bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrategias metodológicas para niños de 3 a 4 años con espectro autista nivel 1: ámbito de identidad y autonomía
Authors: Velastegui López Luis Efrain
Published: February 2025

Esta investigación documental propone una estrategia metodológica para niños de 3 a 4 años con Trastorno del Espectro Autista (TEA) nivel 1, enfocada en sus necesidades educativas en áreas como desarrollo, identidad, autonomía, afectividad y motricidad fina. Dada la creciente prevalencia del TEA, la investigación busca integrar enfoques psicológicos, clínicos y terapéuticos para ofrecer una intervención más completa y adaptada. Se pretende desarrollar una base teórica sólida y estrategias inclusivas que respondan a la diversidad y diferentes niveles de severidad del TEA, destacando la importancia de la intervención temprana y la formación adecuada de los profesionales. En resumen, la estrategia metodológica propuesta está diseñada para atender las particularidades de los niños con TEA nivel 1, integrando un enfoque multidisciplinario que abarca sus necesidades específicas.
Propuesta de requisitos para la aplicación de la Economía Circular en la restauración turística del destino La Habana
Authors: Romaní Bendig Beatriz , Ginarte López Sandra , Espinosa Manfugás Julia Ma , Velasteguí López Luis Efraín
Published: February 2025

Introducción. ONU Turismo defiende la necesidad de emplear la economía circular para la innovación y hacer del turismo una actividad más sostenible. En Cuba se hace imprescindible desarrollar una estrategia que ponga en práctica la economía circular y su aplicación. En el caso del sector de la restauración, este es generador de grandes cantidades de residuos de alimentos y plásticos, lo que no contribuye a la sostenibilidad. El presente estudio está encaminado a la propuesta de requisitos de economía circular para favorecer el máximo rendimiento de los recursos disponibles, reduciendo al mínimo la generación de residuos; y además la creación de oportunidades para un sistema más sostenible e inclusivo. Objetivo. Proponer requisitos para la aplicación de la economía circular en la restauración turística del destino La Habana. Metodología. Para el cumplimiento de este objetivo se realizó una entrevista semiestructurada a los especialistas de calidad y operaciones de alimentos y bebidas del Ministerio de Turismo, y además, se aplicó un cuestionario a los especialistas de calidad y operaciones de alimentos y bebidas de las OSDES Hoteleras, Empresa Extrahotelera Palmares, Ministerio de Comercio Interior (Mincin), así como a los presidentes de la Asociación Culinaria de Cuba, la Asociación de Cantineros de Cuba y la Asociación de Sommeliers de Cuba. Se llevó a cabo una revisión de literatura especializada y normativas establecidas sobre esta temática. El procesamiento de los datos implicó el  cálculo de frecuencias absolutas y relativas, el cálculo del índice del Alfa de Cronbach, así como la realización del Diagrama de Pareto. La validación de la propuesta se realizó por un grupo de expertos, a través del método de ANOCHI. Resultados. Los resultados de la investigación permitieron constatar que existe un marco regulatorio y legal en el país relacionado con la Economía Circular, pero de manera general su conocimiento en el sector turístico es aún incipiente, y que los retos vitales para la aplicación de la Economía Circular en restaurantes turísticos del destino La Habana son: la baja capacitación del personal, la falta de recursos en el destino y la carencia de infraestructura necesaria. Conclusión. La Estrategia para la Transición hacia una Economía Circular del Ministerio de Turismo, es uno de los pilares fundamentales para su desarrollo, siendo la sensibilización y capacitación de los recursos humanos factores claves para su avance. Se elaboró y validó la propuesta requisitos, la cual fue estructurada en requisitos generales y específicos, los que incluyen un total de 14 apartados. Área de estudio general: (Turismo). Área de estudio específica: (Economía Circular). Tipo de estudio: Artículos originales / Original articles.
Comparative Analysis of Sleep Behavior in ASD Children: A Taif City Perspective
Authors: Aljaid Maryam Saud , Alharthi Mazen Saud , Alrubie Sara Sultan , Qattan Faris Mohammed , Almalki Abeer Saad , Alzahrani Essam Saeed , Alnefaie Ghaliah Obaid
Published: February 2025

Background Sleep habits in children with Autism Spectrum Disorder (ASD) are poorly understood despite their significant impact on overall well-being. This study aimed to comprehensively assess sleep behaviors and challenges faced by children diagnosed with ASD in Taif City, targeting individuals under 15 years old. Methodology A cohort of 130 participants, including 41 autistic children and 89 typically developing controls, was recruited using convenience and snowball sampling. Data collection involved analyzing bedtime and wake-up patterns, sleep duration, and specific sleep-related issues. Statistical analyses compared findings between the two groups. Results Autistic children exhibited distinct sleep behavior patterns compared to controls. They showed earlier bedtimes, consistent wake-up times—often earlier than controls— and notably shorter sleep durations (p<0.05). Additionally, autistic children reported significantly higher incidences of snoring and waking up with headaches, indicative of potential sleep disturbances (p<0.05).. Heightened daytime fatigue and a propensity to fall asleep during activities were also observed among autistic children. Conclusion The results show that youngsters in Taif City with autism spectrum disorder (ASD) and their normally developing classmates have very different sleeping habits. In order to enhance the overall quality and well-being of people with ASD, it is necessary to implement focused treatments that address particular difficulties linked to sleep.
BJMS, Volume: 24. Supplementary Issue 2025, Page : 123-132
The Attitudes toward Gender-Inclusive Language among EFL Speakers in Japan
Authors: Sugiyama Yuki
Published: February 2025

This study examines the attitudes of Japanese speakers of English as a foreign language toward gender-inclusive language in English, addressing a gap in research that had primarily focused on native and English as a second language speakers. Data were collected from 816 students attending English classes at a university in Japan. The participants were administered the Japanese version of the Inventory of Attitudes toward Sexist/Nonsexist Language-General, and their demographic variables and egalitarian sex role attitudes were measured. Results indicated that while gender and sexist attitudes significantly influence one’s acceptance of sexist language, factors such as age and academic field do not. Additionally, the study revealed that men who strongly opposed egalitarian sex role attitudes were significantly more likely to hold negative attitudes toward gender-inclusive language compared to women who held similar views. This may be due to women’s expectations of gender-inclusive language and Japan’s cultural context. Although there are limitations, such as imbalances in certain variables and the narrow age range among participants, this study revealed the previously unexamined neutral attitudes of Japanese EFL speakers and identified the factors influencing these attitudes using a generalized linear mixed model. Furthermore, at this stage, where learners hold neutral attitudes, exposing them to gender-inclusive language through English education—a language where changes are less likely to cause discomfort compared to one's native language—could not only prevent misunderstandings in communication during study abroad experiences but also lead to a reassessment of the ingrained gender stereotypes and attitudes within Japanese language and society.
Asexuality in Asia: The Intersection of Tradition, Identity, and Sexual Diversity
Authors: Zhu Yujia
Published: February 2025

This study explores the complex cultural and social dimensions of asexuality in Asian contexts, emphasizing how Confucianism, collectivist traditions, and familial expectations shape distinct experiences of asexual individuals. Employing a systematic literature review methodology, the research draws on empirical and theoretical sources across Asian countries, such as China, Japan, and India, to uncover the multifaceted challenges faced by asexual individuals. Specific findings highlight how Confucian values in East Asia reinforce norms of marriage and reproduction, while familial pressures in South Asia, deeply rooted in Hindu and Islamic traditions, exacerbate the marginalization of asexual identities. The research also examines the impact of stigmatization and limited access to culturally competent care. By contrasting these regional distinctions with Western norms, the study underscores the necessity for culturally sensitive policies and inclusive frameworks. The conclusion offers targeted recommendations, including the implementation of culturally adapted educational programs and healthcare practices to foster visibility and support for asexual individuals in Asia.
APPLYING K-MEANS CLUSTERING FOR GROUPING PAPUA’S DISTRICTS BASED ON POVERTY INDICATORS ANALYSIS
Authors: Fadilah Yusriana Chusna , Sani Asrul , Andrianingsih Andrianingsih
Published: February 2025

In the context of Indonesia's resource-rich development, poverty remains a major challenge, especially in Papua Province which has the highest poverty rate. Although Papua is rich in resources such as minerals, tropical forests, and biodiversity, challenges such as economic inequality, lack of infrastructure, and social conflict hinder economic and social progress. This research aims to implement the K-Means Clustering algorithm to cluster districts/cities in Papua based on poverty indicators, including the percentage of poor people, poverty line, average years of schooling, human development index, poverty depth index, poverty severity index, unemployment rate, and per capita expenditure. The research methodology includes data collection from the Central Statistical Agency (BPS), data processing through cleaning and transformation stages, and application of K-Means Clustering to determine the optimal cluster using the elbow method and silhouette score. The results show that the districts/cities in Papua can be grouped into two main clusters: C0, which indicates high poverty rates and C1, which indicates low poverty rates. This research is expected to provide a strategic foundation for the government to design more focused and effective development policies in reducing poverty in Papua.
SMART ATTENDANCE TRACKING SYSTEM EMPLOYING DEEP LEARNING FOR FACE ANTI-SPOOFING PROTECTION
Authors: Nurhakim Bani , Rifai Ahmad , Kurnia Dian Ade , Sudrajat Dadang , Supriatna Ujang
Published: February 2025

Conventional attendance systems face challenges in accuracy and efficiency, often vulnerable to spoofing and data manipulation. This study addresses these issues by developing a smart attendance system integrating Deep Learning-based facial recognition with anti-spoofing technology. The system ensures secure and reliable attendance authentication while automating and enhancing management processes. Utilizing a convolutional neural network (CNN) architecture, the system processes raw facial images directly without additional feature extraction, improving accuracy and efficiency. A novel training strategy, termed 50 Random Samples-30 Sub-epochs Count-1 Epoch, is introduced to optimize the training process. This strategy involves random sampling during each forward pass and grouping 30 passes as one epoch, enabling the use of complex CNN architectures and automatic dataset expansion. The system achieves 98.90% accuracy in identifying genuine attendance, maintaining a confidence level above 80%, significantly reducing spoofing risks and errors. This innovative solution has significant implications, particularly for educational institutions. It automates attendance tracking, minimizes manual effort, reduces errors, and supports disciplinary enforcement through accurate data. Moreover, its scalability allows for application across various environments, offering benefits to a wide range of institutions. By enhancing data accuracy and operational efficiency, this system sets a foundation for smarter, more reliable attendance management, strengthening administrative practices in education and beyond.
Scientific Innovations from 2024
Authors: EMJ
Published: February 2025

The following highlights showcase the most pivotal, innovative research published across multiple therapeutic areas in medicine in 2024. The selected abstracts mark key advancements in healthcare and highlight future avenues for medical innovation.
Review of the Global Innovation and New Technology (GIANT) Health Event 2024
Authors: EMJ
Published: February 2025

THE RAPID growth of healthcare innovation over the past year has driven transformative changes within the NHS and other government agencies. At the forefront of this movement is Global Innovation and New Technology (GIANT) Health, the UK’s largest community of over 345,000 NHS leaders, clinicians, and health-tech innovators. In December last year, experts came together to discuss and champion the latest innovations in healthcare.
The Implementation of AI in the NHS
Authors: Thornber Katrina
Published: February 2025

SUCCESSFUL integration of AI and machine learning into the NHS depends on the implementation of practical education, at varying levels of intensity, across the entire NHS workforce, medical school students, and the general public. During the NHS National AI Conference on 10th December, ‘Beyond Implementation: Building Healthcare’s AI-Fluent Workforce’, experts discussed the current and future innovative approaches being implemented to improve AI literacy, develop educational AI curricula, and enhance confidence and trust in AI-implemented healthcare systems.
TargetTau-1: A Phase II Trial Evaluating the Efficacy, Safety, and Tolerability of a Monoclonal Antibody Targeting the Tau Protein Microtubule Binding Region in Patients with Early Alzheimer’s Disease
Authors: Stanbury Samantha
Published: February 2025

The annual Clinical Trials in Alzheimer’s Disease (CTAD) Congress brings together global experts to discuss developments in Alzheimer’s disease (AD) clinical research and showcase researchers’ work on AD trials. This article describes a recently initiated Phase II trial of a novel anti-tau monoclonal antibody, BMS-986446, the design for which was presented at the 17th CTAD Congress in Madrid, Spain, on 31st October 2024. BMS-986446 targets the microtubule binding region of the tau molecule to inhibit interneural transmission and prevent pathogenic spread of tau aggregates. The TargetTau-1 study (NCT06268886) will assess the efficacy of BMS-986446 by evaluating clinical, cognitive and functional decline, and tau deposition, and investigate the safety and tolerability profile of BMS-986446 in approximately 475 patients with early AD.
Mass Ornament and Ritournelle
Authors: Lee Alex Taek-Gwang
Published: February 2025

This article discusses Kracauer’s analysis of mass ornament in light of Deleuze’s concept of ritournelle. Kracauer was interested in the spectacle of Tiller Girls and found the principle of the capitalist production process in its ornamental formations. Capitalism destroys any natural organisms for its means and excludes any resistance from its effective procedure. This operation necessarily comes along with calculation and mechanisation. All individuals have scaled up statistics charts and scrambled with machines completely. People have turned into masses who are no longer different in form but simple technical objects that can be equally employed at any point of the globe. Kracauer understood mass ornament as the surface-level expression of global capitalism, which revealed its unconscious. He emphasised the ambivalence of mass ornament and a possible line of escape from capitalist rationality through the emptiness of its formal excess. Deleuze’s concept of ritournelle may shed light on a similar question of mass ornament and push its scope beyond Kracauer’s analysis. The two philosophers seem to share the frame of formalism when they deploy their arguments concerning form and depth; however, Deleuze put forward the issue of temporality in his discussion of ritournelle, a crucial question that Kracauer omits.
Ornamental Behaviours: Mechanisms of Repetition in Urban Communities
Authors: Lee Lenka
Published: February 2025

The interplay between urban and rural lifestyles in the modern era, influenced by globalisation, technological advancements and societal shifts, underscores a complex fusion of cultures and behaviours. This convergence reshapes communal dynamics and territorial perceptions. Drawing from Deleuze and Guattari's philosophical framework, particularly concepts of territory, deterritorialisation and reterritorialisation, this study explores the emergence of urban subcultures resembling rural communities. Through ornamental behaviour and the repetition of cultural events, urban spaces undergo a transformative process akin to ritornello, establishing distinct territories marked by creative expressions. The territories are justified and consolidated by a repeated performance of the social ornament which is a set of rules, practices and material products. All these phenomena, infused with the event (Deleuze) and moments of awe (Leddy), intertwine aesthetics and ethics, promoting community unity and well-being. This inquiry not only clarifies social phenomena but also indicates pathways for a more fulfilling societal existence.
Rhythm and Entropy: Territorial Repetition in Gilles Deleuze and Josef Jedlička
Authors: Kolář Martin
Published: February 2025

This paper focuses on the work of Czech aesthetician and ethnologist Josef Jedlička who describes ornament as a product of territorial rule. In his book The Ornament, Jedlička addresses the problem of ideological control of territorial repetition as an emergence of entropy. To understand Jedlička’s claims of entropic repetition, I propose introducing it in dialogue with Deleuze’s conception of repetition, in which differentiation is not an external but an internal rule of repetition. I argue that Jedlička’s conception of ornament as an externally imposed rule of senseless layering of imposed patterns allows us to understand the risk of social disconnection. In contrast, Deleuze’s account of territorial repetition as a production of erotic rhythm is based on the internal rule of differentiation, which allows us to see social connection as an ongoing variation assembled by desire. The philosophical consequences of these different approaches to repetition are further examined in their divergent readings of Franz Kafka’s work.
Composing and Decomposing: A Deleuzian Account of Ornamental Repetition
Authors: Fišerová Michaela
Published: February 2025

Based on Deleuze’s understanding of creative productivity as an expression of one’s mental desiring-machine, the paper proposes an innovative insight into the ambiguous – constructive and destructive – human need to repeat. To philosophically grasp the aesthetic and material results of such repetitive activity, I propose to complete the Deleuzian concept of assemblage with the concept of ornament, defined as a material result of a repetitive mindset generating arrangements of regularly returning acts and items. I argue that Deleuze’s immanent repetition generates two kinds of ornament: the individual one, such as a personal collection or an artistic style, and the social one, such as an avant-garde movement or subculture fashion. Both ornaments are explained through Deleuze’s concepts of negative and relational deterritorialisation and are further defined by a new reading of Deleuze’s revision of repetition in Freud and Nietzsche. Both kinds of immanent repetition produce ornamental compositions which are threatened by the danger of ornamental decomposition.
Et in Arcadia Ego: Death, Fortitude and the Birth of Wessex in Thomas Hardy’s Far from the Madding Crowd
Authors: Ferguson Trish
Published: February 2025

As has long been recognized, Thomas Hardy’s Far from the Madding Crowd transcends simple pastoral idealization by integrating the harsh realities of labour, economic instability, and mortality into its narrative. The early episodes of the novel, in which the chief characters, Gabriel and Bathsheba, are introduced as potential lovers, culminates in the catastrophic loss of Gabriel’s entire flock of sheep. Other key scenes of the novel also feature untimely deaths – of Fanny Robin and Sergeant Troy – highlighting the persistent shadow of mortality over pastoral life. Written during a period of personal turmoil when Hardy was mourning the suicide of his friend Horace Moule while beginning marriage with Emma Lavinia Gifford, the novel serves as both a pastoral tale and a meditation on death. To keep his promise to the editor of Cornhill of ‘a pastoral tale’, such as would fit with the magazine’s usual fare and tenor required careful management of scenes like the death of the sheep and the opening of Fanny’s coffin. Repeatedly we see the narrator deflect away from the abject and toward the beauty of the surrounding natural world in a narrative strategy often enhanced through allusions to the visual arts. This psychological work in the novel during Hardy’s bereavement is put under pressure in the treatment of Troy, whose life (emerging in the wake of Moule’s death) closely corresponded with that of Moule. Troy’s elimination from the narrative to make way for the pastoral conclusion is brought about by clearly differentiating him from Anglo-Saxon natives of Wessex. Troy, as an ‘outsider’ due to his French lineage that is linked with his flaws, contrasts sharply with the local characters’ Englishness that is tested and proven worthy by contrast in times of adversity. The incursion and removal of ‘outsiders’ in Hardy’s Wessex, first conceptualized in Far from the Madding Crowd, thus reflects a deeper ideological project – the construction and protection of a distinct notion of Englishness.
Efektivitas Game Based Learning Sebagai Strategi Pembelajaran Sejarah Kebudayaan Islam di Madrasah Aliyah Perguruan Mu’allimat Cukir
Authors: Nisa Khoirun , Syamsuddin Ali  , Afifatul Laili
Published: February 2025

Pembelajaran Sejarah Kebudayaan Islam di Madrasah Aliyah Perguruan Mu’allimat sering mengalami kendala dalam meningkatkan antusiasme dan partisipasi siswa. Dengan memasukkan aspek permainan ke dalam proses belajar mengajar, Pembelajaran Berbasis Permainan Game Based Learning muncul sebagai solusi baru untuk masalah ini. Tujuan dari studi ini adalah untuk mengevaluasi Game Based Learning di Madrasah Aliyah Perguruan Mu’allimat sebagai pendekatan pembelajaran Sejarah Kebudayaan Islam. Studi ini menilai bagaimana penerapan Game Based Learning memengaruhi motivasi, pemahaman, dan partisipasi siswa di kelas dalam pembelajaran Sejarah Kebudayaan Islam.Dalam hal ini menunjukkan bahwa penggunaan pembelajaran berbasis permainan Game Based Learning meningkatkan pemahaman siswa tentang peristiwa sejarah Islam, meningkatkan minat mereka dalam mempelajari Sejarah Budaya Islam, dan mendorong kerja sama dan kerja tim siswa. Namun, untuk mencapai penerapan Pembelajaran Berbasis Permainan Game Based Learning sebaik mungkin, kendala yang berkaitan dengan batasan waktu dan teknologi harus diatasi. Semua hal dipertimbangkan, pembelajaran berbasis permainan Game Based Learning telah menunjukkan janji dalam menumbuhkan lingkungan belajar yang menarik dan dinamis, yang dapat meningkatkan hasil belajar siswa di Madrasah Aliyah Perguruan Mu’allimat.
How to Communicate Effectively with Your Child. Module 03
Authors:   HoltIS Association
Published: February 2025

The session "How to Communicate Effectively with Your Child" provides an in-depth exploration of various methods for effective and productive communication, thereby promoting best practices in relationships with others and with children. During this session, parents will explore the theoretical elements of interpersonal communication and discuss the three key components: verbal, paraverbal, and visual. Another essential element of effective communication that they will identify is active listening. To reflect on their own communication style and apply the new elements introduced in the session, the parental educator will encourage parents to participate in activities designed to improve active listening skills and implement "I" messages. This will be achieved through the application of various methods that lead to motivational and balanced communication between parent and child. At the end of the session, the parental educator will ask parents to practice positive interpersonal communication skills with both their children and the adults in their lives. This module is part of the materials dedicated to the training of parental educators.
Artificially intelligent nursing homes: a scoping review of palliative care interventions
Authors: Ronan Isabel , Tabirca Sabin , Murphy David , Cornally Nicola , Saab Mohamad M. , Crowley Patrice
Published: February 2025

Introduction

The world’s population is aging at a rapid rate. Nursing homes are needed to care for an increasing number of older adults. Palliative care can improve the quality of life of nursing home residents. Artificial Intelligence can be used to improve palliative care services. The aim of this scoping review is to synthesize research surrounding AI-based palliative care interventions in nursing homes.

Methods

A PRISMA-ScR scoping review was carried out using modified guidelines specifically designed for computer science research. A wide range of keywords are considered in searching six databases, including IEEE, ACM, and SpringerLink.

Results

We screened 3255 articles for inclusion after duplicate removal. 3175 articles were excluded during title and abstract screening. A further 61 articles were excluded during the full-text screening stage. We included 19 articles in our analysis. Studies either focus on intelligent physical systems or decision support systems. There is a clear divide between the two types of technologies. There are key issues to address in future research surrounding palliative definitions, data accessibility, and stakeholder involvement.

Discussion

This paper presents the first review to consolidate research on palliative care interventions in nursing homes. The findings of this review indicate that integrated intelligent physical systems and decision support systems have yet to be explored. A broad range of machine learning solutions remain unused within the context of nursing home palliative care. These findings are of relevance to both nurses and computer scientists, who may use this review to reflect on their own practices when developing such technology.
Analysis of tumor-infiltrating exhausted T cells highlights IL-6 and PD1 blockade as a combined immunotherapy strategy for non-small cell lung cancer
Authors: Zhang Lulu , Guo Xiyuan , Sun Xiaoke , Liao Jue , Liu Qin , Ye Yingchun , Yang Zhihui , Cressey Ratchada , He Qing , Yuan Qing
Published: February 2025

Objective

Given the limitations of immunotherapy for treating non-small cell lung cancer (NSCLC), we investigated the phenotype and function of exhausted CD8+T cells and analyzed a novel combination immunotherapy to restore the effector killing function of tumor-infiltrating CD8+T lymphocyte (TIL).

Methods

We examined the expression and function of immunosuppressive molecules on CD8+T cells of peripheral blood mononuclear cells (PBMCs) and TILs by using prospectively collected peripheral blood, pleural effusions, and tumor tissues from patients with NSCLC and correlated the results with clinical data. We then evaluated the effect of interleukin 6 (IL-6) stimulation on CD8+T cells. Finally, we assessed the effects of combined blockade of PD1 and IL-6 on macrophage recruitment in a zebrafish macrophage model and CD8+ T cell function and tumor growth in PBMC humanized mouse model.

Results

The expression of exhaustion markers on CD8+ T cells was found to be notably higher in both tumor and paraneoplastic tissues compared to peripheral blood. Furthermore, the degree of CD8+ T cell exhaustion exhibited a progressive increase with proximity to the tumor. When CD8+ T cells from peripheral blood and tumor tissues of NSCLC patients were stimulated with IL-6, the expression level of exhaustion markers, especially PD1, was further elevated. In the in vitro experiment, the combined inhibition of IL-6 and PD1 substantially enhanced the effector killing function of CD8+ T cells in NSCLC pleural effusion samples. In a macrophage-labeled zebrafish model, combined blockade of IL-6 and PD1 enhanced the recruitment of macrophages. In PBMC humanized mouse model, combined blockade of IL-6 and PD1 enhanced the inhibition of tumor growth.

Conclusion

Our data suggest that CD8+ T cells in NSCLC patients were in a state of exhaustion and combined blockade of IL-6 and PD1 to restore CD8+ T cell function to inhibit tumor growth may be an effective clinical strategy for the treatment of NSCLC.
Dicoumarol sensitizes hepatocellular carcinoma cells to ferroptosis induced by imidazole ketone erastin
Authors: Yang Ziwei , Han Tixin , Yang Ruibin , Zhang Yinuo , Qin Yifei , Hou Jialu , Huo Fei , Feng Zhuan , Ding Yaxin , Yang Jiali , Zhou Gang , Wang Shijie , Xie Xiaohang , Lin Peng , Chen Zhi-Nan , Wu Jiao
Published: February 2025

Introduction

Ferroptosis, an iron-dependent form of regulated cell death, is characterized by the lethal accumulation of lipid peroxides on cellular membranes. It not only inhibits tumor growth but also enhances immunotherapy responses and overcomes drug resistance in cancer therapy. The inhibition of the cystine-glutamate antiporter, system Xc–, induces ferroptosis. Imidazole ketone erastin (IKE), an inhibitor of the system Xc– functional subunit solute carrier family 7 member 11 (SLC7A11), is an effective and metabolically stable inducer of ferroptosis with potential in vivo applications. However, tumor cells exhibited differential sensitivity to IKE-induced ferroptosis. The intrinsic factors determining sensitivity to IKE-induced ferroptosis remain to be explored to improve its efficacy.

Methods

Bulk RNA-sequencing data from hepatocellular carcinoma (HCC) and normal liver tissues were collected from The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) databases. Differentially expressed genes were identified and intersected with the ferroptosis-related genes (FRGs) listed in the FerrDb database, yielding the identification of 13 distinct FRGs.

Results

A ferroptosis signature index model (Risk Score) was developed to predict HCC prognosis. And SLC7A11 and NAD(P)H quinone dehydrogenase 1 (NQO1) were identified as candidate FRGs indicating poor prognosis of HCC. Dicoumarol (DIC), an inhibitor of NQO1, was subsequently employed to assess its sensitizing effects on IKE in HCC treatment. In HCC cell lines and the subcutaneous xenograft model, the combined suppression of SLC7A11 and NQO1 significantly enhanced the inhibitory effect on tumor growth by inducing ferroptosis.

Discussion

In conclusion, our findings demonstrate that DIC sensitized HCC cells to IKE-induced ferroptosis in HCC. Moreover, the identification of potential drugs that enhance the susceptibility of HCC cells to ferroptosis could provide novel therapeutic strategies for the treatment of HCC.
Planetary health education in undergraduate medical education in Germany: results from structured interviews and an online survey within the national PlanetMedEd Project
Authors: Grieco Fabio , Parisi Sandra , Simmenroth Anne , Eichinger Michael , Zirkel Janina , König Sarah , Jünger Jana , Geck Eva , Schwienhorst-Stich Eva-Maria
Published: February 2025

Background

In light of the accumulating evidence, awareness and urgency to act upon the three planetary crises – climate change, biodiversity loss, and pollution – the concept of Planetary Health underscores their profound implications for health and promotes actionable solutions to advance both wellbeing and ecological sustainability. Despite (inter)national calls to integrate Planetary Health into health workers’ curricula, the current status of Planetary Health Education in undergraduate medical education in Germany is unclear. This study therefore aimed (a) to assess the current implementation of Planetary Health in undergraduate medical education in Germany and (b) to explore its characteristics as a foundation to develop evidence-informed recommendations for mainstreaming Planetary Health Education in medical schools in Germany.

Methods

The study comprised structured interviews followed by an online survey, both targeting all 39 medical schools in Germany. In 2021, structured interviews were conducted with students, educators and deanery staff at medical schools. In 2023, educators and deanery staff participated in an online survey based on the findings from the interviews.

Findings

In total, 80% of the 39 medical schools participated in the interviews, while 90% took part in the online survey. Based on integrated findings, 35 medical schools (90%) offered Planetary Health Education, with a median of two educational activities, including both stand-alone courses and lectures integrated into other courses. Despite an overall increase since winter semester 2021/2022, most educational activities were electives and not part of the mandatory curriculum. Innovative educational approaches and learning objectives differed significantly between mandatory and elective formats. In contrast to mandatory educational activities, student involvement was reported for the majority of electives and was significantly associated with transformative learning objectives.

Interpretation

Despite a steady rise in teaching activities, mandatory Planetary Health Education remains insufficiently integrated into undergraduate medical education in Germany. Key criteria defining high-quality Planetary Health Education, such as innovative educational approaches, practical skills, and transformative learning, were primarily reflected in electives, that reach only a minority of students. To adequately equip the future healthcare workforce, the current barriers to successfully integrating Planetary Health into medical education must be systematically addressed and overcome.
Proteogenomic annotation of T6SS components identified in Bacteroides fragilis secretome
Authors: Zakharzhevskaya Natalya B. , Shagaleeva Olga Yu , Kashatnikova Daria A. , Goncharov Anton O. , Evsyutina Daria V. , Kardonsky Dmitry A. , Vorobeva Elizaveta A. , Silantiev Artemiy S. , Kazakova Viktoria D. , Kolesnikova Irina V. , Butenko Ivan O. , Vanyushkina Anna A. , Smirnova Svetlana V. , Chaplin Andrei V. , Efimov Boris A.
Published: February 2025

Introduction

Bacteroides fragilis (Bf)’s T6SS locus has been characterized and shown to have functional activity in competition experiments. It has been demonstrated that symbiont nontoxigenic Bf strains have a more effective “weapon” effect on pathogenic Bf, which is realized through the activity of effector-immune (E-I) protein pairs. Intensive study of the T6SS structure has led to an understanding of certain issues related to its functional activity, but the exact regulatory mechanisms of E-I protein pair activity remain unclear. Proteomic annotation of T6SS components and detailed descriptions of all immune-effector pairs are currently available. In this research, we performed detailed proteogenomic analysis and subsequent proteomic annotation of the T6SS components of the toxigenic Bf BOB25.

Material and methods

Fractionated cells, cultivated media and vesicles were prepared for proteome analysis by HPLC-MS/MS. Proteogenomic annotation and comparative genomic study of the T6SS loci of the toxigenic Bf BOB25 were carried out by comparison with the reference genomes of the following Bf strains: JIM10, NCTC 9343 and 638R.

Results

According to the data obtained, T6SS components were represented in all types of the analysed samples. The following components of the T6SS were identified in culture media and cells: ClpV (TssH), TssK, TssC, TssB, Hcp (TssD), and TetR. The predicted effector protein AKA51715.1 (VU15_08315) was also detected in media. The greatest amount of T6SS proteins, including the Hcp protein, was detected in the vesicle samples, which was also observed by TEM. Potential effectors, including AKA51715.1 (VU15_08315), AKA51716.1 (VU15_08320), AKA51728.1 (VU15_08385) and the immune protein AKA51727.1 (VU15_08380), were detected in vesicles.

Discussion

The presence of the immune and effector proteins in the Bf secretome indicates the high activity of the T6SS without bacterial competition. It is possible that the T6SS is also used by bacteria to regulate population size by altering the activity of different repertoires of E-I pairs.
Feasibility of home-based transcranial direct current stimulation combined with personalized word retrieval for improving naming in primary progressive aphasia
Authors: George Allan , McConathey Eric , Vogel-Eyny Amy , Galletta Elizabeth , Pilloni Giuseppina , Charvet Leigh
Published: February 2025

Background/Objectives

Primary progressive aphasia (PPA) is managed with speech-language therapy (SLT) to slow language decline. Pairing transcranial direct current stimulation (tDCS) with SLT can enhance its effects. However, further research is needed to confirm these findings and guide its clinical use. We evaluated the feasibility of providing an intervention combining tDCS with SLT as a home-based and remotely supervised intervention.

Methods

Participants with confirmed PPA who had word-finding difficulties were recruited for an open-label observational study. The intervention consisted of 20 daily sessions over 1 month, each with 45-min of personalized word retrieval training. During the first 30-min, participants received tDCS over the left inferior frontal gyrus (anode F7, cathode O1) at 2.0 mA. Language measures were remotely administered at baseline and intervention end.

Results

We enrolled 10 patients (age: 70 ± 7 years; 60% male) with confirmed logopenic variant (n = 2), semantic variant (n = 2), or unspecified (n = 6) PPA. The intervention was well-tolerated with no treatment-limiting adverse events. All participants completed all sessions, confirming the feasibility of the home-based treatment. There were no declines in language functioning measures, with improved naming for trained vs. untrained items (p = 0.003) and a significant improvement in confrontation naming (p = 0.016) from baseline to intervention end.

Conclusions

Our case series demonstrates that home-based tDCS added to SLT is feasible for patients with PPA. However, larger controlled studies are required to confirm its effectiveness in slowing language decline and to fully determine the benefits of this approach. This approach not only facilitates broader access to participation but also enables the extended treatment necessary to evaluate its clinical benefits, moving this treatment closer to clinical availability as a telehealth treatment.
Dietary index for gut microbiota and its protective role against kidney stones: evidence of diabetes as a mediator from NHANES cross-sectional data
Authors: Wang Lei , Wu Junjun , Jiang Ziwen , Wang Chao , Lin Fuxiang , Zhong Yuxiang , Zhao Pengpeng , Wei Wei , Huang Jianhua , Xu Zhanping
Published: February 2025

Background

The dietary index for gut microbiota (DI-GM) reflects dietary patterns that support gut microbial health and may influence kidney stone (KS) risk. The role of DI-GM and its mediation by diabetes in KS pathogenesis remains unclear.

Objective

To investigate the association between DI-GM and KS prevalence, assess the mediation effect of diabetes, and explore subgroup-specific effects and underlying mechanisms.

Methods

A cross-sectional analysis of NHANES (2007–2018) data was conducted using a stratified, multistage probability sampling design. A total of 19,841 participants were included in the final analysis. Data entry and statistical analysis were performed using Empower version 4.2 (X&Y Solutions, Inc., Boston, MA, United States) and R version 3.4.3 (R Foundation). Multivariable logistic regression was employed to assess the association between DI-GM and KS prevalence, with statistical significance set at p < 0.05. Mediation analysis evaluated diabetes’s contribution to this relationship, and subgroup analyses were conducted based on sex, race/ethnicity, and alcohol consumption.

Results

Higher DI-GM scores were associated with lower KS prevalence (adjusted OR: 0.78, 95% CI: 0.65–0.92 per SD increase). Diabetes mediated 9.27% of this relationship. Subgroup analyses revealed stronger protective effects among females, non-Hispanic Black individuals, and heavy drinkers. Mechanistically, DI-GM may reduce KS risk through gut microbial modulation of oxalate metabolism, urinary citrate excretion, and systemic inflammation.

Conclusion and recommendations

Higher DI-GM scores are associated with reduced KS prevalence, partially mediated by diabetes. These findings highlight the role of dietary interventions targeting gut microbiota in KS prevention and call for longitudinal studies to confirm these results and develop tailored dietary strategies.
A synergistic effect of secondhand smoke with vitamin D deficiency on cognitive impairment in older adults: a cross sectional study
Authors: Li Yan , Shen Qianqian , Chen Chengyu , Yin Xueru , Wang Xinru , Yang Xiyue , Zhang Xueqian , Chen Lei , Xu Jian , Gong Guifang
Published: February 2025

Objectives

To investigate whether exposure to secondhand smoke (SHS) aggravates the detrimental effect of vitamin D deficiency (VDD) on cognitive performance in the elderly.

Methods

Based on National Health and Nutrition Examination Surveys (NHANES) 2011–2014, 1,446 non-smoking participants (≥ 60 years old) with detailed serum 25-hydroxyvitamin D [25(OH)D], concentration of cotinine and tests score of cognitive function were included. Cognitive impairment was defined as having a cognitive score in the lowest quartile. The possible synergistic effect of SHS with VDD on cognitive impairment was evaluated by using a multivariable logistic regression model.

Results

VDD was independently associated with risk of low the Digit Symbol Substitution Test (DSST) scores, increased by nearly 60% [< 34, adjusted odds ratio (aOR) = 1.62, 95% CI: 1.03 ~ 2.53]. Although it only had an association with cognitive impairment indicated by DSST and the Animal Fluency test (AFT) in the crude model, SHS exposure showed significant synergistic effects with VDD on DSST (aOR: 3.03, 95% CI: 1.57 ~ 5.83, Pinteraction = 0.001) and AFT (aOR: 2.40, 95% CI: 1.34 ~ 4.29, Pinteraction = 0.003), respectively, after adjusting for the possible confounders. In further stratified analysis, a more obvious synergistic effect of SHS with VDD on DSST (aOR: 4.73, 95%CI:1.77 ~ 12.68, Pinteraction = 0.002) and AFT (aOR: 5.30, 95%CI: 1.63 ~ 17.24, Pinteraction = 0.006) was found in obese and overweight subjects, respectively.

Conclusion

SHS exposure had synergistic effect with VDD on cognitive impairment among elderly and the interaction effect was more obvious in overweight and obese individuals.
Case report: Unraveling a unique case of male occult breast cancer with axillary intricacies and a comprehensive literature dive
Authors: Xie Xintong , Kong Xiangyi , Jiang Hongnan , Gao Jidong
Published: February 2025

Male breast cancer is a rare neoplasm, accounting for approximately 1% of all breast cancer cases. It typically presents as a painless, retroareolar mass. An exceedingly rare variant is male occult breast cancer, which is primarily characterized by axillary lymph node enlargement without an identifiable primary breast tumor. We report an intriguing case of a septuagenarian patient diagnosed with male occult breast cancer. The patient presented with both axillary lymph node enlargement and an associated axillary skin ulcer, and was subsequently diagnosed with male occult breast cancer with metastases to the axillary and clavicular lymph nodes, as well as more distant sites. His treatment involved a multidisciplinary approach, including HER2-targeted therapy, chemotherapy, axillary lymph node dissection, and radiotherapy. Regular follow-ups have shown that his condition remains stable. Notably, this is the first documented case of male occult breast cancer with distant metastasis that was successfully treated with surgery and radiotherapy following systemic therapy. This case highlights the complex clinical presentation and management of male occult breast cancer. Our findings suggest that surgical intervention may be a feasible option post-downstaging by systemic therapy, even in the presence of distant metastases.
The influence of menopause age on gynecologic cancer risk: a comprehensive analysis using NHANES data
Authors: Abulajiang Yiliminuer , Liu Tao , Wang Ming , Abulai Abidan , Wu Yumei
Published: February 2025

Background

Menopause, a natural transition, affects women’s health risks, including gynecologic cancers. Early menopause, linked to lower estrogen, may increase cancer susceptibility. This study analyzed NHANES data from 1999 to 2020 for 8,219 postmenopausal women to explore the relationship between menopausal age and gynecologic cancers. We used regression models and RCS models to assess the risk.

Methods

This study utilized data from the NHANES spanning 1999 to 2020, focusing on 8,219 postmenopausal women selected through stratified sampling. Variables including socioeconomic factors, health behaviors, nutritional status, and medical history were assessed in relation to participants’ menopausal age and gynecologic cancer prevalence. We analyzed the relationship between menopausal age and gynecologic cancers (cervical, ovarian, and uterine) using multiple regression models. Additionally, we employed RCS models to evaluate nonlinear relationships between menopausal age and gynecologic cancer risk.

Results

Our findings indicate a significant inverse association between menopausal age and the risk of gynecologic cancers. After controlling for confounding factors such as age, race, BMI, and lifestyle variables, a later age at menopause was associated with a reduced risk of cervical, ovarian, and uterine cancers. The RCS model revealed a non-linear, low-L-shaped relationship, particularly highlighting increased cancer risks at younger menopausal ages. Subgroup analyses demonstrated consistent results across demographic and lifestyle factors, confirming the robustness of the observed associations.

Conclusion

This study reveals the link between menopausal age and gynecologic cancer prevalence. Early menopause is a significant risk factor for cervical, ovarian, and uterine cancers. Our findings support tailored cancer screening based on menopausal age, potentially improving preventive care for postmenopausal women.
The digital interactivity of US think tanks’ communications
Authors: Castillero-Ostio Elizabet , Moreno-Cabanillas Andrea , Rodríguez-Fernández Leticia
Published: February 2025

The communicative actions of think tanks play a fundamental role in shaping public policies and social discourse, with their capacity for interaction with diverse audiences being vital to maximizing their influence. This study conducts a quantitative content analysis of the communication tools utilized on the websites of the 25 most influential think tanks in North America, as identified in McGann's (2021) report. It assesses the degree of interactivity fostered by these platforms in their relationship with users, revealing that, while the interactivity of one-way tools is notably high, the options for bidirectional interaction remain at a moderate level, characterized by a predominance of asymmetric resources. The findings suggest that, despite effective information transmission, think tanks must adopt more dynamic and participatory communication strategies that promote genuine dialogue and greater collaboration, thereby adapting to a constantly evolving digital environment that demands stronger connections with diverse audiences.