bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Cross-Sectional Study of Unlocking Childhood Cancer Services during COVID-19 Pandemic: A Pediatric Oncology Tertiary Care Center's Experience from a Developing Country
Authors: Sneha Latha M. , Scott Julius Xavier , Kancharla Adarsh , Jayraman Dhaarani , Kothandan Balaji Thiruvengadam , Koneru Shree Hasitha 
Published: August 2023

Abstract
Introduction The global coronavirus disease 2019 (COVID-19) pandemic has made the provision of cancer care services a challenging task all over the world, even in developed countries. Multiple studies have already reported increased rate of diagnostic delays, interruptions in radiotherapy and chemotherapy administration, and shortage of health care personnel to deliver these services.
Objective The aim of this study was to analyze the impact of strategies used to deliver uninterrupted childhood cancer services at our center during the COVID-19 pandemic.
Materials and Methods This is a cross-sectional study of the children less than 18 years of age admitted at our center between March 2020 and September 2021 to assess the effect of strategies adopted to provide uninterrupted cancer services during the COVID-19 pandemic. All the children with cancer who were managed during the study period were included in the study. The children who had treatment interruptions/lost to follow-up prior to onset of COVID-19 were excluded from the study. The primary outcome was to measure the effect of COVID-19 on delivery of cancer care services. The secondary outcome was to assess whether the strategies followed at our center helped to reduce diagnostic delays or loss to follow-up during the COVID-19 pandemic.
Results Out of total 1,490 admissions, 199 children were managed during the study period. Among the 199 children managed, 124 of them were newly diagnosed, 75 had ongoing treatment, 16 children relapsed, 13 children received palliative care, and 6 families were lost to follow-up. Out of 1,471 tests done, only 16 children and 6 caregivers tested COVID-19 positive during routine screening. Thirty-five underwent surgery and 23 received radiotherapy during this period. Among 199 children, 143 (71.8%) received financial support for hospital expenses, 23 (11.5%) received travel support, 20 (10%) were provided free accommodation, and 15 (7.5%) received home delivery of oral chemotherapy and pain medications. A total of $86,989.05 was supported for diagnostic investigations, COVID-19 testing, chemotherapy, and supportive care; $1,144.90 for travel support; and $17,010.94 was waived off by hospital administration to support the poor families.
Conclusion The shared care model, support from nongovernmental organizations and hospital administration, and utilization of local resources productively and effectively helped to avoid diagnostic delays and treatment interruptions, and provide uninterrupted pediatric cancer care services at our center.
Can you amuse the audience through an interpreter?
Authors: Bartłomiejczyk Magdalena 
Published: August 2023

Abstract
In this article, I investigate how interpreters handle humorous utterances during plenary debates of the European Parliament, focusing on the input by one Polish Member of the European Parliament (MEP), Janusz Korwin-Mikke. The source speeches (in Polish or English) are analysed bottom-up to identify the types of humour favoured by the speaker. The most frequent ones are irony, ad hominem arguments with an element of ridicule, absurdity, and shifts in register. Subsequently, a pragmatically oriented comparative analysis is conducted to assess whether and how individual instances of humour are transferred by interpreters. Additionally, possible side effects are considered, such as shifts accompanying transferred humour and message incoherence resulting from humour loss. Register humour is typically removed by interpreters. The successful handling of absurdity relies mainly on compression and often fails, while ad hominem and irony appear to be relatively less challenging to interpret. Interestingly, irony is occasionally added by interpreters, either to boost the speaker’s comical intent or to distance themselves from his views.
Effects of density on the strength of sexual selection in the laboratory and in nature
Authors: Cothran Rickey D , Schmidenberg David , Stiff Andy R , Wellborn Gary A , Relyea Rick A 
Published: August 2023

Abstract
There is a growing effort to understand how sexual selection varies over space and time under different ecological conditions and how this can maintain variation in sexual traits. An interesting ecological condition is population density, which can either increase or decrease sexual selection depending on the natural history of the species. We examined sexual and natural selection in an undescribed amphipod species (Hyalella sp.) using surveys of two natural populations that increase in density from spring to summer. We also conducted an experiment that directly manipulated density to assess the effects on sexual selection. In the field during spring (low density) and summer (high density), we documented sexual selection on male traits, including body size, gnathopods and antennae. We found that the magnitude and direction of this selection changed from spring to summer and that selection patterns differed between populations. In the experiment, we found no sexual selection occurred at low density, but found significant positive selection on all three male traits at medium and high densities. These results underline the importance of isolating individual ecological factors to determine their role in sexual selection while also documenting patterns in natural populations to understand how selection varies over space and time.
Thiazolidinediones: Recent Development in Analytical Methodologies
Authors: Patel Tarang , Patel Vatsal 
Published: August 2023

Abstract
The instrumental analytical methods that have been developed and utilized for the determination of thiazolidinedione in bulk medications, formulations and biological fluids have been reviewed after an in-depth analysis of the literature published in a variety of analytical and pharmaceutical chemistry-related journals. The approaches covered by this research, which covers the years 2001–2022, include complex methods for analysis, chromatographic techniques and spectrometric analytical procedures. The mobile phase, flow rate, sample matrix, wavelength and other factors identified in the literature were just a few of the parameters used to evaluate thiazolidinediones. The present review focuses on the published analytical techniques for thiazolidinedione analysis that have been previously identified in the literature. The specified outcomes followed extensive learning, and the most recent advances in analytical methods for the identification of pioglitazone, pioglitazone HCl, rosiglitazone, rosiglitazone maleate and lobeglitazone were reviewed. Additionally, this article briefly discusses features of analytical discovery on thiazolidinediones, which will enable readers to access all discoveries in one place with precise outcomes.
Analysis of the Epidemiological Features and Treatment Results of Burn Injuries in a Burn Center in Turkey
Authors: Erdogan Hünkar , Sencan Arzu 
Published: August 2023

Abstract
The aim of the study was to reveal the epidemiological characteristics and clinical course of burn patients who were hospitalized in our burn center between 2015 and 2020 and to compare the results between nationalities. The data were retrospectively evaluated in terms of age, gender, time of admission, the total body surface area burned, the degree of burn, the accident location, the presence of wound infection, surgical intervention, length of hospital stay, mortality, educational status of the parents, and nationality; 59.8% of 1496 cases were male, mean age was 40.38 months. The most common age range was 0-2 years. 78.4% were admitted within the first 24 hours; 50.5% of the admissions were from İzmir and its districts. Burn trauma most commonly occurred indoors in all age groups. The most common cause was scalding. Isolation of microorganism in wound cultures was most commonly detected in second degree burns. The most common infection agent was Pseudomonas aeruginosa. The surgical intervention rate was 19%. The mean length of hospitalization was 14.46 ± 12.17 days. Total burned surface, hospitalization time, the infection, and mortality rate were higher in patients who underwent surgical intervention. Parents were mostly primary school graduates. 11.6% of the patients were of foreign nationality. No significant difference was found in the analyzed parameters between nationalities. In conclusion; burn trauma is most commonly seen in the 0-2 age group, regardless of parental education levels. Therefore, it is of great importance to provide training on burns to families and those responsible for the care of children.
Surgical Casualty Care in Contested Distributed Maritime Operations: Lessons Learned From the Falklands War
Authors: Hughey Scott , Cole Jacob , Brust Adam , Checchi Kyle , Kotler Joshua , Lin Andrew 
Published: August 2023

ABSTRACT
The Falklands Campaign was fought a significant distance from the home base of the British Fleet. The planning and delivery of medical care during this campaign can provide significant lessons for strategic medical planning in other far spread geographic locations, including the Indo-Pacific region. Consideration of doctrine, including Role 1-4 facilities and the golden hour, may need to be reconsidered in light of changing scenarios. New concepts such as the “90-in-90” and “3-in-3” are also discussed as a framework for future planning in the U.S. Indo-Pacific Command area of responsibility.
BSBM-09 IN VIVO CRISPR ACTIVATION SCREEN IDENTIFIES ß-SITE AMYLOID PRECURSOR PROTEIN CLEAVING ENZYME 1 (BACE1) AS A DRIVER OF NON-SMALL CELL LUNG CANCER BRAIN METASTASIS
Authors: Chafe Shawn , Zhai Kui , Aghaei Nikoo , Miletic Petar , Brown Kevin , Mobilio Daniel , Venugopal Chitra , Kieliszek Agata , Hynds Robert , Lam Fred , Moffat Jason , Swanton Charles , Bao Shideng , Singh Sheila 
Published: August 2023

Abstract
Brain metastasis occurs in up to 40% of patients with non-small cell lung cancer (NSCLC). Considerable genomic heterogeneity exists between the primary lung tumour and respective brain metastasis; however, the identity of the genes capable of driving brain metastasis is incompletely understood. Here, we carried out an in vivo genome wide CRISPR activation (CRISPRa) screen to identify molecular drivers of brain metastasis from a NSCLC patient-derived xenograft model. We identified activation of the Alzheimer’s disease associated ß-site amyloid precursor protein cleaving enzyme 1 (BACE1) led to a significant increase in brain metastasis. BACE1 is highly expressed in NSCLC and patients with BACE1 expressed in their metastatic brain tumour survived for shorter periods. Genetic loss with CRISPR-Cas9 or pharmacological inhibition of BACE1 with MK-8931 decreased cell proliferation and sphere forming capacity in vitro. Furthermore, BACE1 knockout and MK-8931 treatment blocked brain metastasis in vivo. Mechanistically, we identified BACE1 activation lead to downstream signalling through MEK and ERK. Together our data highlights the power of in vivo CRISPR screening to identify novel molecular drivers and potential therapeutic targets of NSCLC brain metastasis.
BSBM-17 NOVEL VALIDATED PATIENT-DERIVED MODELS OF A RECTAL CANCER BRAIN METASTASIS
Authors: Barros Guinle Maria Isabel , Tran Caitlynn To-Dyuen , Nasajpour Emon , Xing Yao Lulu , Nakano Michitaka , Nair Indu , Sathe Anuja , Nirschl Jeffrey , Granucci Monica , Prolo Laura M , Ji Hanlee P , Vogel Hannes , Lim Michael , Hayden-Gephart Melanie , Kuo Calvin , Petritsch Claudia K 
Published: August 2023

Abstract
Colorectal adenocarcinomas (CRC) rarely metastasize to the brain, however, survival rates in patients with colorectal brain metastases (CBM) are short, with a median survival of only 4 months from diagnosis. Currently, no evidence-based treatment options against these rare brain metastases are available (PMC). Therefore, characterization of these tumors and development of targeted therapies are imperative.
Optimal models for neoplasms heighten the notoriously low success rate of bench-to-bedside translation. Historically, brain cancer metastases models are established cell lines grown on plastic and transplanted as xenografts (Valiente; PMC7572582). Genomic drift, lack of genetic accuracy and heterogeneity, caused by serial passaging on plastic and in high-serum media, are frequent limitations of these models. Growth in defined media without serum and as 3-dimensional (3-D) spheroids or organoids is thought to improve the fidelity of cancer cell lines (Lee; PMID:16697959; Lo; PMC820864). Despite significant efforts of large collaborative projects (https://hcmi-searchable-catalog.nci.nih.gov/), 3-D rectal brain cancer metastasis models have not been reported.
To address this unmet medical need, we developed 3-D (suspension, organoid) cultures of a rectal adenocarcinoma brain metastasis with moderate to focally poor differentiation. Next-generation sequencing, expression profiling, and immunohistochemistry were performed to validate our models. Our data confirmed that the PDO model contains tumor cells; pathogenic alterations and expression profiles in the models largely match that of the original tumor. Overall, we detected a significant phenotypic overlap with the original tumor sample. Spatial profiling and PDO-derived xenografts are in progress and will facilitate experimental therapeutics. Taken together, our models retained tumor heterogeneity and fidelity from the primary tumor, making this one of the first studies to establish 3-D patient-derived models for disease progression in rectal cancer brain metastases. Collectively, these models will be valuable translational tools for future exploration of targeted therapy, which remains absent in this disease process.
BSBM-19 CROSS-PRESENTATION BY TUMOR-ASSOCIATED MACROPHAGES MEDIATES THE TRANSITION FROM PROGENITOR TO TERMINAL T CELL EXHAUSTION IN PRIMARY AND METASTATIC BRAIN TUMORS
Authors: Polania Jessica Waibl , Hoyt-Miggelbrink Alexandra , Tomaszweski William , Wachsmuth Luke , Lorrey Selena , Fecci Peter 
Published: August 2023

Abstract
Glioblastoma (GBM) and brain metastases remain largely resistant to immunotherapeutic intervention. T cell exhaustion, a differentiation state characterized by loss of function and persistence, contributes to this resistance. Two exhaustion subsets, progenitor (Tex_prog) and terminal (Tex_term), have been identified, where only Tex_prog remain responsive to immunotherapy. To date, the dynamics and characteristics of these exhausted populations in GBM and brain metastases remain unclear. Herein, we identify a striking loss of Tex_prog in a murine model of GBM throughout tumor progression. We elucidate the requirements for Tex_prog to Tex_term transition through characterization of T cell exhaustion progression at the RNA (paired scRNA and TCR sequencing) and protein level (flow-cytometry). Tex_prog are enriched for pathways of migration, cell-cell adhesion, and differentiation, whereas Tex_term primarily upregulate cytotoxic pathways. TCRseq revealed that clonal expansion is concentrated to the Tex_term cluster, suggesting a link between Tex_prog transition and proliferation in response to antigen. Likewise, we defined the necessity of hematopoietic antigen presentation, but not tumor-derived antigen presentation for the Tex_prog to Tex_term transition. Of the antigen presenting cells in the TME, tumor-associated macrophages (TAM) had the greatest expression of tumor-antigen loaded MHC I, illustrating their capacity to cross-present. By depleting TAM, we observed disruption of the Tex_prog transition. Similar results were seen in subcutaneous and intracranial melanoma, highlighting the role of TAM in this process across tumor histology and location. Lastly, we identified additional inflammatory cell-cell interactions between T cells and TAM in mice and humans that may contribute to this phenomenon. Taken together, we define T cell exhaustion dynamics in models of primary and metastatic brain tumors, where tumor-antigen presentation by TAM is a critical mediator of the loss of Tex_prog. We extend these findings to human data to better define these complex interactions, which we aim to leverage to overcome immunotherapy resistance.
BSBM-20 INVESTIGATING THE ROLE OF OXIDATIVE PHOSPHORYLATION (OXPHOS) IN CD4+ T CELL ACTIVATION AND RESPONSE TO ANTI-PD1/ANTI-LAG3 IMMUNOTHERAPY IN MELANOMA BRAIN METASTASIS (MBM)
Authors: Guerrieri Renato , Cortez Jacob , Liu Alice , Jeong Kate-Yeonjae , Knighton Barbara , Ferguson Sherise , Davies Michael 
Published: August 2023

Abstract
Brain metastasis is a frequent and deadly complication of metastatic melanoma. While extracranial metastases (ECMs) are often treatable, MBMs remain a critical treatment (tx) challenge to overcome. We previously showed that MBMs are characterized by increased utilization of OXPHOS compared to ECMs, and OXPHOS inhibition increased expression of immune activation transcriptional signatures in MBMs. Thus, we tested the role of tumor OXPHOS on the immune microenvironment and checkpoint immunotherapy response in a syngeneic mouse model with concurrent intracranial (ICr) and subcutaneous (SQ) tumors. Selective OXPHOS inhibition was achieved via CRISPR-KO of Ndufs4 (mitochondrial complex I) in B16-F10 cells and confirmed via Seahorse Analyzer MitoStress Test. Multiplex cytokine analysis of culture supernatant revealed that NDUFS4 KO increased anti-tumor cytokines IFNγ (p=0.016) and IL-2 (p=0.023) and decreased pro-tumor chemokine CXCL2 (p&lt;0.001). Next, we implanted concurrent ICr and SQ B16-F10 tumors in C57BL/6J mice. Flow cytometry demonstrated decreased CD4+ and CD8+ T cell infiltration of ICr versus SQ tumors in both B16-F10 and NDUFS4 KO tumors (all p&lt;0.001). NDUFS4 KO increased total CD4+ T cells (p=0.041) and activated CD4+ T cells (p&lt;0.001) in ICr tumors. Finally, we tested the efficacy of tx with combination anti-PD1/anti-LAG3 (200μg/100μg intraperitoneal 3x/week) versus isotype controls (Ctrl) in these mice. Compared to Wildtype (WT) tumors with Ctrl tx, we observed improved overall survival (OS) in mice with NDUFS4 KO tumors + Ctrl (HR 0.117; p=0.015), WT tumors + anti-PD1/anti-LAG3 (HR 0.071; p=0.005), and NDUFS4 KO tumors + anti-PD1/anti-LAG3 (HR 0.049; p=0.002). For anti-PD1/anti-LAG3 tx, there was a trend for improved OS with NDUFS4 KO versus WT tumors (HR 0.317; p=0.130). Together, these data implicate tumor OXPHOS in CD4+ T cell immunosuppression and a potential target to enhance response to checkpoint immunotherapy in MBMs.
BSLD-06 UNVEILING THE RE-PROGRAMMING OF CHOROID PLEXUS AND LEPTOMENINGEAL METASTASIS
Authors: Nobre Ana Rita , Wang Helen , Estrera Rachel , Boire Adrienne 
Published: August 2023

Abstract
Leptomeningeal metastasis (LM) is an increasingly common, fatal complication of breast and lung cancer. Despite aggressive treatment, neurologic deficits accumulate rapidly, and patients generally succumb to LM within months. We must expand our limited mechanistic knowledge of this disease. Under homeostatic conditions, choroid plexus (ChP), highly vascularized structures within the brain ventricles, restrict the entry of macromolecules and cells into the leptomeninges; however, select cancer cells can cross this barrier and grow within the leptomeningeal space. We hypothesize that interactions between cancer and ChP niche cells alter both the niche and the cancer cells, ultimately supporting LM. During neurogenesis, the ChP display substantial extracellular matrix (ECM) remodeling, which is elegantly modulated by dynamic spatiotemporal regulation of MMPs, Wnt signaling, among other effector proteins. Similarly, 2-photon imaging of ChP collected from mice harboring LM revealed a profound ECM remodeling of the ChP when compared with naïve mice. This remodeling was accompanied by increased levels of MMP2 and MMP9 in the CSF. Furthermore, single-cell-RNA-sequencing of ChP reveals that Wnt is the top differentially expressed pathway in metastatic ChP in comparison with normal ChP, supporting a role for developmental signaling within the ChP in LM. Interestingly, SPARC, a major ECM modulator in tissue repair and an essential component of the stem cell niche chemoattractant factors secreted by the subventricular zone (SVZ), is enriched in metastatic mouse ChP suggesting that SVZ- and ChP-secreted signals are key in LM progression. The use of clinically-annotated human samples and mouse models of LM, and the integration of transcriptomics and proteomics enabled us to identify key signaling pathways, and capture the re-programming of ChP niche and cancer cells that unlock the leptomeningeal space to cancer cells. The timeframe for this evolution will be further revealed by analysis of mouse and human samples at different stages of cancer progression.
CLRM-03 THE TENTATIVE APPLICATION OF EN BLOC CONCEPT IN THE PEDIATRIC BRAIN TUMOR: EXPERIENCE FROM A LARGE PEDIATRIC CENTER IN CHINA
Authors: Ma Jie 
Published: August 2023

Abstract

BACKGROUND
The less allowable blood loss and tolerance of intraoperative blood loss of children lead to the high rate of massive blood transfusion. The surgical concepts of en bloc resection may contribute to the improvement of brain tumor resection.

OBJECTIVE
To investigate the effects of en bloc concept on short outcomes of pediatric brain tumors and factors associated with the application of en bloc concept.

METHODS
According to the surgical concept involved, the patients were divided into three subgroups-complete en bloc concept, partial en bloc concept and piecemeal concept. The matching-comparison(en bloc group consisting of the first two subgroups and piecemeal group) was conducted to investigate the effect of the en bloc concept on the short-term outcomes. Then the patient data after January 2018, when the en bloc concept was routinely integrated into brain tumor surgery in our medical center, were reviewed and analyzed to find out the predictors associated with the application of en bloc concept.

RESULTS
In the en bloc group, the perioperative outcomes, including hospital stay(p=0.001), PICU stay(p=0.003), total blood loss(p=0.015), transfusion rate(p=0.005) and complication rate(p=0.039), were all significantly improved. The multinomial logistic regression analysis showed that tumor volume, bottom vessel, and imaging features, like encasing nerve or pass-by vessel, finger-like attachment, ratio of “limited line” and ratio of “clear line” remained independent predictors for the application of en bloc concept in our medical center.

CONCLUSION
The application of en bloc concept based on the imaging features can improve the short-term outcomes.