bluuebunny/crossref_metadata_2025 huggingface dataset:
Immoralism and Contextualism
Authors: Jacobson Daniel
Published: August 2023

The twentieth century saw a robust debate over autonomism, the thesis that the moral qualities of artworks are irrelevant to their aesthetic value. Until recently, those philosophers of art who denied autonomism assumed the truth of moralism, the view that the moral defects of artworks, whenever they are aesthetically relevant, count as aesthetic flaws in the work. This assumption was called into question at the end of the century, when it was noted that moral defects in artworks might be aesthetically relevant without figuring as defects; they might instead sometimes figure as aesthetic virtues. This thesis is sometimes referred to as immoralism, but a better term for the view that such moral flaws can figure either as blemishes or virtues of artwork is contextualism. This chapter contends that the best arguments against autonomism support contextualism rather than moralism. Philosophers have failed to appreciate the respects in which audiences do not apply the same moral standards to works of art that they would apply were they real-life spectators of the actions depicted in it (somehow prevented from intervention). Indeed, appreciation of narrative art requires such deviation from responses that would be required by virtue in realistic contexts.
Ethics and Music
Authors: Higgins Kathleen
Published: August 2023

Many ethical issues related to the arts in general apply to music, but the focus in this chapter is on the specific aspects of music that give it ethical power for good or ill. After considering some of music’s physiological and psychological impacts, the author considers three ways in which it can contribute to moral education. Specifically, it can model good interpersonal interaction, help develop virtues useful to constructing good relationships, and provoke feelings of affinity that can motivate pro-social attitudes and dispositions. The musical mechanisms that encourage solidarity, however, can also be exploited for unethical projects. Although sometimes moral criticism is more aptly directed at texts and uses than at music itself, music tends to acquire associations that are hard to eliminate, and responses often reference the composite. To make morally responsible choices regarding music such associations should be considered, particularly those that link specific music with particular groups of people.
Some Moral Features of Theatrical Art
Authors: Hamilton James R.
Published: August 2023

This chapter undertakes three main tasks: it shows, where possible, the current state in theater and performance studies as well as philosophy concerning moral worries about theater; it distinguishes between worries due to specific styles of presentation within theater from those due, instead, to the art-form itself; and it argues that some of these concerns are, in the end, not genuine moral worries at all. While the author does not take a stand on how any of the moral issues are to be resolved, he does take a stand on whether those issues are real. The focus in the entry is on moral issues about theatrical performances per se rather than the contents presented in them. For example, the entry discusses issues that can arise in rehearsal processes, but makes only brief remarks on moral issues arising out of the contents of scripts.
Architecture
Authors: Fisher Saul
Published: August 2023

Ethical issues of architecture arise relative to its processes of creation, its reception and use, and its maintenance and life cycle—all as a function of architecture’s aesthetic or artistic character and values, though not exclusively so. While autonomism and moralism in architecture are much debated, the focus is generally on architecture as art, to the neglect of architectural aesthetics beyond architecture as art. Moreover, as an artform deeply integrated with other, nonart pursuits and domains, architecture generates more complex ethical issues than do artforms that solely count as art. Harder ethical questions, then, include how—in light of such complexities—one may identify morally warranted conditions for architectural works and for gauging their propriety or relevant preferences and, as conceptually prior, what the nature is of moral agency, objects, actions, obligations, properties, virtues, and values in architecture.
Ethics and Video Games
Authors: Bartel Christopher
Published: August 2023

Ethics in video gaming is a broad topic that extends beyond the familiar worries about moral panics. This chapter will first divide ethical issues into internal and external questions. The ethical issues internal to video games arise due to both their status as fictions and their status as games. First, the chapter examines how moral values are inherent within games and how players respond to and play with those values. Next the chapter examines external ethical issues, which are those that focus on the nature of the gaming industry and gaming cultures. The issues discussed here include representations of gender and race in games and the ecological impacts of the gaming industry. Finally, the chapter examines some moral issues that straddle the line between internal and external, and briefly considers problems with multiplayer games, harassment, and trolling.
Art and Pornography
Authors: Eaton A. W.
Published: August 2023

This chapter begins by briefly surveying philosophical discussions of the purported distinction between art and pornography, such as Levinson, Kieran, Mag Uidhir, Maes, and Eaton—with an eye toward isolating potential ethical features of each. “Art” is construed broadly to include popular culture, and pornography is treated not as a monolith but rather as a diverse category of representation that includes queer porn and feminist porn, to name only a few. After reviewing the art versus porn debate (with an eye toward ethical issues), the chapter then puts issues in the pornography literature and the aesthetics-and-ethics literature into conversation with one another. Issues discussed include the ethics of the production of works (both pornographic and artistic), the ethics of fantasy, moral lessons to be gleaned from works, and the influence of works on audience’s character.
Group Agency, Alienation, and Public Art
Authors: Willard Mary Beth
Published: August 2023

This chapter argues that a complete analysis of the ethics of public art must consider not just the ethics of the subject of the art, as in the case of monuments to the immoral, but the way that art is used by the public to define what it means to be part of the public. The author begins by focusing on how public art contributes to the success of group agency, as when aesthetic practices, like placing public art, encourage individuals to align their aims and attitudes with those of the group. When an aesthetic practice of a group fails to engage a member of the group, they may be alienated. When the resulting alienation intersects with other forms of injustice, the placement of the artwork in the public sphere may be unjust even if the artwork considered by itself, or in another context, is ethically unobjectionable.
Ethics of Artistic Authorship
Authors: Gover Karen
Published: August 2023

While much of the conversation concerning ethics and artworks concerns the content of artworks, this chapter looks at the ethical concerns involved in artistic authorship itself: who counts as an artistic author, what artistic authorship entails, and why the seemingly straightforward empirical question of who is responsible for creating a work of art entails ethical questions of credit, property, and ownership. This chapter begins with the general concept of authorship, and then the author explains why authorship of artwork is treated as a distinctive kind. Once the basic contours of authorship have been established, the chapter discusses a series of common variations involving artworks and overlapping ownership claims. The ethical questions can become even more complicated when different people lay claim to one and the same the work as their property, but in different respects.
Cultural Appropriation
Authors: Nguyen C. Thi , Strohl Matthew
Published: August 2023

Cultural appropriation is a broad umbrella term for a number of phenomena related to the borrowing of elements of a culture other than one’s own. This chapter summarizes arguments that have been offered in recent debates among analytic philosophers and other commentators concerning the normativity of cultural appropriation. The authors suggest that most of the views on offer have both strengths and weaknesses and how one adjudicates between them will depend on which theoretical desiderata one prioritizes. The issue is complex and the wide range of relevant considerations often support conflicting positions. The authors think that this state of affairs should lead us to be wary of sweeping generalizations about the normativity of cultural appropriation.
Art and Ethics in Islam
Authors: Leaman Oliver
Published: August 2023

Islam first arose in a cultural environment where poetry was held in high regard, and yet the Qur’an defined itself as nonpoetic, despite the beauty of many of its verses. Poetry was regarded as immoral, and Islam, like religions in general, took a firm line on the significance of ethics in all undertakings. The visual arts often illustrated a moral landscape where truths were displayed at the expense of perspective. The Qur’an and the sayings of the Prophet and his companions are generally taken to focus on beauty’s ability to inflame the passions in generally undesirable ways. Sufism, by contrast, tends to value beauty and link it with religious truth and morality. Many other Islamic schools of thought that are skeptical of the moral value of the arts. This rather disapproving attitude toward the arts has persisted in Islam up to today.
Frances Power Cobbe and Periodical Philosophy
Authors: Hamilton Susan
Published: August 2023

This chapter considers the importance of the nineteenth-century periodical press in women’s philosophical writing by exploring Frances Power Cobbe’s writing on women’s autonomy and humans’ duties to animals. As a working journalist, Cobbe sought to articulate a new ethics of autonomy for women and justice for animals. Writing across the variety of publishing platforms and the multiple time signatures of the periodical press to invite readers to an ethical consideration, Cobbe sought to ensure the widest possible circulation and amplification of her ethical approach to contemporary social and political problems. Her skillful exploitation of new publication venues that also strove to challenge orthodox views and created new conventions of debate is central to her achievements as a thinker.
Helena Petrovna Blavatsky
Authors: Rudbøg Tim
Published: August 2023

This chapter considers Helena Petrovna Blavatsky’s place in the history of philosophy. She is known as a theosophist, but is she, in fact, an overlooked women philosopher? To answer this question, the chapter discusses what the history of philosophy means and the criteria one might propose for accepted inclusion. It takes an intertextual approach to Blavatsky’s role to demonstrate that Blavatsky engaged with philosophy and formulated her views on being, consciousness, space, and time in dialogue with philosophers, including Kant, Fichte, Hegel, and Spencer. Blavatsky considered her project to be philosophy, but her understanding of what true philosophy entails was different from that of many of her contemporaries. The chapter argues that Blavatsky should be considered a philosopher in her own right, though she was also more than a philosopher.
Accompanying LGBTQIA+ Students in the Music Classroom
Authors: McManus Justin , Carter Bruce Allen
Published: August 2023

This chapter discusses the importance of relationship-building and fostering an affirming, welcoming space for LGBTQIA+ students in music classrooms. Specifically, this article borrows the term “accompaniment” from our common musical language to conceptualize the ideal relationship between educators and their LGBTQIA+ music students. The authors conceive of accompaniment as a long-term partnership rooted in empathy, flexibility, and critical listening. Following a brief review of recent music education literature related to LGBTQIA+ students, the authors present two vignettes that describe instances in which students were and were not accompanied on their musical journeys. Finally, the chapter concludes with implications and recommendations for music educators who strive to build lasting, empowering relationships with their queer students.
Fostering Reciprocal and Responsive Musical Relationships in a Youth Instrumental Ensemble
Authors: Legutki Allen R. , Hendricks Karin S. , Smith Tawnya D. , King Kristi N.
Published: August 2023

This chapter profiles the “caring with” approach of orchestral conductor Mark Russell Smith in fostering reciprocal and responsive music relationships in guest conducting situations. This chapter describes the conductor’s progression through Atik’s (1994) stages of interaction with performers, including the establishment of leadership authority and trust, and development of roles and expectations. These stages were evident in his literature choice, rehearsal style, conducting, pacing, community building, guided listening of peer performance, and performing for the students from the podium. It also notes a “caring with” approach to balanced authority and group ownership of the experience. This approach models an alternative to traditional top-down structures, and presents examples of how conductors might nurture increasingly reciprocal and responsive musical relationships over time.
Developing Trust and Empathy Through Peer Mentoring in the Music Classroom
Authors: Goodrich Andrew
Published: August 2023

The pedagogical practice of peer mentoring provides opportunities for students to share their knowledge and experiences in conjunction with the music teacher. Sharing in the learning process during peer mentoring can lead toward developing two salient components of compassionate music teaching: trust and empathy. A learning environment based in trust and empathy may create the foundation for caring relationships in which students and the music teacher co-create learning spaces toward establishing a community of learning. But the potential exists for hierarchies to develop during peer mentoring, where a select group of students may co-create goals with the music teacher. This presents a potential conflict when establishing trust and empathy among all students, for institutional norms may be reified in that students from dominant white populations may control the narrative of learning in the music classroom. It is vital for the music teacher to play a highly active role in ensuring that all students engage in peer mentoring and the co-creation of learning goals. Throughout these processes, then, trust and empathy take on a more substantial role toward establishing a community of learning based in compassionate music teaching where all students feel welcome in the music classroom.
Somatic Self-Care for Music Educators
Authors: Paparo Stephen A.
Published: August 2023

This chapter posits that the soma––the body perceived from within––is an important component of self-care for music educators and their students. Somaesthetics, a pragmatic philosophical discipline, lays the foundation for understanding bodily consciousness and the inclusion of somatic practice as a means to improve self-function. The Feldenkrais Method of somatic education offers a pedagogical framework for learning to observe oneself in action, while developing sensory acuity in order to clarify and improve function and performance. Participation in the Feldenkrais Method as somatic self-care can help educators and their students embody the six characteristics of compassionate music teaching. Recommendations and applications to teaching and learning are provided.
The Sounds of Hope
Authors: Good-Perkins Emily
Published: August 2023

For many Black, Indigenous, People of Color (BIPOC) in the United States, schools are hostile environments where their cultural ways of being are pathologized and blamed. To counter the continued marginalization of children of color in schools, Love, with her abolitionist teaching framework, calls for educators to actively harness the cultural wealth of students’ communities to empower them in the classroom. Music education spaces have the potential to be powerful spaces for self-expression and cultural sustenance if enacted with care and compassion. However, before music classrooms can become “homeplaces” for all children, systemic inequities within music education must first be dismantled. This chapter explores the theoretical and pedagogical nuances of a compassionate, abolitionist music teaching paradigm.
Critical Race Theory and Care in Music Education
Authors: Lewis Amy
Published: August 2023

Understanding systemic racism through a lens of critical race theory can help music educators to critically examine their own practices as teachers and consider how equitable teaching practices might look. This chapter describes the experience of four music educators who learn about CRT and how an understanding of systemic racism can expand the opportunity to emphasize care in the classroom. Critical race theory is a lens through which to understand how race and racism operates in our society. With an understanding of systemic racism through critical race theory, music education practitioners can gain a deeper awareness of power, oppression, and racism in order to transform our profession toward a more caring centered profession. Critical race theory critiques color-neutral ideology where different races and identity points are acknowledged and not ignored. Educators can expand their ability to see, celebrate, and care for students and their differences while simultaneously dismantling oppressive structures.
Cultural Humility and Ethics of Caring in Multicultural Settings of Music Teacher Education
Authors: Ehrlich Amira
Published: August 2023

This chapter explores a new possible paradigm of multiculturalism in the music classroom. Chang et al. (2012) presented the Chinese word QIAN (humbleness) as an acronym representing the attributes of Questioning, Immersion, Active-Listening, and Negotiation. Exploring the practice of a music teacher education in Israel, this chapter reflects on the relevance of this model to the teacher’s positionality as a Jewish Orthodox woman teaching students from diverse Jewish and Arab socioreligious sectors. Examples from practice are presented and analyzed to show how such processes of collective unknowing emanate a paradigm of authentic care. Validation of individual particularities allow us to engage in difficult conversations even while maintaining emotional safety. Care is made possible through a commitment to differences.
Engaged Dissent
Authors: Callander Adrienne
Published: August 2023

This multiple-case study examines the operation and interaction of entrepreneurship and art in the institutional practice of visual artists Nan Goldin, Theaster Gates, and Yayoi Kusama. Case analysis narrows its focus to the exercise of emancipatory, public, and effectual principles of entrepreneurship within aesthetic frameworks informed by art practices ranging from punk to performance to social practice to Pop Art, in tandem with lived experience. Overlaps between cases highlight the role of performance art, sector spanning, and marginalization as factors in all three artists’ instigation of institutional change. As backdrop to the cases, this chapter bridges institutional entrepreneurship and institutional critique to establish a transdisciplinary theoretical baseline for agency. In the process, it discerns the potential for entrepreneurship studies to bolster and renew institutional practice in art.
The Criticism of Eurocentrism and International Law
Authors: Mbengue Makane Moïse , Akinkugbe Olabisi D.
Published: August 2023

This chapter draws on Third World Approaches to International Law (TWAIL) in examining the question: how does the research and teaching of international law in the Global South challenge Eurocentrism in international law. The chapter focuses on the emergent activities within the Global South that pluralize Eurocentric international law’s dominance in the research production, teaching, and practice arenas. The chapter pushes against the unfair over-representation of European countries in the scholarly production and institutions of international law. To illustrate the often-underexplored regional diversity of international law outside Europe, the chapter reflects on the contemporary roles of critical Global South scholars and scholarship in international law, and the sub-fields of international investment law and international human rights law to pluralize the epistemological foundations of the substantive field of international law.
NOVEL APPLICATION OF DEEP ANTERIOR LAMELLAR KERATOPLASTY FOR RETINAL DETACHMENT REPAIR IN TOTALLY OPAQUE CORNEA SECONDARY TO ANIRIDIA
Authors: Simpson Alasdair Innes , Al-Hayouti Huda , Ramaesh Kanna , Saidkasimova Shohista
Published: August 2023

Purpose:

We present a novel approach for managing retinal detachment in a patient with aniridia-related corneal scarring precluding fundal view through a deep anterior lamellar keratoplasty.

Methods:

A 30-year-old female patient who had bilaterally opaque cornea, due to advanced aniridia-related keratopathy presented with, experiencing flashing of light in her right eye. Examination of the retinal fundus was not possible because of the dense corneal scarring and underlying cataract. A superior bullous macula-off retinal detachment was diagnosed on ultrasonography. VA at presentation was hand motions. The corneal scarring extended to the mid-to-deep stroma. We performed a deep anterior lamellar dissection of the opacified corneal stroma, which allowed clear visualization of a dense cataract. The cataract was removed by phacoemulsification and intraocular lens (IOL) inserted. This allowed to proceeding with repair of retinal detachment through pars plana approach. The surgery was completed by a donor deep lamellar keratoplasty.

Results:

This achieved a good fundal view to proceed with phacovitrectomy visualized through the residual corneal layers. Uneventful pars plana vitrectomy, cryotherapy, and sulfur hexafluoride (SF6) gas were performed to reattach the retina. Postoperatively, the graft remains clear at 6 months with a VA of 20/160 in the right eye, a level of vision the patient had not experienced for decades.

Conclusion:

Deep anterior lamellar keratoplasty offered an alternative to temporary keratoprosthesis to achieve a clear view of the retinal fundus and perform pars plana vitrectomy and repair of the retinal detachment.
Predicting direct healthcare costs of general practitioner–guided care in patients with musculoskeletal complaints
Authors: Pellekooren Sylvia , Ben Ângela J. , van Dongen Johanna M. , Pool-Goudzwaard Annelies L. , van Tulder Maurits W. , van den Berg Jesse M. , Ostelo Raymond W.J.G.
Published: August 2023

Information on healthcare utilization and costs of general practitioner (GP)–guided care in patients with musculoskeletal complaints is important for keeping healthcare affordable and accessible. A registry-based study was performed to describe healthcare utilization and costs of GP-guided care in patients with musculoskeletal complaints and to predict having higher direct healthcare costs. Healthcare costs of GP-guided care included all healthcare resources used by patients due to a musculoskeletal condition in 2018. Data were extracted from the database with a 1-year follow-up and descriptively analyzed. A general linear model was developed to predict having higher direct healthcare costs. In total, 403,719 patients were included, of whom 92% only received a single consultation. The number of referrals varied across the different types of complaints. Total annual direct healthcare costs amounted to €39,180,531, of which a key cost driver was referrals. Primary care consultations accounted for the largest part of referral-related costs. For all musculoskeletal conditions combined, the mean annual direct healthcare cost per patient was €97 (SEM = €0.18). Older age, being a woman, low socioeconomic status, spine complaints, high number of musculoskeletal diagnoses, and a high comorbidity score were predictive of having higher direct healthcare costs and explained 0.7% of the variance. This study showed that mean annual direct healthcare costs of GP-guided care in patients with musculoskeletal conditions were relatively low and did not differ considerably across conditions. The predictive model explained a negligible part of the variance in costs. Thus, it is unclear which factors do predict high direct healthcare costs in this population.
The Validity and Reliability of the Workplace Culture of Health Scale–Short Form
Authors: Marenus Michele W. , Marzec Mary , Kilbourne Amy , Colabianchi Natalie , Chen Weiyun
Published: August 2023

Objective

A positive workplace culture of health can have significant benefits for both employees and organizations. The objective of this study was to test the validity and reliability of the Workplace Culture of Health (COH) Scale–Short Form.

Methods

We conducted a confirmatory factor analysis on data collected from a sample of 12,907 employees across 14 organizations. We examined the construct validity of the 14-item short-form version of the Workplace COH scale and assessed its reliability using internal consistency measures.

Results

Our confirmatory factor analysis demonstrated that the Workplace COH Scale–Short Form had strong model fit, indicating good construct validity. In addition, we found that all constructs had strong internal consistency reliability.

Conclusions

Findings suggest that the Workplace COH Scale–Short Form is a valid and reliable way to practically assess workplace culture of health from the employee perspective.
Long-term outcomes (beyond 5 years) of liver transplant recipients—A transatlantic multicenter study
Authors: Palaniyappan Naaventhan , Peach Emily , Pearce Fiona , Dhaliwal Amritpal , Campos-Varela Isabel , Cant Matthew R. , Dopazo Cristina , Trotter James , Divani-Patel Sapna , Hatta Ayiesha A.Z. , Hopkins Laurence , Testa Giuliano , Bilbao Angela , Kasmani Zain , Faloon Sarah , Mirza Darius F. , Klintmalm Goran B. , Bilbao Itxarone , Asrani Sumeet K. , Rajoriya Neil , Aravinthan Aloysious D.
Published: August 2023

The long-term (>5 y) outcomes following liver transplantation (LT) have not been extensively reported. The aim was to evaluate outcomes of LT recipients who have survived the first 5 years. A multicenter retrospective analysis of prospectively collected data from 3 high volume LT centers (Dallas-USA, Birmingham-UK, and Barcelona-Spain) was undertaken. All adult patients, who underwent LT since the inception of the program to December 31, 2010, and survived at least 5 years since their LT were included. Patient survival was the primary outcome. A total of 3682 patients who survived at least 5 years following LT (long-term survivors) were included. Overall, median age at LT was 52 years (IQR 44–58); 53.1% were males; and 84.6% were Caucasians. A total of 49.4% (n=1820) died during a follow-up period of 36,828 person-years (mean follow-up 10 y). A total of 80.2% (n=1460) of all deaths were premature deaths. Age-standardized all-cause mortality as compared to general population was 3 times higher for males and 5 times higher for females. On adjusted analysis, besides older recipients and older donors, predictors of long-term mortality were malignancy, cardiovascular disease, and dialysis. Implementation of strategies such as noninvasive cancer screening, minimizing immunosuppression, and intensive primary/secondary cardiovascular prevention could further improve survival.
CTNNB1 and APC Mutations in Sinonasal Myxoma
Authors: Chen Sonja , Gallant Sara , Cunningham Michael J. , Robson Caroline D. , Church Alanna J. , Perez-Atayde Antonio R. , Al-Ibraheemi Alyaa
Published: August 2023

Sinonasal myxoma (SNM) is a rare, benign mesenchymal neoplasm with distinct clinicopathologic features and aberrant nuclear localization of β-catenin by immunohistochemistry. The molecular underpinnings have been linked to that of a “myxoid variant” of desmoid fibromatosis. Herein, we describe a series of 8 cases of SNM and propose clinical and biologic differences compared with desmoid fibromatosis. Our patient cohort is comprised of 5 males and 3 females (age range: 10 mo to 12 y), 6 of whom are aged less than or equal to 24 months. All presented with facial swelling, reflecting lesions involving the maxillary bone, and all underwent resection. All tumors were variably cellular and comprised of bland spindled to stellate cells in a profusely myxoid background with diffuse nuclear β-catenin expression. All cases of SNM were analyzed by next-generation sequencing using the Oncopanel assay. Three cases failed sequencing, 2 of 5 successful cases exhibited exon 3 CTNNB1 alterations involving the ubiquitin recognition motif, and 3 had adenomatous polyposis coli (APC) deletions. One patient had APC germline testing which was negative. No germline testing was available for the remaining 7 patients. Follow-up data over a range of 1 month to 23 years was available for 7 of the 8 SNMs. One case patient had local recurrence, and all were alive without evidence of disease. This is in contrast to the high recurrence rate typically seen in desmoid fibromatosis, particularly after resection. Our findings expand the spectrum of tumors with underlying WNT/β-catenin pathway and highlight the histologic, clinical, and genetic differences of SNM compared with desmoid fibromatosis. APC deletion raises the possibility of underlying germline alteration and familial adenomatous polyposis.
Public health implementation of pathogen genomics: the role for accreditation and application of ISO standards
Authors: Ballard Susan A. , Sherry Norelle L. , Howden Benjamin P.
Published: August 2023

Pathogen genomics has transitioned rapidly from the research setting into a powerful tool now routinely used in public health microbiology, for surveillance, outbreak investigations and disease control. As these investigations can have significant public health, treatment and legal impacts, we must ensure the accuracy of these results through validation of testing processes. For laboratories working in this space, it is important to approach this work with a quality and accreditation framework in mind, working towards implementation of quality systems and test validation that meet international regulatory standards. Here we outline the key international standards and processes that lead toward accreditation for pathogen genomics.
Different coexistence patterns between apex carnivores and mesocarnivores based on temporal, spatial, and dietary niche partitioning analysis in Qilian Mountain National Park, China
Authors: Cong Wei , Li Jia , Hacker Charlotte , Li Ye , Zhang Yu , Jin Lixiao , Zhang Yi , Li Diqiang , Xue Yadong , Zhang Yuguang
Published: August 2023

Carnivores play key roles in maintaining ecosystem structure and function as well as ecological processes. Understanding how sympatric species coexist in natural ecosystems is a central research topic in community ecology and biodiversity conservation. In this study, we explored intra- and interspecific niche partitioning along spatial, temporal, and dietary niche partitioning between apex carnivores (wolfCanis lupus, snow leopardPanthera uncia, Eurasian lynxLynx lynx) and mesocarnivores (Pallas’s catOtocolobus manul, red foxVulpes vulpes, Tibetan foxVulpes ferrilata) in Qilian Mountain National Park, China using camera trapping data and DNA metabarcoding sequencing data. Our study showed that apex carnivore species had more overlap temporally (coefficients of interspecific overlap ranging from 0.661 to 0.900) or trophically (Pianka’s index ranging from 0.458 to 0.892), mesocarnivore species had high dietary overlap with each other (Pianka’s index ranging from 0.945 to 0.997), and apex carnivore and mesocarnivore species had high temporal overlap (coefficients of interspecific overlap ranging from 0.497 to 0.855). Large dietary overlap was observed between wolf and snow leopard (Pianka’s index=0.892) and Pallas’s cat and Tibetan fox (Pianka’s index=0.997), suggesting the potential for increased resource competition for these species pairs. We concluded that spatial niche partitioning is likely to key driver in facilitating the coexistence of apex carnivore species, while spatial and temporal niche partitioning likely facilitate the coexistence of mesocarnivore species, and spatial and dietary niche partitioning facilitate the coexistence between apex and mesocarnivore species. Our findings consider partitioning across temporal, spatial and dietary dimensions while examining diverse coexistence patterns of carnivore species in Qilian Mountain National Park, China. These findings will contribute substantially to current understanding of carnivore guilds and effective conservation management in fragile alpine ecosystems.
TLR2 Regulates Hair Follicle Cycle and Regeneration via BMP Signaling
Authors: Xiong Luyang , Zhevlakova Irina , West Xiaoxia Z. , Gao Detao , Murtazina Rakhylia , Horak Anthony , Brown J. Mark , Molokotina Iuliia , Podrez Eugene A. , Byzova Tatiana V.
Published: August 2023

The etiology of hair loss remains enigmatic, and current remedies remain inadequate. Transcriptome analysis of aging hair follicles uncovered changes in immune pathways, including Toll-like receptors (TLRs). Our findings demonstrate that the maintenance of hair follicle homeostasis and the regeneration capacity after damage depends on TLR2 in hair follicle stem cells (HFSCs). In healthy hair follicles, TLR2 is expressed in a cycle-dependent manner and governs HFSCs activation by countering inhibitory BMP signaling. Hair follicles in aging and obesity exhibit a decrease in both TLR2 and its endogenous ligand carboxyethylpyrrole (CEP), a metabolite of polyunsaturated fatty acids. Administration of CEP stimulates hair regeneration through a TLR2-dependent mechanism. These results establish a novel connection between TLR2-mediated innate immunity and HFSC activation, which is pivotal to hair follicle health and the prevention of hair loss and provide new avenues for therapeutic intervention.

Hair follicle stem cells TLR2 is required for hair homeostasis and regeneration. While TLR2 stimulation by endogenous ligand promotes hair growth, reduction in TLR2 and its ligand in aging and obesity may diminish hair growth.
IRF5 regulates microglial myelin clearance and cholesterol metabolism after demyelination
Authors: Montilla Alejandro , Zabala Alazne , Calvo Ibai , Mata Paloma , Tomé Irene , Koster Mirjam , Sierra Amanda , Kooistra Susanne M. , Soria Federico Nicolás , Eggen Bart J.L. , Fresnedo Olatz , Fernández José Andrés , Tepavcevic Vanja , Matute Carlos , Domercq María
Published: August 2023

Interferon regulatory factor 5 (IRF5), a transcription factor highly involved in innate immunity that drives microglia/macrophage towards a pro-inflammatory state, has been associated to multiple sclerosis susceptibility but its role in MS pathogenesis is unknown. Here we analysed the role of IRF5 in multiple sclerosis animal models.Irf5-/-mice showed exacerbated damage in the chronic phase of experimental autoimmune encephalomyelitis (EAE) mice, despite an initial delay in its onset, as well as after lysolecithin injection into the spinal cord. Transcriptomic and lipidomic analysis evidence a role of this transcription factor in myelin metabolism and cholesterol homeostasis. Indeed,Irf5-/-mice showed an aberrant accumulation of myelin debris and lipidic structures, such as CE-containing lipid droplets and cholesterol crystals, suggesting that myelin-derived lipids are not properly processed. Cholesterol crystal accumulation leads to an aberrant inflammatory response, which block oligodendrocyte migration into the core of demyelinated lesion and remyelination. Pharmacologically facilitating cholesterol transport reduces lipid droplet accumulation and ameliorates EAE exacerbated damage inIrf5-/-mice. These results reveal for the first time the role of Irf5, a transcription factor necessary to orchestrate the immune responses, in phagocytes lipid metabolism which could be pivotal in regenerative responses such as remyelination.
Dietary amino acids and risk of stroke subtypes: a prospective analysis of 356,000 participants in seven European countries
Authors: Tong Tammy Y.N. , Clarke Robert , Schmidt Julie A. , Huybrechts Inge , Noor Urwah , Forouhi Nita G. , Imamura Fumiaki , Travis Ruth C. , Weiderpass Elisabete , Aleksandrova Krasimira , Dahm Christina C. , van der Schouw Yvonne T. , Overvad Kim , Kyrø Cecilie , Tjønneland Anne , Kaaks Rudolf , Katzke Verena , Schiborn Catarina , Schulze Matthias B. , Mayen-Chacon Ana-Lucia , Masala Giovanna , Sieri Sabina , de Magistris Maria Santucci , Tumino Rosario , Sacerdote Carlotta , Boer Jolanda M.A. , Verschuren W.M. Monique , Brustad Magritt , Nøst Therese Haugdahl , Crous-Bou Marta , Petrova Dafina , Amiano Pilar , Huerta José María , Moreno-Iribas Conchi , Engström Gunnar , Melander Olle , Johansson Kristina , Lindvall Kristina , Aglago Elom K. , Heath Alicia K. , Butterworth Adam S. , Danesh John , Key Timothy J.
Published: August 2023

Background

Previously reported associations of protein-rich foods with stroke subtypes have prompted interest in assessment of individual amino acids. We examined the associations of dietary amino acids with risks of ischaemic and haemorrhagic stroke in the EPIC study.

Methods

We analysed data on 356,142 participants from seven European countries. Dietary intakes of 19 individual amino acids were assessed using validated country-specific dietary questionnaires, calibrated using additional 24-hour dietary recalls. Multivariable-adjusted Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of ischaemic and haemorrhagic stroke in relation to intake of each amino acid. The role of blood pressure as a potential mechanism was assessed in 267,642 (75%) participants.

Results

After a median follow-up of 12.9 years, 4,295 participants had an ischaemic stroke and 1,375 participants had a haemorrhagic stroke. After correction for multiple testing, higher intake of proline (as percent of total protein) was associated with 12% lower risk of ischaemic stroke (HR per 1 SD higher intake 0.88; 95% CI 0.82, 0.94). The association persisted after mutual adjustment for all other amino acids, systolic and diastolic blood pressure. The inverse associations of isoleucine, leucine, valine, phenylalanine, threonine, tryptophan, glutamic acid, serine and tyrosine with ischaemic stroke were each attenuated with adjustment for proline intake. For haemorrhagic stroke, no statistically significant associations were observed in the continuous analyses after correcting for multiple testing.

Conclusion

Higher proline intake was associated with a lower risk of ischaemic stroke, independent of other dietary amino acids and blood pressure.
Plasmatic HIV-1 soluble gp120 is associated with immune dysfunction and inflammation in ART-treated individuals with undetectable viremia
Authors: Benlarbi Mehdi , Richard Jonathan , Bourassa Catherine , Tolbert William D. , Chartrand-Lefebvre Carl , Gendron-Lepage Gabrielle , Sylla Mohamed , El-Far Mohamed , Messier-Peet Marc , Guertin Camille , Turcotte Isabelle , Fromentin Rémi , Verly Myriam Maude , Prévost Jérémie , Clark Andrew , Mothes Walther , Kaufmann Daniel E. , Maldarelli Frank , Chomont Nicolas , Bégin Philippe , Tremblay Cécile , Baril Jean-Guy , Trottier Benoit , Trottier Sylvie , Duerr Ralf , Pazgier Marzena , Durand Madeleine , Finzi Andrés ,   the Canadian HIV,   Aging Cohort Study
Published: August 2023

Background

Chronic inflammation persists in some people living with HIV (PLWH), even during antiretroviral therapy (ART) and is associated with premature aging. The gp120 subunit of the HIV-1 envelope glycoprotein can shed from viral and cellular membranes and can be detected in plasma and tissues, showing immunomodulatory properties even in the absence of detectable viremia. We evaluated whether plasmatic soluble gp120 (sgp120) and a family of gp120-specific anti-cluster A antibodies, which were previously linked to CD4 depletionin vitro, could contribute to chronic inflammation, immune dysfunction, and sub-clinical cardiovascular disease in participants of the Canadian HIV and Aging cohort (CHACS) with undetectable viremia.

Methods

Cross-sectional assessment of plasmatic sgp120 and anti-cluster A antibodies was performed in 386 individuals from CHACS. Their association with pro-inflammatory cytokines, as well as subclinical coronary artery disease measured by computed tomography coronary angiography was assessed using linear regression models.

Results

In individuals with high levels of sgp120, anti-cluster A antibodies inversely correlated with CD4 count (p=0.042) and CD4:CD8 ratio (p=0.004). The presence of sgp120 was associated with increased plasma levels of IL-6. In participants with detectable atherosclerotic plaque and detectable sgp120, sgp120 levels, anti-cluster A antibodies and their combination correlated positively with the total volume of atherosclerotic plaques (p=0.01, 0.018 and 0.006, respectively).

Conclusion

Soluble gp120 may act as a pan toxin causing immune dysfunction and sustained inflammation in a subset of PLWH, contributing to the development of premature comorbidities. Whether drugs targeting sgp120 could mitigate HIV-associated comorbidities in PLWH with suppressed viremia warrants further studies.

Key points

Soluble gp120 is detected in the plasma of people living with HIV-1 with undetectable viremia. The presence of soluble gp120 and anti-cluster A antibodies is associated with immune dysfunction, chronic inflammation, and sub-clinical cardiovascular disease.
Shedding Light on the Dark Genome: Insights into the Genetic, CRISPR-based, and Pharmacological Dependencies of Human Cancers and Disease Aggressiveness
Authors: Kafita Doris , Nkhoma Panji , Dzobo Kevin , Sinkala Musalula
Published: August 2023

Investigating the human genome is vital for identifying risk factors and devising effective therapies to combat genetic disorders and cancer. Despite the extensive knowledge of the “light genome”, the poorly understood “dark genome” remains understudied. In this study, we integrated data from 20,412 protein-coding genes in Pharos and 8,395 patient-derived tumours from The Cancer Genome Atlas (TCGA) to examine the genetic and pharmacological dependencies in human cancers and their treatment implications. We discovered that dark genes exhibited high mutation rates in certain cancers, similar to light genes. By combining the drug response profiles of cancer cells with cell fitness post-CRISPR-mediated gene knockout, we identified the crucial vulnerabilities associated with both dark and light genes. Our analysis also revealed that tumours harbouring dark gene mutations displayed worse overall and disease-free survival rates than those without such mutations. Furthermore, dark gene expression levels significantly influenced patient survival outcomes. Our findings demonstrated a similar distribution of genetic and pharmacological dependencies across the light and dark genomes, suggesting that targeting the dark genome holds promise for cancer treatment. This study underscores the need for ongoing research on the dark genome to better comprehend the underlying mechanisms of cancer and develop more effective therapies.
Exploring Temporal and Sex-Linked Dysregulation in Alzheimer’s Disease Phospho-Proteome
Authors: Yılmaz Serhan , Lopes Filipa Blasco Tavares Pereira , Schlatzer Daniela , Wang Rihua , Qi Xin , Koyutürk Mehmet , Chance Mark R.
Published: August 2023

This study aims to characterize dysregulation of phosphorylation for the 5XFAD mouse model of Alzheimer’s disease (AD). Employing global phosphoproteome measurements, we analyze temporal (3, 6, 9 months) and sex-dependent effects on mouse hippocampus tissue to unveil molecular signatures associated with AD initiation and progression. Our results indicate 1.9 to 4.4 times higher phosphorylation prevalence compared to protein expression across all time points, with approximately 4.5 times greater prevalence in females compared to males at 3 and 9 months. Moreover, our findings reveal consistent phosphorylation of known AD biomarkers APOE and GFAP in 5XFAD mice, alongside novel candidates BIG3, CLCN6 and STX7, suggesting their potential as biomarkers for AD pathology. In addition, we identify PDK1 as a significantly dysregulated kinase at 9 months in females, and the regulation of gap junction activity as a key pathway associated with Alzheimer’s disease across all time points. AD-Xplorer, the interactive browser of our dataset, enables exploration of AD-related changes in phosphorylation, protein expression, kinase activities, and pathways. AD-Xplorer aids in biomarker discovery and therapeutic target identification, emphasizing temporal and sex-specific nature of significant phosphoproteomic signatures. Available at:https://yilmazs.shinyapps.io/ADXplorer

Highlights

Phosphorylation-level dysregulation surpasses protein expression

Higher phospho-dysregulation in females, starting as early as 3-month time point

Novel candidates BIG3, CLCN6, and STX7 exhibit consistent phospho-dysregulation

Developed AD-Xplorer: Online tool to explore Alzheimer’s disease phospho-proteome

In Brief

This study investigates dysregulation of phospho-proteome in an Alzheimer’s disease (AD) mouse model, identifying consistent phosphorylation of established AD biomarkers APOE and GFAP, along with novel candidate biomarkers BIG3, CLCN6, and STX7. In addition, the study observes significant PDK1 dysregulation at 9 months, particularly in females. AD-Xplorer, our interactive tool for exploring temporal and sex-linked phosphorylation changes, protein expression, kinase activities, and pathway enrichment, empowers researchers to gain deeper insights into AD mechanisms and uncover novel biomarkers and therapeutic targets.