Search

Quantitative MRI techniques could be helpful to noninvasively and longitudinally monitor dynamic changes in spinal cord white matter following injury, but imaging and postprocessing techniques in small animals remain lacking. Unilateral C5 hemisection lesions were created in a rat model, and ultrashort echo time magnetization transfer (UTE-MT) and diffusion-weighted sequences were used for imaging following injury. Magnetization transfer ratio (MTR) measurements and preferential diffusion along the longitudinal axis of the spinal cord were calculated as fractional anisotropy or an apparent diffusion coefficient ratio over transverse directions. The area of myelinated white matter was obtained by thresholding the spinal cord using mean MTR or diffusion ratio values from the contralesional side of the spinal cord. A decrease in white matter areas was observed on the ipsilesional side caudal to the lesions, which is consistent with known myelin and axonal changes following spinal cord injury. The myelinated white matter area obtained through the UTE-MT technique and the white matter area obtained through diffusion imaging techniques showed better performance to distinguish evolution after injury (AUCs > 0.94, p < 0.001) than the mean MTR (AUC = 0.74, p = 0.01) or ADC ratio (AUC = 0.68, p = 0.05) values themselves. Immunostaining for myelin basic protein (MBP) and neurofilament protein NF200 (NF200) showed atrophy and axonal degeneration, confirming the MRI results. These compositional and microstructural MRI techniques may be used to detect demyelination or remyelination in the spinal cord after spinal cord injury. [ABSTRACT FROM AUTHOR]

Evaluation of the 3D bone morphology of the glenohumeral joint is necessary for pre-surgical planning. Zero echo time (ZTE) magnetic resonance imaging (MRI) provides excellent bone contrast and can potentially be used in the place of computed tomography. Segmentation of the shoulder anatomy, particularly the humeral head and the acetabulum, is needed for the detailed assessment of each anatomy and for pre-surgical preparation. In this study, we compared the performance of two popular deep learning models based on Google's DeepLab and U-Net to perform automated segmentation on ZTE MRI of human shoulders. Axial ZTE images of normal shoulders (n = 31) acquired at 3-Tesla were annotated for training with DeepLab and 2D U-Net, and the trained model was validated with testing data (n = 13). While both models showed visually satisfactory results for segmenting the humeral bone, U-Net slightly over-estimated while DeepLab under-estimated the segmented area compared to the ground truth. Testing accuracy quantified by Dice score was significantly higher (p < 0.05) for U-Net (88%) than DeepLab (81%) for the humeral segmentation. We have also implemented the U-Net model onto an MRI console for push-button DL segmentation processing. Although this is an early work with limitations, our approach has the potential to improve shoulder MR evaluation hindered by manual post-processing and may provide clinical benefit for quickly visualizing bones of the glenohumeral joint. [ABSTRACT FROM AUTHOR]

We have investigated the concurrence of sleep apnea and pulmonary hypertension in a Veteran population. We retrospectively reviewed 142 patients who underwent chest CT scans and had a dilated main pulmonary artery, defined as a width exceeding 29 mm on axial images. Approximately 40% of patients with pulmonary hypertension had associated sleep apnea. No significant difference in pulmonary artery diameters could be found between the group without sleep apnea and the group with sleep apnea (34.5 ± 4.2 mm vs. 34.7 ± 4.4 mm, p = 0.373). [ABSTRACT FROM AUTHOR]

Ultrasound (US) is an important imaging tool for skeletal muscle analysis. The advantages of US include point-of-care access, real-time imaging, cost-effectiveness, and absence of ionizing radiation. However, US can be highly dependent on the operator and/or US system, and a portion of the potentially useful information carried by raw sonographic data is discarded in image formation for routine qualitative US. Quantitative ultrasound (QUS) methods provide analysis of the raw or post-processed data, revealing additional information about normal tissue structure and disease status. There are four QUS categories that can be used on muscle and are important to review. First, quantitative data derived from B-mode images can help determine the macrostructural anatomy and microstructural morphology of muscle tissues. Second, US elastography can provide information about muscle elasticity or stiffness through strain elastography or shear wave elastography (SWE). Strain elastography measures the induced tissue strain caused either by internal or external compression by tracking tissue displacement with detectable speckle in B-mode images of the examined tissue. SWE measures the speed of induced shear waves traveling through the tissue to estimate the tissue elasticity. These shear waves may be produced using external mechanical vibrations or internal "push pulse" ultrasound stimuli. Third, raw radiofrequency signal analyses provide estimates of fundamental tissue parameters, such as the speed of sound, attenuation coefficient, and backscatter coefficient, which correspond to information about muscle tissue microstructure and composition. Lastly, envelope statistical analyses apply various probability distributions to estimate the number density of scatterers and quantify coherent to incoherent signals, thus providing information about microstructural properties of muscle tissue. This review will examine these QUS techniques, published results on QUS evaluation of skeletal muscles, and the strengths and limitations of QUS in skeletal muscle analysis. [ABSTRACT FROM AUTHOR]

Aim: This review article describes quantitative ultrasound (QUS) techniques and summarizes their strengths and limitations when applied to peripheral nerves. Methods: A systematic review was conducted on publications after 1990 in Google Scholar, Scopus, and PubMed databases. The search terms "peripheral nerve", "quantitative ultrasound", and "elastography ultrasound" were used to identify studies related to this investigation. Results: Based on this literature review, QUS investigations performed on peripheral nerves can be categorized into three main groups: (1) B-mode echogenicity measurements, which are affected by a variety of post-processing algorithms applied during image formation and in subsequent B-mode images; (2) ultrasound (US) elastography, which examines tissue stiffness or elasticity through modalities such as strain ultrasonography or shear wave elastography (SWE). With strain ultrasonography, induced tissue strain, caused by internal or external compression stimuli that distort the tissue, is measured by tracking detectable speckles in the B-mode images. In SWE, the propagation speed of shear waves, generated by externally applied mechanical vibrations or internal US "push pulse" stimuli, is measured to estimate tissue elasticity; (3) the characterization of raw backscattered ultrasound radiofrequency (RF) signals, which provide fundamental ultrasonic tissue parameters, such as the acoustic attenuation and backscattered coefficients, that reflect tissue composition and microstructural properties. Conclusions: QUS techniques allow the objective evaluation of peripheral nerves and reduce operator- or system-associated biases that can influence qualitative B-mode imaging. The application of QUS techniques to peripheral nerves, including their strengths and limitations, were described and discussed in this review to enhance clinical translation. [ABSTRACT FROM AUTHOR]

Magnetic resonance imaging (MRI) is widely regarded as the most comprehensive imaging modality to assess skeletal muscle quality and quantity. Magnetization transfer (MT) imaging can be used to estimate the fraction of water and macromolecular proton pools, with the latter including the myofibrillar proteins and collagen, which are related to the muscle quality and its ability to generate force. MT modeling combined with ultrashort echo time (UTE-MT modeling) may improve the evaluation of the myotendinous junction and regions with fibrotic tissues in the skeletal muscles, which possess short T2 values and higher bound-water concentration. The fat present in muscle has always been a source of concern in macromolecular fraction (MMF) calculation. This study aimed to investigate the impact of fat fraction (FF) on the estimated MMF in bovine skeletal muscle phantoms embedded in pure fat. MMF was calculated for several regions of interest (ROIs) with differing FFs using UTE-MT modeling with and without T1 measurement and B1 correction. Calculated MMF using measured T1 showed a robust trend, particularly with a negligible error (<3%) for FF < 20%. Around 5% MMF reduction occurred for FF > 30%. However, MMF estimation using a constant T1 was robust only for regions with FF < 10%. The MTR and T1 values were also robust for only FF < 10%. This study highlights the potential of the UTE-MT modeling with accurate T1 measurement for robust muscle assessment while remaining insensitive to fat infiltration up to moderate levels. [ABSTRACT FROM AUTHOR]

Tendons and bones comprise a special interacting unit where mechanical, biochemical, and metabolic interplays are continuously in effect. Bone loss in osteoporosis (OPo) and its earlier stage disease, osteopenia (OPe), may be coupled with a reduction in tendon quality. Noninvasive means for quantitatively evaluating tendon quality during disease progression may be critically important for the improvement of characterization and treatment optimization in patients with bone mineral density disorders. Though clinical magnetic resonance imaging (MRI) sequences are not typically capable of directly visualizing tendons, ultrashort echo time MRI (UTE-MRI) is able to acquire a high signal from tendons. Magnetization transfer (MT) modeling combined with UTE-MRI (i.e., UTE-MT-modeling) can indirectly assess macromolecular proton content in tendons. This study aimed to determine whether UTE-MT-modeling could detect differences in tendon quality across a spectrum of bone health. The lower legs of 14 OPe (72 ± 6 years) and 31 OPo (73 ± 6 years) female patients, as well as 30 female participants with normal bone (Normal-Bone, 36 ± 19 years), are imaged using UTE sequences on a 3T MRI scanner. Institutional review board approval is obtained for the study, and all recruited subjects provided written informed consent. A T1 measurement and UTE-MT-modeling are performed on the anterior tibialis tendon (ATT), posterior tibialis tendon (PTT), and the proximal Achilles tendon (PAT) of all subjects. The macromolecular fraction (MMF) is estimated as the main measure from UTE-MT-modeling. The mean MMF in all the investigated tendons was significantly lower in OPo patients compared with the Normal-Bone cohort (mean difference of 24.2%, p < 0.01), with the largest Normal-Bone vs. OPo difference observed in the ATT (mean difference of 32.1%, p < 0.01). Average MMF values of all the studied tendons are significantly lower in the OPo cohort compared with the OPe cohort (mean difference 16.8%, p = 0.02). Only the PPT shows significantly higher T1 values in OPo patients compared with the Normal-Bone cohort (mean difference 17.6%, p < 0.01). Considering the differences between OPo and OPe groups with similar age ranges, tendon deterioration associated with declining bone health was found to be larger than a priori detected differences caused purely by aging, highlighting UTE-MT MRI techniques as useful methods in assessing tendon quality over the course of progressive bone weakening. [ABSTRACT FROM AUTHOR]

A relationship between an acidic pH in the joints, osteoarthritis (OA), and pain has been previously demonstrated. Acidosis Chemical Exchange Saturation Transfer (acidoCEST) indirectly measures the extracellular pH through the assessment of the exchange of protons between amide groups on iodinated contrast agents and bulk water. It is possible to estimate the extracellular pH in the osteoarthritic joint using acidoCEST MRI. However, conventional MR sequences cannot image deep layers of cartilage, meniscus, ligaments, and other musculoskeletal tissues that present with short echo time and fast signal decay. Ultrashort echo time (UTE) MRI, on the other hand, has been used successfully to image those joint tissues. Here, our goal is to compare the pH measured in the knee joints of volunteers without OA and patients with severe OA using acidoCEST-UTE MRI. Patients without knee OA and patients with severe OA were examined using acidoCEST-UTE MRI and the mean pH of cartilage, meniscus, and fluid was calculated. Additionally, the relationship between the pH measurements and the Knee Injury and Osteoarthritis Outcome Score (KOOS) was investigated. AcidoCEST-UTE MRI can detect significant differences in the pH of knee cartilage, meniscus, and fluid between joints without and with OA, with OA showing lower pH values. In addition, symptoms and knee-joint function become worse at lower pH measurements. [ABSTRACT FROM AUTHOR]

Reference 1 Lombardi A.F., Ma Y., Jang H., Jerban S., Tang Q., Searleman A.C., Meyer R.S., Du J., Chang E.Y. AcidoCEST-UTE MRI Reveals an Acidic Microenvironment in Knee Osteoarthritis. AcidoCEST-UTE MRI Reveals an Acidic Microenvironment in Knee Osteoarthritis. Note the higher pH values (yellow and red colors) in patients without OA compared with patients with OA (blue colors). [Extracted from the article]

Simple Summary: It is well established that tobacco smoke is the key player in lung squamous cell carcinoma (LUSC) pathogenesis, and there is growing evidence that electronic cigarette (e-cigarette) vapor may also cause LUSC. Recently, several studies have associated tobacco smoke with differential enhancer RNA (eRNA) expression. However, the effects of tobacco smoke and e-cigarette vapor on eRNA expression in correlation to LUSC outcomes have not been fully elucidated. This study demonstrates that tobacco smoke and e-cigarette vapor may decrease DNA methylation and increase chromosomal alterations at key sites, which ultimately upregulate the expression of oncogenic eRNAs and downregulate the expression of tumor-suppressing eRNAs. Subsequently, we demonstrate that these eRNAs may have altered interactions with immune cells to promote LUSC pathogenesis and reduced patient survival. We hope our results can be validated in future studies, and the key eRNAs we identified may be used as effective targets for more specialized treatments for smoking-mediated LUSC. Tobacco is the primary etiologic agent in worsened lung squamous cell carcinoma (LUSC) outcomes. Meanwhile, it has been shown that etiologic agents alter enhancer RNAs (eRNAs) expression. Therefore, we aimed to identify the effects of tobacco and electronic cigarette (e-cigarette) use on eRNA expression in relation to LUSC outcomes. We extracted eRNA counts from RNA-sequencing data of tumor/adjacent normal tissue and before/after e-cigarette tissue from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO), respectively. Tobacco-mediated LUSC eRNAs were correlated to patient survival, clinical variables, and immune-associated elements. eRNA expression was also correlated to mutation rates through the Repeated Evaluation of Variables Conditional Entropy and Redundance (REVEALER) algorithm and methylated sites through methylationArrayAnalysis. Differential expression analysis was then completed for the e-cigarette data to compare with key tobacco-mediated eRNAs. We identified 684 downregulated eRNAs and 819 upregulated eRNAs associated with tobacco-mediated LUSC, specifically, with the cancer pathological stage. We also observed a decrease in immune cell abundance in tobacco-mediated LUSC. Yet, we found an increased association of eRNA expression with immune cell abundance in tobacco-mediated LUSC. We identified 16 key eRNAs with significant correlations to 8 clinical variables, implicating these eRNAs in LUSC malignancy. Furthermore, we observed that these 16 eRNAs were highly associated with chromosomal alterations and reduced CpG site methylation. Finally, we observed large eRNA expression upregulation with e-cigarette use, which corresponded to the upregulation of the 16 key eRNAs. Our findings provide a novel mechanism by which tobacco and e-cigarette smoke influences eRNA interactions to promote LUSC pathogenesis and provide insight regarding disease progression at a molecular level. [ABSTRACT FROM AUTHOR]

Patients with underlying cardiovascular conditions are particularly vulnerable to severe COVID-19. In this project, we aimed to characterize similarities in dysregulated immune pathways between COVID-19 patients and patients with cardiomyopathy, venous thromboembolism (VTE), or coronary artery disease (CAD). We hypothesized that these similarly dysregulated pathways may be critical to how cardiovascular diseases (CVDs) exacerbate COVID-19. To evaluate immune dysregulation in different diseases, we used four separate datasets, including RNA-sequencing data from human left ventricular cardiac muscle samples of patients with dilated or ischemic cardiomyopathy and healthy controls; RNA-sequencing data of whole blood samples from patients with single or recurrent event VTE and healthy controls; RNA-sequencing data of human peripheral blood mononuclear cells (PBMCs) from patients with and without obstructive CAD; and RNA-sequencing data of platelets from COVID-19 subjects and healthy controls. We found similar immune dysregulation profiles between patients with CVDs and COVID-19 patients. Interestingly, cardiomyopathy patients display the most similar immune landscape to COVID-19 patients. Additionally, COVID-19 patients experience greater upregulation of cytokine- and inflammasome-related genes than patients with CVDs. In all, patients with CVDs have a significant overlap of cytokine- and inflammasome-related gene expression profiles with that of COVID-19 patients, possibly explaining their greater vulnerability to severe COVID-19. [ABSTRACT FROM AUTHOR]

The implications of the microbiome on Coronavirus disease 2019 (COVID-19) prognosis has not been thoroughly studied. In this study we aimed to characterize the lung and blood microbiome and their implication on COVID-19 prognosis through analysis of peripheral blood mononuclear cell (PBMC) samples, lung biopsy samples, and bronchoalveolar lavage fluid (BALF) samples. In all three tissue types, we found panels of microbes differentially abundant between COVID-19 and normal samples correlated to immune dysregulation and upregulation of inflammatory pathways, including key cytokine pathways such as interleukin (IL)-2, 3, 5-10 and 23 signaling pathways and downregulation of anti-inflammatory pathways including IL-4 signaling. In the PBMC samples, six microbes were correlated with worse COVID-19 severity, and one microbe was correlated with improved COVID-19 severity. Collectively, our findings contribute to the understanding of the human microbiome and suggest interplay between our identified microbes and key inflammatory pathways which may be leveraged in the development of immune therapies for treating COVID-19 patients. [ABSTRACT FROM AUTHOR]

In this study, we combined quantitative ultrashort echo time (UTE) magnetic resonance (MR) imaging and an investigation by a probing device with tri-axial force sensor to seek correlations with mechanical properties of human patellar cartilage for in situ evaluation of biomechanical properties. Cartilage blocks (15 × 20 × 5 mm3) were dissected from the patella of six donors; 5 mm square regions of interest from the cartilage blocks were imaged using UTE-MR imaging sequences (T2* and magnetization transfer ratio (MTR)), and mechanical properties were measured using a micro indentation device. Then, the vertical reaction force on the cartilage surface was measured while push-probing forward 3 mm with the probing device at a 30° tilt to the horizontal plane. The results showed a positive correlation between stiffness/elastic modulus and each predictor variable (UTE-T2* (r = 0.240 and 0.255, respectively, UTE-MTR (r = 0.378 and 0.379, respectively), and probing device force (r = 0.426 and 0.423, respectively). Furthermore, multiple linear regression analysis showed the combination of the three predictors had stronger correlation (adjusted r2 = 0.314 (stiffness), 0.323 (elastic), respectively). Our results demonstrate the potential for these non- and less- invasive methods for in situ evaluation of the mechanical properties of cartilage tissue. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the association between high-density mineralized protrusions (HDMPs) and central osteophytes (COs), and describe the varying appearance of these lesions using advanced clinical imaging and a novel histological protocol. Seventeen consecutive patients with clinically advanced knee osteoarthritis undergoing knee arthroplasty were included. Surgical tissues containing the osteochondral region were investigated using computed tomography (CT); a subset was evaluated using confocal microscopy with fluorescence. Tissues from seven subjects (41.2%) contained HDMPs, and tissues from seven subjects (41.2%) contained COs. A significant association between HDMPs and COs was present (p = 0.003), with 6 subjects (35.2%) demonstrating both lesions. In total, 30 HDMPs were found, most commonly at the posterior medial femoral condyle (13/30, 43%), and 19 COs were found, most commonly at the trochlea (5/19, 26.3%). The HDMPs had high vascularity at their bases in cartilaginous areas (14/20, 70%), while the surrounding areas had elevated levels of long vascular channels penetrating beyond the zone of calcified cartilage (p = 0.012) compared to HDMP-free areas. Both COs and HDMPs had noticeable bone-resorbing osteoclasts amassing at the osteochondral junction and in vascular channels entering cartilage. In conclusion, HDMPs and COs are associated lesions in patients with advanced knee osteoarthritis, sharing similar histologic features, including increased vascularization and metabolic bone activity at the osteochondral junction. Future studies are needed to determine the relationship of these lesions with osteoarthritis progression and symptomatology. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is the most common joint disorder in the United States, and the gut microbiome has recently emerged as a potential etiologic factor in OA development. Recent studies have shown that a microbiome is present at joint synovia. Therefore, we aimed to characterize the intra-articular microbiome within osteoarthritic synovia and to illustrate its role in OA disease progression. RNA-sequencing data from OA patient synovial tissue was aligned to a library of microbial reference genomes to identify microbial reads indicative of microbial abundance. Microbial abundance data of OA and normal samples was compared to identify differentially abundant microbes. We computationally explored the correlation of differentially abundant microbes to immunological gene signatures, immune signaling pathways, and immune cell infiltration. We found that microbes correlated to OA are related to dysregulation of two main functional pathways: increased inflammation-induced extracellular matrix remodeling and decreased cell signaling pathways crucial for joint and immune function. We also confirmed that the differentially abundant and biologically relevant microbes we had identified were not contaminants. Collectively, our findings contribute to the understanding of the human microbiome, well-known OA risk factors, and the role microbes play in OA pathogenesis. In conclusion, we present previously undiscovered microbes implicated in the OA disease progression that may be useful for future treatment purposes. [ABSTRACT FROM AUTHOR]

Simple Summary: The cancer microbiome has been suggested to be closely involved in the immune dysregulation that leads to carcinogenesis. Given that pancreatic adenocarcinoma (PAAD) is one of the most lethal cancers, it is important to identify features of the microbiome that may contribute to more deadly PAAD tumors. In this study, we analyzed PAAD patient RNA-sequencing data from The Cancer Genome Atlas (TCGA) to correlate abundance of intra-pancreatic microbes to dysregulation of immune and cancer-associated genes and pathways. We discovered that the presence of several bacteria species within PAAD tumors is linked to metastasis and immune suppression. Furthermore, we found that the increased prevalence and poorer prognosis of PAAD in males and smokers are linked to the presence of potentially cancer-promoting or immune-inhibiting microbes. Further study into the roles of these microbes in PAAD is imperative for understanding how a pro-tumor microenvironment may be treated to limit cancer progression. An intra-pancreatic microbiota was recently discovered in several prominent studies. Since pancreatic adenocarcinoma (PAAD) is one of the most lethal cancers worldwide, and the intratumor microbiome was found to be a significant contributor to carcinogenesis in other cancers, this study aims to characterize the PAAD microbiome and elucidate how it may be associated with PAAD prognosis. We further explored the association between the intra-pancreatic microbiome and smoking and gender, which are both risk factors for PAAD. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance, which was correlated to clinical variables and to cancer and immune-associated gene expression, to determine how microbes may contribute to cancer progression. We discovered that the presence of several bacteria species within PAAD tumors is linked to metastasis and immune suppression. This is the first large-scale study to report microbiome-immune correlations in human pancreatic cancer samples. Furthermore, we found that the increased prevalence and poorer prognosis of PAAD in males and smokers are linked to the presence of potentially cancer-promoting or immune-inhibiting microbes. Further study into the roles of these microbes in PAAD is imperative for understanding how a pro-tumor microenvironment may be treated to limit cancer progression. [ABSTRACT FROM AUTHOR]

Simple Summary: While the intratumor microbiome has been largely unexplored in relation to prostate cancer development, our research shows that microbes may play an anti-tumor or pro-tumor role to significantly alter clinical course in prostate cancer patients. We found that the presence and absence of specific microbes are strongly correlated with known biomarkers of prostate cancer, including increased androgen receptor expression, prostate-specific antigen level, immune-associated gene dysregulation, stem-cell related gene overexpression, cancer pathways, and known chromosomal alterations. Our results provide important insight on potential mechanisms by which intratumor microbes may greatly contribute to prostate cancer progression and prognosis. We hope our results can be validated in future studies, and the key microbes that we identified can be used as effective targets for more specialized prebiotic and probiotic treatments for prostate cancer. Although 1 in 9 American men will receive a diagnosis of prostate cancer (PC), most men with this diagnosis will not die from it, as most PCs are indolent. However, there is a subset of patients in which the once-indolent PC becomes metastatic and eventually, fatal. In this study, we analyzed microbial compositions of intratumor bacteria in PC to determine the influence of the microbiome on metastatic growth. Using large-scale RNA-sequencing data and corresponding clinical data, we correlated the abundance of microbes to immune pathways and PC risk factors, identifying specific microbes that either significantly deter or contribute to cancer aggressiveness. Interestingly, most of the microbes we found appeared to play anti-tumor roles in PC. Since these anti-tumor microbes were overrepresented in tumor samples, we believe that microbes thrive in the tumor microenvironment, outcompete cancer cells, and directly mitigate tumor growth by recruiting immune cells. These include Listeria monocytogenes, Methylobacterium radiotolerans JCM 2831, Xanthomonas albilineans GPE PC73, and Bradyrhizobium japonicum, which are negatively correlated with Gleason score, Tumor-Node-Metastasis (TNM) stage, prostate-specific antigen (PSA) level, and Androgen Receptor (AR) expression, respectively. We also identified microbes that contribute to tumor growth and are positively correlated with genomic alterations, dysregulated immune-associated (IA) genes, and prostate cancer stem cells (PCSC) genes. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic caused by the SARS-CoV-2 virus, overlaps with the ongoing epidemics of cigarette smoking and electronic cigarette (e-cig) vaping. However, there is scarce data relating COVID-19 risks and outcome with cigarette or e-cig use. In this study, we mined three independent RNA expression datasets from smokers and vapers to understand the potential relationship between vaping/smoking and the dysregulation of key genes and pathways related to COVID-19. We found that smoking, but not vaping, upregulates ACE2, the cellular receptor that SARS-CoV-2 requires for infection. Both smoking and use of nicotine and flavor-containing e-cigs led to upregulation of pro-inflammatory cytokines and inflammasome-related genes. Specifically, chemokines including CCL20 and CXCL8 are upregulated in smokers, and CCL5 and CCR1 are upregulated in flavor/nicotine-containing e-cig users. We also found genes implicated in inflammasomes, such as CXCL1, CXCL2, NOD2, and ASC, to be upregulated in smokers and these e-cig users. Vaping flavor and nicotine-less e-cigs, however, did not lead to significant cytokine dysregulation and inflammasome activation. Release of inflammasome products, such as IL-1B, and cytokine storms are hallmarks of COVID-19 infection, especially in severe cases. Therefore, our findings demonstrated that smoking or vaping may critically exacerbate COVID-19-related inflammation or increase susceptibility to COVID-19. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the deadliest cancers in the world. Previous studies have identified the importance of alcohol and hepatitis B (HBV) infection on HCC carcinogenesis, indicating synergy in the methods by which these etiologies advance cancer. However, the specific molecular mechanism behind alcohol and HBV-mediated carcinogenesis remains unknown. Because the microbiome is emerging as a potentially important regulator of cancer development, this study aims to classify the effects of HBV and alcohol on the intratumoral liver microbiome. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to infer microbial abundance. This abundance was then correlated to clinical variables and to cancer and immune-associated gene expression, in order to determine how microbial abundance may contribute to differing cancer progression between etiologies. We discovered that the liver microbiome is likely oncogenic after exposure to alcohol or HBV, although these etiological factors could decrease the abundance of a few oncogenic microbes, which would lead to a tumor suppressive effect. In HBV-induced tumors, this tumor suppressive effect was inferred based on the downregulation of microbes that induce cancer and stem cell pathways. Alcohol-induced tumors were observed to have distinct microbial profiles from HBV-induced tumors, and different microbes are clinically relevant in each cohort, suggesting that the effects of the liver microbiome may be different in response to different etiological factors. Collectively, our data suggest that HBV and alcohol operate within a normally oncogenic microbiome to promote tumor development, but are also able to downregulate certain oncogenic microbes. Insight into why these microbes are downregulated following exposure to HBV or alcohol, and why the majority of oncogenic microbes are not downregulated, may be critical for understanding whether a pro-tumor liver microbiome could be suppressed or reversed to limit cancer progression. [ABSTRACT FROM AUTHOR]

The intra-tumor microbiota has been increasingly implicated in cancer pathogenesis. In this study, we aimed to examine the microbiome in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and determine its compositional differences with relation to age and gender. After grouping 497 LUAD and 433 LUSC patients by age and gender and removing potential contaminants, we identified differentially abundant microbes in each patient cohort vs. adjacent normal samples. We then correlated dysregulated microbes with patient survival rates, immune infiltration, immune and cancer pathways, and genomic alterations. We found that most age and gender cohorts in both LUAD and LUSC contained unique, significantly dysregulated microbes. For example, LUAD-associated Escherichia coli str. K-12 substr. W3110 was dysregulated in older female and male patients and correlated with both patient survival and genomic alterations. For LUSC, the most prominent bacterial species that we identified was Pseudomonas putida str. KT2440, which was uniquely associated with young LUSC male patients and immune infiltration. In conclusion, we found differentially abundant microbes implicated with age and gender that are also associated with genomic alterations and immune dysregulations. Further investigation should be conducted to determine the relationship between gender and age-associated microbes and the pathogenesis of lung cancer. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic is marked by a wide range of clinical disease courses, ranging from asymptomatic to deadly. There have been many studies seeking to explore the correlations between COVID-19 clinical outcomes and various clinical variables, including age, sex, race, underlying medical problems, and social habits. In particular, the relationship between smoking and COVID-19 outcome is controversial, with multiple conflicting reports in the current literature. In this study, we aim to analyze how smoking may affect the SARS-CoV-2 infection rate. We analyzed sequencing data from lung and oral epithelial samples obtained from The Cancer Genome Atlas (TCGA). We found that the receptor and transmembrane protease necessary for SARS-CoV-2 entry into host cells, ACE2 and TMPRSS2, respectively, were upregulated in smoking samples from both lung and oral epithelial tissue. We then explored the mechanistic hypothesis that smoking may upregulate ACE2 expression through the upregulation of the androgen pathway. ACE2 and TMPRSS2 upregulation were both correlated to androgen pathway enrichment and the specific upregulation of central pathway regulatory genes. These data provide a potential model for the increased susceptibility of smoking patients to COVID-19 and encourage further exploration into the androgen and tobacco upregulation of ACE2 to understand the potential clinical ramifications. [ABSTRACT FROM AUTHOR]

Immunotherapy has emerged in recent years as arguably the most effective treatment for advanced hepatocellular carcinoma (HCC), but the failure of a large percentage of patients to respond to immunotherapy remains as the ultimate obstacle to successful treatment. Etiology-associated dysregulation of immune-associated (IA) genes may be central to the development of this differential clinical response. We identified immune-associated genes potentially dysregulated by alcohol or viral hepatitis B in HCC and validated alcohol-induced dysregulations in vitro while using large-scale RNA-sequencing data from The Cancer Genome Atlas (TCGA). Thirty-four clinically relevant dysregulated IA genes were identified. We profiled the correlation of all genomic alterations in HCC patients to IA gene expression while using the information theory-based algorithm REVEALER to investigate the molecular mechanism for their dysregulation and explore the possibility of genome-based patient stratification. We also studied gene expression regulators and identified multiple microRNAs that were implicated in HCC pathogenesis that can potentially regulate these IA genes' expression. Our study identified potential key pathways, including the IL-7 signaling pathway and TNFRSF4 (OX40)- NF-κB pathway, to target in immunotherapy treatments and presents microRNAs as promising therapeutic targets for dysregulated IA genes because of their extensive regulatory roles in the cancer immune landscape. [ABSTRACT FROM AUTHOR]

Papillary thyroid carcinoma (PTC) variants exhibit different prognosis, but critical characteristics of PTC variants that contribute to differences in pathogenesis are not well-known. This study aims to characterize dysregulated immune-associated and cancer-associated genes in three PTC subtypes to explore how the interplay between cancer and immune processes causes differential prognosis. RNA-sequencing data from The Cancer Genome Atlas (TCGA) were used to identify dysregulated genes in each variant. The dysregulation profiles of the subtypes were compared using functional pathways clustering and correlations to relevant clinical variables, genomic alterations, and microRNA regulation. We discovered that the dysregulation profiles of classical PTC (CPTC) and the tall cell variant (TCPTC) are similar and are distinct from that of the follicular variant (FVPTC). However, unique cancer or immune-associated genes are associated with clinical variables for each subtype. Cancer-related genes MUC1, FN1, and S100-family members were the most clinically relevant in CPTC, while APLN and IL16, both immune-related, were clinically relevant in FVPTC. RAET-family members, also immune-related, were clinically relevant in TCPTC. Collectively, our data suggest that dysregulation of both cancer and immune associated genes defines the gene expression landscapes of PTC variants, but different cancer or immune related genes may drive the phenotype of each variant. [ABSTRACT FROM AUTHOR]

The ability to accurately and non-invasively quantify highly concentrated magnetic nanoparticles (MNPs) is desirable for many emerging applications. Ultrashort echo time quantitative susceptibility mapping (UTE-QSM) has demonstrated the capability to detect high iron concentrations. In this study, we aimed to investigate the effect of different sampling trajectories on the accuracy of quantification based on MNPs acquired through UTE-QSM. A phantom with six different MNP concentrations was prepared for UTE-QSM study with different UTE sampling trajectories, including radial acquisition, continuous single point imaging (CSPI), and Cones with four different gradient stretching factors of 1.0, 1.2, 1.4, and 1.6. No significant differences were found in QSM values derived from the different UTE sampling strategies, suggesting that the UTE-QSM technique could be accelerated with extended Cones sampling. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the most common cancers in the United States, but few advancements in treatment options have occurred in the past few decades. This study aims to identify the most clinically relevant long non-coding RNAs (lncRNAs) to serve as potential biomarkers and treatment targets for muscle invasive bladder cancer (MIBC). Using RNA-sequencing data from 406 patients in The Cancer Genome Atlas (TCGA) database, we identified differentially expressed lncRNAs in MIBC vs. normal tissues. We then associated lncRNA expression with patient survival, clinical variables, oncogenic signatures, cancer- and immune-associated pathways, and genomic alterations. We identified a panel of 20 key lncRNAs that were most implicated in MIBC prognosis after differential expression analysis and prognostic correlations. Almost all lncRNAs we identified are correlated significantly with oncogenic processes. In conclusion, we discovered previously undescribed lncRNAs strongly implicated in the MIBC disease course that may be leveraged for diagnostic and treatment purposes in the future. Functional analysis of these lncRNAs may also reveal distinct mechanisms of bladder cancer carcinogenesis.