ABSTRACT
The proceedings contain 92 papers. The topics discussed include: cellular and humoral immune responses after SARS-CoV-2 vaccination in pediatric kidney recipients;adult outcomes of childhood-onset idiopathic nephrotic syndrome: findings from a health insurance database;the genetic landscape and clinical spectrum of nephronophthisis and related ciliopathies;translational profiling of developing podocytes during glomerulogenesis;MAGED2 is required under hypoxia for cAMP signaling by inhibiting MDM2-dependent endocytosis of G-Alpha-S;high throughput investigation of the metabolic flux of intact cortical kidney tubules;peritoneal membrane junction and solute transporter expression and function in health, CKD and PD;and Function and interaction of coronavirus ion channel proteins.
ABSTRACT
SESSION TITLE: Lung Cancer Imaging Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: SARS-CoV-2 pneumonia typically presents with ground-glass and consolidative pulmonary opacities, atypically small cavities may be seen in severe cases. In patients with cavities persisting beyond 12 weeks, an underlying malignancy is a worrisome concern. We present a case of a 39-year old female without significant risk factors for pulmonary malignancy who was found, surprisingly, to have a cavitating adenocarcinoma in the setting of COVID-19 Pneumonia. CASE PRESENTATION: A 39 year old obese African American female, never smoker, with co-existing metabolic syndrome presented to our institution with a four day history of productive cough (without hemoptysis), body aches, fever and fatigue. She denied weight loss or loss of appetite. No known family history of malignancy. She tested positive for SARS-CoV-2. She was clinically stable, hence discharged home with recommendations for quarantine and supportive care. She returned the following day with worsening dyspnea. Her chest radiograph noted a supra-hilar opacity with central lucency, Chest CT revealed wedge-shaped ground-glass and consolidative density in the right lower lobe and a 3.8 x 4.1 cm cavitary right upper lobe mass with mediastinal lymphadenopathy. She received parenteral antibiotic therapy and underwent infectious and autoimmune workup, which was negative. Repeat CT imaging, approximately three months post discharge, revealed persisting cavitary lesion and enlarging mediastinal lymphadenopathy. She underwent Electromagnetic Navigational Bronchoscopy with biopsy and fine needle aspiration of mediastinal lymph nodes (stations 7 and 4R) via endobronchial ultrasound. Biopsy results and fine needle aspiration of lymph nodes revealed adenocarcinoma with tumor cells being positive for TTF-1 and negative for CK20, CDX2, GATA3, PAX8 and Synaptophysin. Next generation sequencing reported several variants including EGFR and Tp53, there was also noted amplification of CDK4 and MDM2. PDL-1 was negative. DISCUSSION: A cavity is a gas-filled space, seen as a lucency or low-attenuation area, within a nodule, mass, or area of parenchymal consolidation. Underlying etiologies are typically classified as infectious, autoimmune and malignant. Cavities are atypical findings on CT imaging in patients with viral pneumonias, including SARS-CoV-2. Those cavities persisting beyond 12 weeks are typically classified as being chronic, with malignancy a key concern in these patients. The most common type of primary cavitary lung cancer is squamous cell carcinoma, in fact Primary Pulmonary Adenocarcinomas are unlikely to cavitate. Treatment options, depending on the presence of targetable mutations, include concurrent chemoradiation, chemoimmunotherapy or oral targeted agent. CONCLUSIONS: Though an atypical presentation, Pulmonary Adenocarcinoma may present as a cavitary lesion, particularly in the presence of persisting or enlarging lymphadenopathy. Reference #1: Gafoor K, Patel S, Girvin F, Gupta N, Naidich D, Machnicki S, Brown KK, Mehta A, Husta B, Ryu JH, Sarosi GA, Franquet T, Verschakelen J, Johkoh T, Travis W, Raoof S. Cavitary Lung Diseases: A Clinical-Radiologic Algorithmic Approach. Chest. 2018 Jun;153(6):1443-1465. doi: 10.1016/j.chest.2018.02.026. Epub 2018 Mar 6. PMID: 29518379. Reference #2: Radiological Society of North America Expert Consensus Document on Reporting Chest CT Findings Related to COVID-19: Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA Scott Simpson, Fernando U. Kay, Suhny Abbara, Sanjeev Bhalla, Jonathan H. Chung, Michael Chung, Travis S. Henry, Jeffrey P. Kanne, Seth Kligerman, Jane P. Ko, and Harold Litt Radiology: Cardiothoracic Imaging 2020 2:2 DISCLOSURES: No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No releva t relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Sulaiman Tijani
ABSTRACT
Atlanta, Georgia, was the grand setting of the Fall 2021 American Chemical Society (ACS) National Meeting & Exposition, subheaded ‘Resilience of Chemistry.’ The meeting was both an in-person and virtual meeting at Georgia World Congress Center, and consisted of poster presentations, oral sessions, symposia, press releases and media briefings from s chosen from thousands of scientific presentations on topics that include food and nutrition, medicine, health, energy, the environment, medicinal chemistry, biological chemistry, and other fields where chemistry plays a central role. Presentations were either in person or virtual, or both, allowing for an almost return to normal meeting attendance since the start of the COVID-19 pandemic, with live interaction possible in a room or online.
ABSTRACT
Comprehensive proteomic studies of HSC derived from bone marrow of healthy human subjects (n = 59) in different age groups (range: 20 - 72 years) showed that aging HSCs are characterized not only by myeloid lineage skewing, senescence associated secretory phenotype (SASP), accumulation of reactive oxygen species (ROS), anti-apoptosis, but prominently by elevated glycolysis, glucose uptake, and accumulation of glycogen. This is caused by a subset of HSC that has become more glycolytic than others and not on a per cell basis. Subsequent comparative transcriptome studies of HSCs from human subjects >60 years versus those from <30 years have confirmed this association of elevated glycolysis with aging transcriptome signature. Provided with this background and based on glucose metabolism levels, we have developed a method to isolate human HSCs (CD34+ cells) from bone marrow into three distinct subsets with high, intermediate, and low glucose uptake (GU) capacity (GU high, GU inter, GU low). For human subjects >60 years old (n=9), the proportions of these subsets are: GU high= 5.4+3.5 %, GU inter= 66.4+22.5 %, GU low= 28.2+21.7 %. For subjects <30 years (n=5), the proportions are GU high= 1.7+1.5 %, GU inter= 66.5+36.9 %, GU low= 31.8+36.7. Single-cell RNA-sequencing (scRNA-seq) studies and gene ontology analysis of biological processes revealed that, compared to the GU inter and GU low subsets, the GU high cells showed a significantly higher expression of genes involved in myeloid development, inflammation response (AIF1, CASP2, ANXA1, ZFP36), anti-apoptosis (GSTP1, NME1, BCL2, DMNT1, BAX), cell cycle checkpoint (MCL1, CDK1, CDK4, EIF5A), histone regulation (BCL6, EGR1, KDM1A, MLLT3), b-galactosidase, and significantly lower expressions of genes involved in lymphoid development, and of MDM4, MDM2, FOXP1, SOX4, RB1. Functional studies indicated that the glycolytic enzymes were elevated in elderly HSCs, and the GU low subset corresponded to primitive and more pluripotent HSCs than the GU interand GU high subsets. Pathway analyses have then demonstrated that the GU high subset is associated with up-regulated p53 as well as JAK/STAT signaling pathways, characteristic of senescent HSCs observed in murine models. Applying Gene Set Enrichment Analysis (GSEA) algorithms, we have compared the scRNA-seq data of CD34+ cells derived from young (<30 years) versus older (>60 years) subjects, as well as the scRNA-seq data from GU high subset versus GU inter and GU lowsubsets from each individual subject (n = 6). The results are shown in Figure 1. In analogy to the comparison between old (>60 years) versus young (<30 years) HSCs (CD34+ cells), GSEA of the GU high versus GU inter and GU low subsets shows the same pattern of changes - significant upregulation of gene-set expressions for (a) inflammatory response (b) G2M checkpoint, (c) MTORC1, (d) ROS, (Fig. 1B), (e) allograft rejection;and down-regulation of gene-set expressions for (f) pluripotency, (g) androgen response, (h) UV response (Fig. 1C) as well as (i) interferon-a induction during SARS-CoV2-infection (data not shown in Fig. 1). Thus, our novel findings of elevated glycolysis coupled with significant activation of MTORC1 in the senescent cells of the HSC compartment have provided evidence for the important role of calorie restriction (CR) for healthy aging of HSCs. In numerous animal models, aging has been shown to be driven by the nutrient-sensing MTORC1 network. In animal models of aging, CR has been reported to deactivate the MTOR pathway, thus slowing aging and delaying diseases of aging. Conclusion: In a series of multi-omics studies, we have demonstrated that the GU high subset is identical to the senescent cells (SCs) in human HSC compartment. Studies in animal models have shown that SCs in murine bone marrow are responsible for driving the aging process, and elimination of this subset by inhibitors of anti-apoptotic factors is able to rejuvenate hematopoiesis in mice. Our present results have provided cellular and molecular evidence that SCs in human HSC compartment re also dependent on anti-apoptotic factors, elevated MTORC1 as well as increased glycolysis for survival. Inhibition of MTORC1 or glycolysis, either by specific inhibitors or by CR, may eliminate senescent HSCs and promote rejuvenation of human hematopoiesis. [Formula presented] Disclosures: No relevant conflicts of interest to declare.