The role of microRNAs in NBS-LRR gene expression and its implications for plant immunity and crop development.

Plants evolved, over millions of years, complex defense systems against pathogens. Once infected, the interaction between pathogen effector molecules and host receptors triggers plant immune responses, which include apoptosis, systemic immune response, among others. An important protein family responsible for pathogen effector recognition is the nucleotide binding site-leucine repeat rich (NBS-LRR) proteins. The NBS-LRR gene family is the largest disease resistance gene class in plants. These proteins are widely distributed in vascular plants and have a complex multigenic cluster distribution in plant genomes. To counteract the genetic load of such a large gene family on fitness cost, plants evolved a mechanism using post transcriptional gene silencing induced by small RNAs, particularly microRNAs. For the NBS-LRR gene family, the small RNAs involved in this silencing mechanism are mainly the microRNA482/2118 superfamily. This suppression mechanism is relieved upon pathogen infection, thus allowing increased NBS-LRR expression and triggering plant immunity. In this review, we will discuss the biogenesis of microRNAs and secondary RNAs involved in this silencing mechanism, biochemical and structural features of NBS-LRR proteins in response to pathogen effectors and the evolution of microRNA-based silencing mechanism with a focus on the miR482/2118 family. Furthermore, the biotechnological manipulation of microRNA expression, using both transgenic or genome editing approaches to improve cultivated plants will be discussed, with a focus on the miR482/2118 family in soybean.

Complications of fibrotic interstitial lung disease for the general radiologist.

Interstitial lung diseases (ILDs) are a heterogeneous group of conditions characterised by non-infective inflammation and scarring of the lung parenchyma. They are not infrequently encountered by the general radiologist in both acute and outpatient reporting settings who may even be the first to make the diagnosis. In the acute setting, patients with ILD can present with respiratory deterioration due to a number of causes and in addition to the common causes of dyspnoea, an acute exacerbation of ILD needs to be considered. An exacerbation can be initiated by common triggers such as infection, pulmonary embolism (PE), and heart failure, and it can also be initiated by an insult to the lung or occur due to an unknown cause. Particular care needs to be taken when interpreting computed tomography (CT) examinations in these patients as the findings of an acute exacerbation are non-specific and patient and technical factors can cause spurious appearances including dependent changes, breathing artefact and contrast medium opacification. In the non-acute setting, patients with ILD are at increased risk of lung cancer and pulmonary hypertension (PH), with lung cancer being a particularly important consideration as treatments carry the risk of triggering an acute exacerbation or deterioration in lung function. Overall, this review aims to provide an overview for the general radiologist of additional factors to consider when interpreting scans in patients with ILD and how the presence of ILD impacts the differential diagnoses and complications that can occur in these patients in both acute and non-acute settings.

COVID-19 Stroke Apical Lung Examination Study 2: a national prospective CTA biomarker study of the lung apices, in patients presenting with suspected acute stroke (COVID SALES 2).

BACKGROUND: Apical ground-glass opacification (GGO) identified on CT angiography (CTA) performed for suspected acute stroke was developed in 2020 as a coronavirus-disease-2019 (COVID-19) diagnostic and prognostic biomarker in a retrospective study during the first wave of COVID-19. OBJECTIVE: To prospectively validate whether GGO on CTA performed for suspected acute stroke is a reliable COVID-19 diagnostic and prognostic biomarker and whether it is reliable for COVID-19 vaccinated patients. METHODS: In this prospective, pragmatic, national, multi-center validation study performed at 13 sites, we captured study data consecutively in patients undergoing CTA for suspected acute stroke from January-March 2021. Demographic and clinical features associated with stroke and COVID-19 were incorporated. The primary outcome was the likelihood of reverse-transcriptase-polymerase-chain-reaction swab-test-confirmed COVID-19 using the GGO biomarker. Secondary outcomes investigated were functional status at discharge and survival analyses at 30 and 90 days. Univariate and multivariable statistical analyses were employed. RESULTS: CTAs from 1,111 patients were analyzed, with apical GGO identified in 8.5 % during a period of high COVID-19 prevalence. GGO showed good inter-rater reliability (Fleiss κ = 0.77); and high COVID-19 specificity (93.7 %, 91.8-95.2) and negative predictive value (NPV; 97.8 %, 96.5-98.6). In subgroup analysis of vaccinated patients, GGO remained a good diagnostic biomarker (specificity 93.1 %, 89.8-95.5; NPV 99.7 %, 98.3-100.0). Patients with COVID-19 were more likely to have higher stroke score (NIHSS (mean +/- SD) 6.9 +/- 6.9, COVID-19 negative, 9.7 +/- 9.0, COVID-19 positive; p = 0.01), carotid occlusions (6.2 % negative, 14.9 % positive; p = 0.02), and larger infarcts on presentation CT (ASPECTS 9.4 +/- 1.5, COVID-19 negative, 8.6 +/- 2.4, COVID-19 positive; p = 0.00). After multivariable logistic regression, GGO (odds ratio 15.7, 6.2-40.1), myalgia (8.9, 2.1-38.2) and higher core body temperature (1.9, 1.1-3.2) were independent COVID-19 predictors. GGO was associated with worse functional outcome on discharge and worse survival after univariate analysis. However, after adjustment for factors including stroke severity, GGO was not independently predictive of functional outcome or mortality. CONCLUSION: Apical GGO on CTA performed for patients with suspected acute stroke is a reliable diagnostic biomarker for COVID-19, which in combination with clinical features may be useful in COVID-19 triage.

The thymus: what's normal and what's not? Problem-solving with MRI.

Anterior mediastinal masses can be difficult to characterise on computed tomography (CT) due to the wide spectrum of normal appearances of thymic tissue as well as the challenge of differentiating between benign and malignant pathologies. Additionally, attenuation of cystic mediastinal lesions can be misinterpreted on CT due to varying attenuation values. Anecdotally, non-vascular magnetic resonance imaging (MRI) of the thorax is underutilised across radiology departments in the UK, but has been shown to improve diagnostic certainty and reduce unnecessary surgical intervention. T2-weighted MRI is useful in confirming the cystic nature of lesions, whereas chemical shift techniques can be utilised to document the presence of macroscopic and intra-cellular fat and thus help distinguish between benign and malignant pathologies. In this review article, we present a practical approach to using MRI for the characterisation of anterior mediastinal lesions based on our clinical experience in a UK district general hospital.

Investigating the impact of non-gated thoracic CT prior to CTCA to reduce layered testing.

AIM: To determine the proportion of computed tomography (CT) coronary angiography (CTCA) referrals with coronary artery calcification (CAC) evident on previous non-cardiac CT imaging and how this impacted the diagnostic yield for CTCA, the requirement for additional diagnostic testing, and the associated costs to confirm or refute obstructive coronary artery disease (CAD). MATERIALS AND METHODS: A retrospective review of CTCA examinations was undertaken between 01/05/2018 and 31/05/2020 in which the examinations were cross referenced for previous non-gated thoracic CT at Royal United Hospitals Bath. Major epicardial vessel CAC on baseline CT was re-evaluated by published semi-quantitative methods, giving a per-patient CAC score (mild = 1-3, moderate = 4-6, severe >6). Subsequent incomplete CTCA diagnostic yield, further testing, and cost implications were examined. RESULTS: Of the 2140 CTCA examinations identified, 13% (280/2140) had a preceding non-gated thoracic CT (53% female, age 63 ± 11 years). The incomplete diagnostic rate increased with CAC grade, mild 32%, (RR 12; 95% CI 4-40), moderate 64% (RR 25; 95% CI 8-80), severe 75%, (RR 29; 95% CI 9-94). Additional diagnostic testing occurred in 4% for the mild CAC category, and 14% and 42% for moderate and severe, respectively. When severe CAC was identified on a non-gated thoracic CT a cost saving of £171/patient (dobutamine stress echo [DSE]) and £61/patient (myocardial perfusion scintigraphy [MPS]) was established with a direct to functional testing pathway. CONCLUSIONS: In patients referred for CTCA where severe CAC was identified on a preceding non-gated thoracic CT a direct to functional testing altered management in 42% of cases and was cost-effective.

Coronary artery calcification on routine CT has prognostic and treatment implications for all ages.

AIMS: Guidelines have recommended reporting coronary artery calcification (CAC) if present on chest CT imaging regardless of indication. This study assessed CAC prevalence, prognosis and the potential clinical impact of its reporting. METHODS: We performed a single-centre retrospective analysis (January-December 2015) of 1400 chest CTs (200 consecutive within each age group: <40, 40-49, 50-59, 60-69, 70-79, 80-89, ≥90). CTs were re-reviewed for CAC presence and severity and excluded if prior coronary intervention. Comorbidities, statin prescription and clinical outcomes (myocardial infarction [MI], stroke, all-cause mortality) were recorded. The impact of reporting CAC was assessed against pre-existing statin prescriptions. RESULTS: 1343 patients were included (mean age 63±20 years, 56% female). Inter- and intra-observer variability for CAC presence at re-review was almost perfect (κ 0.89, p < 0.001; κ 0.90, p < 0.001) and for CAC grading was substantial and almost perfect (κ 0.68, p < 0.001; κ 0.91, p < 0.001). CAC was observed in 729/1343 (54%), more frequently in males (p < 0.001) and rising age (p < 0.001). A high proportion of patients with CAC in all age groups had no prior statin prescription (range: 42% [80-89] to 100% [<40]). The 'number needed to report' CAC presence to potentially impact management across all ages was 2. 689 (51%) patients died (median follow-up 74-months). CAC presence was associated with risk of MI, stroke and all-cause mortality (p < 0.001). After adjusting for confounders, severe calcification predicted risk of all-cause mortality (HR 1.8 [1.2-2.5], p = 0.002). CONCLUSION: Grading of CAC was reproducible, and although prevalence rose with age, prognostic and treatment implications were maintained in all ages.

Barriers to patient recruitment in a poststroke neurorehabilitation multicenter trial in Brazil.

There is a high demand for stroke rehabilitation in the Brazilian public health system, but most studies that have addressed rehabilitation for unilateral spatial neglect (USN) after stroke have been performed in high-income countries. Therefore, the aim of this study was to analyze USN patient recruitment in a multicenter noninvasive brain stimulation clinical trial performed in Brazil and to provide study design recommendations for future studies. We evaluated the reasons for exclusion of patients from a multicenter, randomized, double-blinded clinical trial of rehabilitation of USN patients after stroke. Clinical and demographic variables were compared between the included and excluded patients. A descriptive statistical analysis was performed. Only 173 of the 1953 potential neglect patients (8.8%) passed the initial screening. After screening evaluation, 87/173 patients (50.3%) were excluded for clinical reasons. Cognitive impairment led to the exclusion of 21/87 patients (24.1%). Low socioeconomic status led to the exclusion of 37/173 patients (21.4%). Difficulty obtaining transportation to access treatment was the most common reason for their exclusion (16/37 patients, 43.3%). The analyzed Brazilian institutions have potential for conducting studies of USN. The recruitment of stroke survivors with USN was restricted by the study design and limited financial support. A history of cognitive impairment, intracranial stenting or craniectomy, and lack of transportation were the most common barriers to participating in a multicenter noninvasive brain stimulation trial among patients with USN after stroke.

Barriers to patient recruitment in a poststroke neurorehabilitation multicenter trial in Brazil

There is a high demand for stroke rehabilitation in the Brazilian public health system, but most studies that have addressed rehabilitation for unilateral spatial neglect (USN) after stroke have been performed in high-income countries. Therefore, the aim of this study was to analyze USN patient recruitment in a multicenter noninvasive brain stimulation clinical trial performed in Brazil and to provide study design recommendations for future studies. We evaluated the reasons for exclusion of patients from a multicenter, randomized, double-blinded clinical trial of rehabilitation of USN patients after stroke. Clinical and demographic variables were compared between the included and excluded patients. A descriptive statistical analysis was performed. Only 173 of the 1953 potential neglect patients (8.8%) passed the initial screening. After screening evaluation, 87/173 patients (50.3%) were excluded for clinical reasons. Cognitive impairment led to the exclusion of 21/87 patients (24.1%). Low socioeconomic status led to the exclusion of 37/173 patients (21.4%). Difficulty obtaining transportation to access treatment was the most common reason for their exclusion (16/37 patients, 43.3%). The analyzed Brazilian institutions have potential for conducting studies of USN. The recruitment of stroke survivors with USN was restricted by the study design and limited financial support. A history of cognitive impairment, intracranial stenting or craniectomy, and lack of transportation were the most common barriers to participating in a multicenter noninvasive brain stimulation trial among patients with USN after stroke.

Current pressure on the UK imaging workforce deters imaging research in the NHS and requires urgent attention.

Medical imaging is a multidisciplinary specialty, combining clinical expertise from medical physics, radiography, and radiology, and plays a key role in patient care. Research is vital to ensure the care delivered to patients is evidence-based, and is a core component of clinical governance; however, there are pressures on the imaging workforce, which are significantly impeding imaging research. This commentary presents a research gap analysis pertaining to the multidisciplinary imaging workforce on behalf of the National Institute for Health Research (NIHR) Imaging Workforce Group. Data were summarised from membership surveys of the Royal College of Radiologists, Society and College of Radiographers, and Institute of Physics and Engineering in Medicine; national reports; and feedback from NIHR Clinical Research Network Imaging Champions meeting in 2020/2021. Common barriers to delivering research were found across the multidisciplinary workforce. The key issues were lack of staff, lack of time, and lack of funding to backfill clinical services. Given the ongoing workforce shortages and increasing clinical demands on radiologists, diagnostic radiographers, and medical physicists, these issues must be tackled with a high priority to ensure the future of clinical research within the NHS.

Diagnostic accuracy of an automated artificial intelligence derived right ventricular to left ventricular diameter ratio tool on CT pulmonary angiography to predict pulmonary hypertension at right heart catheterisation.

AIM: To determine the diagnostic accuracy of an automated artificial intelligence derived right ventricle/left ventricle diameter ratio (RV/LV) computed tomography pulmonary angiography (CTPA) analysis tool to detect pulmonary hypertension (PH) in patients with suspected PH referred to a specialist centre. MATERIALS AND METHODS: The present study was a retrospective analysis of a prospectively maintained database of 202 consecutive patients with suspected PH, who underwent CTPA within 12 months of right heart catheterisation (RHC). Automated ventricular segmentation and RV/LV calculation (Imbio LLC, Minneapolis, MN, USA) was undertaken on the CTPA images. PH diagnosis was made using the RHC reference standard. RESULTS: The automated RV/LV correlated more strongly with RHC metrics than main pulmonary artery (MPA) diameter and MPA to ascending aorta diameter ratio (MPA/AA) measured manually (mean pulmonary arterial pressure [mPAP] r=0.535, R2 = 0.287 p<0.001; pulmonary vascular resistance [PVR] r=0.607, R2 = 0.369 p<0.001). In the derivation cohort (n=100), the area under the receiver-operating curve for automated RV/LV discriminating PH was 0.752 (95% confidence interval [CI] 0.677-0.827, p<0.001). Using an optimised Youden's Index of ≥1.12 classified from derivation, automated RV/LV ratio analysis was more sensitive for the detection of PH with higher positive predictive value (PPV) when compared with manual MPA and MPA/AA in the validation cohort (n=102). Automated RV/LV compromise (1.12) and specific (1.335) thresholds were strongly predictive of mortality (log-rank 7.401, p=0.007 and log-rank 16.075, p<0.001 respectively). CONCLUSION: In suspected PH, automated RV/LV diameter thresholds have high sensitivity for PH, outperform manual MPA and MPA/AA and can predict survival.

The effect of left ventricular longitudinal strain on left atrial function and ventricular filling in hypertension.

AIM: To assess the relationship of global longitudinal strain during left atrial (LA) and left ventricular (LV) filling and emptying. MATERIALS AND METHODS: Using magnetic resonance imaging in 47 hypertensive patients, biplane global LV longitudinal strain was evaluated and related to LA and LV filling and emptying (by volumetric analysis), and to pulmonary vein and trans-mitral flow (by phase-contrast imaging). The results were compared to normal subjects. RESULTS: In hypertensive patients, reduced global longitudinal LV strain was associated with reduced LA reservoir (47 ± 10 versus 53 ± 9%, p<0.05), reduced LA conduit function (21 ± 9 versus 32 ± 11%, p<0.004), reduced LA early peak emptying rate (150 ± 77 versus 230 ± 88 ml/s, p=0.007), and slower early LV filling (373 ± 141 versus 478 ± 141 ml/s, p=0.03). LA peak filling rate showed a positive correlation to LV peak emptying rate (R=0.331, p=0.02). CONCLUSION: In hypertensive heart disease, impaired LV longitudinal systolic function causes reduced LA filling and emptying, and this leads directly to impaired LV filling and diastolic dysfunction.

CT coronary angiography-guided cardiovascular risk screening in asymptomatic patients: is it time?

Cardiovascular disease (CVD) is the leading cause of death in the UK, whilst millions live with various forms of the disease. Coronary artery disease constitutes a significant portion of this morbidity and mortality, and is the leading cause of premature death. Increasing focus is thus being placed on the optimisation of CVD prevention, where risk screening plays a key role. Indeed, the decline in age-adjusted cardiovascular mortality achieved up to now has been largely attributed to primary preventative therapies (e.g., statins) introduced earlier in the disease process. National initiatives exist to improve cardiovascular health at a population level, but in its current form, CVD screening at the individual level is predominantly undertaken using multivariate risk scores based on population-based data. These have multiple innate flaws, highlighted in this review. Non-invasive imaging plays a key role in the screening of other disease processes, helping to personalise the screening process. Although the coronary artery calcium score as a screening tool has a role in national and international guidance, whether a shift to screening with computed tomography coronary angiography (CTCA) is now appropriate is open for discussion. Image acquisition techniques continue to improve with reducing radiation exposure and an ever-expanding evidence-base for additional prognostic data offered by CTCA. This enables the potential identification of sub-clinical atherosclerosis, including with novel artificial intelligence techniques. This review aims to report current guidelines regarding cardiac CT imaging in the asymptomatic primary prevention setting, advances in various CT technologies and future opportunities for progress in this field.

Real-world clinical and cost analysis of CT coronary angiography and CT coronary angiography-derived fractional flow reserve (FFRCT)-guided care in the National Health Service.

AIM: To quantify the real-world clinical and cost impact of computed tomography (CT) coronary angiography (CTCA)-derived fractional flow reserve (FFRCT) in the National Health Service (NHS). MATERIALS AND METHODS: Consecutive clinical CTCA examinations from September to December 2018 with ≥1 stenosis of ≥25% underwent FFRCT analysis. The Heart Team reviewed clinical data and CTCA findings, blinded to FFRCT values, and documented hypothetical consensus management. FFRCT results were then unblinded and hypothetical consensus management re-recorded. Diagnostic waiting times for management pathways were estimated. A per-patient cost analysis for diagnostic certainty regarding coronary artery disease (CAD) management was performed using 2014-2020 NHS tariffs for pre- and post-FFRCT pathways. RESULTS: Two hundred and fifty-one CTCAs were performed during the study period. Fifty-seven percent (145/251) had no CAD or stenosis <25%. One study was non-diagnostic. Of the remaining 42% (105/251), two were ineligible for FFRCT and there was a 5% (5/103) failure rate. FFRCT led to a change in hypothetical management in 65% (64/98; p<0.001) patients with a functional imaging test cancelled in 17% (17/98) and a diagnostic angiogram cancelled in 47% (46/98). FFRCT-guided management had a reduced mean time to definitive investigation compared with CTCA alone (28 ± 4 versus 44 ± 4 days; p=0.004). Using the proposed 2020/21 tariff, CTCA + FFRCT for stenosis ≥50% resulted in a diagnostic pathway £44.97 more expensive per patient than usual care without FFRCT. CONCLUSIONS: In the real-world NHS setting, FFRCT-guided management has the potential to rationalise patient management, accelerate diagnostic pathways, and depending on the stenosis severity modelled, may be cost-effective.

A pilot image interpretation teaching intervention to improve competence and confidence of radiographers to detect left ventricular thrombus in routine cardiac MRI scans.

INTRODUCTION: Prompt diagnosis of left ventricular (LV) thrombus is clinically important, as it may require immediate anti-coagulation treatment. The aim of this study was to determine if a teaching intervention delivered by cardiovascular magnetic resonance (CMR) physicians would increase the CMR radiographers' ability to detect LV thrombus on a routine CMR scan. METHODS: A cohort of 25 patients (14 with and 11 without LV thrombus) were identified. A multi-parametric CMR protocol had been performed in all patients. Ten radiographers reviewed the 25 randomised anonymised studies on a workstation, documenting the presence/absence of LV thrombus and their confidence level on a 7-point Likert scale. Two senior CMR fellows then delivered a focused teaching programme to the radiographers and all 25 randomised scans were reassessed 1 month after the teaching intervention. RESULTS: Following dedicated training, there was a significant improvement in correct thrombus identification per radiographer (pre-training: 75 ± 6% vs post-training: 85 ± 6%, p = 0.009). The size of the thrombus was not associated with the likelihood of incorrectly identifying LV thrombus size prior to the training session (p = 0.2), but a trend was observed between smaller thrombus size and incorrect identifications post-training (p = 0.06). The radiographers' overall confidence in assessing the cases prior to the teaching session was high (5.6 ± 0.8 out of 7). Following the teaching session, self-reported confidence did not vary significantly (5.9 ± 0.7 out of 7, p = 0.42). When evaluating the teaching session, radiographers provided very positive feedback, rating the usefulness of the teaching intervention as highly educative (8.8 ± 0.4 out of 10). CONCLUSIONS: This is the first study that has explored the ability and confidence of CMR radiographers in detecting LV thrombus on routine CMR scans as a result of the teaching intervention delivered by CMR physicians. IMPLICATIONS FOR PRACTICE: A teaching intervention can improve CMR radiographers' diagnostic skills and diagnostic confidence.

COVID-19: looking beyond the peak. Challenges and tips for radiologists in follow-up of a novel patient cohort.

As the coronavirus pandemic evolves, the focus of radiology departments has begun to change. The acute phase of imaging a new disease entity whilst rationalising radiology services in the face of lockdown has passed. Radiologists are now becoming familiar with the complications of COVID-19, particularly the lung parenchymal and pulmonary vascular sequelae and are considering the impact follow-up imaging may have on departments already struggling with a backlog of suspended imaging in the face of reduced capacity. This review from the British Society of Thoracic Imaging explores both the thoracic and extra-thoracic complications of COVID-19, recognising the importance of a holistic approach to patient follow-up. The British Thoracic Society guidelines for respiratory follow-up of COVID-19 will be discussed, together with newly developed reporting templates, which aim to provide consistency for clinicians as well as an opportunity for longer-term data collection.

Impact of COVID-19 on UK radiology training: a questionnaire study.

AIM: To understand the impact of COVID-19 on radiology trainee experience and well-being. MATERIALS AND METHODS: A questionnaire designed to capture the impact of COVID-19 on radiology training, working patterns, and well-being was sent to all speciality trainees in a regional UK radiology school. The survey was distributed at the beginning of May 2020 and responses collected over 2 weeks. Trainees were questioned about changes that had occurred over a time period starting at the beginning of the COVID-19 pandemic. All survey responses (n=29) were anonymised and the results were subsequently analysed. RESULTS: Sixty-two percent (29 of 47) of trainees within the deanery, who were spread across seven different hospital sites, responded to the questionnaire. All trainees felt that overall radiology workload had decreased in response to COVID-19. Seventy-two percent (21/29) stated that their workload had significantly decreased. Seventy percent (19/27) reported decreased subspecialty experience, and 19% (5/27) reported a complete lack of subspecialty training. Twenty-four percent (7/29) of trainees were redeployed from radiology to clinical ward-based work. Forty-eight percent reported experiencing a worsening in their well-being compared to before the pandemic. CONCLUSION: The first wave of the COVID-19 pandemic had a significant impact on training and well-being. Lessons learnt from this report should help prepare for a second-wave of COVID-19 or future pandemics.