American Society of Echocardiography COVID-19 Statement Update: Lessons Learned and Preparation for Future Pandemics.

The COVID-19 pandemic has evolved since the publication of the initial American Society of Echocardiography (ASE) statements providing guidance to echocardiography laboratories. In light of new developments, the ASE convened a diverse, expert writing group to address the current state of the COVID-19 pandemic and to apply lessons learned to echocardiography laboratory operations in future pandemics. This statement addresses important areas specifically impacted by the current and future pandemics: (1) indications for echocardiography, (2) application of echocardiographic services in a pandemic, (3) infection/transmission mitigation strategies, (4) role of cardiac point-of-care ultrasound/critical care echocardiography, and (5) training in echocardiography.

Decoupling of degradation from deadenylation reshapes poly(A) tail length in yeast meiosis.

Nascent messenger RNA is endowed with a poly(A) tail that is subject to gradual deadenylation and subsequent degradation in the cytoplasm. Deadenylation and degradation rates are typically correlated, rendering it difficult to dissect the determinants governing each of these processes and the mechanistic basis of their coupling. Here we developed an approach that allows systematic, robust and multiplexed quantification of poly(A) tails in Saccharomyces cerevisiae. Our results suggest that mRNA deadenylation and degradation rates are decoupled during meiosis, and that transcript length is a major determinant of deadenylation rates and a key contributor to reshaping of poly(A) tail lengths. Meiosis-specific decoupling also leads to unique positive associations between poly(A) tail length and gene expression. The decoupling is associated with a focal localization pattern of the RNA degradation factor Xrn1, and can be phenocopied by Xrn1 deletion under nonmeiotic conditions. Importantly, the association of transcript length with deadenylation rates is conserved across eukaryotes. Our study uncovers a factor that shapes deadenylation rate and reveals a unique context in which degradation is decoupled from deadenylation.

How many tRNAs are out there?

In this issue of Molecular Cell, Behrens et al. (2021) address a long-standing challenge in the field of tRNA regulation and develop an approach for measuring tRNA abundance at unprecedented accuracy.

The epitranscriptome beyond m6A.

Following its transcription, RNA can be modified by >170 chemically distinct types of modifications - the epitranscriptome. In recent years, there have been substantial efforts to uncover and characterize the modifications present on mRNA, motivated by the potential of such modifications to regulate mRNA fate and by discoveries and advances in our understanding of N 6-methyladenosine (m6A). Here, we review our knowledge regarding the detection, distribution, abundance, biogenesis, functions and possible mechanisms of action of six of these modifications - pseudouridine (Ψ), 5-methylcytidine (m5C), N 1-methyladenosine (m1A), N 4-acetylcytidine (ac4C), ribose methylations (Nm) and N 7-methylguanosine (m7G). We discuss the technical and analytical aspects that have led to inconsistent conclusions and controversies regarding the abundance and distribution of some of these modifications. We further highlight shared commonalities and important ways in which these modifications differ with respect to m6A, based on which we speculate on their origin and their ability to acquire functions over evolutionary timescales.

Accurate detection of m6A RNA modifications in native RNA sequences.

The epitranscriptomics field has undergone an enormous expansion in the last few years; however, a major limitation is the lack of generic methods to map RNA modifications transcriptome-wide. Here, we show that using direct RNA sequencing, N6-methyladenosine (m6A) RNA modifications can be detected with high accuracy, in the form of systematic errors and decreased base-calling qualities. Specifically, we find that our algorithm, trained with m6A-modified and unmodified synthetic sequences, can predict m6A RNA modifications with ~90% accuracy. We then extend our findings to yeast data sets, finding that our method can identify m6A RNA modifications in vivo with an accuracy of 87%. Moreover, we further validate our method by showing that these 'errors' are typically not observed in yeast ime4-knockout strains, which lack m6A modifications. Our results open avenues to investigate the biological roles of RNA modifications in their native RNA context.

BRCA1 and BARD1 colocalize mainly in the cytoplasm of breast cancer tumors, and their isoforms show differential expression.

BRCA1 has been found to be absent or miss localized in the cytoplasm in a relevant proportion of breast cancer tumors with no germline mutations. BRCA1 main function is in the nucleus, and its interaction with BARD1 is relevant for its nuclear translocation and retention. Our aim was to analyze the sub-cellular localization of BRCA1 and BARD1 in breast cancer tumors, and determine the level of expression of their splice variants BRCA1-Δ11q and BARD1-α and BARD1-ß. BRCA1 and BARD1 expressions were performed by immunohistochemistry and immunofluorescence in 103 breast cancer tumors. Colocalization was determined by confocal microscopy. Transcript variants were determined by qRT-PCR. We found BRCA1 localized in the cytoplasm with BARD1 in 51.4 % of tumors. An exclusive nuclear localization of both proteins was observed in 7/103 tumors (6.8 %). Indeed, these tumors displayed an apparent nucleolar colocalization of BARD1 and BRCA1. In relation to splice variants, there is a tendency to an overexpression of BARD1-α mRNA (30 % of tumors) and a decreased expression of BARD1-ß (41 %). BRCA1 full-length was downregulated in 63 % of tumors, and 37 % showed BRCA1-Δ11q variant overexpressed. Our findings contribute to a better understanding of the expression and sub-cellular localization of BRCA1 in breast cancer tumors. Interaction of BRCA1 and BARD1 seems to be not affected in 58.2 % of tumors, which showed colocalization of both proteins. The absence of BRCA1 in 41 % of tumors reveals a BRCAness phenotype, constituting an excellent marker for therapy sensitivity, to platinum drugs or PARP inhibitors.

A Summary of the American Society of Echocardiography Foundation Value-Based Healthcare: Summit 2014: The Role of Cardiovascular Ultrasound in the New Paradigm.

Value-Based Healthcare: Summit 2014 clearly achieved the three goals set forth at the beginning of this document. First, the live event informed and educated attendees through a discussion of the evolving value-based healthcare environment, including a collaborative effort to define the important role of cardiovascular ultrasound in that environment. Second, publication of these Summit proceedings in the Journal of the American Society of Echocardiography will inform a wider audience of the important insights gathered. Third, moving forward, the ASE will continue to build a ''living resource'' on its website, http://www.asecho.org, for clinicians, researchers, and administrators to use in advocating for the value of cardiovascular ultrasound in the new value-based healthcare environment. The ASE looks forward to incorporating many of the Summit recommendations as it works with its members, legislators, payers, hospital administrators, and researchers to demonstrate and increase the value of cardiovascular ultrasound. All Summit attendees shared in the infectious enthusiasm generated by this proactive approach to ensuring cardiovascular ultrasound's place as ''The Value Choice'' in cardiac imaging.

Achieving high-value cardiac imaging: challenges and opportunities.

Cardiac imaging is under intense scrutiny as a contributor to health care costs, with multiple initiatives under way to reduce and eliminate inappropriate testing. Appropriate use criteria are valuable guides to selecting imaging studies but until recently have focused on the test rather than the patient. Patient-centered means are needed to define the true value of imaging for patients in specific clinical situations. This article provides a definition of high-value cardiac imaging. A paradigm to judge the efficacy of echocardiography in the absence of randomized controlled trials is presented. Candidate clinical scenarios are proposed in which echocardiography constitutes high-value imaging, as well as stratagems to increase the likelihood that high-value cardiac imaging takes place in those circumstances.

Characterization and normal measurements of the left ventricular outflow tract by ECG-gated cardiac CT: implications for disorders of the outflow tract and aortic valve.

RATIONALE AND OBJECTIVES: Studies suggest that electrocardiographically gated coronary computed tomographic angiography provides a clear definition of the left ventricular outflow tract (LVOT), and normal LVOT morphology may not be round, as assumed when the continuity equation is applied during echocardiography. The aims of this study were to demonstrate the morphology of the LVOT on coronary computed tomographic angiography and to establish normal values for LVOT measurements. MATERIALS AND METHODS: Two independent readers retrospectively measured anterior-posterior (AP) and transverse diameters of the LVOT and performed LVOT planimetry on coronary computed tomographic angiographic studies of 106 consecutive patients with normal aortic valves. RESULTS: Excellent interobserver agreement was observed for all measurements (r = 0.78-0.94). The LVOT was ovoid, with a larger transverse diameter than AP diameter during diastole and systole (P < .001). However, the ratio of AP diameter to transverse diameter was closer to 1.0 during systole (P < .001). Mean indexed LVOT area was minimally larger in systole than in diastole (P = .01-.04) and was larger in men than in women during diastole (P ≤ .001) and systole (P ≤ .01). Mean LVOT area indexed to body surface area was 2.3 ± 0.5 cm(2)/m(2) in women and 2.6 ± 0.7 cm(2)/m(2) in men. LVOT area demonstrated significant correlation with aortic root diameter. CONCLUSIONS: The normal LVOT is ovoid in shape. LVOT is more circular during systole, but the AP diameter remains smaller than the transverse diameter throughout the cardiac cycle. The oval shape of the LVOT has important implications when LVOT area is calculated from LVOT diameters. Normal LVOT area values established in this study should facilitate diagnosis of the fixed component of LVOT obstruction.

Prediction of Homograft Aortic Valve Size by Transthoracic and Transesophageal Two-Dimensional Echocardiography.

To avoid the problem of patient valve mismatch we assessed the reliability of echocardiographic measurements in selecting an appropriate-sized homograft aortic valve. Preoperative transthoracic echocardiography (TTE) was performed in 26 consecutive patients undergoing aortic valve replacement with a cryopreserved human homograft; 19 of the patients also had intraoperative transesophageal echocardiography (TTE). The diameters of left ventricular outflow tract (LVOT), aortic annulus, sinuses of Valsalva, and ascending aorta were measured by the same technique in all patients. There was a strong correlation between LVOT diameter measured by intraoperative TEE and homograft aortic valve size selected by the surgeon (r = 0.91, P < 0.001). A good correlation was also found between LVOT measured by preoperative TTE and the homograft valve size (r = 0.82, P = 0.001). The correlation between the homograft aortic valve size and the diameter of aortic annulus was less optimal; the correlation was poor for the diameter of aorta measured at the level of the sinuses of Valsalva and ascending aorta. Measurement of the LVOT diameter by intraoperative TEE and preoperative TTE is reliable and clinically useful for the preparation of homograft aortic valves and selection of proper size, particularly in those patients undergoing repeat aortic valve replacement, with heavily calcified aortic valve or with ascending aortic aneurysm.