Management of Lung Nodules and Lung Cancer Screening During the COVID-19 Pandemic: CHEST Expert Panel Report

Background: The risks from potential exposure to coronavirus disease 2019 (COVID-19), and resource reallocation that has occurred to combat the pandemic, have altered the balance of benefits and harms that informed current (pre-COVID-19) guideline recommendations for lung cancer screening and lung nodule evaluation. Consensus statements were developed to guide clinicians managing lung cancer screening programs and patients with lung nodules during the COVID-19 pandemic. / Methods: An expert panel of 24 members, including pulmonologists (n = 17), thoracic radiologists (n = 5), and thoracic surgeons (n = 2), was formed. The panel was provided with an overview of current evidence, summarized by recent guidelines related to lung cancer screening and lung nodule evaluation. The panel was convened by video teleconference to discuss and then vote on statements related to 12 common clinical scenarios. A predefined threshold of 70% of panel members voting agree or strongly agree was used to determine if there was a consensus for each statement. Items that may influence decisions were listed as notes to be considered for each scenario. / Results: Twelve statements related to baseline and annual lung cancer screening (n = 2), surveillance of a previously detected lung nodule (n = 5), evaluation of intermediate and high-risk lung nodules (n = 4), and management of clinical stage I non–small-cell lung cancer (n = 1) were developed and modified. All 12 statements were confirmed as consensus statements according to the voting results. The consensus statements provide guidance about situations in which it was believed to be appropriate to delay screening, defer surveillance imaging of lung nodules, and minimize nonurgent interventions during the evaluation of lung nodules and stage I non–small-cell lung cancer. / Conclusions: There was consensus that during the COVID-19 pandemic, it is appropriate to defer enrollment in lung cancer screening and modify the evaluation of lung nodules due to the added risks from potential exposure and the need for resource reallocation. There are multiple local, regional, and patient-related factors that should be considered when applying these statements to individual patient care

Elevated <scp>CO₂</scp> interacts with nutrient inputs to restructure plant communities in phosphorus‐limited grasslands

AbstractGlobally pervasive increases in atmospheric CO2 and nitrogen (N) deposition could have substantial effects on plant communities, either directly or mediated by their interactions with soil nutrient limitation. While the direct consequences of N enrichment on plant communities are well documented, potential interactions with rising CO2 and globally widespread phosphorus (P) limitation remain poorly understood. We investigated the consequences of simultaneous elevated CO2 (eCO2) and N and P additions on grassland biodiversity, community and functional composition in P‐limited grasslands. We exposed soil‐turf monoliths from limestone and acidic grasslands that have received &gt;25 years of N additions (3.5 and 14 g m−2 year−1) and 11 (limestone) or 25 (acidic) years of P additions (3.5 g m−2 year−1) to eCO2 (600 ppm) for 3 years. Across both grasslands, eCO2, N and P additions significantly changed community composition. Limestone communities were more responsive to eCO2 and saw significant functional shifts resulting from eCO2–nutrient interactions. Here, legume cover tripled in response to combined eCO2 and P additions, and combined eCO2 and N treatments shifted functional dominance from grasses to sedges. We suggest that eCO2 may disproportionately benefit P acquisition by sedges by subsidising the carbon cost of locally intense root exudation at the expense of co‐occurring grasses. In contrast, the functional composition of the acidic grassland was insensitive to eCO2 and its interactions with nutrient additions. Greater diversity of P‐acquisition strategies in the limestone grassland, combined with a more functionally even and diverse community, may contribute to the stronger responses compared to the acidic grassland. Our work suggests we may see large changes in the composition and biodiversity of P‐limited grasslands in response to eCO2 and its interactions with nutrient loading, particularly where these contain a high diversity of P‐acquisition strategies or developmentally young soils with sufficient bioavailable mineral P.</jats:p

Developing a community-based genetic nomenclature for anole lizards

Background: Comparative studies of amniotes have been hindered by a dearth of reptilian molecular sequences. With the genomic assembly of the green anole, Anolis carolinensis available, non-avian reptilian genes can now be compared to mammalian, avian, and amphibian homologs. Furthermore, with more than 350 extant species in the genus Anolis, anoles are an unparalleled example of tetrapod genetic diversity and divergence. As an important ecological, genetic and now genomic reference, it is imperative to develop a standardized Anolis gene nomenclature alongside associated vocabularies and other useful metrics. Results: Here we report the formation of the Anolis Gene Nomenclature Committee (AGNC) and propose a standardized evolutionary characterization code that will help researchers to define gene orthology and paralogy with tetrapod homologs, provide a system for naming novel genes in Anolis and other reptiles, furnish abbreviations to facilitate comparative studies among the Anolis species and related iguanid squamates, and classify the geographical origins of Anolis subpopulations. Conclusions: This report has been generated in close consultation with members of the Anolis and genomic research communities, and using public database resources including NCBI and Ensembl. Updates will continue to be regularly posted to new research community websites such as lizardbase. We anticipate that this standardized gene nomenclature will facilitate the accessibility of reptilian sequences for comparative studies among tetrapods and will further serve as a template for other communities in their sequencing and annotation initiatives.Organismic and Evolutionary BiologyOther Research Uni

Surveillance of the short-term impact of fine particle air pollution on cardiovascular disease hospitalizations in New York State

<p>Abstract</p> <p>Background</p> <p>Studies have shown that the effects of particulate matter on health vary based on factors including the vulnerability of the population, health care practices, exposure factors, and the pollutant mix.</p> <p>Methods</p> <p>We used time-stratified case-crossover to estimate differences in the short-term impacts of PM_2.5on cardiovascular disease hospital admissions in New York State by geographic area, year, age, gender, co-morbid conditions, and area poverty rates.</p> <p>Results</p> <p>PM_2.5had a stronger impact on heart failure than other cardiovascular diagnoses, with 3.1% of heart failure admissions attributable to short-term PM_2.5exposure over background levels of 5 ug/m³. Older adults were significantly more susceptible to heart failure after short-term ambient PM_2.5exposure than younger adults.</p> <p>Conclusion</p> <p>The short-term impact of PM_2.5on cardiovascular disease admissions, and modifications of that impact, are small and difficult to measure with precision. Multi-state collaborations will be necessary to attain more precision to describe spatiotemporal differences in health impacts.</p

Accurate Expression Profiling of Very Small Cell Populations

BACKGROUND: Expression profiling, the measurement of all transcripts of a cell or tissue type, is currently the most comprehensive method to describe their physiological states. Given that accurate profiling methods currently available require RNA amounts found in thousands to millions of cells, many fields of biology working with specialized cell types cannot use these techniques because available cell numbers are limited. Currently available alternative methods for expression profiling from nanograms of RNA or from very small cell populations lack a broad validation of results to provide accurate information about the measured transcripts. METHODS AND FINDINGS: We provide evidence that currently available methods for expression profiling of very small cell populations are prone to technical noise and therefore cannot be used efficiently as discovery tools. Furthermore, we present Pico Profiling, a new expression profiling method from as few as ten cells, and we show that this approach is as informative as standard techniques from thousands to millions of cells. The central component of Pico Profiling is Whole Transcriptome Amplification (WTA), which generates expression profiles that are highly comparable to those produced by others, at different times, by standard protocols or by Real-time PCR. We provide a complete workflow from RNA isolation to analysis of expression profiles. CONCLUSIONS: Pico Profiling, as presented here, allows generating an accurate expression profile from cell populations as small as ten cells

The Bicarbonate Transporter Is Essential for Bacillus anthracis Lethality

In the pathogenic bacterium Bacillus anthracis, virulence requires induced expression of the anthrax toxin and capsule genes. Elevated CO2/bicarbonate levels, an indicator of the host environment, provide a signal ex vivo to increase expression of virulence factors, but the mechanism underlying induction and its relevance in vivo are unknown. We identified a previously uncharacterized ABC transporter (BAS2714-12) similar to bicarbonate transporters in photosynthetic cyanobacteria, which is essential to the bicarbonate induction of virulence gene expression. Deletion of the genes for the transporter abolished induction of toxin gene expression and strongly decreased the rate of bicarbonate uptake ex vivo, demonstrating that the BAS2714-12 locus encodes a bicarbonate ABC transporter. The bicarbonate transporter deletion strain was avirulent in the A/J mouse model of infection. Carbonic anhydrase inhibitors, which prevent the interconversion of CO2 and bicarbonate, significantly affected toxin expression only in the absence of bicarbonate or the bicarbonate transporter, suggesting that carbonic anhydrase activity is not essential to virulence factor induction and that bicarbonate, and not CO2, is the signal essential for virulence induction. The identification of this novel bicarbonate transporter essential to virulence of B. anthracis may be of relevance to other pathogens, such as Streptococcus pyogenes, Escherichia coli, Borrelia burgdorferi, and Vibrio cholera that regulate virulence factor expression in response to CO2/bicarbonate, and suggests it may be a target for antibacterial intervention

Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments

Mapping and Functional Characterisation of a CTCF-Dependent Insulator Element at the 3′ Border of the Murine Scl Transcriptional Domain

The Scl gene encodes a transcription factor essential for haematopoietic development. Scl transcription is regulated by a panel of cis-elements spread over 55 kb with the most distal 3′ element being located downstream of the neighbouring gene Map17, which is co-regulated with Scl in haematopoietic cells. The Scl/Map17 domain is flanked upstream by the ubiquitously expressed Sil gene and downstream by a cluster of Cyp genes active in liver, but the mechanisms responsible for delineating the domain boundaries remain unclear. Here we report identification of a DNaseI hypersensitive site at the 3′ end of the Scl/Map17 domain and 45 kb downstream of the Scl transcription start site. This element is located at the boundary of active and inactive chromatin, does not function as a classical tissue-specific enhancer, binds CTCF and is both necessary and sufficient for insulator function in haematopoietic cells in vitro. Moreover, in a transgenic reporter assay, tissue-specific expression of the Scl promoter in brain was increased by incorporation of 350 bp flanking fragments from the +45 element. Our data suggests that the +45 region functions as a boundary element that separates the Scl/Map17 and Cyp transcriptional domains, and raise the possibility that this element may be useful for improving tissue-specific expression of transgenic constructs

The local and systemic response to SARS-CoV-2 infection in children and adults

While a substantial proportion of adults infected with SARS-CoV-2 progress to develop severe disease, children rarely manifest respiratory complications. Therefore, understanding differences in the local and systemic response to SARS-CoV-2 infection between children and adults may provide important clues about the pathogenesis of SARS-CoV-2 infection. To address this, we first generated a healthy reference multi-omics single cell data set from children (n=30) in whom we have profiled triple matched samples: nasal and tracheal brushings and PBMCs, where we track the developmental changes for 42 airway and 31 blood cell populations from infancy, through childhood to adolescence. This has revealed the presence of naive B and T lymphocytes in neonates and infants with a unique gene expression signature bearing hallmarks of innate immunity. We then contrast the healthy reference with equivalent data from severe paediatric and adult COVID-19 patients (total n=27), from the same three types of samples: upper and lower airways and blood. We found striking differences: children with COVID-19 as opposed to adults had a higher proportion of innate lymphoid and non-clonally expanded naive T cells in peripheral blood, and a limited interferon-response signature. In the airway epithelium, we found the highest viral load in goblet and ciliated cells and describe a novel inflammatory epithelial cell population. These cells represent a transitional regenerative state between secretory and ciliated cells; they were found in healthy children and were enriched in paediatric and adult COVID-19 patients. Epithelial cells display an antiviral and neutrophil-recruiting gene signature that is weaker in severe paediatric versus adult COVID-19. Our matched blood and airway samples allowed us to study the spatial dynamics of infection. Lastly, we provide a user-friendly interface for this data1 as a highly granular reference for the study of immune responses in airways and blood in children