction
Authors: Strunk M , Fernandez-Mayola M , Hess A , Al-Bazaz S , Ross T L , Bengel F M , Thackeray J T
Published: June 2024

Objectives

Myocardial infarction evokes inflammation and activation of quiescent cardiac fibroblasts, leading to heart failure progression. We hypothesized that targeted molecular imaging of fibroblast activation protein (FAP) on activated fibroblasts could predict subsequent remodeling and monitor fibroblast response to anti-inflammatory therapy.

Methods

In vitro uptake of 68Ga-FAPI-46 was assessed in human cardiac fibroblasts stimulated by supernatant from inflammatory macrophages. C57Bl/6 mice underwent 60min left coronary artery ischemia/ reperfusion (I/R) (n=22) or sham (n=7). Serial 68Ga-FAPI-46 and 18F-FDG PET imaging was performed 1d, 3d, 7d, 14d and 42d after surgery. Left ventricle (LV) function and perfusion defect size were assessed by MRI and SPECT at 6wks. Additional animals were treated with anti-inflammatory enalapril and similarly scanned.

Results

Exposure to M1-like macrophage supernatant increased 68Ga-FAPI46 uptake by cardiac fibroblasts (p=0.01), associated with higher expression of IL-1β (p<0.05) and TGF-β (p=0.003). I/R induced moderate infarct size at 6wks post I/R (18.1±5.3% of LV). I/R animals exhibited increased LV volumes compared to sham (systole, 38±7 vs 21±4µL, p<0.001; diastole, 69±9 vs 49±4µL, p<0.001) and decreased LV ejection fraction (EF)(46±10 vs 58±2%, p<0.001). Serial FAP imaging revealed biphasic upregulation in the infarcted myocardium. Signal intensity 3d after injury was significantly increased (%ID/g, 0.69.±0.1 vs 1.3±0.3, p<0.001). After declining to sham levels at 7d, signal was again elevated 14d after I/R(%ID/g 0.70±0.1 vs 0.94±0.1, p=0.05) before returning to sham levels at 6wks. Signal increase was not restricted to infarct area, but similarly observed in non-infarcted remote myocardium at 3d (p<0.001) and 14d (p<0.05), suggesting involvement of both replacement and reactive fibrosis. There is modest inverse correlation between 3d infarct area FAPI signal and LVEF 6wks later (r=-0.43, p<0.05), but stronger with 14d FAPI signal (r=-0.51, p<0.05). Assuming the elevation at 3d would reflect inflammatory cell infiltration and lead to replacement fibrosis, whereas the later wave would derive from interstitial fibrosis, we treated animals with ACE inhibitor enalapril for 10d, beginning 2d prior to surgery to prevent mobilization of myeloid cells from the spleen. FAPI signal was significantly reduced in the infarct area in enalapril-treated mice at 3d (p=0.05), supporting the notion that early FAP expression is regulated by inflammatory environment.

Conclusions

Molecular imaging of FAP provides a prognostic biomarker of subsequent remodeling reflecting both early inflammation driven replacement and later interstitial fibrosis, ultimately supporting its capacity to monitor novel therapies.
Cardiac amyloidosis beyond Perugini. Can diphosphonate scan tell you more?
Authors: Pereira B , Albergueiro R , Soeiro P
Published: June 2024

Introduction

Cardiac transthyretin amyloidosis is a restrictive cardiomyopathy that poses a diagnostic challenge due to its rarity and overlapping clinical symptoms with other diseases. While [99mTc]Tc-diphosphonate has proven to be sensitive for detecting ATTR, there remains a gap in understanding the correlation between the intensity of cardiac uptake and disease severity.

Purpose

The aim of this study is to investigate whether there is a correlation between the intensity grade and specific clinical and analytical parameters in patients with ATTR amyloidosis.

Methods

A single-tertiary center observational, retrospective, and longitudinal study was conducted, encompassing patients aged ≥ 18 years who underwent bone scintigraphy with [99mTc]Tc-DPD or [99mTc]Tc-HMDP from 2020 to 2021. Inclusion criteria involved patients witha Perugini score of ≥2. Exclusion criteria were applied to individuals lacking follow-up information. Planar anterior images of the chest were reprocessed to assess the maximum and average uptake within regions of interest, encompassing both the heart and the contralateral thoracic region. Clinical, analytical, and imaging data were extracted from available digital records. Statistical analyses using single and multiple linear regression were conducted using R software.

Results

33 patients met the inclusion criteria (85% men, average age: 79 ± 10 years old). Sixteen patients were classified as grade 2, while 17 were classified as grade 3 on the Perugini amyloidosis scale. The radiopharmaceutical used was [99mTc]Tc-HMDP in 25 patients. The main referring specialties were internal medicine (55%) and cardiology (30%). One patient was referred for bone metastasis, and amyloidosis was an incidental finding. Twenty nine patients had hypertension, 21 had atrial fibrillation, 18 were dyslipidemic, 14 had aortic stenosis, 13 had diabetes mellitus, 6 had chronic kidney disease, and 5 had obstructive airway disease. All patients exhibited left ventricular hypertrophy on echocardiography, the average ejection fraction was 50 ± 12 (58% with preserved ejection fraction), septal thickness of 15.87 ± 2.26 mm and relative myocardial wall thickness was 0.60 ± 0.16 mm. Several patients had degenerative articular disease (11 hip prosthesis, 3 carpal tunnel syndrome surgeries, 3 vertebral surgeries).

There were statistically significant associations between an older age and a higher ratio of average counts and the presence of aortic stenosis and a higher ratio of maximum counts. No other correlation was found for other ATTR manifestations (neurological, muscular or cardiac).

Conclusion

Higher intensity of [99mTc]Tc-diphosphonate uptake ratios in ATTR seem to be correlated with aortic stenosis and older age.
Atrial fibroblast activity and atrial fibrillation
Authors: Loganath K , Lakshmanan S , Craig N , Vickneson K , Whittington B , Joshi S , Barton A , Newby D , Williams S , Dweck M
Published: June 2024

Introduction

Atrial fibrosis is a key factor in the development of atrial fibrillation (AF)(1). 68Gallium-labelled fibroblast activation protein inhibitor (68Ga-FAPI) binds to activated fibroblasts, enabling the tracking of fibroblast activation and fibrosis activity (2).

Methods

Participants with heart failure with preserved ejection fraction (HFPEF), aortic stenosis (AS) and healthy volunteers underwent 68Ga-FAPI PET, cardiac magnetic resonance (CMR) imaging and echocardiography. 2 analysers were blinded to the AF status of the participants. Regions with increased visual PET uptake were identified in the atria, their position recorded and the intensity of 68Ga-FAPI activity quantified. When no regions of increased activity were identified regions of interest were drawn in the atrial septum. Maximum standardised uptake values (SUVmax) were recorded and maximum tissue-to-background ratios (TBRmax) were calculated.

Results

In this initial analysis of an ongoing study, 40 (28 with aortic stenosis, 8 with heart failure with preserved ejection fraction and 3 healthy volunteers) participants underwent 68Ga-FAPI PET imaging. 11 participants had AF (2 paroxysmal, 9 persistent). A total of 47 regions of increased visual uptake were identified. All participants with AF demonstrated increased visual 68Ga-FAPI PET in the cardiac atria, which commonly localised to the left atrial wall and the point of insertion of the pulmonary veins into the left atrium. 14 (48.3%) participants without AF demonstrated increased 68Ga-FAPI uptake in their atria. Upon quantification participants with AF had increased 68Ga-FAPI uptake in their atria, with higher SUVmax [2.30 (0.39) in AF vs 1.86 (SD 0.35) without; p<0.05] and TBRmax values [ 1.58 (SD 0.23) in AF vs 1.39 (SD 0.32) without; p<0.05] (Figure 1). In participants without AF, the TBRmax of regions of interest drawn in the atrial septum correlated moderately with left atrial diameter (r=0.50, p= 0.01) on echocardiography

Conclusion

Participants with atrial fibrillation have increased 68Ga-FAPI activity in their cardia atria compared with participants without AF. This technique holds major promise in improving our understanding of fibrosis activity in the pathogenesis of atrial fibrillation.Figure 1
Preventive medication efficacy after 1-year follow-up for graft failure in coronary artery bypass surgery patients: Bayesian network meta-analysis
Authors: Uimonen Mikko , Liukkonen Rasmus , Ponkilainen Ville , Vaajala Matias , Tarkiainen Jeremias , Pakarinen Oskari , Haapanen Marjut , Kuitunen Ilari
Published: June 2024

To compare preventive medications against graft failures in coronary artery bypass graft surgery (CABG) patients after a 1-year follow-up. Systematic review with Bayesian network meta-analysis and meta-regression analysis. We searched PubMed, Scopus, and Web of Science databases in February 2023 for randomized controlled trials, comparing preventive medications against graft failure in CABG patients. We included studies that reported outcomes at 1 year after surgery. Our primary outcome was graft failure After screening 11,898 studies, a total of 18 randomized trials were included. Acetylsalicylic acid (ASA) [odds ratios (OR) 0.51, 95% credibility interval (CrI) 0.28–0.95, meta-regression OR 0.54, 95% CrI 0.26–1.00], Clopidogrel + ASA (OR 0.27, 95% CrI 0.09–0.76, meta-regression OR 0.28, 95% CrI 0.09–0.85), dipyridamole + ASA (OR 0.50, 95% CrI 0.30–0.83, meta-regression OR 0.49, 95% CrI 0.26–0.90), ticagrelor (OR 0.40, 95% CrI 0.16–1.00, meta-regression OR 0.43, 95% CrI 0.15–1.2), and ticagrelor + ASA (OR 0.26, 95% CrI 0.10–0.62, meta-regression OR 0.28, 95% CrI 0.10–0.68) were superior to placebo in preventing graft failure. Rank probabilities suggested the highest likelihood to be the most efficacious for ticagrelor + ASA [surface under the cumulative ranking (SUCRA) 0.859] and clopidogrel + ASA (SUCRA 0.819). The 95% CrIs of ORs for mortality, bleeding, and major adverse cardio- and cerebrovascular events (MACE) were wide. A trend towards increased bleeding risk and decreased MACE risk was observed when any of the medication regimens were used when compared to placebo. Sensitivity analysis excluding studies with a high risk of bias yielded equivalent results. Of the reviewed medication regimens, dual antiplatelet therapy combining ASA with ticagrelor or clopidogrel was found to result in the lowest rate of graft failures.
Allocation of Female Talent and Cross-Country Productivity Differences
Authors: Lee Munseob
Published: June 2024

Cross-country disparities in labour productivity are more pronounced in agriculture than other sectors. I posit that the misallocation of female talent between sectors distorts productivity and formalise a general equilibrium Roy model with gender-specific frictions. If female workers encounter greater barriers in non-agricultural sectors, female workers who are better skilled at non-agricultural jobs may select into the agricultural sector. Analysis of data from sixty-six countries reveals that low-income countries have higher frictions against female workers in non-agricultural sectors. By aligning these frictions with those of the United States, agricultural labour productivity sees gains of 2.5%–7.6%, with GDP per capita rising by 0.5%–1.5% on average.
Long-term outcomes of isolated mechanical versus bioprosthetic mitral valve replacement in different age groups of propensity-matched patients
Authors: Rokui Sorush , Gottschalk Byron , Peng Defen , Groenewoud Rosalind , Ye Jian
Published: June 2024

OBJECTIVES

Prothesis choice in isolated mitral valve replacement for patients aged 75 years or younger remains debated as most studies comparing prothesis type have included large proportions of combined operations and benefits are influenced by concomitant procedures. This study compared long-term outcomes of isolated mechanical versus bioprosthetic mitral valves in different age groups of propensity-matched populations.

METHODS

This is a retrospective, multicentre, propensity-matched observational study. Baseline characteristics, operative details and long-term outcomes (mortality and freedom from surgical/transcatheter reintervention) were collected.

RESULTS

Totally, 1536 isolated mitral valve replacements (806 mechanical, 730 bioprosthetic) were performed between 2000 and 2017. Over 90% of eligible patients successfully underwent propensity matching, yielding 226 each of mechanical and bioprosthetic valves in patients aged <65 years and 171 each of bioprosthetic and mechanical valves in patients aged 65–75 years with median follow-up of 13 years (maximum 20 years). In matched patients <65 years, 10-year survival was superior with mechanical valves versus bioprosthetic valves (78.2% vs 69.8%, P = 0.029), as was 10-year freedom from reintervention (96.2% vs 81.3%, P < 0.001). For matched patients between 65 and 75 years, there were no differences between mechanical and bioprosthetic valves in 10-year survival (64.6% vs 60.8%, P = 0.86) or 10-year freedom from reintervention (94.0% vs 97.2%, P = 0.23). Rates of post-operative stroke, gastrointestinal bleeding, renal failure and permanent pacemaker insertion were similar.

CONCLUSIONS

In patients requiring isolated mitral valve replacement, mechanical valves confer significantly better long-term survival and freedom from reintervention for patients <65 years, while no benefit is observed at age 65–75 years compared to bioprosthetic valves.
A hierarchical structure in the N-glycosylation process governs the N-glycosylation output: prolonged cultivation induces glycoenzymes expression variations that are reflected in the cellular N-glycome but not in the protein and site-specific glycoprofile of CHO cells
Authors: Arigoni-Affolter Ilaria , Losfeld Marie-Estelle , Hennig René , Rapp Erdmann , Aebi Markus
Published: June 2024

N-glycosylation is a central component in the modification of secretory proteins. One characteristic of this process is a heterogeneous output. The heterogeneity is the result of both structural constraints of the glycoprotein as well as the composition of the cellular glycosylation machinery. Empirical data addressing correlations between glycosylation output and glycosylation machinery composition are seldom due to the low abundance of glycoenzymes. We assessed how differences in the glycoenzyme expression affected the N-glycosylation output at a cellular as well as at a protein-specific level. Our results showed that cellular N-glycome changes could be correlated with the variation of glycoenzyme expression, whereas at the protein level differential responses to glycoenzymes alterations were observed. We therefore identified a hierarchical structure in the N-glycosylation process: the enzyme levels in this complex pathway determine its capacity (reflected in the N-glycome), while protein-specific parameters determine the glycosite-specificity. What emerges is a highly variable and adaptable protein modification system that represents a hallmark of eukaryotic cells.
Caregivers’ experience of caring for family members with complex health needs in Latvia
Authors: Petrova Indra , Pipere Anita
Published: June 2024

The article examines the experiences of family caregivers engaged in the provision of long-term care for their relatives with complex health needs within the Latvian context. Semi-structured interviews were conducted with seven caregivers who provide care in cases of dementia, depression, schizophrenia, opioid use, Down syndrome and mild cognitive impairment. A thematic analysis of interview transcripts revealed common themes, such as the initial experiences when encountering a family member’s disorder and the subsequent reactions, as well as the quest for support and resources. Variations mainly centered around differences in formal aspects and childhood experiences of care. Caregivers reported risk factors such as guilt, lack of support from family and friends, financial difficulties, deficiency of professional care and ignoring the caregiver’s own needs. Awareness of personal resources, values and limits, coping with personal stigma and improved overall quality of life were identified as protective factors. The findings underscore several preventive measures that social and mental health services could implement to mitigate the adverse effects of caregiving on caregivers’ lives.
Using Holocaust Education as a “Bridge” to Learning about Apartheid in a South African History Classroom: The Development of “Interpretive Frames” through Comparative Histories
Authors: Robinson Natasha
Published: June 2024

The Grade 9 South African history curriculum teaches the history of the Holocaust as an introduction to the study of apartheid. Students are taught how racial identities are constructed, codified into law, and weaponized for the purposes of discrimination and genocide. They are taught that racialized discrimination can happen anywhere—not only in South Africa—and that we must be vigilant lest it happens again. Curriculum developers—supported by international literature (e.g., UNESCO publications)—believe that learning about the Holocaust will act as a “bridge” to learning about apartheid.1 By teaching young South Africans difficult history that is emotionally, geographically, and temporally removed from their own country, educators believed that students will be better prepared to study the complex history of apartheid. Yet what is the impact of this comparative approach?2 The author’s ten-month ethnographic study explores how Grade 9 students in one majority-White history classroom in Cape Town learned about the Holocaust and apartheid. Developing Epstein’s idea of an “interpretive frame,”3 this empirical study contributes to ongoing debates on whether and how genocides and other atrocities can be meaningfully compared in the history classroom.4 Furthermore, it questions whether using Holocaust education as a “bridge”5 to domestic injustices and persecution will significantly improve historical understanding, tolerance, and moral reasoning.
Revisiting trophectoderm-inner cell mass lineage segregation in the mammalian preimplantation embryo
Authors: Skory Robin M
Published: June 2024

In the first days of life, cells of the mammalian embryo segregate into two distinct lineages, trophectoderm and inner cell mass. Unlike nonmammalian species, mammalian development does not proceed from predetermined factors in the oocyte. Rather, asymmetries arise de novo in the early embryo incorporating cues from cell position, contractility, polarity, and cell–cell contacts. Molecular heterogeneities, including transcripts and non-coding RNAs, have now been characterized as early as the 2-cell stage. However, it’s debated whether these early heterogeneities bias cells toward one fate or the other or whether lineage identity arises stochastically at the 16-cell stage. This review summarizes what is known about early blastomere asymmetries and our understanding of lineage allocation in the context of historical models. Preimplantation development is reviewed coupled with what is known about changes in morphology, contractility, and transcription factor networks. The addition of single-cell atlases of human embryos has begun to reveal key differences between human and mouse, including the timing of events and core transcription factors. Furthermore, the recent generation of blastoid models will provide valuable tools to test and understand fate determinants. Lastly, new techniques are reviewed, which may better synthesize existing knowledge with emerging data sets and reconcile models with the regulative capacity unique to the mammalian embryo.
Counting Arcs of the Same Type
Authors: Trin Marie
Published: June 2024

We prove a general counting result for arcs of the same type in compact surfaces. We also count infinite arcs in cusped surfaces and arcs in orbifolds. These theorems are derived from a result that ensures the convergence of certain measures on the space of geodesic currents.
The Ripple Effects of the Illegitimacy of War
Authors: O'Mahoney Joseph
Published: June 2024

Abstracts

Recent data show systematic changes in the diplomacy and practice of war. Conquests, peace treaties, declarations of war, and state boundary changes have declined or disappeared. There are still wars, but they are increasingly fait accomplis, and their outcomes are often not recognized as legal. How can we explain this wide-ranging but seemingly contradictory transformation? Existing accounts, such as those based on a territorial integrity norm, do not adequately explain these changes. This paper uses norm dynamics theory to show that all of these changes can be explained as ‘ripple effects’ of war becoming illegitimate as a way to solve international disputes. The kinds of rhetorical justifications states can convincingly give for engaging in violence have changed. States are navigating this changed international social environment through legitimacy management behaviors. The paper specifies three types of ripple effect, Reframing, Displacement, and Consistency-Maintenance, corresponding to changes in what states say, the actions they perform, and how the audience reacts. We show how this theory unifies all of the existing data into a single explanatory framework. We also apply the theory to the decline of peace treaties to show how ripple effects play out in more detail.
Endophytic diazotrophic communities from rice roots are diverse and weakly associated with soil diazotrophic community composition and soil properties
Authors: Ferrando Lucía , Rariz Gastón , Martínez-Pereyra Andrea , Fernández-Scavino Ana
Published: June 2024

Aim

Bacteria that promote plant growth, such as diazotrophs, are valuable tools for achieving a more sustainable production of important non-legume crops like rice. Different strategies have been used to discover new bacteria capable of promoting plant growth. This work evaluated the contribution of soil diazotrophs to the endophytic communities established in the roots of rice seedlings cultivated on seven representative soils from Uruguay.

Methods and results

The soils were classified into two groups according to the C and clay content. qPCR, terminal restriction fragment length polymorphism (T-RFLP), and 454-pyrosequencing of the nifH gene were used for analyzing diazotrophs in soil and plantlets’ roots grown from seeds of the same genotype for 25 days under controlled conditions. A similar nifH abundance was found among the seven soils, roots, or leaves. The distribution of diazotrophs was more uneven in roots than in soils, with dominance indices significantly higher than in soils (nifH T-RFLP). Dominant soils’ diazotrophs were mainly affiliated to Alphaproteobacteria and Planctomycetota. Conversely, Alpha, Beta, Gammaproteobacteria, and Bacillota were predominant in different roots, though undetectable in soils. Almost no nifH sequences were shared between soils and roots.

Conclusions

Root endophytic diazotrophs comprised a broader taxonomic range of microorganisms than diazotrophs found in soils from which the plantlets were grown and showed strong colonization patterns.
Synthetic microbial ecology: engineering habitats for modular consortia
Authors: Chen Yue Casey , Destouches Louie , Cook Alice , Fedorec Alex J H
Published: June 2024

Microbiomes, the complex networks of micro-organisms and the molecules through which they interact, play a crucial role in health and ecology. Over at least the past two decades, engineering biology has made significant progress, impacting the bio-based industry, health, and environmental sectors; but has only recently begun to explore the engineering of microbial ecosystems. The creation of synthetic microbial communities presents opportunities to help us understand the dynamics of wild ecosystems, learn how to manipulate and interact with existing microbiomes for therapeutic and other purposes, and to create entirely new microbial communities capable of undertaking tasks for industrial biology. Here, we describe how synthetic ecosystems can be constructed and controlled, focusing on how the available methods and interaction mechanisms facilitate the regulation of community composition and output. While experimental decisions are dictated by intended applications, the vast number of tools available suggests great opportunity for researchers to develop a diverse array of novel microbial ecosystems.
Potential to take root in viticulture? An evaluation of mycorrhizal inoculants on the growth and nutrient uptake of young wine grapes planted in live field soil
Authors: Lueck Madeline R , Moyer Michelle M , Cheeke Tanya E
Published: June 2024

Aims

Incorporating biofertilizers, such as arbuscular mycorrhizal fungal (AM) fungal inoculants, into vineyard management practices may enhance vine growth and reduce environmental impact. Here, we evaluate the effects of commercially available and local AM fungal inoculants on the growth, root colonization, and nutrient uptake of wine grapes (Vitis vinifera) when planted in a field soil substrate.

Methods and results

In a greenhouse experiment, young wine grapes were planted in a field soil substrate and inoculated with one of three commercially available mycorrhizal inoculant products, or one of two locally collected whole soil inoculants. After 4 months of growth, inoculated vines showed no differences in plant biomass, colonization of roots by AM fungi, or foliar macronutrient concentrations compared to uninoculated field soil substrate. However, vines grown with local inoculants had greater shoot biomass than vines grown with mycorrhizal inoculant products.

Conclusions

Although effects from inoculations with AM fungi varied by inoculant type and source, inoculations may not improve young vine performance in field soils with a resident microbial community.
A One-Step Green Microwell Spectrophotometric Assay for the Determination of Certain New Chemotherapeutic Drug Formulations
Authors: Darwish Ibrahim A , Darwish Hany W , Alsalhi Mohammed S
Published: June 2024

Background

The formation of charge-transfer complexes (CTCs) of iodine with five chemotherapeutic drugs used for the treatment of different types of cancer has not been investigated. These drugs are olaparib, seliciclib, vandetanib, dasatinib, and tozasertib. Additionally, these drugs need an appropriate general spectrophotometric assay for their analysis in the dosage forms regardless of the differences in their chemical structures.

Objective

The aim of this study was the development of a novel microwell spectrophotometric assay (MW-SPA) for one-step determination of these drugs via their interactions with iodine, which resulted in instantaneous production of bright lemon-yellow CTCs.

Methods

A spectrophotometric study of the CTCs was conducted, and all CTCs were characterized. Site(s) of interaction on each drug were assigned, and the MW-SPA was developed and applied to the analysis of dosage forms.

Results

The findings confirmed that the reactions proceeded via CTC formation. Beer's law was obeyed over a general concentration range of 1–6 µg/mL. The LODs and LOQs were in the ranges of 0.5–2.1 and 1.5–6.4 µg/mL, respectively. The proposed MW-SPA demonstrated excellent precisions as the relative standard deviations were < 2.24 and 2.23% for the intra- and inter-assay precision, respectively. Recovery studies demonstrated the accuracy of MW-SPA. Successful determination of all drugs in bulk and tablet forms was achieved using the MW-SPA. The environmental sustainability of the proposed methodology was determined, providing evidence of the assay's alignment with the basis of green analytical chemistry. The high throughput of the assay was documented.

Conclusion

In contrast to other existing methods, the MW-SPA described herein was valid for analyzing all drugs at the same wavelength.

Highlights

The assay is useful for routine analysis of drugs in their formulations in QC laboratories.
Effects of pyriproxyfen on development and hormone of the aphis, Aphis craccivora (Hemiptera: Aphididae)
Authors: Li Haolin , Zhang Wenjie , Zhang Yongheng , Guo Xiaxia , Hou Jiangan , Li Honghong , Wei Jiguang , Li Xuesheng
Published: June 2024

Pyriproxyfen (PPF) has been shown to affect the pupal stage and ecdysone levels in holometabolous insects, such as silkworms and mealworms. It remains unknown whether it affects hemimetabolous insects with their hormone levels in insects lacking a pupal stage. In this laboratory study, bioassays were conducted to investigate the effects of varying doses of PPF on Aphis craccivora Koch (Hemiptera: Aphididae). Ultraperformance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) was used to determine the types and titers of juvenile hormone (JH) and 20-hydroxyecdysone (20E). Additionally, the effects of PPF on A. craccivora reproduction and molting, as well as its influence on relevant gene expression, were examined. The results revealed LC50 and LC90 values of 3.84 and 7.49 mg/l for PPF, respectively, after 48 h of exposure. The results demonstrated a significant reduction in the titer of JH III and a significant increase in the titer of 20E following treatment with PPF. However, there was no significant decrease observed in the titer of JH III skipped bisepoxide (JH SB3). A sublethal concentration of PPF was found to inhibit Krüppel homolog 1 (kr-h1) gene expression and reduce aphid reproduction, but it did not significantly impact ecdysone receptor expression and aphid molting. The results of this study demonstrate that PPF exhibits a lethal effect on aphids, thereby providing an effective means of control. Additionally, sublethal concentrations of PPF have been found to inhibit the JH in aphids, resulting in a decline in their reproductive ability and achieving the desired control objectives.