bluuebunny/crossref_metadata_2025_split huggingface dataset:
ICOS-expressing CAR-T cells mediate durable eradication of triple-negative breast cancer and metastasis
Authors: Cao Lixue , Peng Haojie , Chen Yanzhen , Xia Baijin , Zeng Tao , Guo Jialing , Yu Fei , Ye Haiyan , Zhang Hui , Chen Xinxin 
Published: November 2024

BackgroundThe failure of conventional therapies and the propensity for recurrence and metastasis make triple-negative breast cancer (TNBC) a formidable challenge with grim prognoses and diminished survival rates. Immunotherapy, including immune checkpoint blockade and chimeric antigen receptor (CAR)-T cell therapy, presents innovative and potentially more effective strategies for addressing TNBC. Within this context, the inducible costimulator (ICOS), a member of the CTLA4/CD28 family, plays a crucial role in regulating immune responses and T-cell differentiation by binding to its ligand ICOSL. However, the impact of the ICOS/ICOSL axis on cancer varies.MethodsIn this study, immunohistochemistry was conducted to examine the expression level of ICOSL in TNBC tumor tissues. We developed ICOS-enhanced B7H3-CAR-T cells (ICOS-B7H3-CAR) using the third-generation CAR-T cell technology, which featured magnified ICOS expression and targeted the B7H3 antigen. Xenograft and metastasis models of TNBC were conducted to examine the cytotoxicity and durability of CAR-T cells in tumors. Overexpression and CRISPR/Cas9-mediated knockout (KO) techniques were employed to regulate the expression of ICOSL on TNBC cell lines.ResultsNotably, we observed elevated ICOSL expression in TNBC tumor tissues, which correlated with poor survival prognosis in patients with TNBC. Compared with conventional B7H3-CAR-T cells, ICOS-B7H3-CAR-T cells significantly inhibited the tumor growth of TNBC cells both in vitro and in vivo, accompanied by increased secretion of cytokines such as interferon gamma and tumor necrosis factor alpha. Furthermore, the in vivo experiments illustrated that ICOS-B7H3-CAR-T cells exhibited prolonged antitumor activity and could effectively eradicate metastases in a TNBC metastasis model, consequently extending survival. Importantly, manipulating the expression of ICOSL on TNBC cells through overexpression or KO significantly influenced the function of ICOS-B7H3-CAR-T cells. This suggests that the level of ICOSL expression on TNBC cells is critical for enhancing the potent antitumor effects of ICOS-B7H3-CAR-T cells.ConclusionOverall, our study highlights the potential clinical application of ICOS as a promising strategy for combating TNBC recurrence and metastasis.
Exploring small retailers’ perspectives on selling tobacco after the tripling of Tasmania’s tobacco licence fee
Authors: Smith Abby L , Mihrshahi Seema , Freeman Becky 
Published: November 2024

BackgroundLicensing of tobacco retailers, including high retail licence fees, is one tobacco control measure that may reduce tobacco retail availability. Between 2015 and 2018, the tobacco licence fee in Tasmania, Australia, tripled to $A1132/year. We sought to explore small retailer perspectives on selling tobacco following the tripling of the licence fee.MethodsIn-depth semistructured telephone interviews (n=21) were conducted with business owners and managers between March and July 2020. Participants were asked broad questions about their business, attitudes and intentions towards selling tobacco and the perceived importance of tobacco to their business.ResultsParticipants’ perspectives and decision-making about selling tobacco were influenced by an interplay of factors, including tobacco’s perceived core business value and its waning importance in small retail due to declining demand. Although participants frequently reported tobacco as unprofitable, with many describing it as their least profitable product, most continued selling it. The high tobacco licence fee created a tipping point that challenged the cost-benefit balance previously weighted towards selling tobacco. While the fee, alongside the increasing cost of tobacco itself, pushed some retailers towards a critical decision point to stop selling tobacco, others continued to sell tobacco but appear to be headed in the same direction.ConclusionA high annual tobacco licence fee serves as a potential mechanism for phasing out the sale of commercial tobacco in small retailers in a jurisdiction with other strong tobacco control measures.
Reproductive and Metabolic Health Following Exposure to Environmental Chemicals: Mechanistic Insights from Mammalian Models
Authors: Bellingham Michelle , Evans Neil P. , Lea Richard G. , Padmanabhan Vasantha , Sinclair Kevin D. 
Published: November 2024

The decline in human reproductive and metabolic health over the past 50 years is associated with exposure to complex mixtures of anthropogenic environmental chemicals (ECs). Real-life EC exposure has varied over time and differs across geographical locations. Health-related issues include declining sperm quality, advanced puberty onset, premature ovarian insufficiency, cancer, obesity, and metabolic syndrome. Prospective animal studies with individual and limited EC mixtures support these observations and provide a means to investigate underlying physiological and molecular mechanisms. The greatest impacts of EC exposure are through programming of the developing embryo and/or fetus, with additional placental effects reported in eutherian mammals. Single-chemical effects and mechanistic studies, including transgenerational epigenetic inheritance, have been undertaken in rodents. Important translational models of human exposure are provided by companion animals, due to a shared environment, and sheep exposed to anthropogenic chemical mixtures present in pastures treated with sewage sludge (biosolids). Future animal research should prioritize EC mixtures that extend beyond a single developmental stage and/or generation. This would provide a more representative platform to investigate genetic and underlying mechanisms that explain sexually dimorphic and individual effects that could facilitate mitigation strategies.
Effectiveness of Pharmacotherapy in Reducing the Inflammation Process of Spinal Cord Injuries: A Systematic Review of Animal Studies
Authors: Subagio Eko Agus , Wicaksono Pandu , Asadullah Asadullah , Faris Muhammad , Bajamal Abdul Hafid , Susilo Imam , Abdillah Diaz Syafrie 
Published: November 2024

Background: Currently, there is no gold standard technique in SCI therapy. Although there have been many systematic reviews on the pharmacological treatment of inflammation in SCI, there has been no published discussion regarding the effectiveness of anti‐inflammatory pharmacotherapy when viewed from a neuroinflammatory pathway. This research aimed to examine an effective and reliable medication for decreasing inflammation in SCI and, where possible, identify effective pharmacotherapeutic treatment protocols.Methods: We searched SCOPUS, PubMed, PlosOne, and Science Direct, for experimental trials published in English. The keywords included (Pharmacotherapy OR pharmacology OR treatment) AND (traumatic spinal cord injury OR spinal cord OR traumatic OR hemisection of spinal cord OR compression OR traumatic spinal cord injury OR aneurysm clip OR hemisection of spinal cord OR sharp pin injury) AND (Side Effect therapy). In addition, the Basso–Beattie–Bresnahan (BBB) score was used to assess post‐SCI clinical progress.Results: Twelve pilot studies met the inclusion criteria. The highest BBB score was 15, and the best animal performance was tested after the average therapy was on the second week or 14th day. Three pharmacotherapies have fast effectiveness regarding BBB scores: calcitriol, lithium, and valproic acid. As well as a combination of pharmacotherapy therapy with surgical therapy also get significant results.Conclusions: The preliminary findings showed that many inflammatory pathways cause inflammatory agents to have their pathways for inhibition pathways, so they have different ways.
Ferroptotic Neutrophils Induce Immunosuppression and Chemoresistance in Breast Cancer
Authors: Zeng Wenfeng , Zhang Ruihua , Huang Penghan , Chen Minxia , Chen Houying , Zeng Xin , Liu Jiang , Zhang Jiahui , Huang Di , Lao Liyan 
Published: November 2024

Abstract
Inducing ferroptosis in tumor cells is emerging as a strategy for treating malignancies that are refractory to traditional treatment modalities. However, the consequences of ferroptosis of immune cells in the tumor microenvironment need to be better understood in order to realize the potential of this approach. In this study, we discovered that neutrophils in chemoresistant breast cancer are highly sensitive to ferroptosis. Reduction of the acyltransferase MOAT1 in chemoresistance-associated neutrophils induced phospholipid reprogramming, switching the preference from monounsaturated fatty acids to polyunsaturated fatty acids, which increased their susceptibility to ferroptosis. Ferroptotic neutrophils secreted PGE2, IDO, and oxidized lipids that suppressed the proliferation and cytotoxicity of antitumor CD8+ T cells. Furthermore, neutrophil ferroptosis was closely related to a distinct subset of IL1β+CXCL3+CD4+ (Fer-CD4) T lymphocytes, which were enriched in chemoresistant tumors. Fer-CD4 T cells orchestrated neutrophil ferroptosis by modulating MOAT1 expression via IL1β/IL1R1/NF-κB signaling. Moreover, Fer-CD4 T cells secreted CXCL3, IL8, and S100A9 to replenish the neutrophil pool in the tumor microenvironment. Ferroptotic neutrophils in turn fostered Fer-CD4 T-cell differentiation. In spontaneous tumorigenesis mouse models, targeting IL1β+ CD4+ T cells or IL1R1+ neutrophils broke the cross-talk, restraining neutrophil ferroptosis, enhancing antitumor immunity, and overcoming chemoresistance. Overall, these findings uncover the role of neutrophil ferroptosis in shaping the immune landscape and propose appealing targets for restoring immunosurveillance and chemosensitivity in breast cancer.
Significance: In chemoresistant breast cancer, IL1β+CXCL3+CD4+ T cells mediate neutrophil ferroptosis that suppresses antitumor immunity, indicating that interfering with this intercellular cross-talk could be an attractive strategy to reverse chemoresistance.
Homoharringtonine Added to Venetoclax and Azacitidine Improves Outcome and Mitigates Genetic Impact in Relapsed/Refractory AML: A Multicenter Cohort Study
Authors: Yu Guopan , Zhang Yu , Yu Sijian , Yin Zhao , Weng Guangyang , Xu Na , Du Xin , Lin Dongjun , Xiao Jie , Sun Zhiqiang , Zhang Hongyu , Liang Xinquan , Guo Ziwen , Zhao Weihua , Dai Min , Fan Zhiping , Xuan Li , Liu Hui , Xu Dan , Ye Jieyu , Jiang Xuejie , Shi Pengcheng , Jin Hua , Liu Qifa 
Published: November 2024

Abstract

Purpose:
We investigated whether homoharringtonine (HHT) added to venetoclax plus azacitidine (VA) could improve outcomes and counteract the negative effects of genetic patterns in patients with relapsed/refractory acute myeloid leukemia (RR-AML).

Experimental Design:
A multicenter retrospective cohort study of the response and genetic patterns of response to the VA plus HHT (VAH) versus the VA regimens as salvage treatment in patients with RR-AML was performed. The endpoints were the rates of composite complete remission, measurable residual disease, event-free survival, overall survival, and relapse between VAH and VA groups.

Results:
A total of 321 patients (VAH, n = 172; VA, n = 149) were analyzed. Compared with VA, VAH significantly improved the rates of composite complete remission (44.3% vs. 66.3%; P &lt; 0.001), measurable residual disease negativity (34.8% vs. 59.3%; P = 0.002), prolonged overall survival (median: 15.1 months vs. not reached; P &lt; 0.001), and event-free survival (median: 3.8 vs. 13.0 months; P &lt; 0.001). VAH significantly mitigated the negative impact on VA efficacy of mutated FLT3-ITD/TKD, N/KRAS, and t(8;21)/AML1-ETO, as well as the relatively unfavorable effects of the TET2 and DNMT3A mutations. VAH significantly enhanced the response of patients with nonadverse European LeukemiaNet risk, with a trend toward improved response in those with adverse European LeukemiaNet risk, complex karyotype, and DNMT3A+FLT3+NPM1+. The incidence of grade 3 or higher adverse events was comparable between the two groups.

Conclusions:
Our findings suggest the addition of HHT to VA might enhance response and mitigate the negative impact of certain genetic patterns in RR-AML while being well tolerated.
The Capicua C1 Domain Is Required for Full Activity of the CIC::DUX4 Fusion Oncoprotein
Authors: Luck Cuyler , Jacobs Kyle A. , Okimoto Ross A. 
Published: November 2024

Abstract
Rearrangements between genes can yield neomorphic fusions that drive oncogenesis. Fusion oncogenes are made up of fractional segments of the partner genes that comprise them, with each partner potentially contributing some of its own function to the nascent fusion oncoprotein. Clinically, fusion oncoproteins driving one diagnostic entity are typically clustered into a single molecular subset and are often treated a similar fashion. However, knowledge of where specific fusion breakpoints occur in partner genes, and the resulting retention of functional domains in the fusion, is an important determinant of fusion oncoprotein activity and may differ between patients. This study investigates these phenomena through the example of capicua (CIC)::double homeobox 4 (DUX4), a fusion between transcriptional repressor CIC and DUX4 genes, which drives an aggressive subset of undifferentiated round cell sarcoma. Using a harmonized dataset of more than 100 patient fusion breakpoints from the literature, we show that most bona fide CIC::DUX4 fusions retain the C1 domain, which is known to contribute to DNA binding by wild-type CIC. Mechanistically, deletion or mutation of the C1 domain reduces, but does not eliminate, the activation of CIC target genes by CIC::DUX4. We also find that expression of C1-deleted CIC::DUX4 is capable of exerting intermediate transformation-related phenotypes compared with those imparted by full-length CIC::DUX4 but was not sufficient for tumorigenesis in a subcutaneous mouse model. In summary, our results suggest a supercharging role for the C1 domain in the activity of CIC::DUX4.

Significance:
We show in mammalian settings that the capicua C1 functional domain is a supercharger for CIC::DUX4, a poorly studied fusion oncoprotein which drives a rare sarcoma with dismal outcomes.
COMPARATIVE EFFICACY OF METHYLPREDNISOLONE AND TOCILIZUMAB IN PATIENTS WITH A SEVERE FORM OF COVID-19
Authors: Oliynyk O. V. 
Published: November 2024

Background. Recently, we have again noted an increase in the incidence of COVID-19. The treatment of patients with severe coronavirus infection poses a significant medical challenge.
Objectives. The purpose of this research was to compare the efficacy of standard therapy and pulses of methylprednisolone in combination with or without tocilizumab in patients with a severe form of COVID-19.
Patients and methods. In a retrospective study, the medical charts of 220 patients with a severe course of COVID-19 were reviewed. Patients were divided into four groups: those on daily methylprednisolone at a dose of 32 mg enterally; patients who received methylprednisolone pulses (500 mg daily intravenously for three consecutive days, with a subsequent change to the 32 mg of methylprednisolone daily); patients who received a single dose of 400 mg tocilizumab in combination with a 32 mg of methylprednisolone daily; patients who received a single dose of 400 mg tocilizumab in combination with methyl­prednisolone pulse therapy. At the end of therapy, 28-day mortality and the number of intubations in each group one week after the end of therapy were analyzed.
Results. Patients treated with a combination of tocilizumab and pulse methylprednisolone therapy had the lowest risk of death (p<0.001), OR=0.03 (95 % CI 0.01-0.16), compared to patients treated only with 32 mg of methylprednisolone.
Conclusions. Methylprednisolone pulses therapy is more effective than therapy with methylprednisolone at a daily dose of 32 mg. The combination of methylprednisolone and tocilizumab is more effective than the isolated administration of methylprednisolone. The combination of tocilizumab with methylprednisolone pulse therapy had the highest therapeutic effect.
Treatment of Spontaneous Subarachnoid Hemorrhage: A 20‐Year National Inpatient Sample Review
Authors: Feler Joshua , Wolman Dylan , Torabi Radmehr , Chen Jia‐Shu , Teshome Abigail , Sastry Rahul , Doberstein Curtis , Jayaraman Mahesh , Moldovan Krisztina , Mahta Ali 
Published: November 2024

Background
Aneurysmal subarachnoid hemorrhage (aSAH) is a major source of morbidity and mortality, and its management has undergone foundational changes over thepast 2 decades. We reviewed the National Inpatient Sample to outline the changes in severity of illness, surgical management, and patient outcomes over time.

Methods
A retrospective cohort of admissions for spontaneous SAH in the National Inpatient Sample from 2001 to 2020 was reviewed, including those who underwent microsurgical or endovascular surgery to secure a ruptured aneurysm. National incidence was calculated, and multivariable regression was used to identify changes in incidence and outcome through time, segmented by epoch.

Results
Review of the National Inpatient Sample identified 448 655 patients with SAH, of whom 181 590 underwent surgical aneurysm treatment. The incidence of spontaneous SAH fell −0.097 per 100 000 person‐years each year (95%CI, −0.144 to −0.049). Among patients surgically treated for aneurysmal SAH, the proportion of patients <50 years old fell from 40% to 30% between first and final epochs, and the proportion of those in the lowest stroke scale category, roughly equivalent to Hunt and Hess grade 1 or 2, fell from 66% to 45%. The proportion treated by microsurgery fell from 70% to 23% in favor of endovascular surgery. Hospital mortality among these treated cases was stable at 13% throughout the study period despite increasing illness severity indices. After adjustment, there was a 42% reduction of odds of hospital mortality in the final epoch compared with the first.

Conclusion
The incidence of hospitalization for spontaneous SAH fell between 2001 and 2020. Patients undergoing surgery to secure an aneurysm were more severely ill through time yet experienced a stable hospital mortality rate.
A Critique of Deep Engagement, the Social Narrative of US Foreign Policy
Authors: Williams Gregory P. 
Published: November 2024

Abstract
This article offers a critical perspective of the discourse of deep engagement that portrays the United States as the world’s necessary or indispensable power. It describes deep engagement as a social narrative that, like literary narratives, has a story, a plot and an argument. This narrative has persisted in a time of waning hegemony because it makes an apparently appealing moral case for American global leadership. Yet deep engagement remains flawed from a strategic perspective and disregards the history of great-power rise and decline. From a strategic perspective, while hegemons describe their leadership in moral terms, their rhetoric is often betrayed by their actions. From a historical perspective, while hegemons regard their own efforts and values as instrumental to their status, their rise can be credited to a wave of economic and political forces the state cannot control.
An Approach to the Basis of the Right to Freedom of Association According to the Inter-American Court of Human Rights
Authors: Jerez Moreno Rafael 
Published: November 2024

Abstract
As it occurs in any democracy, each State has a particular regulation of the scope of the rights recognized in its constitution and secondary legislation. However, the existence of regional and universal jurisdictions that address human rights to which States have a membership presents a broader view of interpreting these rights and enables a complementary vision with each constitutional system. The right to freedom of association is one example, and this analysis will address it, focusing on the Inter-American System of Human Rights, particularly the Inter-American Court of Human Rights (IACtHR) decisions. This analysis will serve as an initial approach to the evolution of the IACtHR’s interpretation concerning the right to freedom of association, starting with laying down its normative basis in the Inter-American System of Human Rights and later focusing on the decisions of the cases published by the IACtHR addressing this right between 2001–2022.
Freedom of Association: The Case of Poland
Authors: Cyuńczyk Filip 
Published: November 2024

Abstract
The role of this chapter is to show the specifics of freedom of association in Poland. Therefore, in addition to analysing the normative layer, it includes references to the historical state of the law and the practice of interpreting and operationalising this freedom. Through the presentation of legal provisions, I wish to show the local (“domestic”) specificity and situate it in the broader context of the system of constitutional liberal democracy embodied by the 1997 Constitution currently in force in Poland. The operationalisation of freedom of association will be presented on the basis of selected institutions of three particularly relevant statutes: the Law on Associations, the Act on Political Parties and the Act on Trade Unions.
Freedom of Association Doctrine in Finland
Authors: Neuvonen Riku 
Published: November 2024

Abstract
Freedom of association in Finland is an old, fundamental right protected by the Constitution. However, the legislation protecting the right is from the period before the fundamental rights reform of 1995 following Finland’s accession to the Council of Europe in 1990. Key issues are freedom of religion in the registration conditions of religious communities and mandatory membership in student unions. In addition, the Supreme Court and the Supreme Administrative Court have issued rulings that have significantly shaped Finland’s doctrine of freedom of association.
Womanhood as Imagined in Shivani’s Novels and Short Stories
Authors: Bhardwaj Ekta 
Published: November 2024

Abstract
Gaura Pant, popularly known as ‘Shivani’ or ‘Diddi’, was a prominent Hindi writer who contributed immensely to India’s rich literary landscape. Her works reflect nuanced exploration of gender and women’s identity within pre- and postcolonial India. Despite being brought up in a traditional Hindu household, her literary works still managed to traverse established boundaries, challenging patriarchal hierarchies and advocating for women’s empowerment. She published forty prominent literary works along with hundreds of newspaper columns and articles. Most of them are original works in Hindi. This paper unearths prominent themes and constructs within her various short stories, originally written in Hindi, and her well-known novel Bhairavi: The Runaway. While contextualizing her writings with reference to her own life, the paper concludes that Shivani’s works, in exploring the ordinary lives of women within a patriarchal society, are feminist in nature.