bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rab13 Sustains Breast Cancer Stem Cells by Supporting Tumor–Stroma Cross-talk
Authors: Wang Hui , Xu Haibo , Chen Wei , Cheng Mei , Zou Li , Yang Qin , Chan Chi Bun , Zhu Hao , Chen Ceshi , Nie Jianyun , Jiao Baowei 
Published: April 2022

Abstract

Cancer stem cells (CSC) are supported by the tumor microenvironment, and non-CSCs can regain CSC phenotypes in certain niches, leading to limited clinical benefits of CSC-targeted therapy. A better understanding of the mechanisms governing the orchestration of the CSC niche could help improve the therapeutic targeting of CSCs. Here, we report that Rab13, a small GTPase, is highly expressed in breast CSCs (BCSC). Rab13 depletion suppressed breast cancer cell stemness, tumorigenesis, and chemoresistance by reducing tumor-stroma cross-talk. Accordingly, Rab13 controlled the membrane translocation of C-X-C chemokine receptor type 1/2 (CXCR1/2), allowing tumor cells to interact with tumor-associated macrophages and cancer-associated fibroblasts to establish a supportive BCSC niche. Targeting the Rab13-mediated BCSC niche with bardoxolone-methyl (C-28 methyl ester of 2-cyano-3, 12-dioxoolen-1, 9-dien-28-oic acid; CDDO-Me) prevented BCSC stemness in vitro and in vivo. These findings highlight the novel regulatory mechanism of Rab13 in BCSC, with important implications for the development of therapeutic strategies for disrupting the BCSC niche.

Significance:
Targeting Rab13 perturbs formation of the breast cancer stem cell niche by inhibiting cross-talk between cancer cells and the tumor microenvironment, providing a therapeutic opportunity for niche-targeted breast cancer treatment.
Aberrant Nuclear Export of circNCOR1 Underlies SMAD7-Mediated Lymph Node Metastasis of Bladder Cancer
Authors: An Mingjie , Zheng Hanhao , Huang Jian , Lin Yan , Luo Yuming , Kong Yao , Pang Mingrui , Zhang Dingwen , Yang Jiabin , Chen Jiancheng , Li Yuanlong , Chen Changhao , Lin Tianxin 
Published: April 2022

Abstract

Circular RNAs (circRNA) containing retained introns are normally sequestered in the nucleus. Dysregulation of cellular homeostasis can drive their nuclear export, which may be involved in cancer metastasis. However, the mechanism underlying circRNA nuclear export and its role in lymph node (LN) metastasis of bladder cancer remain unclear. Here, we identify an intron-retained circRNA, circNCOR1, that is significantly downregulated in LN metastatic bladder cancer and is negatively associated with poor prognosis of patients. Overexpression of circNCOR1 inhibited lymphangiogenesis and LN metastasis of bladder cancer in vitro and in vivo. Nuclear circNCOR1 epigenetically promoted SMAD7 transcription by increasing heterogeneous nuclear ribonucleoprotein L (hnRNPL)–induced H3K9 acetylation in the SMAD7 promoter, leading to inhibition of the TGFβ-SMAD signaling pathway. Nuclear retention of circNCOR1 was regulated by small ubiquitin-like modifier (SUMO)ylation of DDX39B, an essential regulatory factor responsible for circRNA nuclear-cytoplasmic transport. Reduced SUMO2 binding to DDX39B markedly increased circNCOR1 retention in the nucleus to suppress bladder cancer LN metastasis. By contrast, SUMOylated DDX39B activated nuclear export of circNCOR1, impairing the suppressive role of circNCOR1 on TGFβ-SMAD cascade activation and bladder cancer LN metastasis. In patient-derived xenograft (PDX) models, overexpression of circNCOR1 and inhibition of TGFβ signaling significantly repressed tumor growth and LN metastasis. This study highlights SUMOylation-induced nuclear export of circNCOR1 as a key event regulating TGFβ-SMAD signaling and bladder cancer lymphangiogenesis, thus supporting circNCOR1 as a novel therapeutic agent for patients with LN metastatic bladder cancer.

Significance:
This study identifies the novel intron-retained circNCOR1 and elucidates a SUMOylation-mediated DDX39B–circNCOR1–SMAD7 axis that regulates lymph node metastasis of bladder cancer.
Balancing Innovation, ‘Ordre Public’ and Morality in Human Germline Editing: A Call for More Nuanced Approaches in Patent Law
Authors: Matthews Duncan , Minssen Timo , Nordberg Ana 
Published: April 2022

Abstract
This article analyses the role that ‘ordre public’ and morality exceptions can play in the granting of patents on inventions in the field of human germline editing and the consequences of this policy option. In order to provide the context for such an analysis, the article will, first, provide an overview of the current patent landscape for relevant genome editing technologies, drawing attention to recent patent disputes and, second, examine ‘ordre public’ and morality exceptions under patent law in international, national and regional law, and the implications for innovation and access to novel treatments. The article argues that patent exceptions should not be used as a blunt policy instrument, nor interpreted in a way that is contrary to the patent system’s overall objectives. The ‘ordre public’ and morality based exceptions in the context of human germline editing should not be interpreted and applied in a way which results in outcomes counterproductive to the goal of balancing innovation with the protection of societal higher normative values. Instead, the application of the exception should be based on a sound understanding of both the underlying science as well as the broader ethical, social, and legal implications, thus enabling case-by-case decisions that provide the basis for patent claim amendments and nuanced purpose-bound protection. Further analysis and debate as to the role that such flexibilities can play in the context of genome editing technologies is therefore both necessary and desirable, and can be facilitated in the ways set out in this article.
What Would It Take to Enable Germline Editing in Europe for Medical Purposes?
Authors: Slokenberga Santa 
Published: April 2022

Abstract
Commonly, the regulation on germline editing in Europe is described through the two prohibitions: the prohibition set out in Article 13 of the Convention for the protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine: Convention on Human Rights and Biomedicine and the prohibition that is set out in the EU Clinical Trials Regulation. These prohibitions reflect the European regional position regarding the ethical and legal questions raised by the technology, and an unwillingness to enable such interventions in Europe. Simultaneously, these prohibitions have been shaped prior to the recent breakthroughs in the field, such as the discovery of the CRISPR-Cas technology, which has initiated a new era in the field. This contribution examines what it would take to enable human germline gene editing in Europe for medical purposes. It scrutinises in detail the content and context of the existing bans, as well as mechanisms to lift them. It argues that the bans that are prescribed by each of the European regional legal orders are embedded in strong structures, composed of values and principles. For the human germline gene editing to be enabled in Europe for health-related purposes, the approach to these values and principles needs to change. Only then can the machinery to lift the bans lead to a change.
Genetics and Justice, Non-Ideal Theory and the Role of Patents: The Case of CRISPR-Cas9
Authors: Feeney Oliver 
Published: April 2022

Abstract
There are ongoing concerns of social justice regarding inequalities in the distribution of access to potential genome editing technologies. Working within non-ideal theory, Colin Farrelly advances a justification for the use of patents to speed up the arrival of safe and effective interventions for all, including the socially disadvantaged. This paper argues that such success is less assured when one considers the actual functioning of patents and the practical implications of the patent system in the context of biotechnological innovations. I suggest that non-ideal theoretical approaches risk reverting back to a form of ideal theory if they simply refer to such real-world constraints — e.g. patents — but do not critically assess and fully examine how such constraints manifest themselves in practice. I highlight some considerations that would be important in order to develop and foster a more robust non-ideal approach to justice in biotechnological developments.
Between Rights, Sovereignty and Cooperation
Authors: Camins Emily 
Published: April 2022

Abstract
Although the humanitarian effects of armed conflict are vast and transcend national boundaries, international law does not yet provide an adequate or comprehensive response to the suffering of victims of war. This article argues considerations of State sovereignty have shaped the development of international law on post-war redress, hindering the emergence of individual rights to reparations under international humanitarian law. Meanwhile, alternative models such as victim assistance, which largely preserve sovereignty, are emerging in pockets of international humanitarian law, such as weapons treaties. This article suggests that victim assistance offers a potential model for addressing the harm to victims of armed conflict more broadly.
How Should Theists Respond to Debunking Arguments? A Critique of Hans Van Eyghen’s Arguing from Cognitive Science of Religion
Authors: Launonen Lari 
Published: April 2022

Abstract
Cognitive science of religion has inspired several debunking arguments against theistic belief. Hans Van Eyghen’s book Arguing from Cognitive Science of Religion is the first monograph devoted to answering such arguments. This article focuses on Van Eyghen’s responses to two widely discussed debunking arguments, one by Matthew Braddock and another by John Wilkins and Paul Griffiths. Both responses have potential but also face problems. Even if Van Eyghen manages to show that these authors have not fully excluded the possibility of noninferential theistic belief being underpinned by reliable belief-forming processes, he fails to offer convincing reasons to think the processes are in fact reliable. A positive argument for their reliability might ultimately have to be based on evidence for God’s existence, namely, theistic arguments. The question of the rationality of religious belief (de jure) thus cannot be isolated from the question of God’s existence (de facto).
Hermeneutics of Grief as a Model for the Hermeneutics of Love in Jean-Luc Marion
Authors: Roggero Jorge Luis , Becker Brian 
Published: April 2022

AbstractFrom Jean-Luc Marion’s examination of Gustave Courbet and his painting, it is shown how grief can operate as a model for the hermeneutics of love. This hermeneutics of grief, in turn, makes possible a consideration of all phenomena, and not only the human, as saturated phenomena.
Reflections on Anthrobombing: Experiments in Performing, Publishing and Becoming with (Other) Publics
Authors: Papageorgiou Alexandros , Siotou Alexandra , Papailias Penelope 
Published: April 2022

Abstract
This article is based on a two-year collaborative research program on public anthropology in Greece focused on narrative experimentation with stand-up comedy and alternative publishing with handmade books, or cartoneras. Viewing in anthropology a powerful tool to dismantle prevalent commonsense about nationalism, gender norms and capitalist progress, we “bombed” time-spaces in which academic discourse is not usually present. The embodied experience of performing and publishing in an “anthropological way” outside of spaces of academic communication led to insights about the potential of humor, multimodal forms and performance for anthropology, new questions about “who anthropology is for” and “what makes knowledge anthropological”, and an emergent concern for becoming-with, rather than just bombing, publics.
Comparison of venous pCO2 and exhaust pCO2 for calculating CO2 production during cardiopulmonary bypass
Authors: Gerritse Matthijs , van Hoeven Marloes , Overdevest Eddy 
Published: April 2022

Introduction Carbon dioxide production (VCO2i), oxygen consumption and oxygen delivery can be monitored during cardiopulmonary bypass (CPB) as markers for tissue perfusion. This study examines if inline venous pCO2 (PvCO2) monitoring can be used as an alternative to exhaust gas pCO2 (ExCO2) to calculate VCO2i. Methods PvCO2 and ExCO2 were monitored continuously during 40 elective coronary artery bypass grafting (CABG) procedures. VCO2i was calculated with ExCO2 as well as PvCO2. Results Mean PvCO2 was 0.27 mmHg higher than mean ExCO2 (p < .001). The 95% limits of agreement of PvCO2 and ExCO2 were [‐2.99, 3.53] mmHg which is within the limits proposed by the Clinical Laboratory Improvement Amendments of 2019. VCO2i was calculated using both PvCO2 and ExCO2 (PvVCO2i; ExVCO2i). A strong linear correlation was found for ExVCO2i and PvVCO2i (R2= .94, p < .001). Conclusion In conclusion, the differences in VCO2i calculation between the two methods are unlikely to be clinically relevant during normothermic CABG procedures. VCO2i can be calculated with either a capnograph or inline venous pCO2 monitoring.
A Retrospective Cohort Evaluation of a Pharmacist-Led Approach for Transitioning Patients to an Angiotensin Receptor—Neprilysin Inhibitor
Authors: Rana Krishna , Jay Jessica , Patel Sonalie , Sueta Carla , Deyo Zack 
Published: April 2022

Background: Heart failure guidelines recommend replacing an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) with an angiotensin receptor neprilysin inhibitor (ARNI) to reduce morbidity and mortality in NYHA Class II–III patients with reduced ejection fraction (HFrEF). Objective: This study aims to determine if a pharmacist-led outpatient ARNI replacement and titration program led to more patients achieving target doses of ARNI compared to usual care. Methods: A single health system, retrospective electronic medical record review identified 791 patients with active ARNI prescriptions and at least two outpatient cardiology visits with a pharmacist or usual care provider between January 2015 through September 2018. The primary outcome was the percentage of patients who achieved a target ARNI dose of 97/103 mg twice daily. The secondary outcomes were the median dose achieved, number of visits required to achieve target dose, hospitalizations, and all-cause death. Results: ARNI was initiated and continued by a pharmacist in 64 patients and 727 by usual care. More patients in the pharmacist group, 60.9% (n = 39), achieved target dose vs. 18.0% (n = 131) of patients managed by usual care (95% CI, 0.31–0.55, p < 0.0001). The pharmacist group also had higher median total daily dose of ARNI (200 mg (IQR = 300) vs 100 mg (IQR = 100), p < 0.0001) and more likely to achieve a higher total daily dose in fewer visits. Conclusions: An advanced practice provider pharmacist-led outpatient ARNI replacement and titration program was more effective in achieving target doses of ARNI in HFrEF patients as compared to usual care.
Small intestine necrosis in catastrophic antiphospholipid syndrome: A rare and severe case
Authors: Christiansen Tobias K , Nilsson Anna Christine , Madsen Gunvor I , Voss Anne 
Published: April 2022

Catastrophic antiphospholipid syndrome (CAPS) is a multisystem autoimmune disease with widespread thrombotic events. In this case report, we present a young man with primary antiphospholipid syndrome (PAPS) admitted to the hospital with abdominal pain and vomiting. Abdominal computed tomography showed pneumoperitoneum and acute explorative laparotomy revealed small intestinal necrosis indicating small vessel thrombosis without involvement of large intestine. “Triple therapy” was initiated after surgery and the patient was treated in an intensive care unit for 72 days before being discharged to a rehabilitation clinic. A review of the literature regarding CAPS affecting small intestine shows it is extremely rare and may be associated with higher mortality.
Predictors of postoperative pain, opioid consumption, and functionality after arthroscopic shoulder surgery: A prospective observational study
Authors: Zeeni Carine , Abou Daher Layal , Shebbo Fadia M , Madi Naji , Sadek Nada , Baydoun Hasan , Al-Taki Muhyeddine , Aouad Marie T 
Published: April 2022

Purpose This study aims to identify predictors of postoperative pain and opioid consumption after shoulder surgery to help optimize postoperative pain protocols. Study Design Observational cohort study. Methods One thirty-four patients undergoing arthroscopic shoulder repair were included. Variables related to the patient, surgery and anesthesia were collected and correlated with postoperative pain intensity, analgesic consumption, and functionality up to 1-month post-surgery. We used mixed-effect linear models to estimate the association of gender, interscalene block (ISB), preoperative shoulder pain, non-steroidal anti-inflammatory drugs (NSAIDs) consumption before surgery, and type of surgery with each of the following outcomes: postoperative pain scores, opioid consumption, and functionality. We further analyzed the data for pain scores and opioid consumption per body weight using the multiple linear regression analysis to demonstrate the aforementioned associations specifically at 1 h, 6 h, 12 h, 24 h, 72 h, 1 week and 1 month after surgery. Results Omitting the ISB was associated with higher postoperative pain and cumulative opioid consumption over the first 24 h after surgery. Rotator cuff repair and stabilization surgeries were found to be predictive of higher postoperative pain at 24 h, 72 h, and 1 week and lower functionality at 1 week after surgery. Preoperative shoulder pain and NSAIDs consumption were also predictive of postoperative pain and cumulative opioid consumption. Conclusion Omitting a single shot ISB is a strong predictor of postoperative pain and opioid consumption in the early postoperative phase, beyond which the type of surgery, particularly rotator cuff repair and stabilization surgery, emerges as the most important predictor of postoperative pain and functionality.
The creator did not give me more than I can handle: Exploring coping in parents of Black autistic children
Authors: Lewis Ericka M , Dababnah Sarah , Hollie Kelley R , Kim Irang , Wang Yao , Shaia Wendy E 
Published: April 2022

There is a paucity of studies that center on the lived experiences of Black families raising autistic children, and major gaps remain in our understanding of how parents of Black autistic children cope with stressors. Drawing from the Black family stress and coping model, this mixed-methods study explored coping strategies utilized by parents of Black autistic children. Twenty-two parents completed the Ways of Coping Questionnaire and participated in semi-structured interviews. Using grounded theory methods, we conducted data collection and analyses simultaneously until we did not identify new themes. Our quantitative and qualitative results were generally aligned. We found that parents used an array of coping strategies, at times combining different methods, to address complex stressors. Parents also expressed the need for more social support from providers, as well as a desire for inclusive spaces where they could engage with other parents whom they felt could better relate to the stressors they encountered. Study findings also suggest that kinship support, church involvement, and collective socialization are key protective factors in Black communities. Therefore, understanding the role culture plays in the use and effectiveness of coping strategies is essential to improving healthcare and other systems of care. Lay abstract Parents of Black autistic children use several strategies to cope with daily stressors. These strategies include seeking social support, self-care, and optimism. We asked parents about their experiences receiving treatment services for their autistic child and how they reduce parenting stress. Twenty-two parents completed a coping survey and participated in individual interviews. Few studies have explored the experiences of Black families raising autistic children, and it’s important for healthcare and other systems of care to understand the role culture, race, and ethnicity play in the use of coping strategies. In our study, the majority of parents relied on social support to relieve stress and identified partners, family, and community members, as their most useful sources of support. Connecting with other parents of autistic children, through support groups and social media, also helped parents relieve stress. Parents discussed using self-care activities (e.g. church, exercising, listening to music) to cope with stressors. Several parents described how prayer and meditation helped them reframe stressful situations and gain more patience and appreciation for “what’s important.” The findings of this work demonstrate the need for professionals to have ongoing and deeper conversations about the ways in which parents deal with stressors. In particular, clinicians should leverage the strengths of Black families and promote strategies that are culturally informed and engaged.
Extrinsic venous compression secondary to spine osteophytes
Authors: Gonzalez-Urquijo Mauricio , Torrealba Jose , Vargas Jose Francisco , Mertens Renato , Mariné Leopoldo , Valdés Francisco 
Published: April 2022

Objective This study aims to report two cases of symptomatic extrinsic compression of the inferior vena cava and left iliac vein caused by vertebral osteophytes. Methods We present two case reports of extrinsic venous compression by vertebral osteophytes. Both cases were endovascularly treated, with a successful outcome. A review of the literature of this unusual condition is also presented. Results The first patient is an 80-year-old woman who presented to the vascular surgery clinic with bilateral lower extremity edema and pain. A computed-tomography angiography (CTA) revealed extrinsic compression of the inferior vena cava from enlarged osteophytes. Venography and intravascular ultrasound were performed, confirming the diagnosis. A self-expanding venous stent was successfully deployed in the inferior vena cava relieving the extrinsic compression. The edema resolved the following day and was discharged without complications. The second patient is a 61-year-old male that presented to the emergency department with a left iliofemoral deep venous thrombosis. CTA showed left iliac vein compression by a lumbar osteophyte. Percutaneous thrombectomy was successfully achieved and an expanding stent was deployed covering the entire lesion. One month after the procedure the patient died from COVID-19‐associated respiratory failure. Conclusion Osteophytes must be considered when dealing with extrinsic venous compression, especially in elderly people.