bluuebunny/crossref_metadata_2025 huggingface dataset:
Responding (After Anthropos)
Authors: Briggs Robert
Published: January 2023

This chapter engages with the problem of anthropocentrism, by turning to the naming of the Anthropocene and the investigation of anthropogenesis as exemplary of contemporary attempts to challenge the sovereignty of ‘man’ by underscoring the human species’ status as subject to ecological and biological conditions of life. Wary of the recuperative power of metaphysical humanism, however, the chapter reflects on the extent to which these theoretical developments effectively extricate themselves from the structures of humanism. Following Derrida’s and Foucault’s critiques of the metaphysics of ‘man’ and ‘life’, the discussion interrogates the goal of human species survival implied in calls for action on climate change, calls which ultimately reproduce the anthropocentric logics of environmental mastery that those calls otherwise envision as problematic. In contrast to the recent biological turn in contemporary theory, then, the chapter elaborates a logic of life as fundamentally institutional and prosthetic, a logic that can lead to a thought of response defined not in terms of human sovereignty but rather as emanating from the animal-to-come. It is in view of such a thought of the problem of response that the chapter concludes by engaging with Isabelle Stengers’ characterisation of climate change as ‘the intrusion of Gaia’.
What Hope for the Animal-To-Come?
Authors: Briggs Robert
Published: January 2023

By way of a conclusion, the discussion turns to the problematic of pessimism which surfaces periodically in the preceding chapters. While the thought of the animal-to-come is pursued throughout with a view to imagining a zoopolitics grounded on something other than what Derrida calls a pessimistic anthropology, the prospect of catastrophic climate change provides little cause for optimism vis-à-vis the animal-to-come. And if such is the case, what hope for the animal-to-come? What can hope mean in this context? In addressing this question, various problematisations of the value of hope are reviewed in acknowledgement of the specific forms of violence perpetuated by the use of hope as a political value or strategy. In an attempt to introduce multispecies thinking into the construction of the concept, the chapter concludes by speculating on what may come from thinking through specific instances of animal behaviour and animal interaction as articulations of hope.
Johannes Althusius and Political Society as Pactum
Authors: Kennedy Simon P.
Published: January 2023

This chapter aims to demonstrate Althusius’s role in the desacralisation of the confessional state in Europe and the broader secularisation of political thought. The role of Althusius in this story is mixed. He displays continuity with earlier Reformed thinkers in his theory of natural law and his understanding of the origins of political life. This is, in part, because Althusius’s ideas were deeply imbued with Aristotelianism. These aspects of his thought, his Aristotelianism and his natural law theory, will occupy the initial sections of this chapter. First, we will examine his conception of natural law. Second, we shall address Althusius’s theory of the origins of political society, a theory which was clearly Aristotelian and naturalist. I will argue that these two key elements mean that Althusius retained a sacred foundation for political life. Third, we will see that Althusius played a part in introducing an idea into the Reformed Protestant political theory vocabulary which would influence the tradition in a secular direction. This idea is that of pactum.
Conclusion
Authors: Kennedy Simon P.
Published: January 2023

American public intellectual Yuval Levin once stated that ‘politics is really rooted in political philosophy’, and that political discourse will ‘make much more sense if you see that people are arguing about [different] ways of understanding what the human person is, what human society is, and especially what liberal society is’. In other words, disagreements about political ideology stem from disagreements about political anthropology and about the nature of nature. The history of these conceptions has been the focus of this investigation into various Reformed Protestant thinkers. We have seen that two of them, namely Hobbes and Locke, decoupled the transcendent from their theories of political life. The question that naturally follows is this: what is the consequence of this decoupling for liberal societies today?
Multi-Tentacled Time: Contemporaneity, Heterochrony, Anachronism For Pre-Posterous History
Authors: Bal Mieke , Mitchell W. J. T.
Published: January 2023

The fourth chapter, “Multi-Tentacled Time: Contemporaneity, Heterochrony, Anachronism for Pre-posterous History” analyses time in its multiplicity. This is also a central concern both in narrative theory and in film. After publishing Reading “Rembrandt” (1991) the author was blamed for being ahistorical, which, although not true, was a stimulating incentive to think harder about the issue of historical time. That led to her book Quoting Caravaggio (1999), in which she addressed that critique, and developed a new sense of history in relation to time. But it was when, already immersed in filmmaking, she was working with Hernández Navarro on a large collective video exhibition devoted to the connections between the movement of images and the movement of people, in other words, video and migration (not on migration), that her thinking about temporality took another turn. The last concept in the chapter's title is presented through a theoretical interlude, and is also probed through the author's latest, 2020 short “essay film” It's About Time! This film, the title of which is as ambiguous as the concept of “pre-posterous history”, addresses the world's self-destructive impulse, through the voice of Christa Wolf's character Cassandra, the prophet of doom who will never be believed.
Making Up, Making As: Fiction And/ In/With Reality
Authors: Bal Mieke , Mitchell W. J. T.
Published: January 2023

Another theoretical issue of central importance in narratives in both media is fiction: fiction and/in/with reality. This also weaves together the inseverable connection between documentary and fiction, the two cinematic genres discussed in this book. These are aspects of all narratives, rather than genres or grounds for truth claims. The chapter goes back and forth between two films, whose primary genres are fiction for the one and documentary for the other, and demonstrates how that distinction falls away under the impact of the audio-visual medium. The two cases in this chapter are the fiction, or “docu-drama”, on the historical figures of René Descartes and Queen Kristina of Sweden, on the one hand, and a documentary about a small child on the other. They both remain ambiguous, and speak to each other in the way they each call on the imagination. The former film, a fiction on historical figures, holds fast to the historical documentation that makes the appeal for a revision of our commonplace view of the French philosopher plausible. The latter shows the use of the imagination to grasp a thicker view of reality. The little girl liberates us from such constraints as dogmatic historicity.
Introduction
Authors: Pugsley Peter C.
Published: January 2023

This chapter provides a brief outline of the ways that Japan’s schools are linked to the Western history of disciplinarity and institutionalisation. It explores the rise of the high school film and its particular features that signal either universality or cultural/national specificities.
Beyond the Classroom
Authors: Pugsley Peter C.
Published: January 2023

This chapter illustrates the ways that high school films create a ‘world’ for its characters that exists beyond the confines of the classroom or the schoolyard. Scenes beyond the classroom give audiences insights into Japanese lifestyles and the ways that youth cultures develop. It shows how various modes of transport (buses, trains, bicycles and walking) impact on the journey to and from school, providing a site for character development. The journey also provides for both a greater engagement with the ‘outside’ world and, in some instances, a moment of isolation and contemplation for the student.
Marking a Distinct Society
Authors: Pugsley Peter C.
Published: January 2023

This chapter focuses on the ways in which cinematic high school characters are fleshed out to reflect fully formed individuals within narratives. This enables high school films a larger scope to incorporate and comment on Japanese society and its influence on adolescents. It explores the portrayal of Japanese family life as often peripheral to the emotional growth and development of Japanese youth.
Introduction: Addressing the Politics of Dissent
Authors: Sim Stuart
Published: January 2023

This chapter introduces the main themes of the book, emphasising that it will be defending a 'woke', that is socially liberal, attitude to counter right-wing populism and extremism. It argues that the prejudice and bigotry that drives such populism and extremism puts democracy severely at risk. The Covid pandemic has emboldened many governments to marginalise dissent and political opposition, claiming that emergency powers are necessary to deal with the outbreak. This has helped to entrench an anti-democratic culture in political life that the book will go on to critique in detail. The overall concern of the project will be to confront authoritarianism in whatever area of life we find it asserting itself.
Dissent Under Threat
Authors: Sim Stuart
Published: January 2023

This chapter outlines how dissent has increasingly come under threat in recent years, as governments have deliberately set out to curtail opposition in whatever it form it has been expressing itself. Noting a worrying rise in political authoritarianism and a general turn again dissent in political life, it identifies some of the main examples of these internationally. It also argues that what the political right claims is a 'culture war' against woke attitudes, is in effect a war against dissent. Agreeing with the late American Supreme Court Judge Ruth Bader Ginsburg that 'dissents speak to a future age', it argues that if we do not keep that tradition alive then liberal democracy is at risk of dying out.
The State and Dissent: The Limits of Democracy
Authors: Sim Stuart
Published: January 2023

This chapter examines the various problems that liberal democracy faces in countering authoritarianism, and puts forward several suggestions for changes that could be made to the electoral system to ameliorate these. It works through the pros and cons of proportional representation and federalism, making a case for constant rethinking of such systems to ensure that dissent is not blocked by party-political self-interest. The practice of whistleblowing is strongly defended, and it is argued that it should be seen as a critical method of expressing dissent against authority. The need to regulate both globalisation and neoliberalism is also discussed, as is the continuing problem of racism in democratic societies.
The Unbearable Lightness of Being: Chiasmus, Embodiment, and Interpretation in Maurice Blanchot
Authors: Roth Zoë
Published: January 2023

The fourth chapter takes up the challenge of writing criticism with an embodied form. Maurice Blanchot is a philosopher who has long been read in terms of the negativity, neutrality, and withdrawal of language and the subject. By contrast, this chapter reads his work as producing a form of thought that embodies absence in the figure of the chiasmus. The chapter as a whole functions as a fulcrum at the centre of Formal Matters, transforming the book's structure into a chiasmus that demonstrates how embodiment organizes literary interpretation.
Political Influences: Metamorphosis
Authors: Munro Lachlan
Published: January 2023

From documentary evidence, this chapter analyses Graham’s early political influences, particularly, Robert Owen, John Ruskin, William Morris, and Karl Marx. His close association with Morris, and his conversion to socialism.
Empire: The Insidious Bacillus
Authors: Munro Lachlan
Published: January 2023

Graham’s written attacks on imperial abuses, particularly the abortive ‘Jameson Raid’ in South Africa, sponsored by Cecil Rhodes. Graham’s satirical attacks on racism, particularly in a piece entitled ‘Bloody Niggers’. The controversy surrounding Graham’s pronouncement on political assassination.
Magic: Transformation and Self-determination
Authors: Angus Bill
Published: January 2023

This chapter demonstrates the ways in which crossroads have long been revered as sites of magical interest and have hosted rituals important to the operation of everyday religion and superstition. It documents newly discovered early modern crossroads spells, and places them alongside a variety of crossroads rituals and practices that are described in contemporary and other historical texts. Focusing on the early modern as the era of greatest flourishing for accounts of these magical rites, it takes an isomorphic approach to exploring the unrelenting significance of the crossroads as a site of particular ritual potency.
Music: Going Down to the Crossroads
Authors: Angus Bill
Published: January 2023

In many cultures, crossroads are regarded as geographical ‘thin’ places, giving access to divine or demonic transformative powers beyond the physical world. This chapter considers the Faustian transformations, crossroads soul-selling, and metamorphoses that this idea has generated, especially in relation to music. Finding resonance between musicians across time, from the early modern Robert Johnson who composed tunes for the witches of Shakespeare and Middleton to his seminal early 20th namesake, it connects early narratives of crossroads metamorphosis with more recent formative myths, and reads an early modern debate over the possibilities of transformation as a generative mode of social assertion for the powerless.
An acceleration-oriented form of simple piecewise linearisation in time series to assess seismically damaged structures
Authors: Enokida Ryuta , Kajiwara Koichi
Published: January 2023

This study presents an acceleration-oriented form of simple piecewise linearisation in time series (SPLiTS) to assess the condition of a seismically damaged structure using only its measured acceleration. Its original form could estimate the physical parameters of nonlinear structures in the time domain using inversions of the displacement and acceleration, based on its piecewise linearisation. However, its reliance on measured displacement limited its application only to structures in heavily monitored environments, such as laboratories. To enhance its feasibility for structures with fewer sensors or improper displacement measurement cases, an acceleration-oriented form is introduced, which does not require displacement measurements. To maintain the procedure’s simplicity, the new form retains the basic signal processing techniques: integrations of acceleration and a multi-pass moving-average filtering technique, to obtain the displacement and velocity responses used in the inversion. Based on the principle of SPLiTS, which minimises the central-point shift components, the average filtering technique removes the distortion generated during integration. The new form was examined by applying it to E-Defense shake table experiments on a three-storey steel structure, which contains an improper displacement measurement case. Although the original and new forms reasonably estimated the physical parameters in proper measurement cases, only the new form was effective in the improper case. The examinations confirmed the effectiveness of the acceleration-oriented form relying on the basic techniques and its applicability to estimating physical parameters of the seismically damaged structure for its condition assessment.
Hereditable variants of classical protein tyrosine phosphatase genes: Will they prove innocent or guilty?
Authors: Hendriks Wiljan J. A. J. , van Cruchten Remco T. P. , Pulido Rafael
Published: January 2023

Protein tyrosine phosphatases, together with protein tyrosine kinases, control many molecular signaling steps that control life at cellular and organismal levels. Impairing alterations in the genes encoding the involved proteins is expected to profoundly affect the quality of life—if compatible with life at all. Here, we review the current knowledge on the effects of germline variants that have been reported for genes encoding a subset of the protein tyrosine phosphatase superfamily; that of the thirty seven classical members. The conclusion must be that the newest genome research tools produced an avalanche of data that suggest ‘guilt by association’ for individual genes to specific disorders. Future research should face the challenge to investigate these accusations thoroughly and convincingly, to reach a mature genotype-phenotype map for this intriguing protein family.
Efficacy of lyophilised bacteria-rich faecal sediment and supernatant with reduced bacterial count for treating patients with Clostridioides difficile Infection – A novel method for capsule faecal microbiota transfer
Authors: Varga Adorján , Makszin Lilla , Bufa Anita , Sipos Dávid , Kása Péter , Pál Szilárd , Rosenstiel Philip , Sommer Felix , Kocsis Béla , Péterfi Zoltán
Published: January 2023

Background and aims

Faecal microbiota transfer (FMT) has managed to earn its place in the Clostridioides difficile infection (CDI) guidelines by having comparable efficacy and recurrence rate of fidaxomicin. After more than 100 successful FMT administration through nasogastric tube, we started using hard gelatine capsules filled with lyophilised faecal sediment and supernatant. Our main question was whether uncoated capsules (containing faecal sediment or supernatant) are comparable to the widely used nasogastric tubes in CDI. We also investigated the effect of storage and time on the survival rate of bacteria in the samples.

Methods

We compared the efficacy of our capsules to other treatment options of CDI at the Department of Infectology at the University of Pécs (Hungary). For our study, stool was collected from a single donor. We treated 10 patients with relapsing CDI, 5 of them received supernatant, 5 received sediment. Donor samples were stored on 4 different temperatures and tested to determine the survival rates of bacteria. As pilot projects, we also assessed the changes of bacterial taxa, protein- and lipid compositions. Moreover, we selected 4 patients to compare their samples prior and after FMT by using microbiome (16S amplicon sequencing), protein, and lipid analyses.

Results

4 out of the 5 patients who received supernatant became symptomless within 2 days after FMT. In the sediment group 3 out of 5 patients were cured from CDI. Comparing the supernatant to the sediment, we found significantly lower number of colony-forming units in the supernatant. We found that -80°C is the most suitable temperature to store the samples. The stool lipid profiles of recipients showed a more diverse composition after FMT, and changes in the stool protein profiles were observed as well. In the microbiome analysis, we observed an increase in the alpha diversity after FMT.

Conclusions

Our study of 10 patients showed good efficacy of lyophilised faecal supernatant using capsules. The single donor approach proved to be effective in our investigation. A significantly lower CFU number was sufficient for the effect, the separation can be achieved by widely available instruments. For storage temperature, -20°C was sufficient in our clinical practice.
Anemia is a risk factor for rapid eGFR decline in type 2 diabetes
Authors: Xie Lijie , Shao Xiaoqing , Yu Yifei , Gong Wei , Sun Fei , Wang Meng , Yang Yeping , Liu Wenjuan , Huang Xinmei , Wu Xia , Wu Huihui , Li Yiming , Zhang Zhaoyun , Wen Jie , He Min
Published: January 2023

Objective

To investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes.

Methods

This was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis.

Results

The prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine β2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline.

Conclusion

Anemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.
Incidence of endocrine-related immune-related adverse events in Japanese subjects with various types of cancer
Authors: Iwamoto Yuichiro , Kimura Tomohiko , Iwamoto Hideyuki , Sanada Junpei , Fushimi Yoshiro , Katakura Yukino , Tatsumi Fuminori , Shimoda Masashi , Nakanishi Shuhei , Mune Tomoatsu , Kaku Kohei , Kaneto Hideaki
Published: January 2023

Background

Immune checkpoint inhibitors (ICIs), such as cytotoxic T lymphocyte antigen-4 (CTLA-4) inhibitors, programmed cell death protein 1 (PD-1) inhibitors, and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors, are often used to treat a variety of malignancies. ICIs are known to cause endocrine-related immune-related adverse events (irAEs), but the incidence varies among reports and/or agents. This study evaluated the incidence of endocrine-related irAEs in patients who were treated with ICIs in Japan.

Method

This single-center, retrospective, observational study examined the incidence and clinical characteristics of endocrine-related irAEs in 466 participants who were treated with ICIs at Kawasaki Medical School Hospital.

Result

The mean age of participants with and without endocrine-related irAEs was 69.1 ± 1.8 years and 68.1 ± 1.1 years, respectively, with no difference between them. The overall incidence of any endocrine-related irAEs among the participants was 25.5%. Hypothyroidism was prevalent in 24.3%, hypoadrenocorticism in 3.2%, hypopituitarism in 0.9%, and insulin-dependent diabetes mellitus in 1.1%. Participants receiving combination therapy with CTLA-4 and PD-1 inhibitors had a significantly higher incidence of endocrine-related irAEs than those receiving monotherapy.

Conclusion

Endocrine-related irAEs correlated significantly with survival and mean observation period. There was substantial difference in the incidence of endocrine-related irAEs among various types of ICIs and types of cancer. We should bear in mind that endocrine testing is necessary during the treatment with ICIs.
Cell non-autonomous regulation of cerebrovascular aging processes by the somatotropic axis
Authors: Bickel Marisa A. , Csik Boglarka , Gulej Rafal , Ungvari Anna , Nyul-Toth Adam , Conley Shannon M.
Published: January 2023

Age-related cerebrovascular pathologies, ranging from cerebromicrovascular functional and structural alterations to large vessel atherosclerosis, promote the genesis of vascular cognitive impairment and dementia (VCID) and exacerbate Alzheimer’s disease. Recent advances in geroscience, including results from studies on heterochronic parabiosis models, reinforce the hypothesis that cell non-autonomous mechanisms play a key role in regulating cerebrovascular aging processes. Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) exert multifaceted vasoprotective effects and production of both hormones is significantly reduced in aging. This brief overview focuses on the role of age-related GH/IGF-1 deficiency in the development of cerebrovascular pathologies and VCID. It explores the mechanistic links among alterations in the somatotropic axis, specific macrovascular and microvascular pathologies (including capillary rarefaction, microhemorrhages, impaired endothelial regulation of cerebral blood flow, disruption of the blood brain barrier, decreased neurovascular coupling, and atherogenesis) and cognitive impairment. Improved understanding of cell non-autonomous mechanisms of vascular aging is crucial to identify targets for intervention to promote cerebrovascular and brain health in older adults.
Research progress and development tendency of polymer drilling fluid technology for unconventional gas drilling
Authors: He Yinbo , Jiang Guancheng , Dong Tengfei , Wang Guoshuai , He Jing , Dou Huanjun , Du Mingliang
Published: January 2023

Unconventional gas includes tight sandstone gas, shale gas, coalbed methane, and natural gas hydrate. With huge reserves, unconventional gas has become the most important natural gas resource successor after the end of the “Easy Oil era.” The drilling fluid is an indispensable wellbore working fluid for unconventional gas drilling with multiple functions. The polymer drilling fluid (PDF) is the most common, longest developed, and most diverse drilling fluid type. With advantages of easily controlled rheology, convenient on-site performance maintenance, and specifically low cost and weak environment pollution, the PDF is gradually replacing the oil-based drilling fluid as the first choice for unconventional gas drilling. The invention of the non-disperse low-solid-content PDF in the 1960s shows that PDF technology has entered the stage of scientific development, and until now, its development has generally experienced five stages: beginning, developing, improving, re-developing, and re-improving. Dozens of polymer additives and PDF systems have been invented and applied, which have solved severe drilling problems, greatly improved drilling efficiency, and promoted exploration and development in difficult oil and gas resources. This paper first reviews the research progress of PDF technology according to the timeline by introducing the composition, feature, advantages, and disadvantages of some representative polymer additives and PDF systems, emphatically the function and mechanism of stabilizing wellbores, lubricating drilling tools, and protecting reservoirs of the biomimetic wellbore-strengthening PDF and amphiphobic high-efficiency PDF in unconventional gas drilling. Then, combining future global demands, especially China’s strategic needs of oil and gas exploration and development, the development tendency of PDF technology is critically illustrated by introducing several potential research directions including intelligent PDF, ecological PDF, and PDF for natural gas hydrate and deep layer gas resources.
Enhancing transient stability of power systems using a resistive superconducting fault current limiter
Authors: Alashqar Mohamed , Yang Conghuan , Xue Ying , Liu Zhaoxi , Zheng Weiye , Zhang Xiao-Ping
Published: January 2023

The electricity demand keeps increasing with development and time, which leads to the need to install more generating units in the grid. Therefore, the fault current levels will rise above the limits of the electrical equipment, particularly when the electric grid becomes meshed and interconnected with neighboring networks. Consequently, the electrical equipment needs to be replaced or use a method that will decrease the fault current to be within the permissible boundaries. The existing solutions such as neutral impedance, current limiting reactor (CLR), and bus splitting have negative impacts on the electric grid. The superconducting fault current limiter (SFCL) appears to be a promising solution. In this paper, the resistive SFCL is proposed to enhance the stability of the interconnected power system. The two-area system is used as a case study for the interconnected power system. Also, the optimal value and locations of the resistive SFCL are analyzed. The results show that the system will remain stable without tuning the power system stabilizer (PSS).
Water Conflicts in Sub-Saharan Africa
Authors: Peña-Ramos José Antonio , José López-Bedmar Rafael , Sastre Francisco Javier , Martínez-Martínez Adrián
Published: January 2023

Freshwater is a strategic natural resource in any region of the world, and this is especially true for the Sub-Saharan Africa region. Sub-Saharan Africa states, where water ecosystems are strategic resources, are oriented towards regional conflict rather than cooperation. However, its fossil fuels—principally, oil and natural gas—have constantly been exposed to scientific scrutiny. To compensate for the scarcity of scientific literature on the issue, the article analyses the role of the unequal distribution of freshwater that has been generating conflicts in Sub-Saharan Africa from the time of decolonization. Next, these conflicts are examined. Recommendations on the non-conflictual use of water are provided.
Assessment of ecosystem health based on landscape pattern in ecologically fragile regions at different spatial scales: A case study of Dianchi Lake basin, China
Authors: Lei Dongmei , Zhang Yuan , Ran Yuju , Gao Liping , Li Jie , Li Zhiguo , Mo Jinxiao , Liu Xuan
Published: January 2023

In the process of urbanization, maintaining ecosystem health in ecologically fragile regions is an inevitable requirement for sustainable development in the future, but the ecological health status varies greatly at different spatial scales. Determining the appropriate spatial scale of ecological health assessment is the basis and premise of ecological management and environmental protection policy making. Taking Dianchi Lake basin as the research area, based on the vigor-organization-resilience (VOR) model and landscape pattern index, this study established an assessment system of ecological health to evaluate the ecosystem health status from quadrat, ecological and administrative scales, with the aim to determine a reasonable evaluation scale and strengthen regional sustainability. The results show that: 1) The suitable spatial grain of landscape pattern analysis in Dianchi Lake basin is 150 m. 2) The average values of ecosystem health indices at quadrat scale, ecological scale and administrative scale are 0.5466, 0.4977 and 0.5373, respectively, demonstrating a sub-health state. 3) The most suitable scale for ecological health assessment of Dianchi Lake basin is ecological scale, because taking sub-watershed as ecological unit can ensure the integrity of the evaluated ecosystem to the greatest extent. Multiscale assessment is helpful for eco-environmental management departments to understand the ecosystem health status at different scales and provide a scientific basis for regional eco-environmental management decisions.
Network-based quantitative trait linkage analysis of microbiome composition in inflammatory bowel disease families
Authors: Sharma Arunabh , Junge Olaf , Szymczak Silke , Rühlemann Malte Christoph , Enderle Janna , Schreiber Stefan , Laudes Matthias , Franke Andre , Lieb Wolfgang , Krawczak Michael , Dempfle Astrid
Published: January 2023

Introduction:Inflammatory bowel disease (IBD) is characterized by a dysbiosis of the gut microbiome that results from the interaction of the constituting taxa with one another, and with the host. At the same time, host genetic variation is associated with both IBD risk and microbiome composition.

Methods:In the present study, we defined quantitative traits (QTs) from modules identified in microbial co-occurrence networks to measure the inter-individual consistency of microbial abundance and subjected these QTs to a genome-wide quantitative trait locus (QTL) linkage analysis.

Results:Four microbial network modules were consistently identified in two cohorts of healthy individuals, but three of the corresponding QTs differed significantly between IBD patients and unaffected individuals. The QTL linkage analysis was performed in a sub-sample of the Kiel IBD family cohort (IBD-KC), an ongoing study of 256 German families comprising 455 IBD patients and 575 first- and second-degree, non-affected relatives. The analysis revealed five chromosomal regions linked to one of three microbial module QTs, namely on chromosomes 3 (spanning 10.79 cM) and 11 (6.69 cM) for the first module, chr9 (0.13 cM) and chr16 (1.20 cM) for the second module, and chr13 (19.98 cM) for the third module. None of these loci have been implicated in a microbial phenotype before.

Discussion:Our study illustrates the benefit of combining network and family-based linkage analysis to identify novel genetic drivers of microbiome composition in a specific disease context.
Single-cell analysis reveals melanocytes may promote inflammation in chronic wounds through cathepsin G
Authors: Yakupu Aobuliaximu , Zhang Di , Guan Haonan , Jiang Minfei , Dong Jiaoyun , Niu Yiwen , Tang Jiajun , Liu Yingkai , Ma Xian , Lu Shuliang
Published: January 2023

During acute wound (AW) healing, a series of proper communications will occur between different epidermal cells at precise temporal stages to restore the integrity of the skin. However, it is still unclear what variation happened in epidermal cell interaction in the chronic wound environment. To provide new insights into chronic wound healing, we reconstructed the variations in the epidermal cell-cell communication network that occur in chronic wound healing via single-cell RNA-seq (scRNA-seq) data analysis. We found that the intricate cellular and molecular interactions increased in pressure ulcer (PU) compared to AW, especially the PARs signaling pathways were significantly upregulated. It shows that the PARs signaling pathways’ main source was melanocytes and the CTSG-F2RL1 ligand-receptor pairs were its main contributor. Cathepsin G (CatG or CTSG) is a serine protease mainly with trypsin- and chymotrypsin-like specificity. It is synthesized and secreted by some immune or non-immune cells. Whereas, it has not been reported that melanocytes can synthesize and secrete the CTSG. F2R Like Trypsin Receptor 1 (F2RL1) is a member of proteinase-activated receptors (PARs) that are irreversibly activated by proteolytic cleavage and its stimulation can promote inflammation and inflammatory cell infiltration. In this study, we found that melanocytes increased in pressure ulcers, melanocytes can synthesize and secrete the CTSG and may promote inflammation in chronic wounds through CTSG-F2RL1 pairs, which may be a novel potential target and a therapeutic strategy in the treatment of chronic wounds.
PhageTailFinder: A tool for phage tail module detection and annotation
Authors: Zhou Fengxia , Yang Han , Si Yu , Gan Rui , Yu Ling , Chen Chuangeng , Ren Chunyan , Wu Jiqiu , Zhang Fan
Published: January 2023

Decades of overconsumption of antimicrobials in the treatment and prevention of bacterial infections have resulted in the increasing emergence of drug-resistant bacteria, which poses a significant challenge to public health, driving the urgent need to find alternatives to conventional antibiotics. Bacteriophages are viruses infecting specific bacterial hosts, often destroying the infected bacterial hosts. Phages attach to and enter their potential hosts using their tail proteins, with the composition of the tail determining the range of potentially infected bacteria. To aid the exploitation of bacteriophages for therapeutic purposes, we developed the PhageTailFinder algorithm to predict tail-related proteins and identify the putative tail module in previously uncharacterized phages. The PhageTailFinder relies on a two-state hidden Markov model (HMM) to predict the probability of a given protein being tail-related. The process takes into account the natural modularity of phage tail-related proteins, rather than simply considering amino acid properties or secondary structures for each protein in isolation. The PhageTailFinder exhibited robust predictive power for phage tail proteins in novel phages due to this sequence-independent operation. The performance of the prediction model was evaluated in 13 extensively studied phages and a sample of 992 complete phages from the NCBI database. The algorithm achieved a high true-positive prediction rate (>80%) in over half (571) of the studied phages, and the ROC value was 0.877 using general models and 0.968 using corresponding morphologic models. It is notable that the median ROC value of 992 complete phages is more than 0.75 even for novel phages, indicating the high accuracy and specificity of the PhageTailFinder. When applied to a dataset containing 189,680 viral genomes derived from 11,810 bulk metagenomic human stool samples, the ROC value was 0.895. In addition, tail protein clusters could be identified for further studies by density-based spatial clustering of applications with the noise algorithm (DBSCAN). The developed PhageTailFinder tool can be accessed either as a web server (http://www.microbiome-bigdata.com/PHISDetector/index/tools/PhageTailFinder) or as a stand-alone program on a standard desktop computer (https://github.com/HIT-ImmunologyLab/PhageTailFinder).
Anti-IL-17A antibody-associated de novo vitiligo: Case report and review of literature
Authors: Su Hsing-Jou , Chan Yu-Pei , Shen Peng-Chieh , Ku Cheng-Lung , Ng Chau Yee
Published: January 2023

Interleukin (IL)-17 inhibitor is a biological therapy approved for moderate to severe psoriasis and psoriatic arthritis. The common adverse events of IL-17 inhibitor include injection site reaction, infections, nasopharyngitis, and headache. However, vitiligo associated with the use of IL-17 inhibitors was rarely reported in the previous literature. Here we described a woman who developed de novo vitiligo after 4 months of IL-17A inhibitor treatment for psoriasis and psoriatic arthritis. Upon discontinuation of IL-17A inhibitor and shifting to a broader T cell inhibitor—cyclosporine, our patient had control of both psoriasis and vitiligo and achieved 75% repigmentation after 3 months of oral cyclosporine without phototherapy. Due to the increasing use of anti-IL-17 biologics in psoriasis patients, clinicians should inquire about vitiligo’s history before treatment and inform patients of the possible adverse effects.
Autophagy-related IFNG is a prognostic and immunochemotherapeutic biomarker of COAD patients
Authors: Yue Taohua , Cai Yunlong , Zhu Jing , Liu Yucun , Chen Shanwen , Wang Pengyuan , Rong Long
Published: January 2023

Background

Numerous studies have shown autophagy affects cellular immune responses. This study aims to explore prognosis and immunotherapeutic biomarkers related to autophagy in colon adenocarcinoma (COAD).

Methods

Based on R software, we performed the ssGSEA, differential expression analysis, Kaplan-Meier survival analysis, correlation analysis, and enrichment analysis. For wet experiment, we did qRT-PCR, immunohistochemistry and CCK-8 experiments.

Results

Using autophagy-related genes (ARGs) and the ssGSEA, COAD patients were divided into low and high autophagy groups. For immune score, stromal score, tumor purity, tumor infiltrating immune cells, co-signaling molecules, tumor mutational burden, microsatellite instability, mismatch repair, immune-related pathways, immune signatures, somatic mutations and subtype analysis, high autophagy group might benefit more from immunotherapy. Among 232 ARGs, IFNG was generally significantly correlated with tumor immunotherapy biomarkers (PD-L1, CD8A and cytotoxic T lymphocytes (CTL)). The disease-free survival of high IFNG group was significantly longer than that of low group. On above-mentioned immune-related research, the high IFNG group reached the same conclusion. The qRT-PCR and IHC analysis confirmed that IFNG was significantly higher expressed in dMMR samples compared to pMMR samples. For chemotherapy, the autophagy and IFNG were significantly negatively related to the chemosensitivity to cisplatin; IFNG inhibitor glucosamine increased cisplatin chemoresistance while IFNG increased cisplatin chemosensitivity; IFNG could reverse glucosamine induced chemoresistance. The functional enrichment analysis of IFNG, PD-L1, CD8A and 20 similar proteins were related to the activation of the immune system. The GSEA and ceRNA network partly described interaction mechanisms of IFNG with PD-L1 and CD8A.

Conclusion

Autophagy score and IFNG expression were novel immunotherapy predictive biomarkers, which might play predictive effects through the JAK-STAT signaling pathway. IFNG might be a potential targeted therapy for cisplatin resistant colon cancer. Besides, IFNG was also a prognostic indicator.
The effect of anti-PD-1/PD-L1 antibodies combined with VEGF receptor tyrosine kinase inhibitors versus bevacizumab in unresectable hepatocellular carcinoma
Authors: Zeng Hui , Xu Qi , Wang Jinyu , Xu Xiaoqing , Luo Jun , Zhang Lei , Luo Cong , Ying Jieer , Li Jingjing
Published: January 2023

Introduction

Immune checkpoint inhibition (ICI) plus bevacizumab (BEV) is the standard first-line treatment for unresectable hepatocellular carcinoma (uHCC). We aimed to assess the efficacy and safety of ICI plus bevacizumab and ICI plus receptor tyrosine kinase inhibitor (TKI) in this patient population.

Methods

This retrospective single-institution study enrolled 94 patients with uHCC who received ICI plus TKI or bevacizumab as the first-line treatment. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were used to evaluate treatment efficacy. RECIST v1.1 criteria were used to calculate the objective clinical response. Common Terminology Criteria for Adverse Events were used to report and categorize adverse events.

Results

By the last follow-up interview on May 15, 2022, there were 57 deaths, and 19 patients did not develop disease progression. Thirty patients received sintilimab/atezolizumab plus bevacizumab (ICI + BEV group), and 64 received ICI plus TKI (ICI + TKI group). The median OS was 430 days (95% CI, 266-NA) in the ICI+TKI group and 498 days (95% CI, 349-NA) in the ICI+BEV group (HR, 1.20; 95% CI, 0.69-2.07; P = 0.52). There was no significant difference between the two groups in the median PFS (182 vs. 221 days, P=0.67). In the ICI+TKI group, the ORR and DCR were 28.1% and 67.2%, respectively. In the ICI+BEV group, the ORR and DCR were 26.7% and 66.7%, respectively. The overall incidence of adverse events was similar between the two groups. Palmar-plantar erythrodysesthesia syndrome (23[36%]) occurred only in the ICI + TKI group. Patients who received ICI+BEV were more prone to upper gastrointestinal bleeding (2 [7%]), with one patient with grade 4 requiring emergency DSA treatment.

Conclusion

This study found that ICI+TKI and ICI+BEV as first-line treatments were similar in OS, PFS, and tumor response in uHCC. Different populations are suitable for different regimens because of the different adverse events.
Dendritic cells in inborn errors of immunity
Authors: Gupta Sudhir , Agrawal Anshu
Published: January 2023

Dendritic cells (DCs) are crucial cells for initiating and maintaining immune response. They play critical role in homeostasis, inflammation, and autoimmunity. A number of molecules regulate their functions including synapse formation, migration, immunity, and induction of tolerance. A number of IEI are characterized by mutations in genes encoding several of these molecules resulting in immunodeficiency, inflammation, and autoimmunity in IEI. Currently, there are 465 Inborn errors of immunity (IEI) that have been grouped in 10 different categories. However, comprehensive studies of DCs have been reported in only few IEI. Here we have reviewed biology of DCs in IEI classified according to recently published IUIS classification. We have reviewed DCs in selected IEI in each group category and discussed in depth changes in DCs where significant data are available regarding role of DCs in clinical and immunological manifestations. These include severe immunodeficiency diseases, antibody deficiencies, combined immunodeficiency with associated and syndromic features, especially disorders of synapse formation, and disorders of immune regulation.
Tissue-resident memory T cells in renal autoimmune diseases
Authors: Ginsberg Pauline , Panzer Ulf , Asada Nariaki
Published: January 2023

The discovery of tissue-resident memory T cells (TRM cells) reinterpreted the potential of human tissue-specific immunity. Following T cell receptor (TCR) activation and clonal expansion, effector T cells migrate to peripheral tissues where they remain long-term and differentiate to TRM cells after antigen clearance. This allows for prompt immunological responses upon antigen re-encounter. In addition to their protective properties in acute infections, recent studies have revealed that TRM cells might lead to aggravation of autoimmune diseases, such as lupus nephritis (LN) and anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis (GN). These diseases present as proliferative and crescentic glomerulonephritis (cGN), which is a life-threatening condition leading to end-stage renal disease (ESRD) if left untreated. A better understanding of renal TRM cells might lead to identifying new therapeutic targets for relapsing autoimmune diseases of the kidney. In this review, we summarize the current knowledge of renal TRM cells and discuss their potential pathophysiological roles in renal autoimmune diseases.