Human Experience Research Articles

A Comprehensive Review of Preclinical Models for Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is a reproductive, metabolic, and endocrine disorder with unclear aetiology. PCOS, the most common cause of female reproductive and metabolic disorders, is known to affect more than one in ten women globally. PCOS and associated clinical manifestations are probably underdiagnosed despite their high occurrence. Objective: Alternative animal models have been employed to investigate the causes of PCOS or assess potential treatments. In light of this piece of information, it is challenging to create an animal model that accurately captures all components of this condition; nonetheless, the resemblance of an animal model's biology and/or biochemical characteristics to the phenotypes of PCOS in humans may boost its applicability. Result: The key characteristics of these models are closer to human situations when compared to women with PCOS, as shown by this comparison. The creation and testing of drugs for the treatment of PCOS are necessary. Conclusion:: The overview of PCOS, current preclinical models, and appropriate models chosen in different studies to mimic various phenotypes in PCOS studies are all covered in this review paper. Additionally, we have outlined the benefits and drawbacks of PCOS animal models.

Assessment of clinical symptoms and pathological effects of degenerative arthritis in rats

Degenerative arthritis, particularly affecting the knee joint, is a prevalent condition in Taiwan. While milder cases may only result in slight discomfort during walking, severe cases can lead to significant mobility issues and even loss of basic movement capabilities. Unfortunately, once articular cartilage is lost due to degenerative arthritis, it cannot be regenerated. Currently, the severity of knee joint degeneration is classified into primary, intermediate, and severe stages, which guides the selection of treatment options. These treatments range from non-surgical interventions to surgical procedures. Given the significance of preventing knee joint degeneration, researchers have been exploring various methods. One such approach involves establishing animal models to mimic degenerative arthritis conditions in humans. In this study, researchers utilized anterior cruciate ligament transection (ACLT) combined with medial meniscectomy (MMx) surgery to create a rat model of degenerative arthritis. The successful establishment of this model provides a valuable tool and assessment of clinical symptoms and pathological effects of degenerative arthritis in rats for studying potential drugs and designing therapeutic strategies for degenerative arthritis. By leveraging this rat model, researchers can investigate the efficacy of different pharmaceutical interventions and therapeutic approaches. This could ultimately lead to the development of novel treatments for degenerative arthritis, benefiting individuals suffering from this debilitating condition.

Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice.

A protective human immunodeficiency virus (HIV) vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01B was found to induce VRC01-class bnAb precursors in 97% of vaccine recipients in the IAVI G001 phase 1 clinical trial; however, heterologous boost immunizations with antigens more similar to the native glycoprotein will be required to induce bnAbs. Therefore, we designed core-g28v2 60mer, a nanoparticle immunogen to be used as a first boost following eOD-GT8 60mer priming. We found, using a humanized mouse model approximating human conditions of VRC01-class precursor B cell diversity, affinity, and frequency, that both protein- and mRNA-based heterologous prime-boost regimens induced VRC01-class antibodies that gained key mutations and bound to near-native HIV envelope trimers lacking the N276 glycan. We further showed that VRC01-class antibodies induced by mRNA-based regimens could neutralize pseudoviruses lacking the N276 glycan. These results demonstrated that heterologous boosting can drive maturation toward VRC01-class bnAb development and supported the initiation of the IAVI G002 phase 1 trial testing mRNA-encoded nanoparticle prime-boost regimens.

Beyond Usability: A Critical Analysis of Interface Research

This article addresses the profound and multifaceted understanding of interfaces in the modern technological era, focusing on integrating ontological, ethical, and aesthetical approaches in interface research. It considers various aspects of human-machine interaction from philosophical, ethical, and aesthetic viewpoints, revealing the complex connections between technological progress and human experience. This study provides a comprehensive analysis of contemporary approaches to interface research, covering its complexity and diversity, as well as identifying current trends and challenges in the field. The findings indicate that successful interface study requires an integrated approach, including the analysis of functional, ethical, aesthetic, and cultural aspects. The article highlights the importance of cross-disciplinary research in developing interfaces that can reflect and develop contemporary cultural and social contexts. The conclusions of this article are relevant to the researchers in the field of interface design, implementators, and a broad audience interested in understanding the interplay between technological innovations and the socio-cultural context.

The semiotic phenomenology of inverse alteroception

Abstract Alteroception is the virtual experience of another person’s bodily movement centered in the perspective of the other person. In face-to-face interactions, human beings tend to assume a special mode of alteroception by mutually but tacitly recognizing that ‘your right is on my left and your left is on my right’. Researchers of neonatal cognition and early childhood development describe this mode of alteroception as “reverse” or “inverted”. Inverse alteroception goes beyond mirror-image mimesis to chiastic (crisscrossing) mimesis in acts of intersubjective sense-making; but the cognitive and cultural affordances of this inverse reciprocal ability are largely untreated in the literature. I argue that this unique aspect of human phenomenology deserves closer attention since it enables a broader palette of diagrammatic contrasts that extend far beyond face-to-face interaction. In this paper, I apply insights from Peircean and Greimasian semiotics to argue that salient features of the human lifeworld originate from imaginative mappings of inverse alteroception onto other domains. From diagrams of gesture space and contemporary visual design to the structures of the Proscenium stage, from historic heraldry to Aristotle’s logical square of oppositions and beyond, many visual/spatial designs and their reciprocal interaction with human experience are linked to this ability – an ability that owes its origins, in turn, to the evolution of upright posture.

Preclinical models of bladder cancer: BBN and beyond.

Preclinical modelling is a crucial component of advancing the understanding of cancer biology and therapeutic development. Several models exist for understanding the pathobiology of bladder cancer and evaluating therapeutics. N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN)-induced bladder cancer is a commonly used model that recapitulates many of the features of human disease. Particularly in mice, BBN is a preferred laboratory model owing to a high level of reproducibility, high genetic fidelity to the human condition, and its relative ease of use. However, important aspects of the model are often overlooked in laboratory studies. Moreover, the advent of new models has yielded a variety of methodologies that complement the use of BBN. Toxicokinetics, histopathology, molecular genetics and sex can differ between available models and are important factors to consider in bladder cancer modelling.

Girish Karnad’s Hayavadana : A Thematic Analysis

The essence of folk drama and its expressions, particularly within the context of Indian theatre, using Girish Karnad's play "Hayavadana" as a case study. It highlights how folk drama encapsulates the mindset, lifestyle, and societal perspectives of specific regions, transmitted orally or through performances. Karnad's reworking of folktales and myths for contemporary issues is discussed, emphasizing his fusion of classical and folk elements in his plays. The abstract explores the use of various folk theatrical devices such as Sutradhar, masks, dolls, and actor-audience interaction in "Hayavadana" to convey complex themes of identity, completeness, and the human condition. It also touches upon the adaptability and improvisational nature of folk stories and their relevance across time and space. Overall, it presents a comprehensive analysis of theme of folk traditions inform and enrich contemporary theatre practices.

Digital Resurrection: Challenging the Boundary between Life and Death with Artificial Intelligence

The advancement of Artificial Intelligence (AI) poses challenges in the field of bioethics, especially concerning issues related to life and death. AI has permeated areas such as health and research, generating ethical dilemmas and questions about privacy, decision-making, and access to technology. Life and death have been recurring human concerns, particularly in connection with depression. AI has created systems like Thanabots or Deadbots, which digitally recreate deceased individuals and allow interactions with them. These systems rely on information generated by AI users during their lifetime, raising ethical and emotional questions about the authenticity and purpose of these recreations. AI acts as a mediator between life, death, and the human being, enabling a new form of communication with the deceased. However, this raises ethical issues such as informed consent from users and the limits of digital recreation. Companies offer services like the Digital Resurrection of deceased individuals and the generation of hyper-realistic avatars. Still, concerns arise about the authenticity of these representations and their long-term emotional impact. Interaction with Thanabots may alter perceptions of death and finitude, leading to a potential “postmortal society” where death is no longer viewed as a definitive end. Nevertheless, this raises questions about the value of life and the authenticity of human experiences. AI becomes a bridge between the living and the dead, partially replacing rituals and mystical beliefs. As technology advances, there will be a need for greater transparency in interacting with AI systems and ethical reflections on the role of these technologies in shaping perceptions of life and death. Ultimately, the question arises of whether we should allow the dead to rest in peace and how to balance the pursuit of emotional relief with authenticity and respect for the memory of the deceased. A deeper ethical consideration is needed on how AI alters traditional notions of life, death, and communication in contemporary society. In this research, an interdisciplinary approach was utilized to conduct a comprehensive systematic review of the recent academic literature, followed by a detailed analysis of two key texts. Central ideas were extracted, and recurring themes were identified. Finally, a reflective analysis of the findings was conducted, yielding significant conclusions and recommendations for future research.

Suspending the embodied self in meditation attenuates beta oscillations in posterior medial cortex.

Human experience is imbued by the sense of being an embodied agent. The investigation of such basic self-consciousness has been hampered by the difficulty of comprehensively modulating it in the laboratory while reliably capturing ensuing subjective changes. The present preregistered study fills this gap by combining advanced meditative states with principled phenomenological interviews: Forty-six long-term meditators (19 female, 27 male) were instructed to modulate and attenuate their embodied self-experience during magnetoencephalographic monitoring. Results showed frequency specific (high beta band) activity reductions in frontoparietal and posterior medial cortices (PMC). Importantly, PMC reductions were driven by a subgroup describing radical embodied self disruptions, including suspension of agency and dissolution of a localised first-person perspective. Neural changes were correlated with lifetime meditation and interview-derived experiential changes, but not with classical self-reports. The results demonstrate the potential of integrating in-depth first-person methods into neuroscientific experiments. Furthermore, they highlight neural oscillations in the PMC as a central process supporting the embodied sense of self.Significance statement Human consciousness is not only characterised by the contents of experience, but also by an implicit sense of subjectivity, delineating the perceiving, embodied agent from her environment. The current study addressed this basic sense of self by scrutinising meditation-induced states of self-boundary dissolution using a neurophenomenological approach: In-depth phenomenological interviews assessed core dimensions of self-experience during such states (agency, self-location, first-person perspective), while magnetoencephalography monitored neural oscillatory activity. Full-blown suspension of self-experience was associated with robust reductions of beta-band power in the posterior medial cortex. These results pinpoint a neural candidate mediating our embodied perspective on the world and highlight the unique potential of integrating rigorous phenomenological methods with neuroscientific experiments for the study of consciousness.

Psychological and Brain Responses to Artificial Intelligence's Violation of Community Ethics.

Human moral reactions to artificial intelligence (AI) agents' behavior constitute an important aspect of modern-day human-AI relationships. Although previous studies have mainly focused on autonomy ethics, this study investigates how individuals judge AI agents' violations of community ethics (including betrayals and subversions) compared with human violations. Participants' behavioral responses, event-related potentials (ERPs), and individual differences were assessed. Behavioral findings reveal that participants rated AI agents' community-violating actions less morally negative than human transgressions, possibly because AI agents are commonly perceived as having less agency than human adults. The ERP N1 component showed the same pattern with moral rating scores, indicating the modulation effect of human-AI differences on initial moral intuitions. Moreover, the level of social withdrawal correlated with a smaller N1 in the human condition but not in the AI condition. The N2 and P2 components were sensitive to the difference between the loyalty/betrayal and authority/subversion domains but not human/AI differences. Individual levels of moral sense and autistic traits also influenced behavioral data, especially on the loyalty/betrayal domain. In our opinion, these findings offer insights for predicting moral responses to AI agents and guiding ethical AI development aligned with human moral values.

Neurobrucellosis (Brucella ceti) in striped dolphins (Stenella coeruleoalba): Immunohistochemical studies on immune response and neuroinflammation.

Neurobrucellosis is a shared condition of cetaceans and humans. However, the pathogenesis and immune response in cetacean neurobrucellosis has not been extensively studied. In this multicentric investigation, 21 striped dolphin (Stenella coeruleoalba) neurobrucellosis (Brucella ceti) cases diagnosed over a 10-year period (2012-2022) were retrospectively evaluated. For each case, morphological changes were assessed by evaluating 21 histological parameters. Furthermore, the immunohistochemical expression of Brucella antigen, glial fibrillary acid protein (GFAP), and a selection of inflammatory cell (IBA-1, CD3, and CD20) and cytokine (tumor necrosis factor-alpha [TNF-α], interferon-gamma [IFN-γ], interleukin [IL]-1β, IL-2, and IL-6) markers were investigated. Inflammation of the leptomeninges, ependyma, and/or choroid plexus was lymphohistiocytic, containing macrophages/microglia (IBA-1+), T-cells (CD3+), and B-cells (CD20+) in equal proportion. B-cells occasionally formed tertiary follicles. GFAP expression showed astrocytosis in most cases. Expression of TNF-α, IFN-γ, and IL-2 indicated an intense proinflammatory response, stimulating both macrophages and T-cells. Our results showed that the inflammation and neuroinflammation in neurobrucellosis of striped dolphins mimic human neurobrucellosis and in vitro and in vivo studies in laboratory animals. Cetacean disease surveillance can be exploited to expand the knowledge of the pathogenesis and immunology of infectious diseases, particularly brucellosis, under a One Health approach.

Semantic image sorting method for RSVP presentation

Objective. The rapid serial visual presentation (RSVP) paradigm, which is based on the electroencephalogram (EEG) technology, is an effective approach for object detection. It aims to detect the event-related potentials (ERP) components evoked by target images for rapid identification. However, the object detection performance within this paradigm is affected by the visual disparity between adjacent images in a sequence. Currently, there is no objective metric to quantify this visual difference. Consequently, a reliable image sorting method is required to ensure the generation of a smooth sequence for effective presentation. Approach. In this paper, we propose a novel semantic image sorting method for sorting RSVP sequences, which aims at generating sequences that are perceptually smoother in terms of the human visual experience. Main results. We conducted a comparative analysis between our method and two existing methods for generating RSVP sequences using both qualitative and quantitative assessments. A qualitative evaluation revealed that the sequences generated by our method were smoother in subjective vision and were more effective in evoking stronger ERP components than those generated by the other two methods. Quantitatively, our method generated semantically smoother sequences than the other two methods. Furthermore, we employed four advanced approaches to classify single-trial EEG signals evoked by each of the three methods. The classification results of the EEG signals evoked by our method were superior to those of the other two methods. Significance. In summary, the results indicate that the proposed method can significantly enhance the object detection performance in RSVP-based sequences.

On the Sagnac effect and the consistency of relativity theory

The Sagnac effect is an interferometric phenomenon produced by rotation. It has a rich history and presently has numerous technological applications. Despite some persistent claims to the contrary, we explain why the Sagnac effect does not prove relativity either incorrect or inconsistent. Analyzing such misunderstandings has didactic value because it allows us to review some subtle relativity concepts. It also reveals the importance of basing scientific reasoning on rigorous logical thinking to avoid confusion derived from prejudices based on our limited everyday human experience.

Loss-of-function mutation in DDX53 associated with hereditary spastic paraplegia-like disorder.

DEAD-box helicase 53 (DDX53) is a member of the DEAD-box protein family of RNA helicases. Unlike other family members that are responsible for RNA metabolism, the biological function of DDX53 and its impact on the human condition are unclear. Herein, we found a full-length DDX53 deletion mutation in a hereditary spastic paraplegia-like (HSP-like) patient with lower extremity spasticity, walking disorder, visual impairment, and lateral ventricular white matter lesions. Bioinformatic analysis revealed that DDX53 was mainly expressed in the cerebellar cortex and may function as a tissue-specific RNA helicase. Transcriptome analysis showed that the expression of multiple brain-associated genes involved in synapse organization, neuron function, and neuromuscular junctions was affected by DDX53 depletion. Moreover, RNA immunoprecipitation sequencing (RIP-seq) analysis showed that DDX53 interacted with 176 genes, and 96 of these genes were associated with the execution of neurofunction, particularly in the regulation of cell projection organization and nervous system development. Collectively, although a more specified cell or animal model is required to fully understand the functional role of DDX53 in the human brain, we report for the first time that the patient with DDX53 defects exhibits HSP-like symptoms and that DDX53 is essential for maintaining neuronal function, with loss-of-function mutation in DDX53 potentially leading to HSP due to impaired RNA metabolism in the nervous system. KEY MESSAGES: DDX53 deficiency was first reported to be associated with HSP disorder. DDX53 exhibited minimal impact on mitochondrial function. DDX53 impaired RNA metabolism in the nervous system.

Mediating Spaces: The Scales of Yugoslav Socialist Thought

Beginning with its emergence in the 1870s and carrying through to the wars of the 1990s, Yugoslav socialism was animated by various visions of supranational affiliation: from Balkan federalism to communist Slavism to the nonaligned movement and European unification. These projects were examples of what this article terms mediating spaces: strategies of spatial consolidation designed to mediate their constituent nations’ integration into global capitalist modernity. Throughout the long twentieth century intellectuals on the world periphery set out to secure political sovereignty and economic development at a scale between the national and the global. These spatial projects were particularly pronounced in Yugoslavia, where the fragmentation of multiethnic empires made questions of supranational unity especially urgent. Developing the concept of mediating spaces, this article proposes a mode of intellectual history that approaches the global not as the scope of intellectual mobility or the horizon of historical inquiry, but rather as a generative scale of human experience that conditioned the formation of modern radical thought.

Writing the Unspeakable: Trauma, Memory, and Resistance in Iraqi War Literature

The paper delves into the profound realm of Iraqi war literature, unraveling its multifaceted dimensions. From capturing the visceral traumas induced by conflict to echoing the resonances of resistance, this literature stands as a testament to the Iraqi people's resilience and defiance. Situating the narrative within historical and sociopolitical contexts, the study underscores the universality of trauma and the tenacity of the human spirit. Drawing parallels with global war literature, it highlights shared human experiences across cultures and histories. The paper also examines the redemptive power of literature, emphasizing its role in healing and peacebuilding, while illuminating the unique and diverse voices that constitute the Iraqi war narrative. As Iraq looks towards a future of reconciliation and hope, its literature not only serves as a historical record but also as a beacon, illuminating paths of empathy, understanding, and peace.

Albert Camus and Rachel Bespaloff: Happiness in a Challenging World

Abstract Albert Camus and Rachel Bespaloff had an undeniable influence on the existential thought of the twentieth century. The former, by claiming the world to be silent to our search for meaning, based the concept of happiness in the inherent value of life. The latter grounded her happiness in music and transcendence rather than in the acceptance of the absurd human condition, though the two thinkers seem to agree on the importance of subjective contemplation. In this article, I will offer a reading of Camus’s works that emphasizes his view of happiness in awareness of the absurd. I will then argue for the ethical and political challenges that such happiness causes. Finally, by putting into dialogue the philosophies of Camus and Bespaloff, I wish to show that the two thinkers advocate for the possibility of happiness despite the suffering of the world, and show that this concept, understood as contemplation, can be rooted in the absurd as well as in transcendence.

The potential for senotherapy as a novel approach to extend life quality in veterinary medicine

Cellular senescence, a condition where cells undergo arrest and can assume an inflammatory phenotype, has been associated with initiation and perpetuation of inflammation driving multiple disease processes in rodent models and humans. Senescent cells secrete inflammatory cytokines, proteins, and matrix metalloproteinases, termed the senescence associated secretory phenotype (SASP), which accelerates the aging processes. In preclinical models, drug interventions termed “senotherapeutics” selectively clear senescent cells and represent a promising strategy to prevent or treat multiple age-related conditions in humans and veterinary species. In this review, we summarize the current available literature describing in vitro evidence for senotheraputic activity, preclinical models of disease, ongoing human clinical trials, and potential clinical applications in veterinary medicine. These promising data to date provide further justification for future studies identifying the most active senotherapeutic combinations, dosages, and routes of administration for use in veterinary medicine.

The African Pastor as a Public Figure in Response to Gender-Based Violence in South Africa: A Public Pastoral Intervention

The burgeoning field of public theology has garnered significant scholarly attention. Amidst its multifaceted discussions, a recurring theme asserts that theology plays a vital and irreplaceable role in public discourse. This perspective contends that engaging with matters of public concern from a theological standpoint not only contributes meaningfully to public discourse but also shapes our understanding of the world, human existence, and the divine. Within the African context, particularly in South Africa, gender-based violence (GBV) remains a pressing societal issue despite government and organizational efforts. This article delves into the potential role of pastors as public figures in addressing the persistent challenge of GBV. It explores the implications of pastors assuming public roles within an African context and how this engagement can be instrumental in combating GBV. By drawing on literature related to public practical theology, pastoral care, and GBV in South Africa, the article advocates for proactive public interventions by pastoral ministries. Through synthesizing insights from existing scholarship, it contributes to ongoing discussions at the intersection of theology, pastoral practice, and societal issues, with a specific focus on addressing GBV in the unique South African context.

The semantics of language in Eugène Ionesco’s plays

The goal of this paper is to present the characteristics of Eugène Ionesco’s dramatic texts, a reason why the genre of avant-garde and theatre of the absurd are also considered, with a view to revealing their major ways of functioning. By pointing out the different dimensions of dramatic language, the emphasis is on those elements that differ from current oral and written language. Starting from the times of decadentism, a crisis of character can be noted in the theater around a type of individual who, as an alienated individual, cannot find his identity in a hostile surrounding world. One of the direct consequences of this crisis will be the impossibility of interpersonal communication, which will be best demonstrated with the concept and tenets of the theater of the absurd. In this context, the study of the theater of the 20th century is done from the perspective of cognitive semantics, as an autonomous level of language. The approach is organised around two notions: dramatic conventions and the actual language of the dramatic texts. The interpretative theory rooted in semantics is applied while analysing Ionesco’s short plays. The starting point is the linguistics of the text as described by Eugen Coşeriu. Capturing the meaning and the means by which it is constructed is one of the objectives in accord with the main principles of cognitive linguistics. The way of analysing the meaning in a text is given by the presence of some textual functions, as possibilities provided by language through relationships that the linguistic sign establishes in the discursive act. The specificity of the discourse comes from the combination of verbal and non-verbal elements, in order to highlight the playwright’s original style. The particularities of this type of language based on an ontological representation of the actional nature in human existence are also investigated. There are two dimensions recognisable in the language of literature: one is specific to the genre and the other one is particular, giving originality and uniqueness. The textual meaning in between these dimensions needs to be reconstructed from all their constituents identifiable at different levels of analysis. Ionesco distanced himself from the conventional and traditional theatre, finding a new formula for the dramatic genre in his own vision of what drama should be like. Ionesco’s dramatic work includes short plays and extensive plays in which the author expresses his adversity against totalitarian regimes. He is the representative of the theater of the absurd and anti-theater. The corpus for this research is composed mainly of the plays The Bald Soprano, The Lesson and The Chairs, the most representative plays for the avant-garde spirit, short plays on the theme of language emptied of meaning and non-communication. Language has an impact on thinking and the resulting actions, which relates it to the ontology of human existence. As dramatic language is preponderently structured on dialogical interactions (and less on monologues, soliloquies and asides), its essence can be revealed by decomposing and recomposing them, from the angle of the conventions specific to the dramatic genre. The analysis of the selected fragments from the corpus has the role to highlight their semantic features in terms of conceptual representations.