bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract B037: Elevated mitochondrial activity is a targetable signature of prostate cancer bone metastases
Authors: Su Shang , Liu Ke , Xing Jing , Zhao Yawei , Liu Ruihua , Chen Bin , Li Xiaohong
Published: June 2023

Prostate cancer (PCa) patients’ 5-year survival is only ~30% when metastases develop. Most PCa metastases happen in bone. We seek to identify gene signatures unique for bone-metastatic PCa cells and explore potential drug candidates to specifically target PCa bone metastases (bone met). Using public RNA-Seq datasets, we defined differentially expressed genes (DE) intrinsic to PCa bone met by analyzing the DE between bone mets (MET500) and primary tumors (TCGA) and filtering out the genes shown as the DE between normal bone marrow and prostate (GTex). Similarly, we got DE intrinsic to liver met. These two intrinsic DE were further compared and functional annotation for bone met only DE was performed. We found that the bone met only up-regulated DE were significantly enriched for mitochondrial OXPHOS and electron transport chain (ETC). In contrast, no mitochondria-related terms were enriched in PCa liver met, PCa lymph node met or breast cancer bone met, suggesting unique elevated mitochondrial activities in PCa bone met. We further performed RNA-Seq analyses and determined the DE unique in intratibial xenografts (mimicking bone mets), compared to C4-2B PCa primary tumors, i.e., orthotopic or subcutaneous xenografts. OXPHOS was also positively enriched in the intratibial DE, suggesting that pre-clinical animal models recapitulate functional signatures of PCa patients and can be used for drug testing. Therefore, we hypothesized that inhibiting mitochondrial OXPHOS or ETC complex blocks PCa bone metastases. Excitingly, we found that mitochondrial ETC complex I inhibitor, IACS-010759, showed high potency and specificity in suppressing PCa cell growth without affecting osteoblasts in vitro, and significantly inhibited metastatic development of PCa cells in vivo. In summary, elevated mitochondrial activity appears to be a unique signature and phenotype for PCa bone met and mitochondria-interrupting drugs selectively suppress the growth of PCa cells without affecting normal cells in the bone microenvironment such as osteoblasts. Blocking mitochondria hyperactivation is a potential approach against PCa bone met.

Citation Format: Shang Su, Ke Liu, Jing Xing, Yawei Zhao, Ruihua Liu, Bin Chen, Xiaohong Li. Elevated mitochondrial activity is a targetable signature of prostate cancer bone metastases [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B037.
Abstract B040: Novel immunotherapy strategies targeting PTEN and TP53 defects in advanced prostate cancer
Authors: Shi Wei , Wang Yin , Zhao Yuehui , Zhao Di
Published: June 2023

Prostate cancer is the most diagnosed cancer in men worldwide and the leading cause of cancer death in men worldwide. Genetic inactivation of PTEN and TP53 are common in advanced prostate cancers. Checkpoint immunotherapy has yielded meaningful responses across many cancers but shown modest activity in advanced prostate cancer. Prior studies showed that overexpression of immune checkpoint B7-H3 (CD276) correlates with the increased risks of clinical recurrence, disease spread, and poor outcomes in various cancer types, including prostate cancer. However, the roles of B7-H3 in prostate cancer development and its tumor microenvironment remain unclear, partially due to the lack of tissue-specific deletion mouse models. This gap in knowledge hinders the application of immunotherapy targeting B7-H3 in prostate cancers. To identify PTEN- and p53-associated immune checkpoints, we performed multi-omics analyses of expression patterns of 51 checkpoint molecules in human prostate cancer samples and found that B7-H3 is one of the most significantly overexpressed immune checkpoints in prostate tumors containing PTEN and TP53 genetic inactivation. Mechanistically, we found that the PTEN-AKT pathway co-operates with p53 pathway in modulating B7-H3 expression in cancer cells. In Pten/Trp53 genetically engineered mouse (GEM) models, prostate-specific deletion of Cd276 resulted in markedly delayed tumor progression and reversed immunosuppression in the tumor microenvironment. Furthermore, we developed and evaluated novel combinatorial immunotherapy strategies targeting B7-H3 in advanced prostate cancer with PTEN and TP53 deficiencies.

Citation Format: Wei Shi, Yin Wang, Yuehui Zhao, Di Zhao. Novel immunotherapy strategies targeting PTEN and TP53 defects in advanced prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B040.
Abstract B044: Exosomal cancer-type SLCO1B3 and ABCC3 as potential biomarkers of castration resistant prostate cancer
Authors: Beatson Erica L. , Lee Kristi Y. , Knechel Martina A. , Sommer Elijah R. , Depaz Roger , Risdon Emily N. , Leon Andres F. , Strope Jonathan D. , Price Douglas K. , Chau Cindy H. , Figg William D.
Published: June 2023

Extracellular vesicles (EVs) provide a minimally invasive source of tumor-specific markers for liquid biopsy that can be utilized for cancer detection, diagnosis, or monitoring progression. Our laboratory has previously demonstrated the endogenous expression of all transporter systems in the common prostate cancer cell lines (LNCaP, 22Rv1, PC3, DU-145) using a medium throughput TaqMan-based qRT-PCR assay. We identified the two most differentially expressed transporter genes in castration-resistant prostate cancer cells (CRPC) as the cancer-type solute carrier organic anion transporter family 1B3 (ct-SLCO1B3) and the ATP Binding Cassette Subfamily Member C (ABBC3). Both transporters have been investigated as EV-derived tumor markers; however, their detection in prostate cancer-derived EVs remains to be determined. This study aims to investigate whether ct-SLCO1B31B3 and ABCC3 mRNA exists in prostate cancer-derived EVs and can be further detected using plasma specimens. We isolated EVs from prostate cancer (LNCaP, 22Rv1, PC3, DU-145) cell line supernatant and extracted exosomal RNA for qPCR analyses. Both ct-SLCO1B3 and ABBC3 transcripts were only detected in CRPC-derived EV cells vs androgen-responsive prostate cancer cells. To explore the possibility that both transcripts in CRPC-derived EVs can be detected in plasma, we isolated plasma EVs derived from human prostate cancer xenograft mice, and then performed digital droplet PCR analysis. We demonstrated that ct-SLCO1B3 and ABBC3 are detectable in the DU-145 xenograft mouse model, both in tissues and in plasma-derived EVs. Our results provide evidence that ct-SLCO1B3 and ABCC3 exist in EVs and can be detected (at least) in mouse plasma, potentially supporting their roles as novel, plasma-based biomarkers for monitoring prostate cancer progression.

Citation Format: Erica L. Beatson, Kristi Y. Lee, Martina A. Knechel, Elijah R. Sommer, Roger Depaz, Emily N. Risdon, Andres F. Leon, Jonathan D. Strope, Douglas K. Price, Cindy H. Chau, William D. Figg. Exosomal cancer-type SLCO1B3 and ABCC3 as potential biomarkers of castration resistant prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B044.
Abstract B045: Single cell proteomics as a method to analyze circulating tumor cells in prostate cancer patients
Authors: Horrmann Alec , Sychev Zoi , Drake Justin M.
Published: June 2023

The purpose of this study was to develop a single-cell proteomic protocol capable of analyzing single circulating tumor cells (CTCs). Despite the numerous benefits possible from the analysis of CTCs they have not migrated into clinical use due to difficulty of purification and their minute numbers. Combined, this results in only miniscule amounts of sample, if any, for analysis. Most clinical assays primarily focus on genomic and/or transcriptomic assays, while only a select number of proteomic assays are used and these analyze a handful of targets at most. Recent developments in single-cell proteomics using liquid chromatography tandem mass spectrometry (LC-MS/MS) promise to solve this latter issue and increase the depth of proteome coverage. To analyze CTCs we adapted previously developed single-cell methodologies to be amenable for the analysis of CTCs. Our novel method uses a separately prepared carrier channel as opposed to traditional methods which rely on a large pool of the single-cells of interest. This is necessary since collected CTC’s will not have a large pool of similar cells to draw upon to form a carrier. As the carrier is prepared in bulk it allows for improved quality control measurements to be implemented. This is critical as for clinical use these metrics will be vital for ensuring repeatability and reliability of results. Using our developed protocol, we are able to analyze hundreds of proteins from each simulated CTC. Additionally, we demonstrate that a separately prepared carrier composed of cells from a different lineage still permits the identification of a wide array of proteins within single-cells as well as allows for better quality control over the digestion and TMT labeling efficiencies. In conclusion, our protocol demonstrates its capability to detect and quantify hundreds of proteins from individual cells. If this method was applied towards the analysis of CTCs it would represent by far the most comprehensive method for analysis of the proteome of single CTCs. Together, this provides a foundation for translating proteomic analysis of single CTCs towards guiding individualized cancer treatment in the clinic.

Citation Format: Alec Horrmann, Zoi Sychev, Justin M. Drake. Single cell proteomics as a method to analyze circulating tumor cells in prostate cancer patients [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B045.
Abstract B064: ONECUT2 inhibition, a potential treatment for lethal prostate cancer
Authors: Gallent Brad , Qian Chen , Chatterjee Avradip , Katiki Madhusudhanarao , Murali Ramachandran , Freeman Michael R
Published: June 2023

Prostate cancer (PCa) is the most common cancer and the second most lethal cancer in men, claiming over 30,000 lives each year in the US alone. These PCa patient deaths are typically due to castration-resistant PCa (CRPC) which is resistant to androgen deprivation therapy, androgen receptor signaling inhibitors, and chemotherapies. Our group and others have shown that the transcription factor ONECUT2 (OC2) is a critical driver of CRPC. We have discovered a low molecular weight inhibitor of OC2 (OC2i), known as CSRM617, which inhibits metastatic PCa in cell culture (IC50 of 5-15 uM depending on cell line used) and effectively treats xenograft CRPC tumors in mouse models. We have developed a large series of these OC2i based on the CSRM617 scaffold. A thorough understanding of how these OC2i bind to and inhibit OC2 function are imperative to developing them into a clinically viable treatment option. Our recent work shows CSRM617 binds Fe and that this Fe:CSRM617 complex is necessary in order to inhibit OC2 binding of DNA. We have solved the crystal structure of OC2 bound to its conjugate DNA response element, demonstrating their atomic-level interactions. We are working towards solving a crystal structure of these OC2i bound to OC2 in order understand their specific interactions and make rational modifications to the chemical scaffold for improvements in binding affinity and pharmacokinetic properties.

Citation Format: Brad Gallent, Chen Qian, Avradip Chatterjee, Madhusudhanarao Katiki, Ramachandran Murali, Michael R Freeman. ONECUT2 inhibition, a potential treatment for lethal prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B064.
Abstract B067: CRM1 inhibitor selinexor induces DNA damage repair-related vulnerability in prostate cancer cells
Authors: Kumar Rajendra , Mendonca Janet , Yang Yuhan , Shetty Abhishek , Wilson Lillian , Boyapati Kavya , Topiwala Deven , Soundappan Keerti , Panagopoulos Eleni , Carducci Michael , Kachhap Sushant
Published: June 2023

Background: Advanced metastatic prostate cancer is the second leading cause of death in men in the United States. Androgen deprivation therapy has been used as a front-line therapy; however, despite initial success, it fails subsequently and results in the development of castration-resistant prostate cancer. Due to these unmet therapeutic needs, there is an urgency to identify novel targets to develop next-generation therapeutics. Chromosome region maintenance 1 (CRM1) is one of the seven members of mammalian export proteins that function to export the proteins using nuclear export signal (NES). Several tumors, including prostate cancer, overexpress CRM1 to efflux tumor suppressor proteins to the cytoplasm and exhibit dysregulated nuclear export. CRM1-mediated export can lead to functional inactivation of p53, cyclinD1, p16, p21, and p27. Essential DNA repair proteins such as Rad51 and BRCA1 exhibit leucine-containing hydrophobic residues rich in NES and are known to be shuttled by CRM1. Based on this, we hypothesize that CRM1 inhibition may affect the expression, kinetics, localization, and stability of DNA repair network proteins. Methods: Androgen receptor-positive and negative prostate cancer cells were treated with Selinexor. The dose of the drug and duration was dependent on the endpoint measurement. Cell death was monitored using MTT assay and western blot measurement of cleaved PARP. Total RNA and cell lysate were collected to measure the relative levels of BRCA-1, RAD51, p53, and other members of the DNA repair pathway (HR and NHEJ). DNA damage was estimated using the number of micronuclei and immunofluorescence staining for γ-H2AX and COMET assay. Results: Selinexor treatment in prostate cancer cells affects the functioning of the DNA repair network and can be combined with inhibitors of DNA repair proteins.

Citation Format: Rajendra Kumar, Janet Mendonca, Yuhan Yang, Abhishek Shetty, Lillian Wilson, Kavya Boyapati, Deven Topiwala, Keerti Soundappan, Eleni Panagopoulos, Michael Carducci, Sushant Kachhap. CRM1 inhibitor selinexor induces DNA damage repair-related vulnerability in prostate cancer cells [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr B067.
Abstract IA003: Evolution of AR gene structure during prostate cancer progression
Authors: Dehm Scott M
Published: June 2023

Castration-resistant prostate cancer (CRPC) emerges when endocrine therapies are no longer effective at suppressing activity of the androgen receptor (AR) transcription factor. Our laboratory has implemented DNA sequencing approaches to identify genomic mechanisms contributing to CRPC in prostate cancer cell lines, patient-derived xenografts (PDXs), and clinical specimens. These approaches have revealed AR as one of the most frequently-rearranged genes in CRPC. However the patterns of AR gene rearrangements observed between patients and even between anatomically distinct metastases within a single patient are remarkably complex and heterogeneous. To address this complexity, we analyzed a cohort of prostate cancer specimens using linked-read DNA-sequencing. This approach found that a subset of clinical CRPC metastases had accumulated complex AR rearrangements in conjunction with very high AR copy number, a phenomenon that also occurred in PDX models grown under selective pressure of castration. Using orthogonal approaches of optical genome mapping and fluorescence in situ hybridization, we found that AR residing on extrachromosomal circular DNA (eccDNA) was an underlying mechanism. This study identifies eccDNA as an engine for accumulation of AR gene copy number and structural complexity during CRPC progression.

Citation Format: Scott M Dehm. Evolution of AR gene structure during prostate cancer progression [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA003.
Abstract IA004: Metabolic mechanisms of prostate cancer progression that feed nuclear receptors
Authors: Sharifi Nima
Published: June 2023

The androgen axis is central to prostate cancer physiology and therapy. Androgens are gonadal and extragonadal in origin, both of which stimulate the androgen receptor (AR). The use of medical castration (ADT), adrenal androgen ablation (i.e., abiraterone) and potent AR antagonists (i.e., enzalutamide, apalutamide, darolutamide), has yielded complex clinical states of prostate cancer, including disease states that are resistant to multiple forms of hormonal therapy. One of the major questions that arises is whether men can be identified who will benefit from earlier intensive hormonal therapy. Another question is whether alternative hormonal treatment strategies can be used to address resistance to the current generation of hormonal therapies. We propose that identification of steroid metabolic dependencies is part of the answer to both of these questions. Approximately half of men with prostate cancer inherit an activating missense in the first and rate-limiting enzyme that converts extragonadal precursor steroids to dihydrotestosterone (DHT). The “adrenal-permissive” HSD3B1(1245C) allele encodes for a 3β-hydroxysteroid dehydrogenase-1 (3βHSD1) enzyme that increases tumor DHT synthesis from adrenal DHEA. Heterozygous or homozygous HSD3B1(1245C) inheritance confers poor outcomes after ADT. Furthermore, men with HSD3B1(1245C) inheritance and castration-resistant prostate cancer (CRPC) treated with abiraterone or enzalutamide still have poorer outcomes. Together, these data suggest that directly targeting this metabolic lesion is necessary for optimal therapy in these men. We recently discovered that phosphorylation of the 3βHSD1 tyrosine 344 by the BMX kinase is necessary for androgen biosynthesis and CRPC in xenograft models. These findings have led to the launch of the Maverick clinical trial in the Prostate Cancer Clinical Trials Consortium (PCCTC) that combines abiraterone plus BMX inhibition with abivertinib in men with CRPC. In sum, this accumulating body of evidence suggests that steroid metabolic dependencies should be considered as an essential part of cancer metabolism, particularly in the context of developmental therapeutics for prostate cancer.

Citation Format: Nima Sharifi. Metabolic mechanisms of prostate cancer progression that feed nuclear receptors [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA004.
Abstract IA019: Tumor microenvironment modulation is critical for cellular immunotherapy efficacy
Authors: Dorff Tanya B , Blanchard M Suzette , Murad John , Adkins Lauren , Dhaploa Gaurav , Forman Stephen , Priceman Saul
Published: June 2023

Background: Chimeric antigen receptor (CAR)-engineered T cell therapies are being pursued for the treatment of prostate cancer, among other solid tumors. However the role of lymphodepletion was uncertain for application outside of heme malignancies. We studied the effect of chemotherapy preconditioning on the tumor immune microenvironment along with the impact on CAR-T cell activity. Methods: Immunocompetent mice bearing RM9 prostate tumors lentivirally transduced to express human prostate stem cell antigen (PSCA) and treated with PSCA targeted CAR T cells alone, or after 100 mg/kg cyclophosphamide (Cy). Tumors were evaluated for immune cell subsets infiltration in addition to clinical response. As part of a phase 1 dose escalation trial patients received 100 M PSCA-targeted CAR T cells, manufactured at City of Hope’s cGMP facility, alone or after Cy. CAR T persistence and cytokine levels were evaluated by flow cytometry and luminex, respectively. Results: CAR T cells alone had minimal anti-tumor effect in immune competent mice. Cy was associated with increased CD11c+ DCs and reduced CD206+ M2 macrophages in the tumors. With Cy pre-conditioning followed by infusion of PSCA-CAR T cells, over 40% of mice had complete response (CR) and rejected rechallenge of tumor. 10-fold greater T cell infiltration was noted in tumors after Cy preconditioning, with lesser increase and no anti-tumor effect noted with Cy + mock CAR T cells. In the phase 1 human trial greater CAR T cell expansion and cytokine induction were noted with Cy + PSCA-CAR T compared to PSCA-CAR T alone. Conclusion: Cy functions as a modifier of the prostate cancer tumor microenvironment, facilitating CAR T cell infiltration and expansion. This has resulted in greater activity of PSCA-CAR T cells both in murine models and preliminary human testing. Further study of manipulations to optimize the tumor immune microenvironment will likely be important to maximizing efficacy of cellular immunotherapy in prostate cancer.

Citation Format: Tanya B Dorff, M Suzette Blanchard, John Murad, Lauren Adkins, Gaurav Dhaploa, Stephen Forman, Saul Priceman. Tumor microenvironment modulation is critical for cellular immunotherapy efficacy [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA019.
Abstract IA025: Pursuing novel treatment strategies for advanced prostate cancer
Authors: de Bono Johann
Published: June 2023

While there have been major advances in understanding of prostate cancer biology, and outcomes including survival and quality of life for men suffering from advanced prostate cancer, the development of novel treatment strategies for aggressive prostate cancer remains an unmet medical need. Studies have shown that advanced prostate cancer has considerable inter- and intra-patient heterogeneity and biomarkers supporting disease molecular stratification are also urgently required to further improve outcomes. This presentation will focus on rational, biomarker driven, novel approaches to improve prostate cancer treatment and will discuss novel targets such as B7-H3, and the targeting of tumour-stroma paracrine interactions.

Citation Format: Johann de Bono. Pursuing novel treatment strategies for advanced prostate cancer [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr IA025.
Abstract PR008: Molecular determinants of prostate cancer lineage plasticity
Authors: Wadosky Kristine , Ku Sheng-Yu , Wang Yanqing , Zhang Xiaojing , Wang Jie , Wang Jianmin , Beltran Himisha , Goodrich David W.
Published: June 2023

Androgen deprivation therapy (ADT) has been an effective treatment for advanced prostate cancer (PCa) for decades because PCa retains the lineage specific dependence of normal prostate tissue on androgen receptor (AR) signaling. Unfortunately, nearly all patients will progress through ADT with castrate resistant prostate cancer (CRPC). CRPC is typically associated with reactivation of AR signaling despite ADT. However with widespread clinical deployment of potent AR signaling inhibitors, an increasing fraction of CRPCs (~20) are now observed to lose AR signaling activity and show gene expression patterns consistent with alternative lineage states. These lineage variants share clonal origin with the pre-existing adenocarcinoma, so some PCa cells have sufficient plasticity to reprogram to an AR independent lineage state like neuroendocrine prostate cancer (NEPC) that is recalcitrant to available therapies. The molecular determinants of prostate cancer lineage plasticity are incompletely defined, and this knowledge gap has hindered development of diagnostic and therapeutic approaches necessary to identify and treat prostate cancer lineage plasticity. We present results from experiments testing the contribution of EZH2 and NOTCH signaling to prostate cancer lineage plasticity and NEPC reprogramming. EZH2 expression is elevated in advanced PCa, particularly NEPC, suggesting it drives lineage reprogramming. However, using genetically engineered mice and organoids we find that EZH2 is not required for NEPC reprogramming that occurs in some PCa cells in the absence of the RB1 and TP53 tumor suppressor genes. EZH2 deficiency does alter multi-lineage prostate cancer plasticity, biasing development towards lineage variants observed clinically including amphicrine and double negative prostate cancer. In contrast, data from clinical specimens indicates NOTCH signaling activity declines in NEPC compared to AR+ CRPC. NOTCH signaling suppresses NEPC development in both organoids and genetically engineered mice, and loss of NOTCH signaling is required to maintain the NEPC lineage state. Constitutive NOTCH signaling biases PCa development towards unique lineage variants including AR positive metastatic PCa with luminal differentiation. These results identify EZH2 and NOTCH signaling as molecular determinants of PCa lineage plasticity and NEPC reprogramming with implications for ongoing efforts to target these molecules for PCa therapy.

Citation Format: Kristine Wadosky, Sheng-Yu Ku, Yanqing Wang, Xiaojing Zhang, Jie Wang, Jianmin Wang, Himisha Beltran, David W. Goodrich. Molecular determinants of prostate cancer lineage plasticity [abstract]. In: Proceedings of the AACR Special Conference: Advances in Prostate Cancer Research; 2023 Mar 15-18; Denver, Colorado. Philadelphia (PA): AACR; Cancer Res 2023;83(11 Suppl):Abstract nr PR008.
Learning through Love: A Lover’s Initiation in the Symposium
Authors: Woodruff Paul
Published: June 2023

In the Symposium of Plato, Socrates reports that Diotima once described to him a process of initiation by which a lover rises from desiring one beautiful body to catching sight of what seems to be the Platonic form of beauty. Scholars have debated whether the lover is to make this ascent by a rational process or a non-rational one, or by both working either in concert or independently. This paper argues that love leads and guides a process in this initiation that necessarily involves rational activity. No teaching is necessary or appropriate, so that the process is an example of learning without being taught. The philosophical insight that results is life-changing, but it does not amount to the kind of knowledge that would fully satisfy a Socratic seeker after knowledge.
Efficacy and Safety of Adjunctive and Primary Use of the TightRail Mechanical Cutting Sheath for Lead Extraction
Authors: Sampognaro James R. , Karatela Maham , Lewis Robert K. , Black-Maier Eric , Pokorney Sean D. , Hegland Donald D. , Piccini Jonathan P.
Published: June 2023

Background:

Rotational cutting tools are increasingly used in transvenous lead extraction. There are limited data on their safety and efficacy, particularly when used adjunctively for stalled progression. The aim of this study was to evaluate the utilization, safety, and effectiveness of mechanical rotational cutting tools for transvenous lead extraction.

Methods:

Patients undergoing transvenous lead extraction at a single tertiary center (April 2015 to January 2021, n=586) were included in this retrospective analysis. The study characterized the 251 patients (42.8%) whose cases involved the TightRail mechanical cutting tool.

Results:

Among 251 patients, 526 leads were extracted and TightRail was used for 70.5%. The TightRail was used adjunctively with the laser for 65.2% of leads, 97.8% of the time as the second tool after stalled progression. Using a multivariable logistic regression model, we found that active-fixation leads (odds ratio, 2.78 [95% CI, 1.62–4.78];
P
=0.0002), dual-coil leads (odds ratio, 3.39 [95% CI, 1.87–6.16];
P<0
.0001), and lead dwell time (odds ratio, 1.16 [95% CI for 1-year increase, 1.11–1.21];
P<0
.0001) were factors independently associated with adjunctive TightRail use. Stalled progression requiring TightRail occurred most often in the innominate vein and superior vena cava (59.3%). The clinical success rate was 96.8%, and the rate of major adverse events was 2.8%. Only 1 major adverse event was observed during TightRail use.

Conclusions:

Rotational cutting with TightRail was used in 42.8% of transvenous lead extractions, predominantly in an adjunctive manner after stalled laser progression in the innominate vein and superior vena cava, and more frequently for dual-coil and leads with longer dwell times. Adjunctive TightRail use carries a low risk of major complications.
Association Between Omega‐3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose–Response Meta‐Analysis of Randomized Controlled Trials
Authors: Wang Tianjiao , Zhang Xin , Zhou Na , Shen Yuxuan , Li Biao , Chen Bingshu E. , Li Xinzhi
Published: June 2023

Background

Previous results provide supportive but not conclusive evidence for the use of omega‐3 fatty acids to reduce blood lipids and prevent events of atherosclerotic cardiovascular disease, but the strength and shape of dose–response relationships remain elusive.

Methods and Results

This study included 90 randomized controlled trials, reported an overall sample size of 72 598 participants, and examined the association between omega‐3 fatty acid (docosahexaenoic acid, eicosapentaenoic acid, or both) intake and blood lipid changes. Random‐effects 1‐stage cubic spline regression models were used to study the mean dose–response association between daily omega‐3 fatty acid intake and changes in blood lipids. Nonlinear associations were found in general and in most subgroups, depicted as J‐shaped dose–response curves for low‐/high‐density lipoprotein cholesterol. However, we found evidence of an approximately linear dose–response relationship for triglyceride and non‐high‐density lipoprotein cholesterol among the general population and more evidently in populations with hyperlipidemia and overweight/obesity who were given medium to high doses (>2 g/d).

Conclusions

This dose–response meta‐analysis demonstrates that combined intake of omega‐3 fatty acids near linearly lowers triglyceride and non‐high‐density lipoprotein cholesterol. Triglyceride‐lowering effects might provide supportive evidence for omega‐3 fatty acid intake to prevent cardiovascular events.
Comparison of Boston Criteria v2.0/v1.5 for Cerebral Amyloid Angiopathy to Predict Recurrent Intracerebral Hemorrhage
Authors: Fandler-Höfler Simon , Gattringer Thomas , Enzinger Christian , Werring David J.
Published: June 2023

BACKGROUND:

Intracerebral hemorrhage (ICH) caused by cerebral amyloid angiopathy (CAA) has a high recurrence risk. The Boston criteria, while not designed to predict recurrence, are commonly used for in vivo diagnosis of CAA and have recently been revised to the version 2.0 (v2.0), introducing nonhemorrhagic white matter features. We investigated whether the new v2.0 criteria change ICH recurrence risk in patients with probable CAA.

METHODS:

We assessed ICH recurrence risk in consecutive patients with ICH and available brain magnetic resonance imaging. Patients with macrovascular or structural causes were excluded. Recurrent ICH was determined using electronic health records and confirmed by neuroimaging. We compared ICH recurrence risk for Boston criteria v2.0 versus v1.5 for probable CAA using survival analysis.

RESULTS:

Fifty-nine of 443 patients (13.3%) had recurrent ICH over a median follow-up of 5.7 years (2682 patient-years). Thirty-seven out of one hundred two patients (36.3%) with probable CAA according to the Boston criteria v2.0 had recurrent ICH compared with 36/82 patients (43.9%) according to the v1.5 criteria. Patients with probable CAA according to the Boston v1.5 criteria had a higher ICH recurrence rate (10.9 per 100 person-years [95% CI, 7.8–15.1]) compared with those diagnosed by the v2.0 criteria (8.5 per 100 person-years [95% CI, 6.1–11.7]). The 20 patients defined as probable CAA only by the v2.0 criteria had a very low recurrence rate (0.9 per 100 person-years [95% CI, 0.1–6.7]), lower than those diagnosed using the v1.5 criteria (
P
<0.001).

CONCLUSIONS:

Our findings suggest a wide spectrum of ICH recurrence risk in patients with probable CAA. Patients with ICH diagnosed with CAA based only on the nonhemorrhagic white matter markers introduced in the Boston v2.0 criteria had a much lower risk of recurrence than those diagnosed with the previous Boston criteria v1.5, comparable to that of patients with ICH not fulfilling any probable CAA criteria.
Metal-Organic Frameworks (MOFs) as Solid State Hydrogen Storage System: A Critical Review
Authors: Meena Khushbu , Dixit Shalini , Tripathi Balram
Published: June 2023

Metal organic frameworks (MOFs) are a class of hybrid porous materials which consists inorganic and organic linkers bounded to metal ions. The important properties of MOFs such as greater surface area, synthetic versatility, variable pore size, long range order and inherent structure
makes MOFs very interesting in the field of hydrogen storage. In this manuscript we are reporting a detailed review on metal organic frameworks with the help of available previous reported literature. This review summarizes MOFs structure aspect, synthesis, nomenclature, progress of MOFs,
gas storage applications, energy consumption, hydrogen storage targets, tabulation of MOFs for hydrogen storage and limitations of synthesized MOFs system related technologies, present challenges and importance of MOFs as hydrogen storage system.
Is citizen satisfaction affected by the equivalent framing effect? A study based on situations involving poor government performance
Authors: Gao Xuede , Wang Qian , Shen Xiyun
Published: June 2023

Although numerous studies have confirmed the existence and possible limitations of the equivalent framing effect in performance information evaluation, few studies have examined the conditions under which this framing effect works or does not work. This paper explores the equivalent framing effect of citizen satisfaction in the case of poor government performance by using two investigation experiments, and examines the boundary conditions of this effect in terms of performance information sources and trust in government. The results show that citizen satisfaction is higher when performance information is framed positively, rather than negatively. The findings demonstrate that the equivalent framing effect of citizen satisfaction is moderated by performance information sources and trust in government. This result indicates that equivalent framing effect has a certain fragility, showing heterogeneity with different sources of performance information and different levels of public trust in the government.

Points for practitioners

Truthfully reporting poor performance is the basic requirement for local governments. This study reminds government staff that, on the one hand, low performance is not a scourge, and small changes in poor performance reports may significantly change citizen satisfaction. On the other hand, it is not a panacea to improve citizen satisfaction simply by changing the presentation of performance information. The government should make more efforts to improve the public's confidence in performance information and the government.
Improving recycled carbon fiber by single walled carbon nanotubes in reinforcement of polyamide composites
Authors: Galkov MS , Myasnikova Yu , Marchenko K , Smirnov SN
Published: June 2023

Recycled carbon fibers (rCF) represent an inexpensive alternative to virgin carbon fibers (CF) but the mechanical improvement brought by rCF to polymer composites is noticeably lower than that from CF. In this article we evaluate two methods of coating rCF by single walled carbon nanotubes (SWCNTs), wet and dry, and demonstrate that extremely low concentrations of SWCNTs, ∼0.03%, are sufficient to measurably improve the strength (by 16%), modulus (by 38%), and Izod impact strength (by 52%) of thermoplastic crystalline polyamide polyxylylene adipamide (MXD6) with 30% rCF. The dry method with grinding of rCF and SWCNTs works better than the wet (dip coating) method and the rCF with residual epoxy is better than purified by pyrolysis rCF. We link this improvement of the mechanical properties to the enhanced crystallization rate caused by SWCNTs, which is observed in differential scanning calorimetry (DSC).
Black–White Differences in Offspring Educational Attainment and Older Parents’ Dementia
Authors: Yahirun Jenjira J. , Vasireddy Sindhu , Hayward Mark D.
Published: June 2023

Emerging research documents the health benefits of having highly educated adult offspring. Yet less is known about whether those advantages vary across racial groups. This study examines how offspring education is tied to parents’ dementia risk for Black and White parents in the United States. Using data from the Health and Retirement Study, findings suggest that children’s education does not account for the Black–White gap in dementia risk. However, results confirm that parental race moderates the relationship between children’s education and dementia risk and that the association between children’s education and parents’ dementia risk is strongest among less-educated parents. Among less-educated parents, higher levels of children’s attainment prevent the risk of dementia onset for Black parents, but low levels of offspring schooling increase dementia risk among White parents. The study highlights how offspring education shapes the cognitive health of social groups differently and points to new avenues for future research.
Chemical ‘canaries’: Munitions workers in the First World War
Authors: Fara Patricia
Published: June 2023

In the early twentieth century, scientific innovations permanently changed international warfare. As chemicals traveled out of laboratories into factories and military locations, war became waged at home as well as overseas. Large numbers of women were employed in munitions factories during the First World War, but their public memories have been overshadowed by men who died on battlefields abroad; they have also been ignored in traditional histories of chemistry that focus on laboratory-based research. Mostly young and poorly educated, but crucial for Britain’s military success, these female workers were subjected to procedures of social regulation and consigned to carrying out dangerous chemical procedures causing chronic illness or death; in particular, when TNT died their skin yellow, they were colloquially known as 'canaries.'
Spectacle, Surveillance, and the Ironies of Visual Politics in the Age of Autonomous Images
Authors: Reinhardt Mark
Published: June 2023

Considering formative twentieth-century theories in relation to contemporary technosocial developments, this article examines ideas of spectacle and surveillance as ways of approaching visual politics. I argue that the historically important relationship between the visual and political fields is now intensifying and mutating. First discussing Guy Debord’s The Society of the Spectacle, I show how his influential approach proves inadequate to the politics of image-saturated societies. I next show how critics of imperial and racial spectacles, from Michael Rogin to Claudia Rankine and Tina Campt, provide better ways of engaging power and political contestation in the visual field. Third, I examine how Michel Foucault deployed notions of spectacle in his own work but argued for leaving the term behind, presenting surveillance as not just a different modality of power but also spectacle’s temporal successor. This account remains essential for both historical understanding and reckoning with contemporary surveillance. Fourth, however, as Simone Browne argues, Foucault’s separation between spectacle and surveillance is too stark, his history too prone to occlude race. Furthermore, recent surveillance technologies and practices have changed in ways that confound his terms, while extending and also altering the racial dynamics explored earlier in the essay. Today, even surveillance based on optical media contributes to a “postvisual” image world in which algorithmic, machine-machine communication abets forms of power neither tied to human perception nor graspable as subject formation. With surprising assistance from Debord, I end by discussing the significant theoretical and political challenges posed by the ironies of postvisual visuality.
Evaluation of qualitative and quantitative imaging features of hepatic hemangiomas with and without pseudo-washout sign on gadoxetic acid-enhanced MRI: a descriptive and comparative study
Authors: Aslan Serdar , Onder Ramazan Orkun , Sulun Emrah , Taşdemir Merve Nur
Published: June 2023

Background

Hepatic hemangiomas are the most common benign liver tumors. It is important to know the imaging features of hemangiomas on gadoxetic acid (GA)-enhanced magnetic resonance imaging (MRI).

Purpose

To evaluate the qualitative and quantitative imaging features of hemangiomas on GA-enhanced MRI, and to compare imaging features of hemangiomas with and without pseudo-washout sign (PWS).

Material and Methods

We retrospectively included 93 cases of hemangioma that underwent GA-enhanced MRI. The presence of an enhancement pattern in the arterial phase (AP) and PWSs in the transitional phase (TP) were evaluated. Signal-to-norm ratios (SINorm) of hemangiomas, liver parenchyma, and portal vein (PV) as well as contrast-to-norm ratio (CNorm) were assessed. Additionally, hemangiomas with and without PWSs were defined as two separate subgroups, and imaging features were compared.

Results

Of the 93 cases of hemangiomas, 49 (52.6%) had PWSs in the TP. The mean SINorms of hemangiomas showed the highest value in the AP ( P < 0.05). The mean CNorms showed positive values in the AP, and gradually decreased ( P < 0.05). Hemangiomas with PWSs were significantly rapidly enhanced and smaller in size ( P < 0.05), and the mean SINorms was lower in the TP ( P = 0.023). While the mean CNorms showed a significant difference in the AP between subgroups ( P < 0.001), the enhancement pattern was equal to that of the PV.

Conclusion

When evaluating GA-enhanced MRI, radiologists should utilize quantitative measures in addition to qualitative assessment and should be aware that SI matching with PV in all phases can be a distinguishing finding in the diagnosis of hemangioma.
Anti-adherent activity of nano-coatings deposited by thermionic vacuum arc plasma on C. albicans biofilm formation
Authors: Topcu Ersöz Mirac Berke , Mumcu Emre , Avukat Esra Nur , Akay Canan , Pat Suat , Erdönmez Demet
Published: June 2023

Background:

The purpose of this study was to analyze the anti-adherent activity of nano-coatings deposited by Thermionic Vacuum Arc plasma on C. albicans ATCC 10231 biofilm.

Materials and methods:

A total of 80 disc-shaped (2 × 10 mm) polymethymethacrylate samples were prepared and divided into four groups with 10 samples in each group (Control, ZnO, SnO2, Ag) ( n = 10). Using thermionic vacuum arc plasma, they were coated with ZnO, SnO2, and Ag. 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and Crystal Viole (CV) assays were conducted for biofilm quantification. Scanning electron microscopy (SEM) was used to observe biofilm images of C. albicans biofilm.

Results:

MTT and CV mean values differ statistically significantly between all groups ( p ⩽ 0.05). The SnO2 group had the lowest mean value, whereas the control group received the highest value.

Conclusion:

SnO2 coating shown greater anti-adherent activity than either metal oxides. C. albicans biofilm formation on denture base surfaces is reduced following Thermionic Vacuum Arc plasma coating with SnO2.
Impact of COVID-19 on Lifestyle: A Sample of Iranian Older Adults
Authors: Zanjari Nasibeh , Abootalebi Maliheh , Delbari Ahmad , Abolfathi Momtaz Yadollah
Published: June 2023

The COVID-19 pandemic and prolonged quarantine affect the health behaviors of older adults. We investigated the changes in older adults’ lifestyles during the pandemic in a sample of 1020 people aged 60 years old and over in Tehran. The results revealed that the COVID-19 pandemic had a positive impact on nutritional behaviors and social support while having a negative impact on physical activity and anxiety in older adults. Due to the greater deterioration of health behaviors among unmarried older adults, low socio-economic status, and COVID-19 inpatients, policymakers must pay attention to interventions to promote healthy lifestyles.
The Nationwide Trends and Preparation Requirements of Alternative Route Programs in Special Education
Authors: Day Jamie , Nagro Sarah A. , Mason-Williams Loretta
Published: June 2023

In the United States, there exists a chronic shortage of qualified special education teachers to provide instructional services to students with disabilities. One policy solution developed to increase the number of qualified teachers is alternative routes (ARs), which are broadly defined as nontraditional and accelerated preparation paths to obtain a teaching license. In this longitudinal descriptive study, we investigate (a) the national trends of special education teacher enrollment and completion in AR programs from 2012 to 2020 and (b) the special education teacher preparation requirements in state alternative pathways that are disaggregated by their affiliation with institutions of higher education. Findings reveal that AR programs preparing special education teachers are on the rise within the United States, but they vary significantly on their preparation requirements. Implications for future research and policy recommendations needed within the recruitment and preparation of special education teachers will be discussed.
Evaluating the Role of Inorganic Elements of Camelus Dromedarius Saliva in Protecting Enamel Against Tooth Surface Loss
Authors: Al Razaiki Khalid , Al Khaldi Khalid , Al Harthy Nutayla , Al Wahaibi Ayida , Qutieshat Abubaker
Published: June 2023

The aim of this study was to provide insight into the role of camel's saliva in protecting enamel against erosion and to evaluate the levels of salivary sodium, potassium, calcium, and phosphate ions among 2 groups of camels, those with low-grade tooth surface loss and those with high-grade tooth surface loss. Twenty-eight healthy camels, 5 males and 23 females, aged 20 months to 10 years, were divided into 2 groups. Group I comprise camels with “low-grade tooth surface loss” and Group 2 with “high-grade tooth surface loss.” Unstimulated saliva was collected by a draining method. The samples were then analyzed for sodium, potassium, calcium, and phosphate concentrations using automated chemistry analysis. Data were then statistically analyzed using the unpaired Student's t-test and Pearson correlation coefficient test. The study found the salivary calcium and phosphate concentrations were significantly lower in the “high-grade” erosion group, in comparison with the other group ( P < .0001 and P  =  .0257, respectively). The results also revealed that the more extensive the tooth surface loss, the more carious lesions the subject had ( P  =  .023), and that caries are more common in the anterior teeth, particularly the incisors. The authors conclude that alterations in inorganic elements of saliva, particularly the calcium and phosphate ions, play a major role in the development of resistance to tooth surface loss. This work may represent a direction for future research to develop custom-made preventive supplements, which can protect camelid teeth against tooth surface loss.