Now showing items 21-40 of 3018

    • Citrate shuttling in astrocytes is required for processing cocaine-induced neuron-derived excess peroxidated fatty acids

      Natarajaseenivasan, Kalimuthusamy; Garcia, Alvaro; Velusamy, Prema; Shanmughapriya, Santhanam; Langford, Dianne (2022-11-04)
      Disturbances in lipid metabolism in the CNS contribute to neurodegeneration and cognitive impairments. Through tight metabolic coupling, astrocytes provide energy to neurons by delivering lactate and cholesterol and by taking up and processing neuron-derived peroxidated fatty acids (pFA). Disruption of CNS lipid homeostasis is observed in people who use cocaine and in several neurodegenerative disorders, including HIV. The brain’s main source of energy is aerobic glycolysis, but numerous studies report a switch to β-oxidation of FAs in response to cocaine. Unlike astrocytes, in response to cocaine, neurons cannot efficiently consume excess pFAs for energy. Accumulation of pFA in neurons induces autophagy and release of pFA. Astrocytes endocytose the pFA for oxidation as an energy source. Our data show that blocking mitochondrial/cytosolic citrate transport reduces the neurotrophic capacity of astrocytes, leading to decreased neuronal fitness.
    • The function and clinical implication of circular RNAs in lung cancer

      Sbarro Health Research Organization (SHRO) (Temple University) (2022-10-18)
      Lung cancer is the leading cause of cancer-related deaths worldwide. Despite the recent advent of promising new targeted therapies, lung cancer diagnostic strategies still have difficulty in identifying the disease at an early stage. Therefore, the characterizations of more sensible and specific cancer biomarkers have become an important goal for clinicians. Circular RNAs are covalently close, endogenous RNAs without 5′ end caps or 3′poly (A) tails and have been characterized by high stability, abundance, and conservation as well as display cell/tissue/developmental stage-specific expressions. Numerous studies have confirmed that circRNAs act as microRNA (miRNA) sponges, RNA-binding protein, and transcriptional regulators; some circRNAs even act as translation templates that participate in multiple pathophysiological processes. Growing evidence have confirmed that circRNAs are involved in the pathogenesis of lung cancers through the regulation of proliferation and invasion, cell cycle, autophagy, apoptosis, stemness, tumor microenvironment, and chemotherapy resistance. Moreover, circRNAs have emerged as potential biomarkers for lung cancer diagnosis and prognosis and targets for developing new treatments. In this review, we will summarize recent progresses in identifying the biogenesis, biological functions, potential mechanisms, and clinical applications of these molecules for lung cancer diagnosis, prognosis, and targeted therapy.
    • Diagnostic Accuracy of Elastography and Liver Disease: A Meta-Analysis

      Temple University. Hospital (2022-10-19)
      Background: Ultrasound-based transient elastography (TE) is a non-invasive alternative to liver biopsy for the staging of hepatic fibrosis due to various chronic liver diseases. This meta-analysis aims to assess the diagnostic accuracy of TE for detecting liver cirrhosis (F4) and severe fibrosis (F3) in patients with chronic liver diseases, in comparison to the gold standard liver biopsy. Methods: A systematic search was performed using PubMed search engine following Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) guidelines from inception to May 2021. The meta-analysis studies evaluating the diagnostic accuracy of TE for severe fibrosis and cirrhosis were identified. We conducted a meta-meta-analysis to generate pooled estimates of the sensitivity, specificity, and diagnostic odds ratios (ORs) for F3 and F4 fibrosis stage. Results: We included five studies with a total of 124 sub-studies and 20,341 patients in our analysis. Three studies have reported the diagnostic accuracy of TE in detecting F3/severe fibrosis stage and found 81.9% pooled sensitivity (95% confidence interval (CI): 79.9-83.7%; P < 0.001) (I2 = 0%), 84.7% pooled specificity (95% CI: 81.3-87.6%) (I2 = 81%; P = 0.02). All five studies reported the diagnostic accuracy of TE in detecting F4/liver cirrhosis stage. We found 84.8% pooled sensitivity (95% CI: 81.4-87.7%) (I2 = 86.4%; P < 0.001), 87.5% pooled specificity (95% CI: 85.4-89.3%) (I2 = 90%; P < 0.001) and pooled diagnostic OR (41.8; 95% CI: 3.9 - 56.5) (I2 = 87%; P < 0.001). Conclusions: Ultrasound-based TE has excellent diagnostic accuracy for identifying cirrhosis and liver fibrosis stages 3. Future studies should focus on estimating the diagnostic accuracy of other fibrosis stages in chronic liver disease patients. This will eventually decrease the risk associated with invasive liver biopsy.
    • Truncated Analogues of a G-Quadruplex-Forming Aptamer Targeting Mutant Huntingtin: Shorter Is Better!

      Sbarro Health Research Organization (SHRO) (Temple University) (2022-10-17)
      Two analogues of the MS3 aptamer, which was previously shown to have an exquisite capability to selectively bind and modulate the activity of mutant huntingtin (mHTT), have been here designed and evaluated in their physicochemical and biological properties. Featured by a distinctive propensity to form complex G-quadruplex structures, including large multimeric aggregates, the original 36-mer MS3 has been truncated to give a 33-mer (here named MS3-33) and a 17-mer (here named MS3-17). A combined use of different techniques (UV, CD, DSC, gel electrophoresis) allowed a detailed physicochemical characterization of these novel G-quadruplex-forming aptamers, tested in vitro on SH-SY5Y cells and in vivo on a Drosophila Huntington’s disease model, in which these shorter MS3-derived oligonucleotides proved to have improved bioactivity in comparison with the parent aptamer.
    • Salivary microRNA profiling dysregulation in autism spectrum disorder: A pilot study

      Kalemaj, Zamira; Marino, Maria Michela; Santini, Annamaria Chiara; Tomaselli, Giovanni; Auti, Amogh; Cagetti, Maria Grazia; Borsello, Tiziana; Constantino, Antonella; Inchingolo, Francesco; Boccellino, Mariarosaria; Di Domenico, Marina; Tartaglia, Gianluca Martino; Di Domenico|0000-0002-6201-4200 (2022-10-18)
      Introduction: Autism spectrum disorders (ASD) are the most prevalent neurobiological disorders in children. The etiology comprises genetic, epigenetic, and environmental factors such as dysfunction of the immune system. Epigenetic mechanisms are mainly represented by DNA methylation, histone modifications, and microRNAs (miRNA). The major explored epigenetic mechanism is mediated by miRNAs which target genes known to be involved in ASD pathogenesis. Salivary poly-omic RNA measurements have been associated with ASD and are helpful to differentiate ASD endophenotypes. This study aims to comprehensively examine miRNA expression in children with ASD and to reveal potential biomarkers and possible disease mechanisms so that they can be used to improve faction between individuals by promoting more personalized therapeutic approaches. Materials and methods: Saliva samples were collected from 10 subjects: 5 samples of children with ASD and 5 from healthy controls. miRNAs were analyzed using an Illumina Next-Generation-Sequencing (NGS) system. Results: Preliminary data highlighted the presence of 365 differentially expressed miRNAs. Pathway analysis, molecular function, biological processes, and target genes of 41 dysregulated miRNAs were assessed, of which 20 were upregulated, and 21 were downregulated in children with ASD compared to healthy controls. Conclusion: The results of this study represent preliminary but promising data, as the identified miRNA pathways could represent useful biomarkers for the early non-invasive diagnosis of ASD.
    • Deficient Sarcolemma Repair in ALS: A Novel Mechanism with Therapeutic Potential

      Li, Ang; Yi, Jianxun; Li, Xuejun; Dong, Li; Ostrow, Lyle; Ma, Jianjie; Zhou, Jingsong; Ostrow|0000-0001-7158-5243 (2022-10-17)
      The plasma membrane (sarcolemma) of skeletal muscle myofibers is susceptible to injury caused by physical and chemical stresses during normal daily movement and/or under disease conditions. These acute plasma membrane disruptions are normally compensated by an intrinsic membrane resealing process involving interactions of multiple intracellular proteins including dysferlin, annexin, caveolin, and Mitsugumin 53 (MG53)/TRIM72. There is new evidence for compromised muscle sarcolemma repair mechanisms in Amyotrophic Lateral Sclerosis (ALS). Mitochondrial dysfunction in proximity to neuromuscular junctions (NMJs) increases oxidative stress, triggering MG53 aggregation and loss of its function. Compromised membrane repair further worsens sarcolemma fragility and amplifies oxidative stress in a vicious cycle. This article is to review existing literature supporting the concept that ALS is a disease of oxidative-stress induced disruption of muscle membrane repair that compromise the integrity of the NMJs and hence augmenting muscle membrane repair mechanisms could represent a viable therapeutic strategy for ALS.
    • Unusual reactivity of a flavin in a bifurcating electron-transferring flavoprotein leads to flavin modification and a charge-transfer complex

      Mohamed-Raseek, Nishya; Van Galen, Cornelius Jonathan; Stanley, Robert; Miller, Anne-Frances; van Galen|0000-0003-4840-5333 (2022-11-30)
      From the outset, canonical electron transferring flavoproteins (ETFs) earned a reputation for containing modified flavin. We now show that modification occurs in the recently recognized bifurcating (Bf) ETFs as well. In Bf ETFs, the 'electron transfer' (ET) flavin mediates single electron transfer via a stable anionic semiquinone state, akin to the FAD of canonical ETFs, whereas a second flavin mediates bifurcation (the Bf FAD). We demonstrate that the ET FAD undergoes transformation to two different modified flavins by a sequence of protein-catalyzed reactions that occurs specifically in the ET site, when the enzyme is maintained at pH 9 in an amine-based buffer. Our optical and mass spectrometric characterizations identify 8-formyl flavin early in the process and 8-amino flavins (8AFs) at later times. The latter have not previously been documented in an ETF to our knowledge. Mass spectrometry of flavin products formed in Tris or bis-tris-aminopropane solutions demonstrates that the source of the amine adduct is the buffer. Stepwise reduction of the 8AF demonstrates that it can explain a charge transfer band observed near 726 nm in Bf ETF, as a complex involving the hydroquinone state of the 8AF in the ET site with the oxidized state of unmodified flavin in the Bf site. This supports the possibility that Bf ETF can populate a conformation enabling direct electron transfer between its two flavins, as has been proposed for cofactors brought together in complexes between ETF and its partner proteins.
    • Interethnic Influencing Factors Regarding Buttocks Body Image in Women from Nigeria, Germany, USA and Japan

      Wallner, Christoph; Kruber, Svenja; Adebayo, Sulaiman Olanrewaju; Ayandele, Olusola; Namatame, Hikari; Olonisakin, Tosin Tunrayo; Olapegba, Peter O.; Sawamiya, Yoko; Suzuki, Tomohiro; Yamamiya, Yuko; Wagner, Maximilian Johannes; Drysch, Marius; Lehnhardt, Marcus; Behr, Björn (2022-10-14)
      Background: Body image research deals a lot with awareness of the body as an entity. Studies that consider individual anatomical aspects and place them in an intercultural context are rarely present. Methods: For this purpose, general data, body perception and judgment of body images from 2163 (48% female and 52% male) participants from Germany, Nigeria, the USA and Japan were evaluated as part of a survey. Results: There were clear differences in the personal body image of the participants’ own buttocks, the buttocks as a beauty ideal and the way in which dissatisfaction was dealt with in different countries. In addition to sexual well-being (importance score: 0.405 a.u.), the country of origin (0.353), media consumption (0.042) and one’s own weight (0.069) were also identified as influencing factors for satisfaction with one’s own buttocks. A clear evolution could be derived regarding a WHR (waist-to-hip ratio) of well below 0.7, which was consistently favored by the participants but also propagated by influencers through images (p < 0.001). In this context, participants who indicated celebrities as role models for the buttocks showed a correspondingly high level of dissatisfaction with their own buttocks (R = −0.207, p < 0.001, ρ = −0.218). Conclusion: Overall, a highly significant correlation was shown between the consumption frequency of Instagram, TikTok and pornography with the negative perception of women’s own buttocks.
    • Impact of environmental programs on student test scores mediated by school attendance rate

      Ye, Bo; Yucel, Recai; Qu, Yanji; Thurston, George; Deng, Xinlei; Ryan, Ian; Lin, Shao (2022-10-13)
      Background: Little is known regarding whether environmental programs affect student academic performance. We examined if the association between EPA Tools for School (TfS) policies or other environmental programs and student test scores were mediated by student attendance. Methods: The 2015 School Building Condition Survey (BCS) was linked with School Report data provided by the New York State Education Department (NYSED). BCS includes school building information from 2,956 public schools while School Report data provides school attendance and test scores for different subjects in NYS. We conducted causal mediation analysis to investigate direct and indirect effects of TfS or other programs, via improving attendance, on test scores for each course while controlling for school-level socio-demographics. Results: EPA TfS policies were significantly associated with a lower percent of “low total score” for overall math, overall science, and multiple specific subjects (all P < 0.05). Furthermore, the associations between TfS and test scores in algebra II, trigonometry, and chemistry were significantly mediated by student attendance rate (-1.376 and -0.563 respectively). Other IAQ programs were also associated with a smaller percent of low-score students in multiple subject tests (all P <0.05). We found a mediated proportion of 6 to 43% by attendance in the association between other IAQ programs and high score academic performance. Implementing TfS and other programs can reduce the proportion of students receiving overall low scores by 2.66% and 1.37%, respectively. Conclusion: EPA TfS and other IAQ programs improved student test scores in multiple subjects in NYS public schools and was partially mediated by improving attendance rate
    • Splenosis in patient undergoing robotic assisted laparoscopic radical prostatectomy

      Fox Chase Cancer Center (Temple University) (2022-10-22)
      Splenosis is a benign condition that is often found in patients with a history of trauma. Most cases are intra-abdominal due to direct seeding of surrounding structures. We report a case of splenosis in the pelvis found in a 59-year-old male during a robotic prostatectomy.
    • Class A Orphans in GtoPdb v.2022.3

      Alexander, Stephen P. H.; Battey, Jim; Benson, Helen E.; Benya, Richard V.; Bonner, Tom I.; Davenport, Anthony P.; Singh, Khuraijam Dhanachandra; Eguchi, Satoru; Harmar, Anthony; Holliday, Nick; Jensen, Robert T.; Karnik, Sadashiva; Kostenis, Evi; Liew, Wen Chiy; Monaghan, Amy E.; Mpamhanga, Chido; Neubig, Richard; Pawson, Adam J.; Pin, Jean-Philippe; Sharman, Joanna L.; Spedding, Michael; Spindel, Eliot; Stoddart, Leigh; Storjohann, Laura; Thomas, Walter G.; Tirupula, Kalyan; Vanderheyden, Patrick (2022-10-13)
      Table 1 lists a number of putative GPCRs identified by NC-IUPHAR [161], for which preliminary evidence for an endogenous ligand has been published, or for which there exists a potential link to a disease, or disorder. These GPCRs have recently been reviewed in detail [121]. The GPCRs in Table 1 are all Class A, rhodopsin-like GPCRs. Class A orphan GPCRs not listed in Table 1 are putative GPCRs with as-yet unidentified endogenous ligands.
    • Molecular and Physiological Effects of Browning Agents on White Adipocytes from Bone Marrow Mesenchymal Stromal Cells

      Sbarro Health Research Organization (SHRO) (Temple University) (2022-10-12)
      Two different types of adipose depots can be observed in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). The primary role of WAT is to deposit surplus energy in the form of triglycerides, along with many metabolic and hormonal activities; as thermogenic tissue, BAT has the distinct characteristic of using energy and glucose consumption as a strategy to maintain the core body temperature. Under specific stimuli—such as exercise, cold exposure, and drug treatment—white adipocytes can utilize their extraordinary flexibility to transdifferentiate into brown-like cells, called beige adipocytes, thereby acquiring new morphological and physiological characteristics. For this reason, the process is identified as the ‘browning of WAT’. We evaluated the ability of some drugs, including GW501516, sildenafil, and rosiglitazone, to induce the browning process of adult white adipocytes obtained from differentiated mesenchymal stromal cells (MSCs). In addition, we broadened our investigation by evaluating the potential browning capacity of IRISIN, a myokine that is stimulated by muscular exercises. Our data indicate that IRISIN was effective in promoting the browning of white adipocytes, which acquire increased expression of UCP1, increased mitochondrial mass, and modification in metabolism, as suggested by an increase of mitochondrial oxygen consumption, primarily in presence of glucose as a nutrient. These promising browning agents represent an appealing focus in the therapeutic approaches to counteracting metabolic diseases and their associated obesity.
    • Role of glycosphingolipid SSEA-3 and FGF2 in the stemness and lineage commitment of multilineage differentiating stress enduring (MUSE) cells

      Sbarro Health Research Organization (SHRO) (Temple University) (2022-10-12)
      Objectives: Multilineage differentiating Stress Enduring (MUSE) cells are endogenous, stress-resistant stem cells, expressing pluripotency master genes and able to differentiate in cells of the three embryonic sheets. Stage-Specific Embryonic Antigen 3 (SSEA-3), a glycosphingolipid (GSL), is the marker for identifying MUSE cells and is used to isolate this population from mesenchymal stromal cells. GSLs modulate signal transduction by interacting with plasma membrane components. The growth factor FGF2, important for MUSE cells biology, may interact with GSLs. Specific cell surface markers represent an invaluable tool for stem cell isolation. Nonetheless their role, if any, in stem cell biology is poorly investigated. Functions of stem cells, however, depend on niche external cues, which reach cells through surface markers. We addressed the role of SSEA-3 in MUSE cell behaviour, trying to define whether SSEA-3 is just a marker or if it plays a functional role in this cell population by determining if it has any relationship with FGF2 activity. Results: We evidenced how the SSEA-3 and FGF2 cooperation affected the self-renewal and clonogenic capacity of MUSE cells. The block of SSEA-3 significantly reduced the multilineage potential of MUSE cells with production of nullipotent clones. Conclusions: We contributed to dissecting the mechanisms underlying MUSE cell properties for establishing successful stem-cell-based therapies and the promotion of MUSE cells as a tool for the in vitro disease model.
    • Editorial: New insights in Mycobacterium tuberculosis

      Natarajaseenivasan, Kalimuthusamy (2022-10-13)
    • Risk for bipolar spectrum disorders associated with positive urgency and orbitofrontal cortical grey matter volume

      Carroll, Ann L.; Damme, Katherine S. F.; Alloy, Lauren B.; Bart, Corinne P.; Ng, Tommy Ho-Yee; Titone, Madison; Chein, Jason; Cichocki, Anna C.; Armstrong, Casey C.; Nusslock, Robin; Ng|0000-0003-4402-0081; Titone|0000-0002-0721-1623; Chein|0000-0002-8430-7899 (2022-10-13)
      Bipolar spectrum disorders (BSDs) are associated with reward hypersensitivity, impulsivity, and structural abnormalities within the brain’s reward system. Using a behavioral high-risk study design based on reward sensitivity, this paper had two primary objectives: 1) investigate whether elevated positive urgency, the tendency to act rashly when experiencing extreme positive affect, is a risk for or correlate of BSDs, and 2) examine the nature of the relationship between positive urgency and grey matter volume in fronto-striatal reward regions, among individuals at differential risk for BSD. Young adults (ages 18–28) screened to be moderately reward sensitive (MReward; N = 42), highly reward sensitive (HReward; N = 48), or highly reward sensitive with a lifetime BSD (HReward + BSD; N = 32) completed a structural MRI scan and the positive urgency subscale of the UPPS-P scale. Positive urgency scores varied with BSD risk (MReward < HReward < HReward + BSD; ps≤0.05), and positive urgency interacted with BSD risk group in predicting lateral OFC volume (p <.001). Specifically, the MReward group showed a negative relationship between positive urgency and lateral OFC volume. By contrast, there was no relationship between positive urgency and lateral OFC grey matter volume among the HReward and HReward + BSD groups. The results suggest that heightened trait positive urgency is a pre-existing vulnerability for BSD that worsens with illness onset, and there is a distinct relationship between positive urgency and lateral OFC volume among individuals at high versus low risk for BSD. These findings have implications for understanding the expression and development of impulsivity in BSDs.
    • ecochange: An R-package to derive ecosystem change indicators from freely available earth observation products

      Lara Henao, Wilson; Londoño, Maria C.; Gonzalez, Ivan; Gutierrez‐Velez, Victor H.; Lara|0000-0003-3527-1380 (2022-10-11)
      Spatial resources accessible for the derivation of biodiversity indicators of the class ecosystem structure are sparse and disparate, and their integration into computer algorithms for biodiversity monitoring remains problematic. We describe ecochange as an R-package that integrates spatial analyses with a monitoring workflow for computing routines necessary for biodiversity monitoring. The ecochange comprises three modules for data integration, statistical analysis and graphics. The first module currently downloads and integrates diverse remote sensing products belonging to the essential biodiversity class of structure. The module for statistical analysis calculates RasterStack ecosystem-change representations across areas of interest; this module also allows focusing on species habitats while deriving changes in a variety of indicators, including ecosystem areas, conditional entropy and fractal dimension indices. The graphics module produces level and bar plots that ease the development of indicator reports. Its functionality is described with an example workflow to calculate ecosystem-class areas and conditional entropy across an area of interest contained in the package documentation. We conclude that ecochange features procedures necessary to derive ecosystem structure indicators integrating the retrieval of spatially explicit data with the use of workflows to calculate/visualize biodiversity indicators at the national/regional scales.
    • E2F1 promotes cell cycle progression by stabilizing spindle fiber in colorectal cancer cells

      Fang, Zejun; Lin, Min; Chen, Shenghui; Liu, Hong; Zhu, Minjing; Hu, Yanyan; Han, Shanshan; Wang, Yizhang; Sun, Long; Zhu, Fengjiao; Xu, Chengfu; Gong, Chaoju (2022-10-11)
      Background: E2F1 is a transcription factor that regulates cell cycle progression. It is highly expressed in most cancer cells and activates transcription of cell cycle-related kinases. Stathmin1 and transforming acidic coiled-coil-containing protein 3 (TACC3) are factors that enhance the stability of spindle fiber. Methods: The E2F1-mediated transcription of transforming acidic coiled-coil-containing protein 3 (TACC3) and stathmin1 was examined using the Cancer Genome Atlas (TCGA) analysis, quantitative polymerase chain reaction (qPCR), immunoblotting, chromatin immunoprecipitation (ChIP), and luciferase reporter. Protein–protein interaction was studied using co-IP. The spindle structure was shown by immunofluorescence. Phenotype experiments were performed through MTS assay, flow cytometry, and tumor xenografts. Clinical colorectal cancer (CRC) specimens were analyzed based on immunohistochemistry. Results: The present study showed that E2F1 expression correlates positively with the expression levels of stathmin1 and TACC3 in colorectal cancer (CRC) tissues, and that E2F1 transactivates stathmin1 and TACC3 in CRC cells. Furthermore, protein kinase A (PKA)-mediated phosphorylation of stathmin1 at Ser16 is essential to the phosphorylation of TACC3 at Ser558, facilitating the assembly of TACC3/clathrin/α-tubulin complexes during spindle formation. Overexpression of Ser16-mutated stathmin1, as well as knockdown of stathmin1 or TACC3, lead to ectopic spindle poles including disorganized and multipolar spindles. Overexpression of wild-type but not Ser16-mutated stathmin1 promotes cell proliferation in vitro and tumor growth in vivo. Consistently, a high level of E2F1, stathmin1, or TACC3 not only associates with tumor size, lymph node metastasis, TNM stage, and distant metastasis, but predicts poor survival in CRC patients. Conclusions: E2F1 drives the cell cycle of CRC by promoting spindle assembly, in which E2F1-induced stathmin1 and TACC3 enhance the stability of spindle fiber.
    • Trends in Diet Quality by Race/Ethnicity among Adults in the United States for 2011–2018

      Tao, Meng-Hua; Liu, Jia-Liang; Nguyen, Uyen-Sa D. T. (2022-10-08)
      This study aimed to investigate time trends in diet quality and the consumption of major food groups and nutrients by race/ethnicity among adults in the United States. Dietary data from 19,192 adults aged ≥ 20 years from four National Health and Nutrition Survey (NHANES) cycles (2011–2018) were included. The Healthy Eating Index (HEI) 2015 scores (range: 0–100; higher scores indicate better diet quality) and dietary consumption of food groups and nutrients were estimated for each cycle. Linear regression was used to test trends. For the overall population, the estimated overall HEI-2015 scores significantly decreased (p for trend = 0.011). However, decreases were observed in the estimated consumption of added sugars and total carbohydrates, while the estimated consumption of soy products and polyunsaturated fatty acids was significantly increased. A significant decrease in overall HEI-2015 score was observed in the non-Hispanic white group, but not in other racial/ethnic groups. Decreases in added sugar intake were found in the non-Hispanic black and Hispanic groups; sodium intake significantly decreased in the non-Hispanic Asian group. From 2011 to 2018, there was a decrease in estimated overall diet quality in US adults; however, there were improvements in certain nutrients and dietary components. Nevertheless, disparities in diet quality exist among racial/ethnic groups.
    • Subpathway Analysis of Transcriptome Profiles Reveals New Molecular Mechanisms of Acquired Chemotherapy Resistance in Breast Cancer

      Huo, Yang; Shao, Shuai; Liu, Enze; Li, Jin; Tian, Zhen; Wu, Xue; Zhang, Shijun; Stover, Daniel; Wu, Huanmei; Cheng, Lijun; Li, Lang; Wu|0000-0003-0346-6044 (2022-10-05)
      Chemoresistance has been a major challenge in the treatment of patients with breast cancer. The diverse omics platforms and small sample sizes reported in the current studies of chemoresistance in breast cancer limit the consensus regarding the underlying molecular mechanisms of chemoresistance and the applicability of these study findings. Therefore, we built two transcriptome datasets for patients with chemotherapy-resistant breast cancers—one comprising paired transcriptome samples from 40 patients before and after chemotherapy and the second including unpaired samples from 690 patients before and 45 patients after chemotherapy. Subsequent conventional pathway analysis and new subpathway analysis using these cohorts uncovered 56 overlapping upregulated genes (false discovery rate [FDR], 0.018) and 36 downregulated genes (FDR, 0.016). Pathway analysis revealed the activation of several pathways in the chemotherapy-resistant tumors, including those of drug metabolism, MAPK, ErbB, calcium, cGMP-PKG, sphingolipid, and PI3K-Akt, as well as those activated by Cushing’s syndrome, human papillomavirus (HPV) infection, and proteoglycans in cancers, and subpathway analysis identified the activation of several more, including fluid shear stress, Wnt, FoxO, ECM-receptor interaction, RAS signaling, Rap1, mTOR focal adhesion, and cellular senescence (FDR < 0.20). Among these pathways, those associated with Cushing’s syndrome, HPV infection, proteoglycans in cancer, fluid shear stress, and focal adhesion have not yet been reported in breast cancer chemoresistance. Pathway and subpathway analysis of a subset of triple-negative breast cancers from the two cohorts revealed activation of the identical chemoresistance pathways.
    • Comparative Effectiveness of Front-Line Ipilimumab and Nivolumab or Axitinib and Pembrolizumab in Metastatic Clear Cell Renal Cell Carcinoma

      Fox Chase Cancer Center (Temple University) (2022-10-06)
      Background: Treatment of metastatic renal cell carcinoma (mRCC) is rapidly evolving with new combination therapies demonstrating improved response rates and survival. There are no head-to-head prospective trials comparing an immunotherapy doublet with an immunotherapy/tyrosine-kinase inhibitor-based combination. We compare real-world outcomes in patients treated with axitinib/pembrolizumab (axi/pembro) or ipilimumab/nivolumab (ipi/nivo). The primary endpoints were overall-survival (OS) and real-world progression-free survival (rwPFS). Patients and Methods: We used a de-identified database to select patients diagnosed with clear cell mRCC and treated with front-line axi/pembro or ipi/nivo from 2018 to 2022. Analyses are adjusted using propensity score-based inverse probability of treatment weighting, balancing age, gender, insurance, race, IMDC risk, and nephrectomy status. We compared survival by treatment groups using weighted and unweighted Kaplan–Meier curves with log-rank tests and weighted Cox proportional hazards regressions. Results: We included a total of 1506 patients with mRCC who received frontline axi/pembro (n = 547) or ipi/nivo (n = 959). Median follow-up time was 20.0 months (range: 0.2-47.6). Baseline demographics were similar between the 2 cohorts. Adjusted median OS for the full population was 28.9 months for axi/pembro and was 24.3 months for ipi/nivo (P = .09). Twenty-four-month survival was 53.8% for axi/pembro treated patients and 50.2% for ipi/nivo treated patients. rwPFS was 10.6 months for axi/pembro treated patients and 6.9 months for ipi/nivo treated patients. Treatment with axi/pembro conferred improved survival in the IMDC favorable risk strata, with no significant difference in survival observed within the full cohort. Conclusions: In this retrospective, real-world study of patients treated with front-line combination therapy, patients with IMDC favorable risk disease had better survival when treated with axi/pembro compared to ipi/nivo. However, survival for the entire population and the 24-month median overall survival were not statistically different between treatment groups. Longer follow-up is necessary to discern any emerging significant differences.