bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prehospital endotracheal intubation for traumatic out-of-hospital cardiac arrest and improved neurological outcomes
Authors: Yamamoto Ryo , Suzuki Masaru , Takemura Ryo , Sasaki Junichi 
Published: November 2024

BackgroundPatients with traumatic out-of-hospital cardiac arrest (t-OHCA) require on-scene airway management to maintain tissue oxygenation. However, the benefits of prehospital endotracheal intubation remain unclear, particularly regarding neurological outcomes. Therefore, this study aimed to evaluate the association between prehospital intubation and favourable neurological outcomes in patients with t-OHCA.MethodsThis retrospective cohort study used a Japanese nationwide trauma registry from 2019 to 2021. It included adult patients diagnosed with traumatic cardiac arrest on emergency medical service arrival. Glasgow Outcome Scale (GOS) scores, survival at discharge and presence of signs of life on hospital arrival were compared between patients with prehospital intubation and those with supraglottic airway or manual airway management. Inverse probability weighting with propensity scores was used to adjust for patient, injury, treatment and institutional characteristics, and the effects of intubation on outcomes averaged over baseline covariates were shown as marginal ORs.ResultsA total of 1524 patients were included in this study, with 370 undergoing intubation before hospital arrival. Prehospital intubation was associated with favourable neurological outcomes at discharge (GOS≥4 in 5/362 (1.4%) vs 10/1129 (0.9%); marginal OR 1.99; 95% CI 1.12 to 3.53; p=0.021) and higher survival to discharge (25/370 (6.8%) vs 63/1154 (5.5%); marginal OR 1.43; 95% CI 1.08 to 1.90; p=0.012). However, no association with signs of life on hospital arrival was observed (65/341 (19.1%) vs 147/1026 (14.3%); marginal OR 1.09; 95% CI 0.89 to 1.34). Favourable outcomes were observed only in patients who underwent intubation with a severe chest injury (Abbreviated Injury Score ≥3) and with transportation time to hospital >15 min (OR 14.44 and 2.00; 95% CI 1.89 to 110.02 and 1.09 to 3.65, respectively).ConclusionsPrehospital intubation was associated with favourable neurological outcomes among adult patients with t-OHCA who had severe chest injury or transportation time >15 min.
Association of innate versus specific immunity with heart failure incidence: a prospective study
Authors: Wang Junxue , Zhang Ziteng , Sun Ying , Yu Bowei , Wang Yuying , Lu Yingli , Yu Jiao , Wang Ningjian , Xia Fangzhen 
Published: November 2024

BackgroundImmune disorders are key heart failure (HF) triggers, but little is known about whether the status of immunity affects the incidence of HF. To explore this, we used blood cell counts and derived ratios to investigate the association between immunity status markers and HF incidence.MethodsThe number and proportion of peripheral blood leucocytes in a physiological state are related to the body’s immune status. Neutrophils, monocytes, SII (systemic immune-inflammatory index), NLR (neutrophil-to-lymphocyte ratio), and PLR (platelet-to-lymphocyte ratio) serve as innate immunity status markers, while lymphocytes and LMR (lymphocyte-to-monocyte ratio) serve as specific immunity status markers. 330 362 UK Biobank (UKB) participants were finally examined. Cox proportional hazard models were used to explore the relationship between immunity status markers and HF incidence. Flexible parametric survival models were used to capture time-varying relationships between blood cell ratios and HRs for HF. Subgroup analyses were conducted by age, sex, and body mass index. Finally, sensitivity analyses were performed to validate the results.ResultsDuring a median follow-up of 14.1 years, 9611 (2.9%) participants developed HF. Neutrophils, monocytes, SII, and NLR were positively associated with HF incidence, with fully adjusted per SD increment HR (95% CI) of 1.20 (1.17 to 1.22), 1.09 (1.07 to 1.12), 1.12 (1.10 to 1.14), and 1.16 (1.14 to 1.18), respectively. Platelets, lymphocytes, and LMR were inversely correlated with HF incidence, with fully adjusted per SD increment HR (95% CI) of 0.97 (0.95 to 1.00), 0.97 (0.95 to 0.99), and 0.90 (0.88 to 0.92), respectively.ConclusionsThe innate immunity status markers were positively associated with HF incidence, while specific immunity status markers exhibited an inverse association, offering novel insights for HF prediction and intervention.
Understanding and Addressing LGBTQ+ Cancer Health Disparities
Authors: Hastert Theresa A. 
Published: November 2024

Abstract
Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) cancer survivors disproportionately experience physical and mental health comorbidities compared with their heterosexual and cisgender counterparts. A recent study by Waters and colleagues evaluates associations between LGBTQ+ identity and physical and mental health comorbidities and activity limitations using Behavioral Risk Factor Surveillance System data. Consistent with previous work, their findings suggest that LGBTQ+ survivors have higher odds of several chronic conditions, including asthma, depressive disorders, heart attacks, kidney disease, stroke, and diabetes, as well as reporting disabilities related to vision and cognition and difficulty with activities of daily living, including walking, dressing, and running errands. Waters and colleagues expand on previous work by providing estimates separately for sexual orientation and gender identity. Their results for lesbian, gay, and bisexual survivors were similar to those for LGBTQ+ survivors overall. In novel findings, they report much stronger associations between identifying as transgender or gender nonconforming and nearly all comorbidities compared with cisgender survivors, including those who identify as lesbian, gay, or bisexual. This commentary advocates for the importance of future work considering the drivers of disparities in cancer outcomes based on sexual orientation and gender identity.
See related article by Waters et al., p. 1405
Metabolic Syndrome and Risks of Breast Cancer Outcomes for Luminal, Triple-Negative, and HER2-Overexpressing Subtypes
Authors: Loroña Nicole C. , Othus Megan , Malone Kathleen E. , Linden Hannah M. , Tang Mei-Tzu C. , Li Christopher I. 
Published: November 2024

Abstract

Background:
We evaluated the association between metabolic syndrome (MetS; obesity plus two metabolic risk factors) and breast cancer outcomes according to molecular subtype.

Methods:
This population-based prospective cohort consisted of 3,267 women ages 20 to 69 years diagnosed with a first primary invasive breast cancer from 2004 to 2015 in the Seattle–Puget Sound region. Breast cancer was categorized into three subtypes based on estrogen receptor (ER), progesterone receptor, and HER2 expression: luminal (ER+), triple-negative (ER−/progesterone receptor negative/HER2−), and HER2-overexpressing (H2E; ER−/HER2+) subtypes. We used time-varying Cox models to assess the association of prevalent and incident MetS with risks of recurrence, breast cancer–specific mortality (BCSM), and all-cause mortality (ACM).

Results:
MetS was associated with a greater risk of recurrence [HR, 3.24; 95% confidence interval (CI), 1.13–9.33] and BCSM (HR, 5.34; 95% CI, 2.32–12.31) only for the H2E subtype and greater risks of ACM for luminal (HR, 1.92; 95% CI, 1.37–2.68), H2E (HR, 5.09; 95% CI, 2.51–10.32), and all cases combined (HR, 1.90; 95% CI, 1.42–2.53). We also observed heterogeneity in recurrence and mortality outcomes across specific components of MetS and molecular subtypes.

Conclusions:
MetS is associated with ACM among women with breast cancer and with BCSM among women with the H2E subtype.

Impact:
These results highlight the importance of managing comorbidities to decrease the risk for adverse outcomes among breast cancer survivors.
Oncogenic KRAS Mutations Confer a Unique Mechanotransduction Response to Peristalsis in Colorectal Cancer Cells
Authors: Clevenger Abigail J. , Collier Claudia A. , Gorley John Paul M. , Colijn Sarah , McFarlin Maygan K. , Solberg Spencer C. , Kopetz Scott , Stratman Amber N. , Raghavan Shreya A. 
Published: November 2024

Abstract
Colorectal cancer tumors start as polyps on the inner lining of the colorectum, in which they are exposed to the mechanics of peristalsis. Our previous work leveraged a custom-built peristalsis bioreactor to demonstrate that colonic peristalsis led to cancer stem cell enrichment in colorectal cancer cells. However, this malignant mechanotransductive response was confined to select colorectal cancer lines that harbored an oncogenic mutation in the Kirsten rat sarcoma virus (KRAS) gene. In this study, we explored the involvement of activating KRAS mutations on peristalsis-associated mechanotransduction in colorectal cancer. Peristalsis enriched cancer stem cell marker Leucine-rich repeat–containing G protein–coupled receptor 5 (LGR5) in KRAS mutant lines in a Wnt ligand–independent manner. Conversely, LGR5 enrichment in wild-type KRAS lines exposed to peristalsis were minimal. LGR5 enrichment downstream of peristalsis translated to increased tumorigenicity in vivo. Differences in mechanotransduction were apparent via unbiased gene set enrichment analysis, in which many unique pathways were enriched in wild-type versus mutant lines. Peristalsis also triggered β-catenin nuclear localization independent of Wnt ligands, particularly in KRAS mutant lines. The involvement of KRAS was validated via gain and loss of function strategies. Peristalsis-induced β-catenin activation and LGR5 enrichment depended on the activation of the MEK/ERK cascade. Taken together, our results demonstrated that oncogenic KRAS mutations conferred a unique peristalsis-associated mechanotransduction response to colorectal cancer cells, resulting in cancer stem cell enrichment and increased tumorigenicity. These mechanosensory connections can be leveraged in improving the sensitivity of emerging therapies that target oncogenic KRAS.
Implications: Oncogenic KRAS empowers colorectal cancer cells to harness the mechanics of colonic peristalsis for malignant gain independent of other cooperating signals.
Exploring the Interplay of Diet, Obesity, Immune Function, and Cancer
Authors: Fu Yumin , Guo Xinyu , Sun Linmao , Cui Tianming , Wang Jiabei , Liu Yao , Liu Lianxin 
Published: November 2024

Summary:
This commentary provides an in-depth exploration of the intricate relationships among diet, obesity, immune function, and cancer, highlighting the potential role of dietary interventions as complementary therapies in cancer treatment. Multiple analyses underscore the importance of personalized dietary strategies in cancer management and identify opportunities for further research in this evolving field.
Redefining the Gastric Microbes in Promoting Gastric Tumorigenesis: The Rise of the Non–H. pylori Microbiome
Authors: Wong Chi Chun , Yu Jun 
Published: November 2024

Summary:
Gastric cancer remains one of the top cancers in China compared with Western countries, mainly attributed to the high rates of Helicobacter pylori infection. However, recent discoveries on the non–H. pylori gastric microbiome have led to a paradigm shift in our understanding of microbial risk factors driving gastric cancer, which will impact future screening and prevention strategies.
Drugging p53: Barriers, Criteria, and Prospects
Authors: Song Huaxin , Xiao Shujun , Wu Jiaqi , Lu Min 
Published: November 2024

Summary:
Pharmacologically targeting tumor suppressors necessitates an unprecedented strategy of restoring, rather than conventionally inhibiting, protein function, and p53, the most commonly mutated protein in cancer, has thus remained undruggable. In this study, we address long-standing misconceptions in the field and gaps in the scientific logic for a p53 function–restoration strategy, identify four barriers for drugging mutant p53, and accordingly propose effectiveness evaluation criteria, clinical-translating norms, and prospects for mutant p53 rescue compounds.
Immunogenicity and Efficacy of Personalized Adjuvant mRNA Cancer Vaccines
Authors: Berraondo Pedro , Cuesta Raquel , Sanmamed Miguel F. , Melero Ignacio 
Published: November 2024

Summary:
In this issue, Gainor and colleagues report on the immunogenicity of personalized neoantigen-encoding mRNA vaccines that elicit measurable polyfunctional CD8+ and CD4+ T-cell responses in patients whose tumors have been resected. Reactivity is substantiated to 20% to 30% of the predicted MHC-I and MHC-II epitopes in four patients with NSCLC postsurgically treated with the vaccine alone and in 12 patients with melanoma treated with their individualized vaccines plus pembrolizumab in the context of a phase 1 clinical trial (NCT03313778).
See related article by Gainor et al., p. 2209
Dynamic Evolution of Fibroblasts Revealed by Single-Cell RNA Sequencing of Human Pancreatic Cancer
Authors: Dimitrieva Slavica , Harrison Jon M. , Chang Jonathan , Piquet Michelle , Mino-Kenudson Mari , Gabriel Millicent , Sagar Vivek , Horn Heiko , Lage Kasper , Kim Julie , Li Gang , Weng Shaobu , Harris Cynthia , Kulkarni Anupriya S. , Ting David T. , Qadan Motaz , Fagenholz Peter J. , Ferrone Cristina R. , Grauel Angelo L. , Laszewski Tyler , Raza Alina , Riester Markus , Somerville Tim , Wagner Joel P. , Dranoff Glenn , Engelman Jeffrey A. , Kauffmann Audrey , Leary Rebecca , Warshaw Andrew L. , Lillemoe Keith D. , Fernández-del Castillo Carlos , Ruddy David A. , Liss Andrew S. , Cremasco Viviana 
Published: November 2024

Abstract
Cancer progression and response to therapy are inextricably reliant on the coevolution of a supportive tissue microenvironment. This is particularly evident in pancreatic ductal adenocarcinoma, a tumor type characterized by expansive and heterogeneous stroma. Herein, we employed single-cell RNA sequencing and spatial transcriptomics of normal, inflamed, and malignant pancreatic tissues to contextualize stromal dynamics associated with disease and treatment status, identifying temporal and spatial trajectories of fibroblast differentiation. Using analytical tools to infer cellular communication, together with a newly developed assay to annotate genomic alterations in cancer cells, we additionally explored the complex intercellular networks underlying tissue circuitry, highlighting a fibroblast-centric interactome that grows in strength and complexity in the context of malignant transformation. Our study yields new insights on the stromal remodeling events favoring the development of a tumor-supportive microenvironment and provides a powerful resource for the exploration of novel points of therapeutic intervention in pancreatic ductal adenocarcinoma.

Significance:
Pancreatic cancer remains a high unmet medical need. Understanding the interactions between stroma and cancer cells in this disease may unveil new opportunities for therapeutic intervention.
Spatial Context of Immune Checkpoints as Predictors of Overall Survival in Patients with Resectable Colorectal Cancer Independent of Standard Tumor–Node–Metastasis Stages
Authors: Kong Hao , Yang Qingxin , Wu Chunwei , Wu Xiangji , Yan Xinrui , Huang Li-Bin , Chen Lu , Zhou Zong-Guang , Wang Ping , Jiang Hong 
Published: November 2024

Abstract
Although immune checkpoint blockade therapy has shown promising results in a small subset of patients with colorectal cancer with high microsatellite instability, the majority of patients with colorectal cancer do not respond to immune checkpoint blockade therapy. The main obstacle to the success of immunotherapy in cancer treatment is the exhaustion of tumor-infiltrating lymphocytes (TIL). Elucidating the spatial organization of immune checkpoints within the tumor microenvironment (TME) could pave the way for the development of novel prognostic tools and therapeutic strategies to enhance antitumor immune responses. To clarify the spatial and functional diversity of TILs in the colorectal TME, we performed multiplexed IHC to examine the exhaustion of TILs in the TME, the expression of PD-1 and T-cell immunoglobulin and mucin domain–containing protein 3 (TIM-3), which are major biomarkers of T-cell exhaustion, and least absolute shrinkage and selection operator method–Cox analyses of the correlation between colorectal cancer prognosis and TME features. For proof of concept, the antitumor efficacy of TIM-3 and PD-1 dual blockade in colorectal cancer was further evaluated in a CT26 s.c. tumor model of human colorectal cancer. We found that the spatial context of PD-1 and TIM-3 successfully predicted the overall survival of patients with colorectal cancer independent of tumor–node–metastasis stage. Dual targeting of PD-1 and TIM-3 in mouse tumor models inhibited tumor progression and reduced T-cell exhaustion, indicating a potential strategy for improving the clinical treatment of colorectal cancer.

Significance:
The identification of specific spatial patterns of immune checkpoint expression that correlate with overall survival in patients with colon cancer suggests a potential prognostic tool for risk stratification and treatment selection. These findings pave the way for the development of novel therapeutic strategies to enhance antitumor immune responses.
Single-Cell Analysis of Bone Marrow CD8+ T Cells in Myeloid Neoplasms Reveals Pathways Associated with Disease Progression and Response to Treatment with Azacitidine
Authors: Tasis Athanasios , Papaioannou Nikos E. , Grigoriou Maria , Paschalidis Nikolaos , Loukogiannaki Catherine , Filia Anastasia , Katsiki Kyriaki , Lamprianidou Eleftheria , Papadopoulos Vasileios , Rimpa Christina Maria , Chatzigeorgiou Antonios , Kourtzelis Ioannis , Gerasimou Petroula , Kyprianou Ioannis , Costeas Paul , Liakopoulos Panagiotis , Liapis Konstantinos , Kolovos Petros , Chavakis Triantafyllos , Alissafi Themis , Kotsianidis Ioannis , Mitroulis Ioannis 
Published: November 2024

Abstract
CD8+ T cells are crucial for antitumor immunity. However, their functionality is often altered in higher-risk myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). To understand their role in disease progression, we conducted a comprehensive immunophenotypic analysis of 104 pretreatment bone marrow (BM) samples using mass and flow cytometry. Our findings revealed an increased frequency of CD57+CXCR3+ subset of CD8+ T cells in patients who did not respond to azacitidine (AZA) therapy. Furthermore, an increased baseline frequency (&gt;29%) of the CD57+CXCR3+CD8+ T-cell subset was correlated with poor overall survival. We performed single-cell RNA sequencing to assess the transcriptional profile of BM CD8+ T cells from treatment-naïve patients. The response to AZA was linked to an enrichment of IFN-mediated pathways, whereas nonresponders exhibited a heightened TGF-β signaling signature. These findings suggest that combining AZA with TGF-β signaling inhibitors targeting CD8+ T cells could be a promising therapeutic strategy for patients with higher-risk MDS and AML.

Significance:
Immunophenotypic analysis identified a BM CD57+CXCR3+ subset of CD8+ T cells associated with response to AZA in patients with MDS and AML. Single-cell RNA sequencing analysis revealed that IFN signaling is linked to the response to treatment, whereas TGF-β signaling is associated with treatment failure, providing insights into new therapeutic approaches.
Similarity Distractors Increase the Burden of Chinese Character Selection and Updating in Working Memory
Authors: Li Hongli , Zhao Xin 
Published: November 2024

Abstract
Attentional mechanisms are the primary processes for performing working memory (WM) tasks and can prevent distractors from interfering with the content representations stored in WM. However, our understanding of the mechanisms by which attention affects WM remains limited. As such, we analyzed ERPs of the character n-back task to investigate Chinese character selection, updating, and maintenance in WM. In Experiment 1, we collected electroencephalography data from 27 participants aged 18–25 years to explore the influence of false-character interference and symbol interference on a neural activity in the character n-back task. The results suggest that RT was longer in the false-character interference condition. The N2pc and P300 amplitudes were smaller; however, the slow wave amplitude did not differ significantly. In Experiment 2, we used a single-symbol interference and a multiple-symbol interference to establish whether the number of interferences affected the neural activity in the character n-back task. Thirty participants (aged 19–25 years) took part in the experiment. The findings imply that a longer RT and a larger N2pc amplitude occurred in the multiple-symbol interference condition, but not in the P300 and slow wave conditions. Our findings indicate that distractors that are similar to characters may produce greater interference in character recognition and affect the subsequent updating, whereas the number of distractors may only interfere with early character selection, but not with updating and maintenance phases.
Differential predation pressure on island pit vipers shape their niches and defensive behavior
Authors: Banci Karina R.S. , Siqueira Lucas H.C. , Torello-Viera Natália F. , Marques Otavio A.V. 
Published: November 2024

Abstract
Animals are naturally exposed to several predators, and, given that a single encounter with a predator may cause prey’s death, natural selection will strongly act upon its defensiveness. Therefore, defensive behavior is strongly shaped by predation pressure. Predation rate in islands tends to be relaxed due to lower abundance of predators. The aim of this study was to test the hypothesis that predation rates upon the two island pit vipers Bothrops alcatraz and B. insularis would be lower than correlated mainland B. jararaca. Additionally, we evaluated the defensive behavior of these island snakes in the field to compare with the mainland B. jararaca. Predation pressure upon the insular species was assessed utilizing plasticine replicas, and we evaluated their defensive behavior to approach. These data were compared to those previously reported for B. jararaca. We found a lower predation pressure on B. insularis (from the smaller area) than on B. alcatraz and B. jararaca from the urban mainland forest fragment (areas with intermediate size), and all of them showed lower predation pressure than B. jararaca from the continuous mainland forested area. In the field, island snakes show narrower defensive repertoire than B. jararaca, since most B. insularis fled, and B. alcatraz either fled or remained immobile on approach. Apparently, the predation pressure to which these island pit vipers are exposed shapes their defensive behavior, as well as the niches exploited by them.
Religion in Right-Wing Ecological Discourse. A Critical Content Analysis of a Far Right Periodical
Authors: Gärtner Claudia 
Published: November 2024

Abstract
While the climate crisis was denied for many years in right-wing movements, shifts in discourse have become apparent recently. Right-wing populists and extremists are developing their own narratives, such as population growth in the Global South. Religious references also become relevant in these right-wing narratives but empirical studies on religion in right-wing environmental discourse have been rare for the German-speaking region so far. The paper examines religious motifs and arguments in the new-right periodical Die Kehre representing the line of thought of the new-right discourse on ecology. 15 issues of the journal are analysed with the help of the structuring qualitative content analysis. The analysis aims to develop a first descriptive assessment of the significance of religion in the right-wing ecological discourse. Therefore, this paper is also critical to the thesis that religion contributes substantially to global climate justice.