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Patients with cancer are at increased risk of myocardial infarction (MI) and stroke. Guidelines do not address lipid profile targets for these patients. Within the lipid profiles, we hypothesized that patients with cancer develop MI or stroke at lower low density lipoprotein cholesterol (LDL-C) concentrations than patients without cancer and suffer worse outcomes. We linked nationwide longitudinal MI, stroke and cancer registries from years 2007–2017. We identified 42,148 eligible patients with MI (2421 prior cancer; 39,727 no cancer) and 43,888 eligible patients with stroke (3152 prior cancer; 40,738 no cancer). Median LDL-C concentration was lower in the prior cancer group than the no cancer group at incident MI [2.43 versus 3.10 mmol/L, adjusted ratio 0.87 (95% CI 0.85–0.89)] and stroke [2.81 versus 3.22 mmol/L, adjusted ratio 0.93, 95% CI 0.91–0.95)]. Similarly, median triglyceride and total cholesterol concentrations were lower in the prior cancer group, with no difference in high density lipoprotein cholesterol. Prior cancer was associated with higher post-MI mortality [adjusted hazard ratio (HR) 1.48, 95% CI 1.37–1.59] and post-stroke mortality (adjusted HR 1.95, 95% CI 1.52–2.52). Despite lower LDL-C concentrations, patients with prior cancer had worse post-MI and stroke mortality than patients without cancer.

A 28-year-old man presented with central exertional pleuritic chest pain, associated with dyspnoea and reduced effort tolerance on the background of 1-week of upper respiratory tract infection like symptoms with recent overseas travel to Southeast Asia. Physical examination was unremarkable. Electrocardiogram showed sinus rhythm. Raised high-sensitivity troponin-T levels were noted. Transthoracic echocardiogram demonstrated normal ejection fraction and no regional wall motion abnormalities. Computer tomography (CT) coronary angiogram did not show obstructive coronary artery disease or structural abnormalities. The patient subsequently developed diarrhoea and abdominal discomfort localised to the right iliac fossa. Given this, intraabdominal imaging was performed and revealed features of ileocolitis. Stool Polymerase Chain Reaction testing detected Enteropathic Escherichia Coli. As no cause for raised troponins was found, a cardiac MRI was performed. On late gadolinium enhancement (LGE) imaging, there was subtle basal to mid septal midwall and inferolateral subepicardial uptake. LGE pattern and tissue characterisation parameters suggested recent episode of mild myocarditis. He was treated with a course of intravenous antibiotics with improvement of symptoms. Repeat cardiac MRI also demonstrated interval improvement 1 month after the acute event with only residual subtle subepicardial enhancement in the basal inferolateral wall.

The coronavirus disease-2019 (COVID-19) pandemic has had an unprecedented impact leading to novel adaptations in post-graduate medical education for cardiovascular and general internal medicine. Whilst the results of initial community COVID-19 vaccination are awaited, continuation of multimodality teaching and training that incorporates telelearning will have enduring benefit to post-graduate education and will place educational establishments in good stead to nimbly respond in future pandemic-related public health emergencies. With the rise in innovative virtual learning solutions, medical educators will have to leverage technology to develop electronic educational materials and virtual courses that facilitate adult learning. Technology-enabled virtual learning is thus a timely progression of hybrid classroom initiatives that are already adopted to varying degrees, with a need for faculty to serve as subject matter experts, to host and moderate online discussions, and to provide feedback and overall mentorship. As an extension from existing efforts, simulation-based teaching (SBT) and learning and the use of mixed reality technology should also form a greater core in the cardiovascular medicine curriculum. We highlight five foundational themes for building a successful e-learning model in cardiovascular and general post-graduate medical training: (1) digital solutions and associated infrastructure; (2) equity in access; (3) participant engagement; (4) diversity and inclusion; and (5) patient confidentiality and governance framework. With digitalisation impacting our everyday lives and now how we teach and train in medicine, these five guiding principles provide a cognitive scaffold for careful consideration of the required ecosystem in which cardiovascular and general post-graduate medical education can effectively operate. With due consideration of various e-learning options and associated infrastructure needs; and adoption of strategies for participant engagement under sound and just governance, virtual training in medicine can be effective, inclusive and equitable through the COVID-19 era and beyond.

Cardiovascular disease is the worldwide leading cause of mortality among survivors of cancer due in part to the cardiotoxicity of anticancer therapies. This paper explores the progress in precision cardio-oncology, particularly in genetic testing and therapeutics, and its impact on cardiovascular diseases in clinical and laboratory settings. These advancements enable clinicians to better assess risk, diagnose conditions, and deliver personalised, cost-effective therapeutics. Through case studies of cancer-therapy-related cardiac dysfunction, clonal haematopoiesis of indeterminate potential, and polygenic risk scoring, we demonstrate the benefits of incorporating precision genomics in individualised care in cardio-oncology. Furthermore, leveraging real-world genomic data in clinical settings can advance our understanding of long noncoding RNAs and microRNAs, which play important regulatory roles in cardio-oncology. Additionally, employing human-induced pluripotent stem cells to stratify risk and guide prevention strategies represents a promising avenue for modelling precision cardio-oncology. While these advancements showcase the significant progress in genetic approaches, they also raise substantial ethical, legal, and societal concerns. Regulatory oversight of genetic and genomic technologies should therefore evolve suitably to keep up with rapid advancements in technology and analysis. Provider education is crucial for the appropriate use of new genetic and genomic applications, including on the existing protection available for patients regarding genetic information. This can provide confidence for diverse study groups to advance genetic studies looking to develop a comprehensive understanding and effective clinical applications for heterogeneous populations. In clinical settings, the implementation of genetic and genomic applications within electronic medical records can offer point-of-care clinical decision support, thus providing timely information to guide clinical management decisions.

Cardiovascular magnetic resonance (CMR) is an important cardiac imaging tool for assessing the prognostic extent of myocardial injury after myocardial infarction (MI) and for assessing the efficacy of potential cardioprotective therapies in reducing MI size and preventing adverse left ventricular (LV) remodelling in reperfused MI. However, manual contouring and analysis can be time-consuming with interobserver and intraobserver variability, which can in turn lead to reductions in accuracy and precision of analysis. There is thus a need to automate CMR scan analysis in MI patients to save time, increase accuracy, reproducibility and precision. Automated imaging analysis techniques based on artificial intelligence (AI) that are developed with machine learning (ML), and more specifically deep learning (DL) strategies, can enable efficient, robust, accurate and clinician-friendly tools to be developed to improve both clinician productivity and quality of patient care. In this regard, we have identified the analysis of MI CMR scans as a use case to develop our prototype solution for automated CMR analysis. In order to train, test and validate our automated model, we used MI CMR scans from the CONDI-2/ERIC-PPCI and IMMACULATE trials. Remote ischaemic conditioning (RIC) with transient ischaemia and reperfusion applied to the arm has been shown to reduce MI size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI), although the CONDI-2/ERIC-PPCI trial failed to report any benefit of RIC on the incidences of cardiac death and hospitalisation for heart failure at 12 months following STEMI. We discuss the scientific basis of RIC and describe the cardioprotective potential of RIC and chronic RIC (CRIC) in various cardiac conditions including STEMI and cancer therapeutics-related cardiotoxicity. The effect of limb RIC on MI size and left ventricular ejection fraction (LVEF) was investigated in a pre-planned CMR substudy of the CONDI-2/ERIC-PPCI trial. We summarise the results of this trial and describe the journey towards attainment of manual analysis gold standard through expert observer analysis of MI CMRs from this substudy. Finally, manually annotated MI CMRs from the CONDI-2/ERIC-PPCI substudy were used as testing and training data for the development of an automated analysis solution prototype, with a separate cohort of studies from the IMMACULATE study being used for internal validation. This has also been summarised in the graphical abstract below.In summary, we have shown that AI, ML and more specifically DL can improve efficiency and accuracy in the assessment of important prognostic imaging biomarkers in MI CMR scans through the development of an automated CMR analysis tool called CardiacApp. Global collaboration through open-source publication of codes and datasets will help to further advance the field and improve governance, safety and quality control through knowledge sharing. Future directions include the incorporation of automated analysis within clinical trials that assess clinical outcomes, and the extension of existing ML applications to a wider range of imaging biomarker analysis within heterogenous patient cohorts.

Dysbiosis, departure of the gut microbiome from a healthy state, has been suggested to be a powerful biomarker of disease incidence and progression 1 – 3 . Diagnostic applications have been proposed for inflammatory bowel disease diagnosis and prognosis 4 , colorectal cancer prescreening 5 and therapeutic choices in melanoma 6 . Noninvasive sampling could facilitate large-scale public health applications, including early diagnosis and risk assessment in metabolic 7 and cardiovascular diseases 8 . To understand the generalizability of microbiota-based diagnostic models of metabolic disease, we characterized the gut microbiota of 7,009 individuals from 14 districts within 1 province in China. Among phenotypes, host location showed the strongest associations with microbiota variations. Microbiota-based metabolic disease models developed in one location failed when used elsewhere, suggesting that such models cannot be extrapolated. Interpolated models performed much better, especially in diseases with obvious microbiota-related characteristics. Interpolation efficiency decreased as geographic scale increased, indicating a need to build localized baseline and disease models to predict metabolic risks. The definition of a 'healthy' microbiome is impacted by geographic regional variations.

Thousands of genes have been well demonstrated to play important roles in cancer progression. As genes do not function in isolation, they can be grouped into “networks” based on their interactions. In this study, we discover a network regulating Claudin-4 in gastric cancer. We observe that Claudin-4 is up-regulated in gastric cancer and is associated with poor prognosis. Claudin-4 reinforce proliferation, invasion, and EMT in AGS, HGC-27, and SGC-7901 cells, which could be reversed by miR-596 and miR-3620-3p. In addition, lncRNA-KRTAP5-AS1 and lncRNA-TUBB2A could act as competing endogenous RNAs to affect the function of Claudin-4. Our results suggest that non-coding RNAs play important roles in the regulatory network of Claudin-4. As such, non-coding RNAs should be considered as potential biomarkers and therapeutic targets against gastric cancer. Non-coding RNAs can modify the expression of proteins in cancer networks. Here the authors reveal a regulatory network in gastric cancer whereby claudin-4 expression is reduced by specific miRNAs, which are in turn bound by specific lncRNAs acting as competing endogenous RNAs (ceRNAs), resulting in increased claudin-4 expression.

Nonlinear transmission lines (NLTLs) are nonlinear electronic circuits used for parametric amplification and pulse generation, and it is known that left-handed NLTLs support enhanced harmonic generation while suppressing shock wave formation. We show experimentally that in a left-handed NLTL analogue of the Su-Schrieffer-Heeger (SSH) lattice, harmonic generation is greatly increased by the presence of a topological edge state. Previous studies of nonlinear SSH circuits focused on solitonic behaviours at the fundamental harmonic. Here, we show that a topological edge mode at the first harmonic can produce strong propagating higher-harmonic signals, acting as a nonlocal cross-phase nonlinearity. We find maximum third-harmonic signal intensities five times that of a comparable conventional left-handed NLTL, and a 250-fold intensity contrast between topologically nontrivial and trivial configurations. This work advances the fundamental understanding of nonlinear topological states, and may have applications for compact electronic frequency generators. Higher harmonic generation can be enhanced in left-handed nonlinear transmission lines. Here Wang et al. show that the presence of a topological edge state in a circuit analogue of the Su-Schrieffer-Heeger model can increase this enhancement even further.

Previous studies have shown that structure has a significant influence on the mechanical deformation of unsaturated loess, but there is little published information focused on the influence mechanism of microstructure and mesostructure on the mechanical properties of loess. In this paper, the unsaturated undisturbed loess and its remolded loess under the same physical condition were taken as the research objects. The unsaturated triaxial shear tests with constant suction and net confining pressure were carried out, and the microstructure differences between the two are compared by using SEM and CT scanning to reveal the influence of structure on strength characteristics. The test results show that the cohesion and internal friction angle of undisturbed loess are greater than those of remolded loess. The angle of undisturbed soil particles is obvious, and the particles are bracket contact with good cementation. The remolded loess particles are close to round shape, and the particles are inlaid contact with destroyed cementation. The average radius of undisturbed soil is higher than that of remolded soil, indicating that there are bracket pores in undisturbed soil, but the bracket structure and macropores are deformed during shear deformation, and good structural and cementation ensure the strength of loess specimens.

Background The metabolic syndrome (MetS) epidemic is associated with economic development, lifestyle transition and dysbiosis of gut microbiota, but these associations are rarely studied at the population scale. Here, we utilised the Guangdong Gut Microbiome Project (GGMP), the largest Eastern population-based gut microbiome dataset covering individuals with different economic statuses, to investigate the relationships between the gut microbiome and host physiology, diet, geography, physical activity and socioeconomic status. Results At the population level, 529 OTUs were significantly associated with MetS. OTUs from Proteobacteria and Firmicutes (other than Ruminococcaceae) were mainly positively associated with MetS, whereas those from Bacteroidetes and Ruminococcaceae were negatively associated with MetS. Two hundred fourteen OTUs were significantly associated with host economic status (140 positive and 74 negative associations), and 157 of these OTUs were also MetS associated. A microbial MetS index was formulated to represent the overall gut dysbiosis of MetS. The values of this index were significantly higher in MetS subjects regardless of their economic status or geographical location. The index values did not increase with increasing personal economic status, although the prevalence of MetS was significantly higher in people of higher economic status. With increased economic status, the study population tended to consume more fruits and vegetables and fewer grains, whereas meat consumption was unchanged. Sedentary time was significantly and positively associated with higher economic status. The MetS index showed an additive effect with sedentary lifestyle, as the prevalence of MetS in individuals with high MetS index values and unhealthy lifestyles was significantly higher than that in the rest of the population. Conclusions The gut microbiome is associated with MetS and economic status. A prolonged sedentary lifestyle, rather than Westernised dietary patterns, was the most notable lifestyle change in our Eastern population along with economic development. Moreover, gut dysbiosis and a Western lifestyle had an additive effect on increasing MetS prevalence.