The prognostic value of artificial intelligence to predict cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

Aims: Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results: In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with >50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01-1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01-1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13-2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion: Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.

Artificial intelligence-enabled electrocardiogram (AI-ECG) does not predict atrial fibrillation following patent foramen ovale closure.

Background: Atrial fibrillation (AF) is a known complication following patent foramen ovale (PFO) closure. AI-enabled ECG (AI-ECG) acquired during normal sinus rhythm has been shown to identify individuals with AF by noting high-risk ECG features invisible to the human eye. We sought to characterize the value of AI-ECG in predicting AF development following PFO closure and investigate key clinical and procedural characteristics possibly associated with post-procedural AF. Methods: We performed a retrospective analysis of patients who underwent PFO closure at our hospital from January 2011 to December 2022. We recorded the probability (%) of AF using the Mayo Clinic AI-ECG dashboard from pre- and post-procedure ECGs. The cut-off point of ≥ 11 %, which was found to optimally balance sensitivity and specificity in the original derivation paper (the Youden index) was used to label an AI-ECG "positive" for AF. Pre-procedural transesophageal echocardiography (TEE) and pre- and post-procedure transcranial doppler (TCD) data was also recorded. Results: Out of 93 patients, 49 (53 %) were male, mean age was 55 ± 15 years with mean post-procedure follow up of 29 ± 3 months. Indication for PFO closure in 69 (74 %) patients was for secondary prevention of transient ischemic attack (TIA) and/or stroke. Twenty patients (22 %) developed paroxysmal AF post-procedure, with the majority within the first month post-procedure (15 patients, 75 %). Patients who developed AF were not significantly more likely to have a positive post-procedure AI-ECG than those who did not develop AF (30 % AF vs 27 % no AF, p = 0.8).Based on the PFO-Associated Stroke Causal Likelihood (PASCAL) classification, patients who had PFO closure for secondary prevention of TIA and/or stroke in the "possible" group were significantly more likely to develop AF than patients in "probable" and "unlikely" groups (p = 0.034). AF-developing patients were more likely to have post-procedure implantable loop recorder (ILR) (55 % vs 9.6 %, p < 0.001), and longer duration of ILR monitoring (121 vs 92.5 weeks, p = 0.035). There were no significant differences in TCD and TEE characteristics, device type, or device size between those who developed AF vs those who did not. Conclusions: In this small, retrospective study, AI-ECG did not accurately distinguish patients who developed AF post-PFO closure from those who did not. Although AI-ECG has emerged as a valuable tool for risk prediction of AF, extrapolation of its performance to procedural settings such as PFO closure requires further investigation.

Transcriptomic analysis of paired healthy human skeletal muscles to identify modulators of disease severity in DMD.

Muscle damage and fibro-fatty replacement of skeletal muscles is a main pathologic feature of Duchenne muscular dystrophy (DMD) with more proximal muscles affected earlier and more distal affected later in the disease course, suggesting that different skeletal muscle groups possess distinctive characteristics that influence their susceptibility to disease. To explore transcriptomic factors driving differential gene expression and modulating DMD skeletal muscle severity, we characterized the transcriptome of vastus lateralis (VL), a more proximal and susceptible muscle, relative to tibialis anterior (TA), a more distal and protected muscle, in 15 healthy individuals using bulk RNA sequencing to identify gene expression differences that may mediate their relative susceptibility to damage with loss of dystrophin. Matching single nuclei RNA sequencing data was generated for 3 of the healthy individuals, to infer cell composition in the bulk RNA sequencing dataset and to improve mapping of differentially expressed genes to their cell source of expression. A total of 3,410 differentially expressed genes were identified and mapped to cell type using single nuclei RNA sequencing of muscle, including long non-coding RNAs and protein coding genes. There was an enrichment of genes involved in calcium release from the sarcoplasmic reticulum, particularly in the myofibers and these myofiber genes were higher in the VL. There was an enrichment of genes in "Collagen-Containing Extracellular Matrix" expressed by fibroblasts, endothelial, smooth muscle and pericytes, with most genes higher in the TA, as well as genes in "Regulation Of Apoptotic Process" expressed across all cell types. Previously reported genetic modifiers were also enriched within the differentially expressed genes. We also identify 6 genes with differential isoform usage between the VL and TA. Lastly, we integrate our findings with DMD RNA sequencing data from the TA, and identify "Collagen-Containing Extracellular Matrix" and "Negative Regulation Of Apoptotic Process" as differentially expressed between DMD compared to healthy. Collectively, these findings propose novel candidate mechanisms that may mediate differential muscle susceptibility in muscular dystrophies and provide new insight into potential therapeutic targets.

The Cenomanian/Turonian boundary in light of new developments in terrestrial palynology.

The Cenomanian/Turonian boundary interval is associated with an oceanic anoxic event (OAE 2,  94.0 Ma) during one of the warmest episodes in the Mesozoic. To date, plant responses to these climatic conditions are known only from the northern mid-latitudinal succession in Cassis, France. There, conifer-dominated and angiosperm-dominated vegetation types alternate. However, whether the exceptional environmental conditions had an impact on plant reproduction is unknown to date. We applied a new environmental proxy based on spore and pollen teratology on palynological samples from the Cassis succession, to explore if this phenomenon also occurs across the OAE 2. The observed frequencies of<1% malformed spores and pollen grains suggest that plant reproduction was not affected during the Cenomanian/Turonian boundary interval. While the effects of continental Large Igneous Province(s) on plant reproduction have shown to produce abnormal spore or pollen morphologies as evidence for severe environmental pollution, by contrast the effects of oceanic LIP(s) seems to be inconsequential.

Biomarker and compound-specific isotope records across the Toarcian CIE at the Dormettingen section in SW Germany.

The Toarcian oceanic anoxic event (T-OAE) is associated with a prominent negative carbon isotope excursion (CIE; ~ 183 million years (Myr)). About 10-m-thick organic matter-rich sediments accumulated during the T-OAE in the Southwest German Basin (SWGB). Rock-Eval, maceral and biomarker analysis were used to determine variations of environmental conditions across the CIE interval. Carbon isotope records were determined for various n-alkanes, pristane and phytane to contribute to the reconstruction of the paleo-environment and to study the factors controlling molecular δ13C values. Geochemical redox indicators provide evidence for photic zone anoxia during the Toarcian CIE, which reached its maximum after deposition of the "Unterer Stein" marker horizon. The 2α-methylhopane index suggests enhanced activity of diazotrophic cyanobacteria, which is also supported by nitrogen isotope data. This distinguishes the SWGB from other basins with Toarcian black shale. Oxygen-depleted conditions, albeit with lower intensity continued after the CIE. All investigated compounds replicate the negative CIE, but the magnitudes vary considerably. The largest shift is observed for n-C27 (9‰) and reflects the combined effect of the global CIE and a major change in organic matter input (termination of terrigenous organic matter input). The shift for short-chain n-alkanes, pristane, and phytane, interpreted to reflect marine biomass, varies between 4.5 and 5.0‰. This is the highest value observed so far for any Toarcian section. δ13C values of pristane and phytane reach a minimum near the base of the CIE interval and increase upsection. Thus, the maximum negative isotope shift predates the strongest basin restriction by about 450 thousand years (kyr).

What is the value given by consumers to nutritional label information? Results from a large investigation in Europe.

RATIONALE: Nutrition labels on prepackaged foods have been widely advocated as a medium to foster healthier eating habits in the general population. OBJECTIVE: The study is aimed at understanding how people value nutritional information on food labels, in particular for front-of-pack labeling. METHODS: A phone-assisted survey of 7550 consumers in 16 European countries was conducted. People were asked about their opinion on nutritional information provided at different levels, from the media to public institutions, and their commitment to healthy behavior. The value of pack labeling was estimated using a willingness-to-pay (WTP) elicitation technique. RESULTS: Older age groups (>45 years old), members of a larger family, people of low income or low education, and those who perceived themselves to be obese valued front-of-pack nutritional labeling. WTP estimates across all countries provided an average accepted added price of $4.32 to the overall yearly food expenditure (95% confidence interval, 3.33-3.68). CONCLUSIONS: Overall, perceived value of labeling is low. However, factors affecting the value for consumer of nutritional labeling appear to be strictly linked to the socioeconomic and health status of the respondents.