bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of IL-25/IL-17RA improves immune-related adverse events of checkpoint inhibitors and reveals antitumor activity
Authors: Hu Xizi , Bukhari Shoiab M , Tymm Carly , Adam Kieran , Lerrer Shalom , Henick Brian S , Winchester Robert J , Mor Adam 
Published: March 2024

BackgroundImmune checkpoint inhibitors (ICIs) have improved outcomes and extended patient survival in several tumor types. However, ICIs often induce immune-related adverse events (irAEs) that warrant therapy cessation, thereby limiting the overall effectiveness of this class of therapeutic agents. Currently, available therapies used to treat irAEs might also blunt the antitumor activity of the ICI themselves. Therefore, there is an urgent need to identify treatments that have the potential to be administered alongside ICI to optimize their use.MethodsUsing a translationally relevant murine model of anti-PD-1 and anti-CTLA-4 antibodies-induced irAEs, we compared the safety and efficacy of prednisolone, anti-IL-6, anti-TNFɑ, anti-IL-25 (IL-17E), and anti-IL-17RA (the receptor for IL-25) administration to prevent irAEs and to reduce tumor size.ResultsWhile all interventions were adequate to inhibit the onset of irAEs pneumonitis and hepatitis, treatment with anti-IL-25 or anti-IL-17RA antibodies also exerted additional antitumor activity. Mechanistically, IL-25/IL-17RA blockade reduced the number of organ-infiltrating lymphocytes.ConclusionThese findings suggest that IL-25/IL-17RA may serve as an additional target when treating ICI-responsive tumors, allowing for better tumor control while suppressing immune-related toxicities.
DWI scrolling artery sign for the diagnosis of giant cell arteritis: a pattern recognition approach
Authors: Seitz Luca , Bucher Susana , Bütikofer Lukas , Maurer Britta , Bonel Harald M , Lötscher Fabian , Seitz Pascal 
Published: March 2024

ObjectivesTo investigate the diagnostic accuracy of a pattern recognition approach for the evaluation of MRI scans of the head with diffusion-weighted imaging (DWI) in suspected giant cell arteritis (GCA).MethodsRetrospectively, 156 patients with suspected GCA were included. The ‘DWI-Scrolling-Artery-Sign’ (DSAS) was defined as hyperintense DWI signals in the cranial subcutaneous tissue that gives the impression of a blood vessel when scrolling through a stack of images. The DSAS was rated by experts and a novice in four regions (frontotemporal and occipital, bilaterally). The temporal, occipital and posterior auricular arteries were assessed in the T1-weighted black-blood sequence (T1-BB). The diagnostic reference was the clinical diagnosis after ≥6 months of follow-up.ResultsThe population consisted of 87 patients with and 69 without GCA; median age was 71 years and 59% were women. The DSAS showed a sensitivity of 73.6% and specificity of 94.2% (experts) and 59.8% and 95.7% (novice), respectively. Agreement between DSAS and T1-BB was 80% for the region level (499/624; kappa(κ)=0.59) and 86.5% for the patient level (135/156; κ=0.73). Inter-reader agreement was 95% (19/20; κ=0.90) for DSAS on the patient level and 91.3% (73/80; κ=0.81) on the region level for experts. For expert versus novice, inter-reader agreement for DSAS was 87.8% on the patient level (137/156; κ=0.75) and 91.2% on the region level (569/624; κ=0.77).ConclusionsThe DSAS can be assessed in less than 1 min and has a good diagnostic accuracy and reliability for the diagnosis of GCA. The DSAS can be used immediately in clinical practice.
Sex differences in cytokines and adipokines in obese patients with PsA and controls undergoing a weight loss intervention
Authors: Landgren Anton Jonatan , Jonsson Charlotte A , Bilberg Annelie , Eliasson Björn , Torres Linda , Dehlin Mats , Jacobsson Lennart , Gjertsson Inger , Larsson Ingrid , Klingberg Eva 
Published: March 2024

ObjectiveIn this post hoc analysis of a previously published study, we compared cytokines and adipokine levels in women and men with psoriatic arthritis (PsA) at baseline (BL) and 6 months (M6) following a weight loss intervention.MethodsPatients with PsA (n=41) between 25 and 75 years of age, with body mass index (BMI)≥33 kg/m2were included in a weight loss intervention with a very low energy diet (VLED) for 12 or 16 weeks depending on BL BMI<40 or ≥40 kg/m2. As controls (n=39), obese individuals, already planned for VLED treatment were recruited and matched for sex, age and weight to the patients with PsA. Cytokines and adipokines were measured at BL and M6.ResultsAt BL, serum levels of interleukin (IL)-23, leptin and high molecular weight-adiponectin were higher in women with PsA compared with men, whereas serum levels of interferon (IFN)-γ, IL-12/IL-23 p40 and IL-13 were significantly lower in women. Serum IL-23 was significantly reduced at M6 compared with BL in women but not in men with PsA. In women with PsA, the reduction in IL-23 at M6, ∆IL-23, were positively correlated with ∆Disease Activity Score 28 C reactive protein (CRP) (Spearman’s correlation (rS)=0.486, p=0.016), ∆CRP (rS=0.468, p=0.021), ∆leptin (rS=0.683, p<0.001) and negatively correlated with ∆total-adiponectin (rS=−0.433, p=0.035). Also in women, ∆Disease Activity in Psoriatic Arthritis was positively correlated with ∆tumour necrosis factor-α (rS=0.417, p=0.034), ∆IL-1β (rS=0.550, p=0.034), ∆IFN-γ (rS=0.414, p=0.035) and ∆leptin (rS=0.410, p=0.038). None of these correlations were significant in men with PsA.ConclusionsWomen and men with PsA differed with regard to serum levels of cytokines and adipokines before and after weight loss.
Impact of COVID status and blood group on complications in patients in hemorrhagic shock
Authors: Brill Jason Bradley , Mueck Krislynn M , Cotton Madeline E , Tang Brian , Sandoval Mariela , Kao Lillian S , Cotton Bryan A 
Published: March 2024

ObjectiveAmong critically injured patients of various blood groups, we sought to compare survival and complication rates between COVID-19-positive and COVID-19-negative cohorts.BackgroundSARS-CoV-2 infections have been shown to cause endothelial injury and dysfunctional coagulation. We hypothesized that, among patients with trauma in hemorrhagic shock, COVID-19-positive status would be associated with increased mortality and inpatient complications. As a secondary hypothesis, we suspected group O patients with COVID-19 would experience fewer complications than non-group O patients with COVID-19.MethodsWe evaluated all trauma patients admitted 4/2020–7/2020. Patients 16 years or older were included if they presented in hemorrhagic shock and received emergency release blood products. Patients were dichotomized by COVID-19 testing and then divided by blood groups.Results3281 patients with trauma were evaluated, and 417 met criteria for analysis. Seven percent (29) of patients were COVID-19 positive; 388 were COVID-19 negative. COVID-19-positive patients experienced higher complication rates than the COVID-19-negative cohort, including acute kidney injury, pneumonia, sepsis, venous thromboembolism, and systemic inflammatory response syndrome. Univariate analysis by blood groups demonstrated that survival for COVID-19-positive group O patients was similar to that of COVID-19-negative patients (79 vs 78%). However, COVID-19-positive non-group O patients had a significantly lower survival (38%). Controlling for age, sex and Injury Severity Score, COVID-19-positive patients had a greater than 70% decreased odds of survival (OR 0.28, 95% CI 0.09 to 0.81; p=0.019).ConclusionsCOVID-19 status is associated with increased major complications and 70% decreased odds of survival in this group of patients with trauma. However, among patients with COVID-19, blood group O was associated with twofold increased survival over other blood groups. This survival rate was similar to that of patients without COVID-19.
Gravitational radiation of a spherically symmetric source in f(R)-gravitation
Authors: Ky Pham Van , Hong Van Nguyen Thi , Anh Ky Nguyen 
Published: March 2024

AbstractIt is shown that Birkhoff’s theorem for the general theory of relativity is overcome in the f(R)-theory of gravitation. That means, the f(R)-theory of gravitation, unlike Einstein’s general theory of relativity, does not forbid gravitational radiation from a spherically symmetric source (whether stationary or non-stationary). As a consequence, in the f(R)-theory a spherically symmetric gravitational deformation (e.g., collapse/expansion or pulsation) could emit gravitational waves (of tensor- and scalar polarization modes), a phenomenon impossible in the general relativity. A test model is examined and it turns out that the gravitational radiation is strongest when the surface of the deforming object is in the vicinity of the (modified) event horizon, even suddenly flares up just outside the latter. In this letter, within the f(R)-theory of gravitation, a gravitational wave equation and a formula for the gravitational emission power are derived. These formulae, along with searching for signals, can be used for the experimental test of the f(R)-theory. In general, including the spherically symmetry case, gravitational radiation of both tensor- and scalar polarization modes are allowed, although under some circumstance the contribution of scalar modes is strongly suppressed.
Quantifying quantumness in three-flavor neutrino oscillations
Authors: Bittencourt V. A. S. V. , Blasone M. , De Siena S. , Matrella C. 
Published: March 2024

AbstractWe characterize quantum correlations encoded in a three-flavor oscillating neutrino system by using both plane-wave and wave-packet approach. By means of the Complete Complementarity Relations (CCR) we study the trade-off of predictability, local coherence and non-local correlations in terms of the relevant parameters, chosen from recent neutrino experiments. Although the CCR describe very well the contributions associated to bipartite correlations, an attempt of promoting these relations to include the genuine tri-partite contributions in the pure-state case leads to a not completely meaningful result. However, we provide an analysis of the genuine tripartite contributions both for the pure instance and for the mixed case, independently of CCR.
Human mobility reshaped? Deciphering the impacts of the Covid-19 pandemic on activity patterns, spatial habits, and schedule habits
Authors: Bouzaghrane Mohamed Amine , Obeid Hassan , González Marta , Walker Joan 
Published: March 2024

AbstractDespite the historically documented regularity in human mobility patterns, the relaxation of spatial and temporal constraints, brought by the widespread adoption of telecommuting and e-commerce during the COVID-19 pandemic, as well as a growing desire for flexible work arrangements in a post-pandemic work, indicates a potential reshaping of these patterns. In this paper, we investigate the multifaceted impacts of relaxed spatio-temporal constraints on human mobility, using well-established metrics from the travel behavior literature. Further, we introduce a novel metric for schedule regularity, accounting for specific day-of-week characteristics that previous approaches overlooked. Building on the large body of literature on the impacts of COVID-19 on human mobility, we make use of passively tracked Point of Interest (POI) data for approximately 21,700 smartphone users in the US, and analyze data between January 2020 and September 2022 to answer two key questions: (1) has the COVID-19 pandemic and its associated relaxation of spatio-temporal activity patterns reshaped the different aspects of human mobility, and (2) have we achieved a state of stable post-pandemic “new normal”? We hypothesize that the relaxation of the spatiotemporal constraints around key activities will result in people exhibiting less regular schedules. Findings reveal a complex landscape: while some mobility indicators have reverted to pre-pandemic norms, such as trip frequency and travel distance, others, notably at-home dwell-time, persist at altered levels, suggesting a recalibration rather than a return to past behaviors. Most notably, our analysis reveals a paradox: despite the documented large-scale shift towards flexible work arrangements, schedule habits have strengthened rather than relaxed, defying our initial hypotheses and highlighting a desire for regularity. The study’s results contribute to a deeper understanding of the post-pandemic “new normal”, offering key insights on how multiple facets of travel behavior were reshaped, if at all, by the COVID-19 pandemic, and will help inform transportation planning in a post-pandemic world.
Abstract 1014: Disparities of triple negative breast cancer in Mississippi
Authors: Kaur Navdeep , Khan Javaria A. , Mao Jinghe , Melvin Diva , Hassan Muhammad M. , Zho Xinchun 
Published: March 2024

Abstract
Background: Triple-negative breast cancer (TNBC) accounts for about 10-15% of all breast cancers nationwide with disparities of incidence and outcomes among races, geographic locations, and other factors. This study is aimed to analyze the differences in the rate of TNBC, patient conditions at time of diagnosis, and death from TNBC among women in Mississippi.
Methods: A retrospective study was conducted to serially review breast cancer cases diagnosed in the University of Mississippi Medical Center during May 2016 to May 2023. The entire breast cancer population was then stratified by race. The rate of TNBC, age and BMI at time of diagnosis, the rate of expiration were compared between African American (AA) and Caucasian American (CA) women with breast cancer. Two-tailed Student’s T-test was used to calculate the difference in mean values, and Chi-Square Test was used to compare the difference in rates or percentages. The significant p value was set at p&lt;0.05.
Results: In total 291 women with breast cancer, AA patients were 195 (67.01%), CA patients were 88 (30.24%), and other were 8 (2.75%). The mean age of all patients was 58.3 years-old (ranged 24-97). The mean BMI was 31.19. The patients with TNBC were 109 (37.46%) in entire studied population. A total of 32 (1.6%) patients, including 14 TNBC and 18 non-TNBC were expired with an average age of 61.84 and an average survival time of 20 months from diagnosis to expiration. As compared to CA patient population, AA breast cancer patients had onset at younger age (58.08±0.88 vs. 59.18±1.36), had a higher BMI (31.79±0.62 vs. 28.25±1.05, p=0.017), higher percentage of TNBC (41.54% vs. 30.68%, p=0.082 and OR=1.605), and higher rate of expiration (11.28% vs, 9.1%). Also, as compared to CA expired patients with breast cancer, AA expired patients had higher BMI (29.57 vs. 28.61), shorter survival time (17.5 months vs. 19.4 months), and died at younger age (61.84-year old vs. 66.38-year old) with a higher proportion of TNBC subtype (54.6% vs 12.5%, p=0.045, OR=9.6).
Conclusions: Breast cancer is greatly disparate racially between AA and CA and geographically between Mississippi and US national average. The disparities are manifested in the proportion of TNBC subtype, age at onset of breast cancer, BMI at time of diagnosis, and death rate.
Citation Format: Navdeep Kaur, Javaria A. Khan, Jinghe Mao, Diva Melvin, Muhammad M. Hassan, Xinchun Zho. Disparities of triple negative breast cancer in Mississippi [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1014.
Abstract 1044: Low-cost, high-sensitivity InSituPlex® mIF assays on the Parhelia Omni-Stainer™
Authors: Hwang Kevin , Duro Lauren , Veith Alex , Wedin Nelson , Samusik Nikolay , Lee Je H. 
Published: March 2024

Abstract
Background: Multiplex immunofluorescence (mIF) is an important tool for extracting complex phenotypic information from normal or diseased tissues, and provides accurate and predictive insights on the tissue microenvironment faster. For patient samples in translational and clinical research, high sensitivity, specificity, and reproducibility are critical; however, throughput and cost considerations are also important in designing clinical studies. Enabling an easy-to-use high-performance assay such as InSituPlex® on robust and affordable auto-stainers like the Parhelia Omni-Stainer™ can allow researchers to gain a deeper understanding of the tissue micro-environment through high-quality multiplexed biomarker detection in a fraction of the time and cost.
Methods: We performed Ultivue InSituPlex® assays with OmniVUE™ panels using the Parhelia Omni-Stainer™, a low-cost, high-throughput tissue auto-stainer with reduced requirements for reagents with a minimal dead volume. We compared the whole-slide staining performance across replicates using human tonsil and tumor tissue arrays across multiple independent runs over multiple days. The stained slides were scanned using the Zeiss AxioScan.Z1 high-throughput imaging system, and image batches were processed using Ultivue’s UltiStacker.AI and UltiAnalyzer.AI software.
Results: Tighter temperature control of the slide in the Omni-Stainer supports optimal InSituPlex® signal amplification. Intra-run and inter-day analysis on serial sections of human tonsil and tumor tissue arrays demonstrated a high degree of consistency in InSituPlex® assay performance, specifically with marker-specific signal intensities and cell densities. The Omni-Stainer facilitates the use of low reagent volumes at each step of the assay due to its efficient reagent use, thus lowering the cost of reagents per slide.
Conclusions: This study demonstrated a fast, simple and robust workflow to perform high-performance InSituPlex® mIF assays on the low-cost, high-throughput Parhelia Omni-Stainer™. Ultivue’s configurable OmniVUE™ mIF panels can be run on the Omni-Stainer with reduced associated reagent costs per slide. This workflow can support larger clinical and translational studies in a more cost-effective fashion, leading to in-depth analysis of tissue microenvironment through highly precise multiplexed biomarker detection.
Citation Format: Kevin Hwang, Lauren Duro, Alex Veith, Nelson Wedin, Nikolay Samusik, Je H. Lee. Low-cost, high-sensitivity InSituPlex® mIF assays on the Parhelia Omni-Stainer™ [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1044.
Abstract 1071: Circulation of rare events in the liquid biopsy for early detection of lung mass lesions
Authors: Shah Anya , Resnick Karen , Mason Jeremy , Kuhn Peter , Nieva Jorge , Shishido Stephanie 
Published: March 2024

Abstract
Lung cancer screening with low-dose CT scans (LDCT) has reduced mortality for patients with high-risk smoking histories. However, this method of screening remains imperfect. High rates of false positive scans expose patients to additional morbidity as they pursue subsequent diagnostic evaluation. Real-world application of screening LDCT remains low. Finally, current screening guidelines exclude those without smoking histories, a population which comprises up to a quarter of lung cancer patients. We sought to explore the utility of liquid biopsy (LBx) in lung cancer patients and its use in early cancer screening and diagnosis. Using the third generation High-Definition Single Cell Assay (HDSCA3.0) workflow, we analyzed 99 peripheral blood samples divided into three cohorts: Normal Donors (ND, n=50) who were healthy volunteers with no known pathology, Screening CT patients (CT, n=25) who underwent standard LDCT screening with resultant Lung-RADS 1-2, Biopsy patients (BX, n=24) who had abnormal CT scans requiring tissue biopsy. The ND group was used to characterize baseline epithelial, mesenchymal, endothelial, and immune cells, alongside acellular events (oncosomes). For the CT and BX patients, demographic information including age, gender, and average BMI was roughly equivalent, however average pack-years smoked differed owing to 10 (42%) patients in the BX group who had no prior smoking history. A total of 14 (58%) BX patients were diagnosed with primary lung cancer (BX+), of which 11(75%) were adenocarcinoma, 2 (19%) were squamous cell carcinoma and 1 (6%) was small cell. Across the cohorts we observed intra- and interpatient heterogeneity of rare events including multiple phenotypic rare cell populations and oncosomes. The comparison of the rare event enumerations between the ND, CT, BX+, and BX- cohorts revealed a greater incidence of total events, total rare cells and oncosomes, as well as specific cellular phenotypes in the CT and BX cohorts compared to the ND cohort. LBx analytes were detected at a significant elevation in the BX samples compared to the CT samples, but there was no significant difference between BX+ and BX- samples. The data supports the utility of the LBx in distinguishing patients with an alveolar mass lesion from those without, providing a mechanism for screening prior to LDCT to better inform clinical workup and avoid unnecessary radiation exposure and biopsy.
Citation Format: Anya Shah, Karen Resnick, Jeremy Mason, Peter Kuhn, Jorge Nieva, Stephanie Shishido. Circulation of rare events in the liquid biopsy for early detection of lung mass lesions [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1071.
Abstract 1095: Prox1 transcription factor and its downstream signaling - A new therapeutic target for rhabdomyosarcoma
Authors: Gizaw Nebeyu Y. , Böhling Tom , Sampo Mika , Alitalo Kari , Kivela Riikka M. 
Published: March 2024

Abstract
Rhabdomyosarcoma (RMS) stands as the predominant soft tissue sarcoma in children, characterized by a high-grade neoplasm composed of cells resembling skeletal myoblasts. Despite being prevalent, patients with metastatic or recurrent rhabdomyosarcoma still experience poor outcomes, underscoring the necessity for novel treatments. We have recently shown that PROX1 is a critical factor in RMS tumor growth and myogenic characteristics (Gizaw NY, et al. PNAS 2022). As PROX1 has previously been associated with tumor metabolism in colorectal cancer, we investigated further its role in RMS metabolism. Our findings demonstrate that PROX1 plays a crucial role in regulating RMS cell metabolism. Specifically, silencing of PROX1 resulted in decreased lipid and oxidative metabolism, which was accompanied by an increase in glycolysis and triglyceride accumulation. RNA sequencing and Gene Set Enrichment Analysis revealed downregulation of all genes involved in the cholesterol synthesis pathway in PROX1-silenced RMS cells. Our studies further reveal that inhibiting cholesterol synthesis, akin to PROX1 silencing, can effectively inhibit RMS cell growth. Our results provide novel insights into the role of PROX1 in RMS metabolism and highlight the potential of PROX1-regulated metabolic pathways as promising targets for the development of novel RMS therapies.
Citation Format: Nebeyu Y. Gizaw, Tom Böhling, Mika Sampo, Kari Alitalo, Riikka M. Kivela. Prox1 transcription factor and its downstream signaling - A new therapeutic target for rhabdomyosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1095.