bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance of a prehospital HEART score in patients with possible myocardial infarction: a prospective evaluation
Authors: Cooper Jamie G , Ferguson James , Donaldson Lorna A , Black Kim M M , Livock Kate J , Horrill Judith L , Davidson Elaine M , Scott Neil W , Lee Amanda J , Fujisawa Takeshi , Lee Kuan Ken , Anand Atul , Shah Anoop S V , Mills Nicholas L 
Published: June 2023

IntroductionThe History, Electrocardiogram (ECG), Age, Risk Factors and Troponin (HEART) score is commonly used to risk stratify patients with possible myocardial infarction as low risk or high risk in the Emergency Department (ED). Whether the HEART score can be used by paramedics to guide care were high-sensitivity cardiac troponin testing available in a prehospital setting is uncertain.MethodsIn a prespecified secondary analysis of a prospective cohort study where paramedics enrolled patients with suspected myocardial infarction, a paramedic Heart, ECG, Age, Risk Factors (HEAR) score was recorded contemporaneously, and a prehospital blood sample was obtained for subsequent cardiac troponin testing. HEART and modified HEART scores were derived using laboratory contemporary and high-sensitivity cardiac troponin I assays. HEART and modified HEART scores of ≤3 and ≥7 were applied to define low-risk and high-risk patients, and performance was evaluated for an outcome of major adverse cardiac events (MACEs) at 30 days.ResultsBetween November 2014 and April 2018, 1054 patients were recruited, of whom 960 (mean 64 (SD 15) years, 42% women) were eligible for analysis and 255 (26%) experienced a MACE at 30 days. A HEART score of ≤3 identified 279 (29%) as low risk with a negative predictive value of 93.5% (95% CI 90.0% to 95.9%) for the contemporary assay and 91.4% (95% CI 87.5% to 94.2%) for the high-sensitivity assay. A modified HEART score of ≤3 using the limit of detection of the high-sensitivity assay identified 194 (20%) patients as low risk with a negative predictive value of 95.9% (95% CI 92.1% to 97.9%). A HEART score of ≥7 using either assay gave a lower positive predictive value than using the upper reference limit of either cardiac troponin assay alone.ConclusionsA HEART score derived by paramedics in the prehospital setting, even when modified to harness the precision of a high-sensitivity assay, does not allow safe rule-out of myocardial infarction or enhanced rule-in compared with cardiac troponin testing alone.
Early rituximab treatment reduces long-term disability in aquaporin-4 antibody-positive neuromyelitis optica spectrum
Authors: Park Su Yeon , Kwon Young Nam , Kim Sunyoung , Kim Seung-Hyun , Kim Jong Kuk , Kim Jun-Soon , Nam Tai-Seung , Min Young Gi , Park Kyung Seok , Park Jin-Sung , Seok Jin Myoung , Sung Jung-Joon , Sohn Eunhee , Shin Kyong Jin , Shin Jin-Hong , Shin Ha Young , Oh Seong-il , Oh Jeeyoung , Yoon Byeol-A , Lee Sanggon , Lee Jong-Mok , Lee Hye Lim , Choi Kyomin , Huh So-Young , Jang Myoung-jin , Min Ju-Hong , Kim Byoung Joon , Kim Sung-Min 
Published: June 2023

BackgroundNeuromyelitis optica spectrum disorder (NMOSD) causes relapsing inflammatory attacks in the central nervous system, leading to disability. As rituximab, a B-lymphocyte-depleting monoclonal antibody, is an effective in preventing NMOSD relapses, we hypothesised that earlier initiation of rituximab can also reduce long-term disability of patients with NMOSD.MethodsThis multicentre retrospective study involving 19 South Korean referral centres included patients with NMOSD with aquaporin-4 antibodies receiving rituximab treatment. Factors associated with the long-term Expanded Disability Status Scale (EDSS) were assessed using multivariable regression analysis.ResultsIn total, 145 patients with rituximab treatment (mean age of onset, 39.5 years; 88.3% female; 98.6% on immunosuppressants/oral steroids before rituximab treatment; mean disease duration of 121 months) were included. Multivariable analysis revealed that the EDSS at the last follow-up was associated with time to rituximab initiation (interval from first symptom onset to initiation of rituximab treatment). EDSS at the last follow-up was also associated with maximum EDSS before rituximab treatment. In subgroup analysis, the time to initiation of rituximab was associated with EDSS at last follow-up in patients aged less than 50 years, female and those with a maximum EDSS score ≥6 before rituximab treatment.ConclusionsEarlier initiation of rituximab treatment may prevent long-term disability worsening in patients with NMOSD, especially among those with early to middle-age onset, female sex and severe attacks.
Does medical humanities matter? The challenge of COVID-19
Authors: Macnaughton Jane 
Published: June 2023

Medical humanities has tended first and foremost to be associated with the ways in which the arts and humanities help us to understand health. However, this is not the only or necessarily the primary aim of our field. What the COVID-19 pandemic has revealed above all is what the field ofcriticalmedical humanities has insisted on: the deep entanglement of social, cultural, historical life with the biomedical. The pandemic has been a time for reinstating the power of expertise of a particular kind, focusing on epidemiology, scientific modelling of potential outcomes and vaccine development. All of this delivered by science at speed.It has been challenging for medical humanities researchers to find purchase in these debates with insights from our more contemplative, ‘slow research’ approaches. However, as the height of the crisis passes, our field might now be coming into its own. The pandemic, as well as being productive of scientific expertise, also demonstrated clearly the meaning of culture: that it is not a static entity, but is produced and evolves through interaction and relationship. Taking a longer view, we can see the emergence of a certain ‘COVID-19 culture’ characterised by entanglements between expert knowledge, social media, the economy, educational progress, risk to health services and people in their socio-economic, political ethnic and religious/spiritual contexts. It is the role of medical humanities to pay attention to those interactions and to examine how they play out in the human experience and potential impact of the pandemic. However, to survive and grow in significance within the field of healthcare research, we need to engage not just to comment. There is a need for medical humanities scholars to assert our expertise in interdisciplinary research, fully engaged with experts by experience, and to work proactively with funders to demonstrate our value.
Impact of string interactions on the space–time evolution of hadronic vertices
Authors: Chakraborty Smita , Lönnblad Leif 
Published: June 2023

AbstractWe investigate the space–time picture of string evolution and hadron production in a fully string-based model for high energy collisions involving heavy-ions. We find that although the density of strings is quite large at the time of hadronization in a central heavy-ion collision, the initial overlap between them right after the collisions is not necessarily large. We also find that when including string-string interactions using the so-called shoving model, the density of strings is decreased which should dampen the rapid increase in string tension in the rope hadronization with multiplicity that we found in a previous paper.
Effects of Astragalus membranaceus Polysaccharides on Growth Performance, Physiological and Biochemical Parameters, and Expression of Genes Related to Lipid Metabolism of Spotted Sea Bass, Lateolabrax maculatus
Authors: Huang Zhangfan , Ye Youling , Xu Anle , Li Zhongbao 
Published: June 2023

This experiment investigated the effects of Astragalus membranaceus polysaccharides (AMP) on growth, physiological and biochemical parameters, and the expression of lipid metabolism-related genes in spotted sea bass, Lateolabrax maculatus. A total of 450 spotted sea bass (

10.44
±
0.09

g) were divided into six groups and were given diets with different levels of AMP (0, 0.2, 0.4, 0.6, 0.8, and 1.0 g/kg) for 28 days, respectively. Results indicated that dietary intake of AMP significantly improved fish weight gain, specific growth rate, feed conversion, and trypsin activity. Meanwhile, fish fed with AMP manifested significantly higher serum total antioxidant capacity and activity of hepatic superoxide dismutase, catalase, and lysozyme. Lower triglyceride and total cholesterol were noted in fish fed with AMP (

P
<
0.05

). Moreover, hepatic ACC1 and ACC2 were downregulated by dietary intake of AMP, and PPAR-α, CPT1, and HSL were upregulated accordingly (

P
<
0.05

). Parameters with significant difference were analyzed by quadratic regression analysis, and results showed that 0.6881 g/kg of AMP is the optimal dosage for spotted sea bass in size (

10.44
±
0.09

g). In conclusion, dietary intake of AMP can improve the growth, physiological status, and lipid metabolism of spotted sea bass, thereby indicating its promise as a potential dietary supplement.
Substantia Nigra Echogenicity Signal Correlated with Clinical Features in Patients with Parkinson’s Disease in Xinjiang
Authors: Wei Rurui , Zhang Yan , Li Peishan , Xu Zeheng , Zhang La , He Yan , Wu Qinfen , Shi Youcai , Yuan Yang , Aisha Abudula 
Published: June 2023

Background. Transcranial sonography (TCS) is a noninvasive test that can reveal structural changes in the substantia nigra (SN) in Parkinson’s disease (PD). The purpose of this study was to investigate the relationship between SN signatures and clinical features in PD patients in a multiethnic region of China. Methods. A total of 147 patients with PD were included in the study, and all of whom had underwent a TCS examination. Clinical information was collected from PD patients, and motor and nonmotor symptoms were assessed using assessment scales. Results. There were differences in the substantia nigra hyperechogenicity (SNH) area between age of onset, visual hallucinations (VH), and UPDRS3.0 II scores (

P

< 0.05), patients with late onset PD had a greater SNH area than early onset (0.326 ± 0.352 vs. 0.171 ± 0.194), and PD patients presenting with VH had a greater SNH area than those without hallucinations (0.508 ± 0.670 vs. 0.278 ± 0.659), and further multifactorial analysis showed that a high SNH area was an independent risk factor for development of VH. The area under the ROC curve for predicting VH from the SNH area in PD patients was 0.609 (95% CI: 0.444–0.774). There was a positive correlation between the SNH area and UPDRS3.0-II scores, but further multifactorial analysis showed that SNH was not an independent predictor of the UPDRS3.0-II score. Conclusion. A high SNH area is an independent risk factor for development of VH, there is a positive correlation between the SNH area and UPDRS3.0 II score, and TCS has guiding significance in predicting clinical VH symptoms and activities of daily living in PD patients.
Abstract A007: Modulation of HER2 as a mechanism for AR expression
Authors: Low Daniel K.Y. , Wilkinson Scott , King Isaiah M. , Trostel Shana Y. , Sowalsky Adam G. 
Published: June 2023

Abstract
Background: Intense neoadjuvant androgen deprivation therapy (inADT) is an emerging treatment paradigm for localized high-risk prostate cancer, but in certain patients a subset of tumors will recur after surgery. In tumors with endogenously low androgen receptor (AR) activity, expression of the EGFR family protein HER2 was enriched. We sought to investigate the role of HER2 in driving the proliferation of prostate cancer under androgen-depleted environments. We hypothesized that overexpression of HER2 would decrease AR activity, while its knockdown would conversely increase AR expression beyond baseline levels. Methods: The AR-expressing 22Rv1 and LNCaP prostate cancer cell lines were cultured and plated for transfection. HER2 overexpression was achieved using an exogenous HER2 (ERBB2) plasmid, while HER2 knockdown was performed using siRNA, alongside controls for both groups. Cell lysates were collected at 24-, 48-, and 72-hour time points. Western blotting was performed to examine HER2, AR, PSA, and actin expression. Results: Western blot analysis confirmed successful overexpression and knockdown of HER2, using an exogenous HER2 plasmid and siRNA, respectively. In 22Rv1 and LNCaP cells overexpressing HER2, AR (and AR-V7 in 22Rv1 cells) levels were decreased compared to the control cells. Conversely, 22Rv1 and LNCaP cells with knockdown of HER2 exhibited elevated AR expression. Biological replicates to confirm these findings are in progress. Additional studies will also examine the impact of HER2 signaling and activity on downstream pro-proliferative pathways. Conclusions: Manipulation of HER2 expression highlights a potential role of EGFR family proteins as a mechanism for prostate cancer growth in androgen-deprived environments. Future studies will validate this finding at the RNA level using qPCR and probe downstream targets of HER2 using western blotting. These preliminary findings have implications for the treatment of advanced tumors for which inADT is not a viable option. Targeting HER2 and its downstream signaling pathways represent an intriguing mechanism to overcome resistance to androgen deprivation therapy in newly-diagnosed, treatment-naïve patients.
Citation Format: Daniel K.Y. Low, Scott Wilkinson, Isaiah M. King, Shana Y. Trostel, Adam G. Sowalsky. Modulation of HER2 as a mechanism for AR expression [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 A007.
Abstract A077: MicroRNA drivers of resistance to androgen deprivation therapy in prostate cancer
Authors: Saunders Philippa C. , Fletcher Claire 
Published: June 2023

Abstract
INTRODUCTION: Prostate cancer is the most prevalent malignancy affecting Western males. It is initially an androgen-dependent disease: androgens bind to the androgen receptor and drive expression of genes that promote proliferation and evasion of apoptosis. Despite reduced androgen dependence in advanced prostate cancer, androgen receptor signalling remains a key driver of growth. Androgen deprivation therapy (ADT) is therefore a first line treatment approach and works well initially, but resistance inevitably develops. Abiraterone and Enzalutamide are drugs widely used in ADT and are androgen synthesis and androgen receptor signalling inhibitors respectively. The shortage of other treatment options means acquired resistance to these drugs is a major clinical problem. MicroRNAs (miRs) are important mediators of post-transcriptional gene regulation and show altered expression in cancer. Several have been linked to the development of resistance to ADT. Manipulation of such miRs may be a pathway to breakthrough treatments for advanced prostate cancer. This study aimed to validate ADT resistance-implicated miRs and their clinically relevant targets. MATERIALS AND METHODS: Small RNA-sequencing of Abiraterone- and Enzalutamide-resistant C42 prostate cancer cells identified subsets of miRs dysregulated as compared to parental cells. Real-Time Quantitative Reverse Transcription PCR (qRT-PCR) was used to validate altered expression of candidate ADT resistance-implicated miRs 195-5p, 497-5p and 29a-5p in ADT-resistant and -responsive prostate cancer cell lines, patient-derived xenografts (PDXs) and primary prostate cancer explants. RESULTS AND DISCUSSION: This study suggests a possible role for miR-497-5p in the development of ADT resistance in prostate cancer. MiR-497-5p expression was increased in ADT-resistant versus ADT-responsive prostate cancer cells. Importantly, miR-497-5p expression was also increased in Enzalutamide-treated, castrated (ADT-mimicking) PDXs versus intact PDXs. MiR-195-5p was also elevated in ADT-resistant versus -responsive prostate cancer cells, while there was a drop in miR-29a-5p expression. Candidate clinically relevant targets of miR-497-5p in prostate cancer were identified by mining AGO-PAR-CLIP-seq data sets and may include AVL9 and FZD6. CONCLUSION: In summary, this study identified microRNAs that are implicated in prostate cancer resistance to androgen deprivation therapy and could represent novel therapeutic targets for advanced disease.
Citation Format: Philippa C. Saunders, Claire Fletcher. MicroRNA drivers of resistance to androgen deprivation therapy in 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 A077.
Abstract A083: Low dose abiraterone in prostate cancer - Safety, efficacy and pharmacoeconomic implications
Authors: Acharya Suryakanta 
Published: June 2023

Abstract
Background and aim: Survival has improved in metastatic castration-resistant prostate cancer (mCRPC) because of the development of effective drugs such as abiraterone acetate, but universal accessibility to treatment is not always possible because of cost constraints in lower- and middle-income countries. Abiraterone in fasting state is the standard of care in mCRPC. Despite a large food effect, it was administered under fasting conditions in its pivotal trials. Recently, the National Comprehensive Cancer Network (NCCN) has included low-dose abiraterone (250 mg/day) with food as an alternative treatment option to full-dose abiraterone (1,000 mg/day) fasting. This translates to 75% cost reduction. This study aims to find safety, efficacy and pharmacoeconomic implications of low dose abiraterone in mCRPC. Materials and Methods: In this cohort study mCRPC Patients with progression were offered low dose abiraterone with low fat meal along with prednisone 5 mg twice daily. Prostate-specific antigen (PSA) was assessed monthly and toxicity assessment was made every week. Final PSA response (≥ 50% reduction) and toxicity assessment were done at 12 weeks. In case of grade IV toxicity (Anemia, Hypertension, Hypokalemia, Hypocalcemia – CTC AE V5.0) because of higher drug bioavailability, patient would be offered full dose abiraterone. 10 patients were offered low dose abiraterone in 2022. Results: 6 out of 10 patients achieved desired PSA response at 12 weeks which is a bit on higher side compared to standard dose abiraterone (recent literature). Fortunately, none of the patient developed grade IV toxicity. This finding was assuring, and no patient shifted to standard dosing. Conclusions: Low dose abiraterone (with low-fat breakfast) is noninferior to full dose abiraterone with respect to PSA metrics. Toxicity is the major thing to look at and given the pharmacoeconomic implications it’s imperative to adopt this strategy in places where affordability is the issue. Let the patients have something rather than nothing!
Citation Format: Suryakanta Acharya. Low dose abiraterone in prostate cancer - Safety, efficacy and pharmacoeconomic implications [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 A083.
Abstract B003: EVI1 oncogenic role in non-canonical AR driven lethal prostate cancer
Authors: Gulla Surendra , Bard Jonathan E. , VanderWeele David J. , Kelly Kathleen , Adelaiye-Ogala Remi 
Published: June 2023

Abstract
Androgen receptor (AR) remains active in castration-resistant prostate cancer (CRPC), and AR cistrome can become extensively reprogrammed with disease progression. Recent findings from our group and others have shown an association with non-canonical AR signature with resistance to enzalutamide. However, the complete mechanism is not fully revealed. EVI1 belongs to the zinc-finger transcription factor family, and overexpression of EVI1 is associated with poor patient outcomes. However, its role in the context of resistance to AR-targeted therapy remains unclear. Our preliminary data from ChIP-seq and GSEA analysis shows a significant enrichment of EVI1 target gene-set captured from annotated enzalutamide-resistant AR binding sites. Hypothesis: EVI1 cooperates in regulating the non-canonical AR activity associated with resistance to AR targeted therapy and blocking EVI1 may overcome resistance to target therapy. Methods : Using a PDX model of advanced enzalutamide-resistant CRPC, we performed single-cell ATAC-seq + gene expression multi-omic assay. Next, we determined the enrichment of canonical vs. non-canonical AR signatures across cell populations. Using motif analysis and transcription factor foot printing, we determine EVI1 (MECOM) motif z score and enrichment. Results: Our findings demonstrate enrichment of non-canonical AR signatures in distinct population of cells following exposure to enzalutamide. In addition, the subpopulation of cells enriched for non-canonical AR cistrome also exhibited high EVI1 (MECOM) motif z-scores. Conclusion : Our data suggests a potential link between EVI1 and non-canonical AR signaling. Ongoing mechanistic studies will provide insight mechanism by which EVI1 controls non canonical AR activity and its vulnerabilities.
Citation Format: Surendra Gulla, Jonathan E. Bard, David J. VanderWeele, Kathleen Kelly, Remi Adelaiye-Ogala. EVI1 oncogenic role in non-canonical AR driven 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 B003.
Abstract B005: The oncogenic transcription factor ERG has distinct roles and signaling regulation in different prostate cancer cell types
Authors: Hollenhorst Peter C. , Rajendran Saranya , Jerde Travis J. 
Published: June 2023

Abstract
Background: ERG is the most common oncogene in prostate cancer, as it is aberrantly expressed in about 50% of cases due to the TMPRSS2/ERG gene rearrangement. ERG is not normally expressed in the adult prostate. The normal function of ERG is confined to hematopoietic stem cells and blood vessels. Aberrant expression of ERG in prostate epithelial cells is oncogenic when combined with mutations that activate the PI3K/AKT signaling pathway. The RAS/MAPK pathway can also regulate ERG function through direct phosphorylation of ERG by ERK. The function of these regulatory events and how they can be exploited to develop therapy for ERG-positive prostate cancer remains unclear. Results: ERG expression in prostate basal epithelial cells drives epithelial to mesenchymal transition and stemness properties. This function requires ERG phosphorylation via a positive feedback loop with the TLR4 signaling pathway, and can be repressed by a TLR4 inhibitor. Activation of the PI3K/AKT pathway rearranges the ERG cistrome and alters ERG function, where ERG now promotes luminal epithelial differentiation. In the presence of activated AKT, new ERG targets include genes involved in vascular development and ERG phosphorylation is regulated through a positive feedback loop with the VEGF signaling pathway. Conclusions: ERG function in basal and luminal prostate epithelial cells appear to mirror ERG functions in hematopoietic stem cells and blood vessels, respectively. These findings suggest strategies of combinatorial inhibition of ERG function in both cell types.
Citation Format: Peter C. Hollenhorst, Saranya Rajendran, Travis J. Jerde. The oncogenic transcription factor ERG has distinct roles and signaling regulation in different prostate cancer cell types [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 B005.