Cryoablation for the treatment of breast cancer: immunological implications and future perspectives. Utopia or reality?

Cryoablation is a minimally invasive technique currently employed in breast cancer care, that uses freeze and thaw cycles to treat benign breast lesions, small breast cancers or focal sites of metastatic disease in patients not eligible for surgery. The final goal of this procedure is to destroy breast cancer cells using extreme cold. In addition, several studies have shown that this technique seems to have an enhancing effect on the immune response, especially by increasing the expression of tumor neoantigens specific to tumor cells, which are then attacked and destroyed. Exploiting this effect, cryoablation in combination with immunotherapy could be the key to treating early-stage breast cancers or patients who are unsuitable for surgery. According to some recent studies, there are other potential tools that could be used to enhance the therapeutic effect of cryoablation, such as FE3O4 nanoparticles or the manipulation of aquaporin expression. The aim of this narrative review is to summarize the current evidence regarding the use, indications, advantages and disadvantages of cryoablation in the treatment of breast cancer.

Public History: The Infrastructural Utopia of Metropa.

Metropa, an "art and peace project" by artist and musician Stefan Frankenberger, envisions a future European railroad network through the visual metaphor of an urban subway map, offering both an infrastructural and a political proposal for the future of the European continent. This essay explores Frankenberger's vision from a historical perspective, tracing the origins of the its visual language, its relationship with past trans-European railway projects, and its political implications. The article concludes that, although metropa's technical and political ambitions are deeply connected to the present, its visual appeal and references to historical precedents enhance its affective and political impact.

A Food Utopia? Italian Colonial Visions of Tripolitania and Cyrenaica, 1911-13.

This article explores the uses of utopian rhetoric of food plenty in Italian colonial visions before the First World War. It examines the travel writings of three leading Italian journalists, Enrico Corradini, Arnaldo Fraccaroli, and Giuseppe Bevione, who visited the Ottoman provinces of Tripolitania and Cyrenaica and campaigned for their colonization by Liberal Italy. By reconstructing their utopian rhetoric of food plenty, this article seeks to show the relevance of arguments about food and agriculture produce to early twentieth century colonial visions, shedding light on an aspect of Italian political thought that has been hitherto marginalized in existing historical scholarship.

Tofogliflozin long-term effects on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes mellitus lacking a history of cardiovascular disease: a 2-year extension study of the UTOPIA trial.

BACKGROUND: This study aimed to assess the long-term effects of tofogliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression and major clinical parameters in patients with type 2 diabetes lacking an apparent history of cardiovascular disease. METHODS: This was a prospective observational 2-year extension study of the "Using TOfogliflozin for Possible better Intervention against Atherosclerosis for type 2 diabetes patients (UTOPIA)" trial, a 2-year randomized intervention study. The primary endpoints represented changes in the carotid intima-media thickness (IMT). Secondary endpoints included brachial-ankle pulse wave velocity (baPWV) and biomarkers for glucose metabolism, lipid metabolism, renal function, and cardiovascular risks. RESULTS: The mean IMT of the common carotid artery (IMT-CCA) significantly decreased in both the tofogliflozin (- 0.067 mm, standard error 0.009, p < 0.001) and conventional treatment groups (- 0.080 mm, SE 0.009, p < 0.001) throughout the follow-up period; however, no significant intergroup differences in the changes (0.013 mm, 95% confidence interval (CI) - 0.012 to 0.037, p = 0.32) were observed in a mixed-effects model for repeated measures. baPWV significantly increased in the conventional treatment group (82.7 ± 210.3 cm/s, p = 0.008) but not in the tofogliflozin group (- 17.5 ± 221.3 cm/s, p = 0.54), resulting in a significant intergroup difference in changes (- 100.2 cm/s, 95% CI - 182.8 to - 17.5, p = 0.018). Compared to the conventional treatment group, tofogliflozin significantly improved the hemoglobin A1c and high-density lipoprotein cholesterol levels, body mass index, abdominal circumference, and systolic blood pressure. The frequencies of total and serious adverse events did not vary significantly between the groups. CONCLUSIONS: Tofogliflozin was not associated with improved inhibition of carotid wall thickening but exerted long-term positive effects on various cardiovascular risk factors and baPWV while showing a good safety profile.

Phenotyping the obesities: reality or utopia?

In this thematic issue on phenotyping the obesities, prominent international experts offer an insightful and comprehensive collection of articles covering the current knowledge in the field. In order to actually capture all the polyhedral determinants of the diverse types of obesity, the granularity of the phenotypic information acquired must be expanded in the context of a personalized approach. Whilst the use of precision medicine has been successfully implemented in areas like cancer and other diseases, health care providers are more reluctant to embrace detailed phenotyping to guide diagnosis, treatment and prevention in obesity. Given its multiple complex layers, phenotyping necessarily needs to go beyond the multi-omics approach and incorporate all the diverse spheres that conform the reality of people living with obesity. Potential barriers, difficulties, roadblocks and opportunities together with their interaction in a syndemic context are analyzed. Plausible lacunae are also highlighted in addition to pointing to the need of redefining new conceptual frameworks. Therefore, this extraordinary collection of state-ofthe-art reviews provides useful information to both experienced clinicians and trainees as well as academics to steer clinical practice and research in the management of people living with obesity irrespective of practice setting or career stage.

Rethinking disaster utopia: the limits of conspicuous resilience for community-based recovery and adaptation.

While some communities appear to blossom in the wake of a disaster, others are left to struggle in the ashes. This paper introduces the concept of 'conspicuous resilience' to understand how emergent community-based recovery efforts privilege some needs while marginalising others, contributing to uneven forms of recovery. Drawing on a qualitative case study of the deadly Montecito debris flow in Southern California, United States, in January 2018, an in-depth examination of emergent community-based resilience efforts is gauged next to the social construction of unmet needs. Conspicuous acts of resilience centred around gaps in social and financial support as well as desires for protection from future debris flows. In defining and addressing needs, community-based interventions mirrored existing social inequalities and uneven relationships of power, promoting a false sense of equality and security while reinforcing private interests. To address the limits of conspicuous resilience, a justice-oriented politics of disaster recovery is needed.

Seeking utopia: Psychologies' waves toward decoloniality.

This paper provides a review of empirical studies published with a decolonial epistemic approach in psychology. Our goal was to better understand how decolonial approaches are being practiced empirically in psychology, with an emphasis on community-social psychology. We first discuss the context of colonization and coloniality in the research process as orienting information. We identified 17 peer-reviewed empirical articles with a decolonial approach to psychology scholarship and discerned four waves that characterize the articles: relationally-based research to transgress fixed hierarchies and unsettle power, research from the heart, sociohistorical intersectional consciousness, and desire-based future-oriented research to rehumanize and seek utopia. Community-social psychology research with a decolonial approach has the potential to remember grassroots efforts, decolonizing our world.

Targeting Vitamin D Deficiency to Limit Exacerbations in Respiratory Diseases: Utopia or Strategy With Potential?

Patients with respiratory diseases such as cystic fibrosis, chronic obstructive pulmonary disease, or asthma often experience an acute worsening of respiratory symptoms, termed exacerbations. Although the course of exacerbations is disease specific, they are mostly triggered by a respiratory infection. Exacerbations often require hospitalization and are an important cause of mortality. Treatments of exacerbations aim to minimize the negative impact and to prevent subsequent events. Despite many existing therapy options, many patients do not benefit from therapy and suffer from recurrent events. Vitamin D deficiency is a worldwide problem and is extremely prevalent in these patients. Vitamin D, known for its calcemic effects, also has immunomodulatory and anti-infectious actions and can therefore be a possible agent to treat or prevent exacerbations. This review will focus on vitamin D as a potential candidate to treat or prevent exacerbations in CF, COPD, and asthma.

Controlled human infection with SARS-CoV-2 to study COVID-19 vaccines and treatments: bioethics in Utopia.

A number of papers have appeared recently arguing for the conclusion that it is ethically acceptable to infect healthy volunteers with severe acute respiratory syndrome coronavirus 2 as part of research projects aimed at developing COVID-19 vaccines or treatments. This position has also been endorsed in a statement by a working group for the WHO. The papers generally argue that controlled human infection (CHI) is ethically acceptable if (1) the risks to participants are low and therefore acceptable, (2) the scientific quality of the research is high, (3) the research has high social value, (4) participants give full informed consent, and (5) there is fair selection of participants. All five conditions are necessary premises in the overall argument that such research is ethically acceptable. The arguments concerning risk and informed consent have already been critically discussed in the literature. This paper therefore looks specifically at the arguments relating to condition 3 'high social value' and condition 5 'fair selection of participants' and shows that whereas they may be valid, they are not sound. It is highly unlikely that the conditions that are necessary for ethical CHI trials to take place will be fulfilled. Most, if not all, CHI trials will thus be well intentioned but unethical.

Should We Aim to Create a Perfect Healthy Utopia? Discussions of Ethical Issues Surrounding the World of Project Itoh's Harmony.

To consider whether or not we should aim to create a perfect healthy utopia on Earth, we focus on the SF novel Harmony (2008), written by Japanese writer Project Ito, and analyze various issues in the world established in the novel from a bioethical standpoint. In the world depicted in Harmony, preserving health and life is a top priority. Super-medicine is realized through highly advanced medical technologies. Citizens in Harmony are required to strictly control themselves to achieve perfect health and must always disclose their health information to the public and continuously prove their health. From a bioethical standpoint, the world in Harmony is governed by a "healthy longevity supremacy" principle, with being healthy equated to being good and right. Privacy no longer exists, as it is perceived ethical for citizens to openly communicate health-related information to establish one's credibility. Moreover, there is no room for self-determination concerning healthcare because medical interventions and care are completely routinized, automated, centralized, and instantly provided. This is a situation where the community exhibits extremely powerful and effective paternalism. One can argue that healthy longevity is highly preferred. But is it right to aim for a perfectly healthy society at all costs? Should we sacrifice freedom, privacy, vivid feelings, and personal dignity to achieve such a world? In our view, the answer is no, as this would require the loss of many essential values. We conclude by proposing an alternative governing principle for future healthcare, and refer to it as the "do-everything-in-moderation" principle.

[Parkinson Networks in Germany: Future or Utopia?] / Parkinson-Netzwerke in Deutschland: Zukunft oder Utopie?

BACKGROUND: Parkinson's disease requires a close interaction between different care partners from the point of diagnosis in order to provide the best possible care for patients. However, the treatment reality shows that there are often still significant gaps in care. In recent years it has been recognised that the formation of networks can contribute to improving the care of Parkinson's patients. OBJECTIVES: To present the current status of the development of Parkinson's networks in Germany, the available evidence and the future of Parkinson's networks. MATERIAL AND METHODS: Experiences from existing networks in Germany were systematically recorded on the basis of personal reports and publications. The existing national and international evidence was summarised, and critical success factors and hurdles were analysed. In addition, possible future scenarios were developed. RESULTS: There are many integrated approaches to improve the care of Parkinson's patients. However, this is usually subject to the initiative at individual locations, without binding conditions being created for this by the legislator or the funding agencies outside of model projects. DISCUSSION: It must be noted that it is currently very difficult to implement a problem-free and cost-efficient development of intersectoral network structures within the existing possibilities of the German health care system. The high personal commitment of individual actors currently forms the basis of existing regional networks. An overarching health policy concept is needed to further promote the content and infrastructure of Parkinson's disease networks.

History of science and its utopian reconstructions.

In recent years explicitly utopian visions have reappeared across the political spectrum. To a surprising degree these visions have drawn on histories and science and technology. What should scholars of Science and Technology Studies (STS) and History and Philosophy of Science (HPS) make of these developments? The concept of utopia has often been treated with considerable distrust in these fields, as an indication of closed end-directed blueprints, or as an indication of fantasies of limitless technological improvement and purification of categories. Alongside this uneasiness, however, HPS and STS scholars have also projected transformative ambitions, seeking to recover from the past different ways of knowing and relating to the human and non-human world. By engaging with critiques of utopia from thinkers including Karl Popper, Otto Neurath, Bruno Latour, Isabelle Stengers and Donna Haraway, and exploring some of the utopian strands which have recurred in studies of science and technology-including the longing for integration, the association of science with planning, and the ways in which feminist scholars have envisaged alternative forms of science-we can understand the ongoing, and often unrecognised, utopian dimensions of HPS and STS.

Failed utopias and practical chemistry: the Priestleys, the Du Ponts, and the transmission of transatlantic science, 1770-1820.

Eighteenth-century events, replete with Dickensian dualities, brought two Enlightenment families to America. Pierre-Samuel du Pont and Joseph Priestley contemplated relocating their families decades before immigrating. After arriving, they discovered deficiencies in education and chemistry. Their experiences were indicative of the challenges in transmitting transatlantic chemistry. The Priestleys were primed to found an American chemical legacy. Science connected Priestley to British manufacturers, Continental chemists, and American statesmen. Priestley's marriage into the Wilkinson ironmaster dynasty, and Lunar Society membership, helped his sons apprentice, and befriend manufacturer-chemist Thomas Cooper. However, ideological persecution forced them from England. Priestley's plans for his sons to inherit Wilkinson's ironworks evaporated; in America, efforts to establish manufactories, colonies, farms, and a college miscarried. Cooper taught college chemistry, but his materialism provoked dismissals. The Du Ponts were unlikely founders of an industrial-chemistry empire. Du Pont's philosophy promulgated that agriculture, not industry, produced wealth. Eleuthère-Irénée apprenticed in France's gunpowder administration, however, plans for his succession died and director Antoine Lavoisier, a family friend, was executed. E.-I. and Du Pont's arrest precipitated relocation to America. Du Pont's utopian colony and schemes proved unrealistic. Nevertheless, E.-I.'s gunpowder manufactory-utilizing transatlantic contacts and privileged knowledge of advanced French chemistry-succeeded through practical application.

Integrating Typhoid Fever Within the Sustainable Development Goals: Pragmatism or Utopia?

Several decades following the first estimates of the global burden of typhoidal salmonellosis (infections caused by Salmonella Typhi and Salmonella Paratyphi), this disorder remains a major cause of morbidity worldwide with an estimated 17 million cases annually. The risk factors for typhoid include poverty, poor living conditions with unsafe water and lack of adequate sanitation, and unsafe foods-all reasons for the disease burden being highest among such populations including urban slums. A recent review of typhoid trends globally and in specific countries suggests that the relative contributions of these risk factors to disease burden reduction as well as persistence have varied. There is also the risk of periodic outbreaks related to introduction of relatively virulent drug-resistant strains or movements of vulnerable populations, including those in conflict zones. Most countries of the world are now aligning their health and multisectoral strategies to address the Sustainable Development Goals (SDGs) and targets, which were agreed upon by all countries of the world in September 2015. Though neglected so far, there are huge opportunities for mainstreaming typhoid prevention and control strategies within the SDGs. This article reviews some of the approaches that may help elevate typhoid to a higher level of awareness in public health programs and policy and to ensure that investments in major public health preventive measures are made part of the universal health coverage agenda.

Viral species, viral genomes and HIV vaccine design: is the rational design of biological complexity a utopia?

A common logical confusion is prevalent in the whole of biology, namely that biological species are viewed both as an abstract category in an hierarchical classification and as a concrete kind of organism. This is partly due to the fact that the vast majority of living organisms do not have common names that differ from the Latin name of the species to which the organism belongs. However, it is somewhat astonishing that the same confusion exists in virology since every virus has a common name, different from the species name to which the virus belongs, which could be used to refer to the infectious viral entity as a concrete material object. The original 1991 ICTV definition of virus species stated that a virus species is a polythetic class of viruses and thus that a species is a class, namely a conceptual construction of the mind and not a physical, real object located in space and time. In 2013, the ICTV redefined a virus species no longer as a class but as a material object consisting of a monophyletic group of viruses that were all physically part of the species. This new definition is reminiscent of an earlier school of thought known as bionominalism which considered species to be concrete individuals rather than classes. Both bionominalism and the new ICTV definition are based on the logical fallacy of reification which treats abstractions such as classes as if they were concrete physical entities. The implications of this new ontology of virus species for virus taxonomy and for the possibility of incorporating nucleotide metagenomic sequences in the current ICTV classification is discussed.

Robert Owen, utopian socialism and social transformation.

This paper critically scrutinizes accounts of Robert Owen's life and works focusing on his purported "utopianism" and his supposedly deficient "socialism." It suggests that such positions have relied on questionable assertions about the potential of particular modes of social transformation, and a failure to acknowledge the distinction Owen makes between the practical arrangements necessary to begin the process of transformation, and those arrangements that would ultimately prevail in "the new moral world." It also argues that such accounts may contribute to the development of fatalistic narratives surrounding cooperative values and projects involving strategic compromise. In response, the paper reconsiders the significance of Owen through the lens of a "strategic presentism" that considers how Owen's ideas can be thought of as significant contributions to theorizing social transformation.

Utopian Vision: A Grand Solution for a Scholarly Dilemma.

Reconciling the Zen-like paradox on the back of every red penny-"out of many, one"-is not for the faint of heart. It is a diversity motto, and a lofty desire that the United States claims to covet. But can its citizens, undocumented or otherwise, even agree on what it is? Is not the desire to maintain a strong sense of community in conflict with a Noah's Ark conception of diversity? Using my personal experience in an intentional community determined to foster racial integration, I explore the complicated possibility of having it both ways. To do so, however, we must construct a notion of community, diversity, and The Good Life that will make us believe and work for this synthesis. Our reactions to the word "utopia" offer a glimpse of the challenges ahead.