bluuebunny/crossref_metadata_2025_split huggingface dataset:
TMIC-82. CHARACTERIZATION OF GENETIC MARKERS AND BIOLOGICAL PROCESSES UNDERLYING THE TRANSITION OF GLIOBLASTOMA CELLS FROM A DIFFERENTIATED TO A STEM-CELL-LIKE STATE
Authors: Mekonnen Mahlet , Chandla Anubhav , Suresh Meera , Aguirre Brian , Gur Shir , Wadehra Madhuri , Yang Isaac 
Published: November 2024

Abstract

BACKGROUND
The main drivers of Glioblastoma (GBM) tumor growth are elevated angiogenesis and heightened characteristics of stemness. These driving factors make GBM an extremely invasive and aggressive tumor. While the GBM tumor microenvironment can be classified into several molecular subtypes, one common characteristic is the atypical induction of various signal transduction pathways including the receptor tyrosine kinases (RTKs), pro-angiogenic, and stem-cell-determining transcription factors, which all play important roles in GBM tumor formation, growth, and progression.

OBJECTIVE
To investigate the regulations of RTKs, pro-angiogenic, and stem-cell–determining transcription factors in two different tumor environments - monolayer cultures that induce a more differentiated state and neurosphere cultures that select for stem-like cells.

METHODS
Neurosphere- and monolayer-forming cell samples were cultured from four primary GBM cell lines including HK-336, HK-374, U87, and GS-154. RNA sequencing was performed at the Technology Center for Genomics and Bioinformatics at the University of California, Los Angeles. The transcriptomic data findings were validated by qPCR and western blot assays.

RESULTS
Our transcriptomic data revealed the significant upregulation of EGFR, PDGFR-α, VEGFA, and SOX2 in the neurosphere-forming HK-336, HK-374, U87, and GS-154 primary GBM cells. Consistent with the transcriptomic data, western blot, and qPCR assays demonstrated significantly higher expressions of these genes in the neurosphere-forming compared to the monolayer-forming GBM cells. Neurosphere-forming GBM cells possess stem-cell-like characteristics with the ability to self-renew and differentiate via the induction of various genes and disease progression pathways.

CONCLUSIONS
Neurosphere-forming GBM cells demonstrate upregulation of SOX2, EGFR, PDGFR-α, and VEGFA in RNA sequencing, western blot, and qPCR assays. Multipotent drug therapies designed to target multiple gene regulation pathways involving RTKs, pro-angiogenic, and stem-cell-determining transcription factors may be necessary to effectively treat GBM. Understanding the underlying mechanisms driving these aberrant cellular pathways could provide valuable insights for developing targeted therapies against this aggressive brain cancer.
TMIC-83. ABERRANT EGFR ACTIVATION SUPPORTS ENHANCED TUMOR-MYELOID CROSSTALK AND IMPAIRS EFFECTOR T CELL INFILTRATION AND FUNCTION IN GLIOBLASTOMA
Authors: Pioso Marissa , Li Marissa , Sanchez Julio , Tamayo Andrea , Grausam Katie , Breunig Joshua , Nathanson David , Prins Robert 
Published: November 2024

Abstract
Glioblastoma (GBM) is known to display a highly suppressive tumor immune microenvironment (TIME) dominated by myeloid cells with low T cell infiltration. Aberrant epidermal growth factor receptor (EGFR) activation is observed in ~50% of GBM patients via amplification and the constitutively active EGFRvIII variant, however the impact of EGFR activation on the brain TIME and T cell-mediated anti-tumor immunity remains poorly understood. Single cell transcriptomic and receptor-ligand interaction analyses of paired newly diagnosed GBM tumor and intratumoral CD45+ immune cells revealed increased crosstalk between EGFR activated tumors and EGFR ligand-expressing tumor-associated myeloid cells. Therefore, a novel orthotopic murine EGFRvIII-expressing glioma model wherein the mEGFRvIII gene is under a tetracycline-off system (MADR-mEGFRvIII) was leveraged to identify how EGFR signaling impacts overall TIME composition and the phenotype of intratumoral and systemic T cells in vivo. Temporal flow cytometric immunophenotyping following tumor or mock (saline) implantation identified no significant shift in T cell infiltration within the brain or cervical lymph nodes (cLNs). In contrast, one week of doxycycline-mediated genetic EGFR ablation conferred a significant survival benefit and was associated with enhanced intratumoral T cell infiltration as well as diminished tumor-associated F4/80+ myeloid cells compared to vehicle treated animals. Further characterization revealed genetic EGFR ablation enhanced recruitment of CXCR3+, TNFα+, and TIGIT+ CD4 T cells to the tumor, while the prevalence of these populations contracted in CD4 and CD8 T cells within the draining cLNs. In vitro, pharmacologic EGFR inhibition enhanced antigen-specific Pmel-1 T cell killing of gp100-expressing MADR-mEGFRvIII tumor cells and was associated with increased IFNγ secretion by ELISA. Collectively, our work demonstrates that aberrant EGFR signaling promotes an immunosuppressive brain TIME with reduced T cell infiltration potentially via tumor-myeloid signaling. Targeting this oncogenic axis may therefore reprogram the TIME and directly enable enhanced trafficking of effector T cells to the tumor.
Disparities in end-of-life care and place of death in people with malignant brain tumors—A Swedish registry study
Authors: Ozanne Anneli , Öhlén Joakim , Nyblom Stina , Jakola Asgeir Store , Smits Anja , Larsdotter Cecilia 
Published: November 2024

Abstract

Background
Malignant brain tumors often lead to death. While improving future treatments is essential, end-of-life care must also be addressed. To ensure equitable palliative care, understanding the place of death is crucial, as disparities may lead to inequity of care. This study aims to identify the place of death in adults with malignant brain tumors in Sweden, and the potential associations with official palliative care status by the ICD-10 code Z51.5, sociodemographic factors, health service characteristics, and healthcare service utilization.

Methods
A population-level registry study examined the place of death among adults who died of malignant brain tumors in Sweden from 2013 to 2019. Descriptive statistics, univariable, and multivariable binary logistic regression analyses were performed.

Results
We identified 3,888 adults who died from malignant brain tumors. Of these, 64.4% did not receive an official palliative care status. Specialized palliative care was not utilized in 57.2% at the place of death and in 80% of nursing home deaths. In the last month of life, 53.5% of hospital deaths involved 1 transfer, while 41.8% had 2 or more transfers. The odds ratio (OR) of dying in hospital versus at home was higher, with 2 or more transfers (OR 0.63 [0.40, 0.99]). The OR of dying in a hospital versus at home showed significant regional differences.

Conclusions
Despite the severity of their diagnosis, only a minority of patients utilized specialized palliative services at death, and this varied by the place of death. Significant regional disparities were found between hospital and home deaths, indicating unequal end-of-life palliative care in this patient group.
Effects of Vitamin C Supplements on Clinical Outcomes and Hospitalization Duration for Patients with Coronavirus Disease 2019 (COVID-19): A Systematic Review and Meta-Analysis
Authors: Qin Maorong , Xu Kun , Chen Zhuo , Wen Xiaojie , Tang Yifu , Gao Yangyu , Zhang Hao , Ma Xingming 
Published: November 2024

Abstract

Context
Vitamin C has been used as an essential antioxidant to reduce the inflammatory response associated with pneumonia and acute respiratory distress syndrome in patients with the 2019 coronavirus disease (COVID-19), but its effect on clinical outcomes remains controversial and inconclusive.

Objective
The purpose of this study was to conduct a meta-analysis and systematic review to assess the effects of vitamin C supplementation on the severity of COVID-19 in hospitalized patients.

Data Sources
Web of Science, Embase, Cochrane Library, PubMed, CNKI, CSTJ, Wan fang, and CBM databases were searched for publications between January 2020 and December 2023 that met the inclusion criteria.

Data Extraction
The meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. A randomized controlled trial, cohort studies, and retrospective studies in which vitamin C supplementation was supplemented as monotherapy or in combination, compared with placebo, no treatment, or other standard treatment without vitamin C were included.

Data Analysis
After screening, 22 studies, with a total of 6831 patients, were selected for assessment. Odds ratios (ORs) with 95% CIs were calculated using fixed- and random-effects models. The meta-analysis showed significant effects of vitamin C on alleviating clinical outcomes in patients with COVID-19 (OR = 0.76, 95% CI = 0.65–0.89, P = .0007) but no shortening of the length of hospitalization (OR = 1.16, 95% CI = −0.13–2.44, P = .08) compared with the control group. Notably, vitamin C supplements significantly reduced the mortality risk (OR = 0.64, 95% CI = 0.51–0.80, P = .0001) and the incidence of severity (OR = 0.59, 95% CI = 0.43–0.80, P = .0006) in COVID-19 patients.

Conclusion
The findings suggest that vitamin C supplements may have a beneficial effect on clinical outcomes, as well as reducing severity and mortality in COVID-19 patients, but more clinical randomized controlled trials are needed to evaluate the role of vitamin C in treating COVID-19.

Systematic Review Registration
PROSPERO registration no. CRD42023491517.
Potato Intake and the Risk of Overweight/Obesity, Hypertension, Diabetes, and Cardiovascular Disease: A Systematic Review and Meta-analysis of Observational Studies
Authors: Su Yuhao , Liu Xiaoning , Jiang Bin , He Haitian , Li Fengjuan , Li Xinying , Wang Yanqi , Chen Xiaojuan , Wang Xiaojie , Luo Jun , Chen Lifang , Wu Jun , Hu Fulan , Zhang Ming , Hu Dongsheng , Ma Jianping , Qin Pei 
Published: November 2024

Abstract

Context
Results from observational studies and meta-analyses examining the relationship between total, fried, and nonfried potato intake and cardiometabolic disease remain conflicted.

Objective
The aim was to synthesize existing evidence on the relationships between total potato intake and specific types of potato intake with the risk of overweight/obesity, hypertension, diabetes, gestational diabetes mellitus (GDM), cardiovascular disease (CVD), coronary heart disease (CHD), and stroke.

Data Sources
Systematic searches were conducted in PubMed, Embase, and Web of Science until July 13, 2023.

Data Extraction
Data extracted from studies included first author, publication year, location, data source, follow-up duration (cohort studies only), demographics, sample size, cases, outcomes, exposure and outcome types, measurements, adjustments, study design, potato intake categories, and adjusted risk estimates (odds ratio, relative risk [RR], hazard ratio) with 95% CIs.

Data Analysis
Random-effects models were applied to estimate the summary RRs and 95% CIs.

Results
Fifty-one articles (103 studies) were identified in the current meta-analysis. Comparing the highest with the lowest categories of total potato intake, total potato intake was not associated with hypertension (summary RR = 1.07; 95% CI: 0.95, 1.21), diabetes (1.08; 95% CI: 0.96, 1.22), GDM (1.16; 95% CI: 0.86, 1.57), CHD (1.00; 95% CI: 0.99, 1.02), CVD (0.97; 95% CI: 0.91, 1.03), or stroke (0.97; 95% CI: 0.88, 1.06); fried potato intake was not associated with overweight/obesity (1.24; 95% CI: 0.90, 1.70) or GDM (1.03; 95% CI: 0.97, 1.09) but was significantly associated with increased diabetes risk (1.16; 95% CI: 1.04, 1.30); nonfried potato intake was significantly associated with increased diabetes risk (1.05; 95% CI: 1.01, 1.10) but not hypertension (1.06; 95% CI: 0.97, 1.15).

Conclusion
Total potato intake was not associated with an increased risk of hypertension, diabetes, GDM, or cardiometabolic disease, but both fried and nonfried potato intake may increase the risk of diabetes but not other cardiometabolic diseases. Future cohort studies are needed to explore the association between different types of potato intake and cardiometabolic disease. In addition, the limited number of studies on total potato intake and overweight/obesity/heart failure, fried potato intake and CHD/stroke/heart failure, and nonfried potato intake and overweight/obesity/GDM/CHD/CVD/heart failure prevented us from conducting an analysis.

Systematic Review Registration
PROSPERO registration no. RD42023454244.
Search for exoplanetary ring systems with TESS
Authors: Umetani Tsubasa , Aizawa Masataka , Ezoe Yuichiro , Ishisaki Yoshitaka 
Published: November 2024

Abstract
Photometric surveys for exoplanetary ring systems have not yet confirmed any object with Saturn-sized rings. We systematically analyse 308 TESS planet candidates, mainly comprising giant short-period planets orbiting nearby bright stars. These targets are selected based on the optimistic detectability of rings, assuming a favourable ring orientation. We develop a pipeline with a two-step noise reduction and compare the fitting results of both ringless and ringed transit models to the resulting phase-folded light curves. Although we identify six systems where ringed models are statistically favoured, visual inspection of the signals suggests that none of them is conclusively attributed to the presence of rings. Assuming the ring orientation favourable for detection, we determine the $3\sigma$ upper limits on ring sizes for 125 objects. Using these ring size limits, we derive upper limits on the ring occurrence rate, such as rings with an outer radius larger than 1.8 times the planetary radii occurring at rates lower than 2%. However, these limits can be relaxed if tidal alignment between the spin and orbital axes holds. We explore an alternative detection method using transit depth variations by ring precession and estimate that 10 and 13 systems are likely detectable in TESS and Kepler data, respectively.
The histone deacetylase RhHDA15 represses petal senescence by epigenetically regulating reactive oxygen species homeostasis in rose
Authors: Qin Meizhu , Wu Zhicheng , Zhang Chengkun , Jiang Yunhe , Jiang Cai-Zhong , Sun Xiaoming , Gao Junping 
Published: November 2024

Abstract
Epigenetic modifications play vital roles in many biological processes. Flower senescence involves epigenetic factors that influence the chromatin state and gene expression. However, the molecular mechanism underlying the role of histone deacetylation in regulating flower senescence has not been elucidated. Here, we demonstrate that histone deacetylation is involved in flower senescence by fine-tuning reactive oxygen species (ROS) homeostasis in rose (Rosa hybrida). Our data reveal that the histone lysine deacetyltransferase RhHDA15 inhibits ROS accumulation and petal senescence by downregulating the expression of NADPH OXIDASE/RESPIRATORY BURST OXIDASE HOMOLOG (RhRboh) genes. Furthermore, the transcription factor RELATED TO ABI3/VP1 2 (RhRAV2) recruits RhHDA15 and the co-repressor TOPLESS (RhTPL) to suppress flower senescence by reducing H3 lysine 9 acetylation (H3K9ac) at the RhRbohA1/2 promoter and thus directly inhibiting precocious RhRbohA1/2 expression. Our work sheds light on an epigenetic mechanism in which histone deacetylation plays a crucial role in controlling petal senescence by precisely fine-tuning ROS homeostasis, providing insights into the regulatory network of organ senescence.
Antibiotic contaminants and their impact in Gingee River, Puducherry: insights from SPE-UPLC–MS/MS and zebrafish study
Authors: Gokul Patharaj , Sobanaa Murugesan , Hari Krishna Kumar S , Prathiviraj Ragothaman , Pamanji Rajesh , Suseela Medapati Nikitha Lakshmi , Vallamkonda Bhaskar , Setia Aseem , Selvin Joseph , Muthu Madaswamy S 
Published: November 2024

Abstract
The accumulation of antibiotic residues in ecosystems is intricately tied to the proliferation of bacterial resistance to antibiotics, with far-reaching consequences for the health and welfare of both humans and animal well-being. The analytical approach integrates solid phase extraction (SPE) with ultra performance liquid chromatography-mass spectrometry (UPLC–MS/MS) for quantification of multiclass antibiotic residues. Upon applying the aforementioned method to analyse water samples collected from the Gingee River, revealed the existence of five distinct antibiotics. This is the first study reporting antibiotic concentration in the Gingee River, Puducherry. The concentrations of nalidixic acid, sulfamethoxazole, and tetracycline were determined to be 8.5, 6.9, and 4.8 μg/L, respectively. Metronidazole and trimethoprim were detected at concentrations below the quantifiable limit. The microbial study of water samples also indicated that Shigella sp. and Acinetobacter sp. were the most predominant bacterial species present. Our preliminary observation underscores the importance of comprehending the intricate relationship between the presence of antibiotics in water and the concurrent proliferation of antibiotic-resistant bacteria within bacterial populations in the Gingee River. Further, we evaluated the developmental toxicity of environmentally relevant concentrations of antibiotics in zebrafish. The zebrafish model confirms that these antibiotics are sublethally hazardous to human health at environmentally relevant concentrations. This integrated approach allows unique views on the environmental impact of antibiotic residues, their role in the evolution of antibiotic resistance, and their impact on human health.
Analog Serious Games for Medical Education: A Scoping Review
Authors: Edwards Sarah L. , Zarandi Aryana , Cosimini Michael , Chan Teresa M. , Abudukebier Monica , Stiver Mikaela L. 
Published: November 2024

Abstract

Purpose
Serious games are increasingly used in medical education to actively engage learners. Analog serious games are a nondigital subset of serious games with specific purposes that go beyond entertainment. This scoping review describes the literature pertaining to analog serious games and provides recommendations regarding gaps and emerging directions for future research.

Method
The authors conducted a scoping review following the Arksey and O’Malley framework, searching 3 databases (MEDLINE, Embase, and CINAHL) for studies of analog serious games designed for physician-track learners published from January 2013 through December 2023. Two authors independently screened the titles and abstracts, whereas 1 of 5 authors screened each full text and extracted data from eligible records. The authors iteratively analyzed the data within numerous categories and coded the findings to examine how the field has evolved during the past decade.

Results
The searches retrieved 3,955 records with 865 duplicates. The authors reviewed 3,090 title and abstract records and 202 full-text records. Eighty-eight records met the inclusion criteria, including research reports, conference abstracts, descriptive reports, and short innovation reports. The peak years for publications were 2019 and 2023 (15 publications each). Fewer abstracts and articles were published during the beginning of the COVID-19 pandemic (i.e., 2020–2022). The most common scholarship type was description studies (63 [72%]), whereas the dominant game formats were board games (51 [58%]) and card games (33 [38%]). Most studies tested analog serious games with medical students (60 [68%]) and/or residents and fellows (39 [44%]), with numerous studies including mixed study populations.

Conclusions
This scoping review demonstrates moderate growth within the field of analog serious games, along with numerous opportunities for future research. Although analog game–based learning cannot entirely replace traditional pedagogical approaches, analog serious games have potential to meaningfully complement education for physician-track learners in all medical training stages.
The climate crisis – actions to prioritize for anaesthesiologists
Authors: Lawin-O’Brien Roberta , Schwartz Elliot S. , Montgomery Hugh , Nurok Michael , Coburn Mark 
Published: November 2024

Purpose of review
Climate change is the biggest threat to human health and survival in the twenty-first century. Emissions associated with healthcare contribute to climate change and there are many personal and professional actions that can reduce carbon emissions. This review highlights why action is necessary and what anaesthetists and healthcare workers can do.

Recent findings
Encouraging continuing research regarding sustainable anaesthesia and expanding education at all levels to include climate action is key. Professionally, actions include limiting use of single-use equipment, reducing reliance on volatile gas inhalational anaesthesia, and adopting low fresh gas flow techniques. Personal actions such as climate-conscious travelling, spending, and eating are important, especially when shared to create climate positive movements.

Summary
This article shows that, while patient safety and quality of care must remain healthcare's top priority, considering the climate implications of care is part of that duty. Many actions that reduce the carbon impact of care simultaneously improve the quality of care and reduce financial cost. More research into sustainable healthcare is needed. Departments and hospitals and must create environments in which climate conversations are welcomed and can result in positive advancements.
Patient-reported and Clinical Outcomes following Gender-affirming Chest Surgery: A Comparison of Binary and Nonbinary Transmasculine Individuals
Authors: Roblee Cole V. , Arteaga Rebecca , Taritsa Iulianna , Ascha Mona , Weissman Joshua P. , Hackenberger Paige , Perez Megan , Ellis Marco , Jordan Sumanas W. 
Published: November 2024

Background:
Nonbinary individuals assigned female at birth are increasingly presenting for gender-affirming chest surgery (GCS). However, little is known about psychosocial outcomes in this group. We compare patient-reported and clinical outcomes after GCS between nonbinary and binary transmasculine individuals who underwent GCS.

Methods:
We performed an institutional retrospective chart review. Demographic information, medical comorbidities, history of gender-affirming medical care, operative details, and complications were collected and compared between nonbinary and binary patients. Two validated patient-reported outcomes measures, the Gender Congruence and Life Satisfaction (GCLS) scale and the chest dysphoria measure were administered postoperatively.

Results:
A total of 281 patients were included, of which 40.6% (114) identified as nonbinary and 59.4% (167) identified as binary transgender men. Fewer nonbinary patients used testosterone (P < 0.001). Nonbinary patients underwent a wider variety of masculinizing chest operations than binary patients, with fewer nonbinary patients electing for free nipple-areolar complex grafts (P < 0.001) and more nonbinary patients undergoing breast reduction (P = 0.001). A total of 137 (48.7%) patients responded to postoperative surveys. Nonbinary and binary respondents had comparable scores on the overall GCLS (P = 0.86), GCLS chest subscale (P = 0.38), and chest dysphoria measure (P = 0.40). The absence of nipple-areolar complex grafts was associated with higher GCLS chest scores (P = 0.004).

Conclusions:
Nonbinary individuals have similarly positive outcomes following GCS compared with binary individuals. Surgeons should be aware of greater medical and surgical heterogeneity in this population and seek to understand individual patients’ goals and priorities.