Search Results (7,315)

The ribosome in eukaryotic cells is a macromolecular complex composed of four ribonucleic acids and over 80 proteins. This organelle facilitates protein synthesis in cells, and its activity is strongly upregulated in human cancers. Immune cells, a variety of cellular stressors and numerous structurally and mechanistically distinct anti-cancer agents have been shown to induce ribosomal RNA degradation in tumour cells in vitro and in vivo—a phenomenon we termed “RNA disruption”. RNA disruption can be quantified in cultured cell lines and patient samples using the RNA disruption assay (RDA). Unlike well-known high-throughput anti-cancer drug sensitivity assays, RDA can distinguish between dying and arrested tumour cells, making it an attractive assay for anti-cancer drug discovery and development. Low tumour RNA disruption during neoadjuvant chemotherapy (as measured using RDA) is strongly associated with residual disease and reduced disease-free survival, making it a potentially valuable chemo-resistance assessment tool. High RNA disruption may also indicate chemo-responsiveness. RDA holds the prospect of being a useful tool to escalate or de-escalate neoadjuvant chemotherapy in cancer patients. Moreover, the assay’s ability to predict treatment outcomes during neoadjuvant chemotherapy may permit its use in adaptive clinical trials and in drug approval by regulatory agencies. This review provides insight into the cellular processes involved in chemotherapy-induced RNA disruption. It also describes the results of clinical studies on tumour RNA disruption in cancer patients and suggests possible approaches that could be considered for the utilization of RDAs in the clinical management of breast cancer patients undergoing current neoadjuvant chemotherapy regimens. Full article

The pursuit of universal, symmetric semantic representations within large language models (LLMs) faces a fundamental challenge: the inherent asymmetry of natural languages. Different languages exhibit vast disparities in syntactic structures, lexical choices, and cultural nuances, making the creation of a truly shared, symmetric embedding space a non-trivial task. This paper aims to address this critical problem by introducing a novel framework to forge robust and symmetric multilingual sentence embeddings. Our approach, named DACL (Dynamic Asymmetric Contrastive Learning), is anchored in two powerful asymmetric learning paradigms: Contrastive Learning and Dynamic Curriculum Learning (DCL). We extend Contrastive Learning to the multilingual context, where it asymmetrically treats semantically equivalent sentences from different languages (positive pairs) and sentences with distinct meanings (negative pairs) to enforce semantic symmetry in the target embedding space. To further refine this process, we incorporate Dynamic Curriculum Learning, which introduces a second layer of asymmetry by dynamically scheduling training instances from easy to hard. This dual-asymmetric strategy enables the model to progressively master complex cross-lingual relationships, starting with more obvious semantic equivalences and advancing to subtler ones. Our comprehensive experiments on benchmark cross-lingual tasks, including sentence retrieval and cross-lingual classification (XNLI, PAWS-X, MLDoc, MARC), demonstrate that DACL significantly outperforms a wide range of established baselines. The results validate our dual-asymmetric framework as a highly effective approach for forging robust multilingual embeddings, particularly excelling in tasks involving complex linguistic asymmetries. Ultimately, this work contributes a novel dual-asymmetric learning framework that effectively leverages linguistic asymmetry to achieve robust semantic symmetry across languages. It offers valuable insights for developing more capable, fair, and interpretable multilingual LLMs, emphasizing that deliberately leveraging asymmetry in the learning process is a highly effective strategy. Full article

Paratuberculosis is a chronic zoonotic bacterial infection, primarily affecting ruminants. This review examines the disease in the Arabian Peninsula, focusing on distribution, molecular diversity, prevalence, and associated risk factors. Following PRISMA guidelines, a systematic search was conducted in PubMed, Scopus, and Web of Science. After duplicate removal and eligibility screening, data extraction, analysis, and quality assessment were performed. Pathogen sequences were retrieved from NCBI GenBank for phylogenetic analysis. The review included a total of 31 published articles from 1997 to 2025, of which 26 were used in the meta-analysis. Most studies (n = 12) were published between 2011 and 2015, predominantly from Saudi Arabia (n = 22), with no reports from Qatar, Bahrain, or Yemen. The majority of the studies involved camels and sheep (n = 16 on each species), followed by cattle (n = 9), goats (n = 7), humans (n = 2), and buffalo (n = 1). Phylogenetic analysis delineates two major clades—Type S and Type C—suggesting greater genetic diversity in Type S. The estimated pooled seroprevalence and pathogen prevalence in livestock ruminants were 8.1% and 22.4%, respectively. Herd-level estimated pooled seroprevalence was 26.9%. Small ruminants (19.3%) were more sero-prevalent than large ruminants (7.4%), with goats (28.7%) significantly (p < 0.01) more affected than sheep (21.5%), camel (9.8%), and cattle (6.6%). Clinical signs in ruminants included chronic diarrhea, emaciation, anorexia, alopecia, wry neck, and dehydration. The reviewed study patterns and findings suggest high pathogen diversity and a significant risk of transboundary transmission at the human–animal interface in this region. A One Health surveillance approach is crucial, particularly on farms with diarrheic and emaciated animals. Establishing a national surveillance plan and phased (short-, intermediate-, and long-term) control programs is essential to mitigate economic losses, limit transmission, overcome the cultural barrier, and protect public health. Full article

Black Canadians are one of the fastest-growing groups in Canada, with 59% of this population comprising immigrants. Ongoing systemic racism and discrimination have serious consequences for the mental health of Black Canadians. While research and policy efforts to address the mental health needs of this population are ongoing, a greater understanding of the healing practices relevant to this diverse population is needed. This scoping review synthesized and discussed key features of culturally inclusive, affirming, and contextually relevant approaches and practices for mental health care and healing with Black Canadians, as well as identified limitations and gaps in the current research. This study followed the PRISMA guidelines for scoping reviews and conducted a search in PsycINFO, MEDLINE, Embase, SocINDEX, CINAHL, Sociological Abstracts, and Global Health in October 2023. A total of 34 articles met the inclusion criteria. The review identified that most studies were conducted in one Canadian province (i.e., Ontario) and involved diverse perspectives, including service users and providers. The thematic review of articles revealed limited research regarding specific interventions, but identified many commonly reported features of culturally and contextually relevant approaches to mental health care and healing for Black Canadians that broaden the scope of mental health care beyond Euro-Western clinical models, including taking a holistic and empowerment-based approach, engaging in culturally affirming care, a social justice approach, community-centred and collaborative healing, and the necessity of practitioner education. Recommendations for practice, policy, education, and research are provided to support more inclusive and responsive mental health care systems for Black Canadians. Full article

Background/Objectives: Pacific peoples in Aotearoa, New Zealand experience the highest burden of gout globally, yet there is still a lack of awareness and understanding of the disease. A Pacific community group and Pacific health professional network co-designed Pacific gout resources to improve understanding. The aim of this study is to identify and discuss the current state and perceptions of Pacific gout education, and explore health professionals’ views on Pacific co-designed resources and their usefulness in clinical settings. Methods: The Fa’afaletui model was utilised to conduct semi-structured Talanga interviews with 14 health professionals in Auckland, New Zealand who work in primary care clinics. The interview explored their views on providing gout education and on the feasibility of the Pacific co-designed gout resources. Talanga interviews were audio recorded and thematically analysed. Results: Overall, health professionals responded positively to the co-designed resources, identifying the benefits of supporting primary care consultations and improving Pacific patients’ understanding of gout. The key findings were summarised in five main themes: (1) health system barriers to gout education, (2) misleading information, (3) health professionals’ experiences of providing health education, (4) general impressions of Pacific co-designed resources, and (5) the feasibility of Pacific co-designed educational resources in a clinical setting. Conclusions: This study presents the views of health professionals in providing health education related to gout and on the feasibility of Pacific co-designed educational resources. It reinforces the significance of involving communities in the design and implementation of interventions to ensure they are culturally safe, relevant, and have long-term impacts on gout management. Full article

Background: Cellulosimicrobium, formerly known as the Oerskovia genus, is a Gram-positive organism known for its characteristic bright yellow colonies. While abundant in nature, it is very rarely linked to pathogenesis in humans. While there is no classical presentation for Cellulosimicrobium-associated infections, cases tend to be foreign body-related or involve immunocompromised patients. Rates of Cellulosimicrobium-associated infections have been hypothesised to rise in the future, due to rising numbers of immunocompromised patients in the community and increasing usage of foreign bodies such as prostheses and long-term catheters. Existing technical difficulties regarding misidentifying cultures as other species (often other coryneforms) may also play a significant role in the low number of documented cases, and this may change in the near future with diagnostic advancements such as whole genomic sequencing. Case Presentation: A 57-year-old immunocompetent Irish male presented with concomitant neck and lung masses. Notably, this was found to be directly following a recent dental procedure. During extensive investigations, Cellulosimicrobium was isolated from biopsied lung tissue using 16S ribosomal ribonucleic acid gene-sequencing analysis. The patient was treated with long-term oral amoxicillin and safely discharged, with both masses showing measurable reductions in size on subsequent imaging. Conclusions: Should Cellulosimicrobium represent the causative pathological organism in this case, then we believe this to represent a potential novel documented presentation of the organism’s pathogenesis in humans. We provide detailed discussion surrounding the successful management of this patient and the evaluation of the evolving differential diagnosis throughout this case. Full article

Non-urbanized areas (NUAs), including residual urban green areas, urban parks, agricultural, natural and semi-natural areas, are a fundamental part of the green infrastructure. They are essential in sustaining life and future development, providing a series of ecosystem services (ESs) vital to human society. However, the rapid expansion of urban areas has led to a significant reduction in green spaces. Land-take, reducing available land resources, impacts ecosystem functionality, making it crucial to preserve high-quality territories and the relative ESs provided. In this context, the aim of this study was to evaluate the reduction in ESs due to the land-take having occurred in the last 20 years in the Province of Monza–Brianza, the Italian province with the highest land-take. To achieve this goal, authors used the official data of land use/cover of the Lombardy Region, with three time thresholds (T0: 1999–2003, T1: 2012–2013, T2: 2021) and applied a methodology for ESs assessment originally developed for the municipal level, adapting it to the provincial scale. The study analyzes trends in land-take and land-use changes and assesses how these changes have led to variations in ES provision. The approach involves calculating multiple indices reflecting different ESs provided by NUAs: provisioning ESs coming from agriculture, regulating ESs provided by natural resources, cultural ESs provided by landscape. Findings reveal that urban expansion has decreased provisioning ESs coming from agriculture, while ESs provided by landscape and natural resources have remained stable or improved, respectively. The natural quality index has improved due to conservation policies, despite the high land-take recorded. Anyway, although regional policies have mitigated some negative effects, the overall reduction in green spaces remains a critical issue. Full article

Food tourism is growing in travel experiences, with tourists increasingly drawn to culturally authentic and aesthetically engaging food. Understanding the psychological and experiential factors shaping these preferences is crucial for enhancing tourist visit intentions. Therefore, this study examines the factors such as attitudes (ATT), subjective norms (SN), perceived behavioural control (PBC), and food aesthetic experience (FAE) that influence tourists’ behavioural intentions towards food preferences (BIFP) in Goa, India. The research extends the theory of planned behaviour (TPB) by incorporating food aesthetic experiences as a mediating factor. A quantitative approach was employed, involving a structured questionnaire based on a five-point Likert scale, administered to 217 tourists visiting Goa, India, who were selected through a random sampling method. Data were analysed using Partial Least Squares–Structural Equation Modelling (PLS-SEM) through SmartPLS 4.0. Results show that attitudes, subjective norms, perceived behavioural control, and food aesthetic experience significantly influence tourists’ behavioural intentions towards food preferences. Food aesthetic experience emerged as a strong mediator, particularly between attitudes, perceived behavioural control, and tourists’ behavioural intentions towards food preferences. These findings highlight the role of sensory appeal in shaping culinary choices. The study concludes that a holistic approach, supported by cultural education and stakeholder collaboration, can enrich tourist experiences and support food tourism development. Full article

Background: Scedosporium apiospermum is a filamentous fungus increasingly recognized as an opportunistic pathogen in immunocompromised hosts, though rare infections in immunocompetent individuals with structural lung disease have been reported. Its diagnosis and management remain challenging due to non-specific clinical presentation and intrinsic resistance to multiple antifungal agents. Case Presentation: We report the case of a 66-year-old immunocompetent woman with idiopathic bilateral non-cystic fibrosis bronchiectasis, who presented with subacute cough and increased sputum production. Chest high-resolution CT revealed new subsolid and ground-glass infiltrates superimposed on stable bronchiectatic changes. Bronchoalveolar lavage (BAL) cultures isolated S. apiospermum as the sole pathogen. The patient was treated with oral voriconazole (200 mg BID) for 4 weeks, followed by a 4-week course of aerosolized amphotericin B. Clinical and radiological improvement was observed, and no relapse occurred during follow-up. Discussion: This case highlights the potential for S. apiospermum to cause clinically relevant pulmonary infection in structurally abnormal but immunocompetent lungs. Non-CF bronchiectasis may facilitate fungal colonization due to impaired mucociliary clearance and chronic mucus retention. Combined antifungal therapy involving systemic voriconazole and inhaled amphotericin B (though not yet standardized) was employed based on clinical rationale and the available literature, resulting in favorable outcomes. Conclusions:S. apiospermum pulmonary infection, although rare in immunocompetent hosts with bronchiectasis, should be considered in cases of new or persistent infiltrates. Early recognition and individualized antifungal strategies, including the potential role of inhaled agents, may improve clinical outcomes. This case reinforces the importance of multidisciplinary collaboration in the management of complex fungal infections in chronic airway disease. Full article

Axon polarization is a fundamental process in neuronal development, providing the structural basis for directional signaling in neural circuits. Precise control of axon specification is, thus, essential for the bottom-up construction of neuronal networks with defined architecture and connectivity. Although neurite length and elongation timing have both been implicated as determinants of axonal fate, their relative contributions have remained unresolved due to technical limitations in manipulating these factors independently in conventional culture systems. Here, we developed a constructive neuroengineering platform based on modifiable agarose gel microstructures that enables dynamic, in situ control of neurite outgrowth length and timing during neuronal cultivation. This approach allowed us to directly address whether axon polarization depends primarily on neurite length or the order of neurite extension. Using a single-neurite elongation paradigm, we quantitatively defined two length thresholds for axon specification: a critical length of 43.3 μm, corresponding to a 50% probability of axonal differentiation, and a definitive length of 95.4 μm, beyond which axonal fate was reliably established. In experiments involving simultaneous or sequential elongation of two neurites, we observed that neurite length—not elongation order—consistently predicted axonal identity, even when a second neurite was introduced after the first had already begun to grow. The presence of a competing neurite modestly elevated the effective critical length, suggesting inhibitory interactions that modulate length thresholds. These findings provide the first direct experimental confirmation that neurite length is the primary determinant of axon polarization and demonstrate the utility of constructive microfabrication approaches for dissecting fundamental principles of neuronal polarity. Our platform establishes a powerful experimental foundation for future efforts to achieve complete control over axon and dendrite orientation during the engineered construction of functional neuronal circuits. Full article

This study seeks to develop and evaluate a methodological framework for assessing the tourism potential of hillforts, by using a selected sample of 25 of these heritage resources located in the Lower Silesia Voivodeship. This region, as one of Poland’s most popular among domestic and international tourists, is increasingly confronting overtourism at its primary attractions. Concurrently, it possesses underutilised cultural assets, notably 250 remnants of gords/hillforts (grodziska in Polish) spanning various historical periods and dispersed across the whole area. Thus, to ensure the universality of the method, samples of hillforts from three main topographic zones of Lower Silesia were selected. In addition to the aim of testing the method, a secondary objective of the research involved conducting a preliminary assessment of selected hillforts’ tourism potential in different parts of the voivodeship. The methodology combined desk research and field studies across all selected archaeological sites. Concerning the primary objective, the developed assessment tool effectively replicated the multidimensional analytical framework characteristic of established methodologies, yielding reliable outcomes for evaluating gords’ tourism potential. However, modifications to the scoring system are recommended to enhance methodological precision. Regarding analysis of the 25 surveyed hillforts, the results indicate that objects from all zones mainly demonstrate high tourism potential, suggesting an opportunity for transformation into tourist attractions. The integration of hillforts into existing tourism infrastructure could significantly contribute to localised sustainable development across the region. The primary significance of these heritage resources lies in their capacity to facilitate the diversification of tourism offerings across distinct areas of the voivodeship. This development holds particular strategic value for northern poviats currently peripherally engaged in tourism economy. Moreover, by leveraging hillforts, communities obtain assets important in the process of building a common identity around cultural/historical place while safeguarding monuments. Concurrently, the most attractive southern poviats will benefit from the new attractions as they can help in mitigating overtourism pressures at overcrowded places, being an interesting alternative to the top attractions. This approach aligns with strategies to disperse tourist flows through specialised archaeological tourism products, thereby balancing economic benefits and local communities’ well-being with heritage preservation. Full article

Objectives: Animal studies have demonstrated that mesenchymal stem cell-conditioned medium (MSC-CM) possesses various therapeutic effects, including anti-inflammatory and anti-fibrotic properties. This study investigated the efficacy and safety of administering MSC-CM as a treatment for patients with generalized fatigue. Methods: The MSC-CM used in this study was derived from human adipose tissue and umbilical cord-derived mesenchymal stem cells cultured in a medium free of animal-derived components to avoid the risk of infection. This MSC-CM has recently been shown to possess anti-inflammatory effects and has been reported to be safe for human administration. With the expectation of alleviating fatigue symptoms through its anti-inflammatory effects, it was administered to patients intravenously and by inhalation. Safety and changes in subjective symptoms were evaluated, and blood biomarkers related to inflammation and oxidative stress were measured. Results: In this trial involving 19 patients experiencing fatigue, no serious side effects were observed following MSC-CM administration. Nearly half of the patients reported symptom improvement after a single dose, and some exhibited signs of reduced inflammation. Conclusions: This report presents the first investigation of systemic MSC-CM treatment for generalized fatigue, paving the way for more targeted studies on dosage and treatment frequency. These findings offer new hope and possibilities for treating fatigue, providing valuable insights into the clinical application of MSC-CM. Full article

Older adults with a refugee life experience have a disproportionate burden of mental health problems compared to non-refugee aging populations. Community-based participatory research (CBPR) is a promising approach to identify the challenges and strengths of older refugee adults and identify solutions to mental health disparities. We present a case study of one such CBPR program of research with older ethnic Nepali Bhutanese adults resettled in North America, Project Bhalakushari. We highlight the many opportunities to integrate older adults and members of the broader Bhutanese community in activities throughout the research process, starting with forming academic–community partnerships, identifying the needs and strengths of the community, conducting research, and sharing study findings with a broad audience of community members, health practitioners, policy-makers, and academics. Our case study emphasizes that a successful, culturally informed partnership should consider the involvement of the entire community, regardless of age, in the initiative to secure buy-in and support and maximize the positive impact of the work. We identify concrete strategies to overcome challenges specific to conducting research, with a focus on recruitment, outreach, and data collection. Full article

Handover of patient care is the most common form of communication across hospitals. Enabling effective handover has been identified as a key priority for patient safety. This Human Factors Ergonomics socio-technical systems study aims to understand the current system of handover within departments, across departments, and at the interface of provider services, and then use this knowledge to co-design recommendations to enable resilience in clinical handover. The Systems Engineering Initiative for Patient Safety 3.0 (SEIPS3.0) framework is used to take a systems approach to observing clinical handover. Over 26 h of handover, involving 218 healthcare professionals handing over patient care across an acute hospital setting and at the interface of two external ambulance service systems, was observed. From these observations of clinical handovers, we co-designed—with the input of 41 medical, nursing, health, and social care professionals, quality and safety professionals, and patient partners—70 recommendations for enabling resilience in handover using two socio-technical systems analysis frameworks: SEIPS3.0 and the Cube. These 70 recommendations were inductively coded, and ten emergent properties that can support resilience in handover were identified, including person-centred care, multi-disciplinary team working, culture, communication, evidence-based practice, operations management, education, digitally enabled care, evidence-based design, and understanding context. This study contributes important knowledge for healthcare professionals and Human Factors Ergonomics practitioners on the systemic enablers of resilience in clinical handover in acute hospital settings. Full article

Proponents of Sexual Script Theory posit that men and women differ in their sexual behaviors/motivations, often due to culturally ingrained expectations. When these expectations are violated, individuals may face stigma, particularly in nontraditional contexts like mixed-sex threesomes (MSTs). This study examined gender differences in heterosexual adults’ anticipated stigma and willingness to accept various sexual offers, including dyadic and MST offers involving same- and other-sex partners, through the lens of the backlash effect (i.e., the anticipation of stigma for participating in sexual behaviors that contradict societal expectations). A total of 540 heterosexual U.S. adults read vignettes depicting hypothetical sexual invitations and completed measures assessing anticipated stigma and willingness to engage. Results revealed that men anticipated less stigma and were more willing to accept sexual offers than women. Participants also anticipated less stigma and reported greater willingness to accept other-sex dyadic offers as compared to same-sex or MST offers. However, men reported the highest anticipated stigma and lowest willingness for same-sex dyadic offers, suggesting a novel backlash effect against men engaging in gender non-conforming behaviors. These findings offer support for the persistence of the sexual double standard and provide evidence for gendered backlash effects, including those impacting heterosexual men. Full article