bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract B048: Galectin-3 regulation of immunosuppression in Ewing sarcoma
Authors: Maharjan Yunash , Tufino Adriana C. , Dey Sreya , Mukherjee Elina , Bailey Kelly M. 
Published: September 2024

Abstract
Objective: Ewing sarcoma is a fusion oncoprotein-driven cancer most commonly diagnosed in adolescents. Utilizing single-cell RNAseq of human Ewing tumors, we have previously demonstrated that Galectin-3, an immunosuppressive lectin family member protein, is expressed in both Ewing tumor cells and in CD8 T cells in the Ewing tumor microenvironment, a finding not noted in CD8 T cells infiltrating osteosarcomas. Galectin-3 serves to modulate tumor immunobiology through multiple mechanisms, including interactions with the immune checkpoint protein LAG3. In addition to Galectin-3, Galectin-3BP (binding protein) is also expressed in Ewing sarcoma and can bind to and modulate Galectin-3 function. Here, we aim to determine the role of Galectin-3 and Galectin-3BP on Ewing tumor immunosuppression. Methods: CHLA10 and TC32 human Ewing sarcoma tumor cells -/+ LGALS3 (gene encoding galectin-3) expression were generated using CRISPR/Cas 9 technology. T cells primed again human Ewing tumor cells were generated. The galectin-3 inhibitor TD-139 was also utilized. In vitro IncuCyte live cell monitoring assays, ELISA, and co-culture apoptosis assays were conducted. In vivo analyses of tumor growth, metastasis, and immune cell infiltration were conducted on Ewing tumors developed in immunocompetent, humanized mice and immunodeficient NSG mice. Peripheral blood and spleen controls were also analyzed. Results: CRISPR/Cas 9 knock-out of LGALS3 in both CHAL10 and TC32 cell lines was successful. GSEA of RNAseq data demonstrate distinct developmental signatures and flow cytometry analyses demonstrate altered immune cell signatures in LGALS3 KO Ewing tumors versus controls developed in humanized mice. ELISA demonstrates Galectin-3 is secreted by some Ewing tumors, the functional implications of which are under ongoing investigation. Expression of Galectin-3 and Galectin-3BP alone versus co-expression impacts the net effect of on Ewing tumor behavior. Conclusion: This work contributes to the understanding of galectin-3 on inflammatory responses and tumor progression in Ewing sarcoma. Understanding the complex relationship of Galectin-3 and Galectin-3BP on immunobiology provides valuable clues to best disrupt Galectin-3 mediated immunosuppression and promote enhanced tumor control.
Citation Format: Yunash Maharjan, Adriana C. Tufino, Sreya Dey, Elina Mukherjee, Kelly M. Bailey. Galectin-3 regulation of immunosuppression in Ewing sarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B048.
Abstract B080: Survivorship care models for childhood cancer survivors in low- and middle-income countries: A scoping review
Authors: Lecce Celine , Denburg Avram E. , Gupta Sumit , Martiniuk Alexandra , Qi Ariel 
Published: September 2024

Abstract
Childhood cancer survivors require specific care that includes monitoring for late effects of cancer therapy. Current knowledge on how to deliver survivorship care is based on experience in high-income countries, which may not be applicable to other settings. We thus conducted a scoping review to characterize and describe the models of survivorship care available to childhood cancer survivors in low- and middle-income countries (LMICs). Fifty-one studies were selected from a comprehensive literature search of 8 electronic and 2 grey-literature databases followed by title, abstract, and full-text screening. Elements of survivorship care were categorized within the domains of the Quality of Cancer Survivorship Care Framework using representative Children’s Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers guidelines for childhood cancer survivors. The Quality of Cancer Survivorship Care Framework is comprised of 5 domains related to survivorship care services, and 4 domains related to health care delivery. From the 51 studies chosen for data extraction, 61 LMICs were identified. Of these 61 LMICs, only 11 countries reported having active survivorship care services. The most reported services in the included papers from LMICs are related to the surveillance and management of chronic medical conditions and psychosocial effects. Of the countries that that reported survivorship services, literature from India reported on the four fundamental health care delivery domains identified by the Quality Cancer Survivorship Care Framework, which include clinical structure, communication and decision-making, care coordination, and patient/caregiver experience. Additionally, 8 of the 11 countries publishing about their survivorship care documented access to specialty medical care and healthcare professionals for childhood cancer survivors, such as onco-endocrinologists and psychologists. There are patient, clinician, and health system-related barriers to developing and implementing survivorship care in LMICs. Efforts to optimize the delivery of survivorship care include increased patient and family education about treatment late effects, optimized healthcare provider staffing, staff education, and training, and implementation of standardized practice guidelines that are resource-stratified and therefore applicable in multiple settings.
Citation Format: Celine Lecce, Avram E. Denburg, Sumit Gupta, Alexandra Martiniuk, Ariel Qi. Survivorship care models for childhood cancer survivors in low- and middle-income countries: A scoping review [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B080.
Abstract B081: EWS::FLI1 alters DNA damage induced protein dynamics at the RNAPII CTD
Authors: Stoja Aiola , Xu Xiaoping , Libich David S , Bishop Alexander J. R. 
Published: September 2024

Abstract
Ewing sarcoma (EwS) is an aggressive pediatric bone cancer with limited treatment options, highlighting a drastic need for novel therapeutics. EwS is driven by translocation of the EWSR1 low complexity domain and most often the DNA binding domain of FLI1, making up the oncogenic fusion protein EWS::FLI1. Accumulating evidence suggests that EWS::FLI1 alters the biophysical properties of EWS and EWS::FLI1 phase separated condensates. We have previously shown that EWS::FLI1 prevents the release of the double strand break (DSB) repair protein BRCA1 from RNA Polymerase II (RNAPII) complexes, inhibiting BRCA1 mediated DSB repair. However, how EWS::FLI1 alters protein dynamics at the RNAPII complexes is not understood. In this work we show that EWS::FLI1 co-localization to RNAPII C-Terminal Domain (CTD) protein hubs causes enhanced phase separation, imitating a hardening of RNAPII CTD condensates. Additionally, we find that treatment with DNA damaging agents decreases BRCA1 occupancy at RNAPII CTD protein hubs. Expression of EWS::FLI1 in this in cellulo system suggests inhibition of BRCA1 release from RNAPII phase separated entities upon DNA damage. Overall, this data indicates that EWS::FLI1 mediated changes in phase state alters heterotypic protein-protein interactions at the RNAPII complexes. Furthermore, we find that RNAPII CTD phase separated entities are refractory to THZ1 drug treatment. This underscores the physiological significance condensate biology plays in drug efficacy and drug resistance. In conclusion, our results prompt further investigation into EWS::FLI1 affects on protein-protein interactions at RNAPII condensates. Our findings are novel as we look at heterotypic phase condensate biology in cellulo, whereas most phase studies are conducted in vitro and focus on homotypic interactions. Moreover, though much work was conducted on BRCA1 and RNAPII interaction and damage-induced release in the 1990s and early 2000s, little is understood about the relationship of BRCA1 and RNAPII and certainly not in the context of EWS::FLI1. Importantly, this work provides a basis for the physiological role of condensate biology in EWS::FLI1 mediated BRCA1 and RNAPII protein-protein dynamics.
Citation Format: Aiola Stoja, Xiaoping Xu, David S Libich, Alexander J. R. Bishop. EWS::FLI1 alters DNA damage induced protein dynamics at the RNAPII CTD [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B081.
Abstract IA021: Neogenes induced by oncogenic chimeric transcription factors as potential targets for therapy
Authors: Petit Floriane , Lalanne Ana , Collin Céline , Waterfall Joshua , Lantz Olivier , Delattre Olivier 
Published: September 2024

Abstract
We recently showed that oncogenic chiemeric transcription factors (OCTF) of various pediatric cancers induce the expression of highly tumor-specific long intergenic non coding RNAs which are not expressed in normal tissues and which we called neogenes. Since recent reports indicate that such LincRNA may not be as non-coding as initially thought we sought for potential peptides encoded by these neogenes. Using the EWSR1::FLI1 chimera of Ewing sarcoma as a paradigm of such chimeras and through Riboseq profiling and whole cell proteomics we indeed show that some of these neogenes encode peptides. Immunopeptidomic experiments were performed on a series of Ewing sarcoma cell lines and PDX and further showed that peptides encoded by Ewing-specific neogenes are associated with MHC-Class I molecules at the surface of Ewing cells. Ewing peptide-specific CD8 T-cells were isolated from healthy donors. We show that these cytotoxic T-cells can be activated by Ewing cells to secrete cytokins, They can also kill Ewing cells. This killing is specific for the MHC-Class I types, specific for Ewing sarcoma cells as compared to other tumor types and is strictly deendent upon the expression of EWSR1::FLI1 that regulates the neogenes and of the expression of the neogene encoding the peptide. These data support the idea that OCTF-specific neogenes may constitute an interesting resource for various immunotherapy approaches including vaccination, BiTE or TCR-T-cell therapy.
Citation Format: Floriane Petit, Ana Lalanne, Céline Collin, Joshua Waterfall, Olivier Lantz, Olivier Delattre. Neogenes induced by oncogenic chimeric transcription factors as potential targets for therapy [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr IA021.
Experimental TET2 Clonal Hematopoiesis Predisposes to Renal Hypertension Through an Inflammasome-Mediated Mechanism
Authors: Polizio Ariel H. , Marino Lucila , Min Kyung-Duk , Yura Yoshimitsu , Rolauer Luca , Cochran Jesse D. , Evans Megan A. , Park Eunbee , Doviak Heather , Miura-Yura Emiri , Good Miranda E. , Wolpe Abigail G. , Grandoch Maria , Isakson Brant E. , Walsh Kenneth 
Published: September 2024

BACKGROUND:
Hypertension incidence increases with age and represents one of the most prevalent risk factors for cardiovascular disease. Clonal events in the hematopoietic system resulting from somatic mutations in driver genes are prevalent in elderly individuals who lack overt hematologic disorders. This condition is referred to as age-related clonal hematopoiesis (CH), and it is a newly recognized risk factor for cardiovascular disease. It is not known whether CH and hypertension in the elderly are causally related and, if so, what are the mechanistic features.

METHODS:
A murine model of adoptive bone marrow transplantation was employed to examine the interplay between Tet2 (ten-eleven translocation methylcytosine dioxygenase 2) clonal hematopoiesis and hypertension.

RESULTS:

In this model, a subpressor dose of Ang II (angiotensin II) resulted in elevated systolic and diastolic blood pressure as early as 1 day after challenge. These conditions led to the expansion of Tet2-deficient proinflammatory monocytes and bone marrow progenitor populations. Tet2 deficiency promoted renal CCL5 (C-C motif ligand 5) chemokine expression and macrophage infiltration into the kidney. Consistent with macrophage involvement, Tet2 deficiency in myeloid cells promoted hypertension when mice were treated with a subpressor dose of Ang II. The hematopoietic Tet2
−/−
condition led to sodium retention, renal inflammasome activation, and elevated levels of IL (interleukin)-1β and IL-18. Analysis of the sodium transporters indicated NCC (sodium-chloride symporter) and NKCC2 (Na
+
-K
+
-Cl
−
cotransporter 2) activation at residues Thr53 and Ser105, respectively. Administration of the NLRP3 (NLR family pyrin domain containing 3) inflammasome inhibitor MCC950 reversed the hypertensive state, sodium retention, and renal transporter activation.

CONCLUSIONS:
Tet2-mediated CH sensitizes mice to a hypertensive stimulus. Mechanistically, the expansion of hematopoietic Tet2-deficient cells promotes hypertension due to elevated renal immune cell infiltration and activation of the NLRP3 inflammasome, with consequences on sodium retention. These data indicate that carriers of TET2 CH could be at elevated risk for the development of hypertension and that immune modulators could be useful in treating hypertension in this patient population.
CADA-PRO: A Patient Questionnaire Measuring Key Cognitive, Motor, Emotional, and Behavioral Outcomes in CADASIL
Authors: Di Folco Cécile , Jabouley Aude , Reyes Sonia , Machado Carla , Guey Stéphanie , Hervé Dominique , Fernandes Fanny , Agossa Joseph , Chabriat Hugues , Tezenas du Montcel Sophie 
Published: September 2024

BACKGROUND:
Cerebral small vessel disease (cSVD) of ischemic type, either sporadic or genetic, as cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), can impact the quality of daily life on various cognitive, motor, emotional, or behavioral aspects. No instrument has been developed to measure these outcomes from the patient’s perspective. We thus aimed to develop and validate a patient-reported questionnaire.

METHODS:
In a development study, 79 items were generated by consensus between patients, family representatives, and cSVD experts. A first sample of patients allowed assessing the feasibility (missing data, floor and ceiling effect, and acceptability), internal consistency, and dimensionality of a first set of items. Thereafter, in a validation study, we tested a reduced version of the item set in a larger sample to assess the feasibility, internal consistency, dimensionality, test-retest reliability, concurrent validity, and sensitivity to change.

RESULTS:
The scale was developed in 44 patients with cSVD and validated in a second sample of 89 individuals (including 43 patients with CADASIL and 46 with another cSVD). The final CADASIL Patient-Reported Outcome scale comprised 18 items covering 4 categories of consequences (depression/anxiety, attention/executive functions, motor, and daily activities) of the disease. The proportion of missing data was low, and no item displayed a major floor or ceiling effect. Both the internal consistency and test-retest reliability were good (Cronbach alpha=0.95, intraclass correlation coefficient=0.88). In patients with CADASIL, CADASIL Patient-Reported Outcome scores correlated with the modified Rankin Scale, Starkstein Apathy Scale, Hospital Anxiety and Depression scale, Working Memory Index, and trail making test times. In patients with other cSVDs, CADASIL Patient-Reported Outcome correlated only with Hospital Anxiety and Depression scale and Starkstein Apathy Scale.

CONCLUSIONS:
The CADASIL Patient-Reported Outcome may be an innovative instrument for measuring patient-reported outcomes in future cSVD trials. Full validation was obtained for its use in patients with CADASIL, but further improvement is needed for its application in other cSVDs.
Polemics on Perfection: Maimonides’ Last Law on Slaves Resolves the Debate
Authors: Navon Mois 
Published: September 2024

Abstract
“What is the summum bonum?” This question is, without exaggeration, the ultimate existential question. Of no less import is its corollary: how is one to achieve this summum bonum? Maimonides’ Guide for the Perplexed endeavors to provide the answers. That said, the precise intent of Maimonides answers has generated no less perplexity than the original questions. Indeed, modern Jewish philosophers have spared no ink in trying to ascertain Maimonides’ intentions on human perfection. In this essay, I seek not to add yet another perspective on Maimonides’ intentions but to provide compelling support for existing positions; support found – worlds apart from the ivory towers where philosophers spill their ink – in the private quarters of a Canaanite slave. It is my thesis that Maimonides, in his last Law on Slaves, provides us with the answers to the ultimate existential questions and, accordingly, with a resolution to the perennial polemics on perfection.
Linking Boundary Organizations to Coproduce Actionable Knowledge: A Case Study of Ice Forecasting for Great Lakes Navigation
Authors: Gill Devin , Jagannathan Kripa , Fujisaki-Manome Ayumi , Field Victoria , Channell Kimberly , Lemos Maria Carmen 
Published: September 2024

Abstract
Navigating the Great Lakes during icy conditions poses significant safety challenges for the shipping sector. Available ice information is uncertain and fragmented, and navigators must seek out multiple sources for information at the spatial and temporal scales they require, if the information is available at all. Navigators have expressed that they require more highly localized and easily usable information for current and predicted ice conditions to support decision-making. In this study, we seek to meet this information need by applying a boundary organization chain (BOC) approach to facilitate the coproduction of an actionable short-term Great Lakes ice forecast. We focus on two main aspects of this research: 1) producing an actionable decision-support product that meets the needs of Great Lakes ice navigators and 2) contributing to the knowledge coproduction scholarship on BOCs by providing a detailed account of our methods to create a BOC and coproduce an actionable ice forecast. Our results support incorporating existing communities of practice (COPs) into BOCs to enhance the coproduction of actionable knowledge, specifically through increasing their complementarity and embeddedness. COPs are informal networks of users that meet voluntarily to share knowledge and develop professional skills, which we found naturally builds the coproduction capacities of participants (e.g., embeddedness and complementarity). We also find that COP members are well positioned to disseminate coproduced knowledge across wider user groups.

Significance Statement
In this study, we identified critical gaps in available ice information to support Great Lakes winter navigation, including predictions of current ice concentration and thickness at localized spatial scales and predicted ice movement. We coproduced an ice forecast with a format that is accessible and usable for navigators, while increasing crew and vessel safety by enabling more informed decisions regarding where and when to travel. We also contributed to theoretical understanding of how boundary organization chains work in context to coproduce actionable knowledge. This is a burgeoning area of research with a small number of empirical studies. By expanding both its thematic breadth (e.g., ice forecasting) and methodological approach (an in-depth account of our engagement efforts), we believe we critically contribute to the existing literature.
Rituximab in IgG4 Related Disease: A Retrospective Study from a Single Tertiary Care Centre
Authors: Somashekar Meghana , Duggal Lalit , Jain Neeraj 
Published: September 2024

Background: IgG4-related disease (IgG4-RD) is a multi-organ, fibro-inflammatory disorder characterised by tumefactive lesions. Corticosteroids are the first line of treatment. Rituximab (RTX) has been reported to be effective in IgG4-RD. It is reserved as a second-line agent and is a useful treatment option for those with intolerance to corticosteroids or have steroid and immunomodulator refractory disease. Objectives: To assess the response to treatment with RTX in patients with IgG4-related disease at the end of 6 months. Methods: A total of 27 patients diagnosed with IgG4-RD and treated with at least 1g of RTX were included. Patient demographics, clinical data and investigations were noted. Response to RTX was noted at the end of 6 months in terms of clinical improvement, decrease in or normalisation of serum IgG4 levels, withdrawal of steroids or disease-modifying antirheumatic drugs (DMARDs) and the calculation of the IgG4RD responder index (RI). Results: Out of the 27 patients treated with RTX, one patient expired and two were lost to follow-up. Of the remaining 24 patients, nine are off steroids; four patients are off treatment. Among the nine who are off steroids, eight patients had orbital and periorbital involvement. Fourteen patients had elevated IgG4 levels. Post RTX, normalisation of IgG4 levels was achieved in six patients. The average RI before and after RTX was 4.79 (2–10) and 1.33 (0–4), respectively. Conclusions: Patients with IgG4-RD who were intolerant or refractory to steroids and other DMARDs showed significant improvement after RTX infusion, especially in orbital and periorbital involvement. It suggests that RTX may be beneficial in the management of IgG4-RD.
The effect of a self-management programme on blood pressure levels among people with hypertension: a randomised controlled trial
Authors: Polsook Rapin , Aungsuroch Yupin 
Published: September 2024

Background: Hypertension (HT) progression and complications depend on blood pressure levels. Managing blood pressure can reduce complications, increase well-being and improve quality of life. Purpose: The study examined how an app-based self-management programme affected HT patients’ blood pressure. Methods: The Police General Hospital in Thailand employed a randomised controlled trial design between June 2022 and June 2023. Forty-eight people were randomly split into two groups using permuted blocks: the control group ( n = 24) and the experimental group ( n = 24). The experimental group monitored their blood pressure for 4 weeks using a combination of apps and the phone, whereas the control group received standard care. The information was gathered by measuring blood pressure. Descriptive statistics and t-tests for independence were employed to analyse the data. Results: The independent t-test results revealed a statistically significant reduction in the systolic blood pressure levels of the experimental group after the intervention ( t = 2.945, df = 46, p = 0.005). However, no significant decrease was observed in the diastolic blood pressure levels of the experimental group after the intervention ( t = 0.877, df = 46, p = 0.385). Conclusion: This study provides evidence for the effectiveness of a self-management programme utilising a mobile application in reducing blood pressure levels.