Homologous recombination deficiency (HRD) testing can inform cancer treatment decisions, particularly regarding the use of poly (ADP-ribose) polymerase (PARP) inhibitors. However, uptake of HRD testing is inconsistent across healthcare settings. This review aimed to explore healthcare provider and patient perspectives on the use of HRD testing in cancer care. A narrative review was conducted to identify studies reporting on individual views, perceptions, and experiences with HRD testing. Literature searches were performed in Embase, Medline, CINAHL, and PsycINFO for English-language articles published between 2000 and 2026. Eligible studies used quantitative, qualitative, or mixed-methods approaches. Findings were analyzed using the Health Belief Model to identify perceived benefits, barriers, and factors influencing test uptake. Sixteen studies were included, covering both healthcare provider and patient perspectives. The most commonly reported facilitator was the perceived benefit of HRD testing in informing treatment decisions, particularly for guiding PARP inhibitor use. Patients emphasized the importance of provider recommendations in their decision to undergo testing. Reported barriers included lack of healthcare provider knowledge, limited access to testing, inconsistent clinical guidelines, financial concerns, and low patient awareness. While both patients and healthcare providers recognize the value of HRD testing in cancer care, uptake is limited by informational and structural barriers. Efforts to improve access and implementation should include the development of standardized guidelines, provider and patient education, and policy strategies to ensure equitable access. Further research is needed to assess more patient perspectives and the real-world impact of HRD testing on care delivery and outcomes.
Pheochromocytomas and paragangliomas (PPGL) are rare but potentially life-threatening neuroendocrine tumors whose diagnosis relies primarily on the biochemical detection of excessive catecholamine production or metabolism. Plasma free metanephrines and urinary fractionated metanephrines remain the cornerstone biomarkers recommended for initial screening. However, their performance is influenced by substantial pre-analytical and analytical variability, requiring strict standardization in sampling conditions and assay methodology. The emergence of liquid chromatography-tandem mass spectrometry (LC-MS/MS) has improved specificity, but inter-laboratory variability and lack of harmonized cut-offs still challenge reproducibility. Chromogranin A (CgA), while broadly used in neuroendocrine tumor monitoring, shows poor diagnostic accuracy for PPGL. Recent advances in molecular profiling, metabolomics, and artificial intelligence (AI) suggest future opportunities for more integrated diagnostic pathways, although these approaches remain investigational in PPGL. This review critically examines the current biochemical tools used in PPGL diagnosis, discusses pitfalls and limitations, and focuses on unresolved analytical vulnerabilities, inter-laboratory variability, and the translational implications of these issues for routine laboratory practice, while also proposing perspectives for optimization, including emerging biomarkers, integrative diagnostics, and harmonization strategies.
The skeleton is a frequent site of metastatic spread, leading to skeletal-related events (SREs) such as pathological fractures, spinal cord compression, and refractory pain that profoundly impact patient survival and quality of life. Traditionally managed by a triad of radiotherapy, surgery, and systemic treatments, the landscape of bone metastasis care has undergone a major paradigm shift. Interventional Radiology (IR) has emerged as the "fourth pillar" of oncology, evolving from a palliative last-resort tool into a proactive specialty integrated into precision medicine and multidisciplinary decision-making. Through high-resolution image guidance, IR provides critical diagnostic tissue sampling for molecular profiling, immediate mechanical reinforcement via hybrid stabilization-combining percutaneous osteosynthesis and cementoplasty-and local tumor control through thermal ablation and cryoablation. Beyond its mechanical and local effects, an emerging body of research highlights the immunomodulatory potential of cryoablation and thermablation technics. IR-induced tumor necrosis may act as a potent "in situ" vaccine, releasing tumor-associated antigens and damage-associated molecular patterns that could trigger a systemic abscopal effect, especially when synergistic with immune checkpoint inhibitors. This review details the state-of-the-art IR techniques, from devascularization via embolization to advanced cryoablation, emphasizing their strategic integration into modern care pathways. It highlights the transition from simple symptom management to aggressive, curative-intent strategies in the era of personalized oncology, where IR serves as a bridge between conservative medical therapy and invasive surgical intervention.
Recent data support the existence of a "gut-lung axis" (GLA), yet it's role in chronic respiratory diseases, like cystic fibrosis (CF), is under investigation. In this review we explore the potential linkages and underlying mechanisms for gut-lung interaction axis, in terms of rationale (same embryonic and anatomical origins), microbial and immune interactions, and recent advances on GLA role in chronic lung diseases, with a focus on GLA research relevant to CF. The introduction of CFTR modulators has revolutionized CF management, dramatically reshaping the disease's clinical course by improving ion transport, mucosal hydration and mucociliary clearance. CFTR modulators are known to improve anion channel function, which has resulted in physiological and microbiological changes to the respiratory tract and gastrointestinal tract, which are likely to impact the GLA and are explored in this review. While there is a growing literature for the role of the GLA in regulating lung physiology in health and disease, additional work is warranted to elucidate molecular mechanisms by which the GLA mediates pathogenesis of disease. The ultimate goal would be to apply mechanistic understanding from the bench to the bedside to enable more personalized treatment strategies that both guide and improve lung disease management, especially in the CF field.
Remnant cholesterol (RC) has emerged as an atherogenic lipid fraction that may be associated with residual cardiovascular risk beyond low density lipoprotein cholesterol (LDL-C). However, its role in peripheral artery disease (PAD) has not been fully characterized. We analyzed data from National Health and Nutrition Examination Survey (NHANES) 1999-2004 including adults aged ≥40 years with available ankle-brachial index (ABI), lipid measurements and relevant covariates. Weighted logistic regression models were used to examine the association between RC and PAD. Discordance between RC and LDL-C was assessed using clinical equivalence approach to evaluate its association with PAD. The remnant cholesterol inflammatory index (RCII) and relevant mediation analyses were used to assess the role of inflammation. Among 3111 participants, higher RC levels were independently associated with a higher prevalence of PAD. In discordance analyses, discordantly low RC was generally associated with a lower prevalence of PAD, whereas discordantly high RC demonstrated attenuated associations after full adjustment. Higher RCII was associated with increased PAD risk, and C-reactive protein (CRP) partially mediated the association between RC and PAD. Higher RC is associated with an increased prevalence of PAD and may provide complementary risk information beyond LDL-C. Systemic inflammation partially mediates this association, supporting a potential relevance of RC in PAD risk stratification.
Despite rapid advances in artificial intelligence (AI) capabilities, clinical integration remains limited, partly due to an incomplete understanding of physicians' real-world engagement and determinants of adoption. We conducted an international cross-sectional survey between June and September 2024 using a 30-item questionnaire translated into 13 languages, analysing 1049 complete responses from 50 countries and territories. Most respondents reported fundamental to advanced understanding of AI (86.5%) and believed it would improve clinical practice (80.2%), particularly in efficiency (53.5%), timeliness (52.0%), and effectiveness (44.0%). However, only 27.8% had used AI in practice, and 17.7% had received formal training. Mann-Whitney analyses showed that positive attitudes and formal training were associated with greater AI understanding, familiarity and usage (all p ≤ 0.008). In multivariable regression, physicians with formal training were more than three times as likely to use AI (adjusted OR 3.40; 95% CI 2.31-5.01; p < 0.001), and those working in institutions with AI technologies were more than eight times as likely (adjusted OR 8.43; 95% CI 5.74-12.34; p < 0.001). These findings indicate a persistent gap between awareness and adoption driven primarily by structural factors, particularly the absence of formal AI training and limited institutional investment in AI technologies.
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Medication adherence is essential for treatment effectiveness, yet the uptake of adherence-supporting tools in routine care remains suboptimal. This study assessed Italian healthcare professionals' knowledge, perceived utility, and willingness to recommend medication adherence tools, and explored perceived barriers to their adoption. A questionnaire targeting healthcare professionals working in inpatient or outpatient settings across Italy was developed and validated by a panel of seven experts. It was anonymously distributed online between October and December 2023 to physicians, pharmacists, and nurses. The survey included open-ended and Likert-scale questions investigating use, perceived usefulness, barriers, and future willingness to recommend specific medication adherence tools. Data were analyzed using descriptive statistics, and differences by professional category were evaluated using Chi-square or Fisher's exact tests. Open-ended responses were analyzed through a multi-step conventional content analysis independently conducted by two researchers. A total of 660 healthcare professionals participated, including pharmacists (35%), nurses (26%), general practitioners (22%), geriatricians or internists (8.6%), and other medical doctors (8.5%). Overall, knowledge and recommendation regarding medication adherence tools were limited, with awareness ranging from 40.0% to 94.7% depending on the tool. Traditional tools such as pillboxes and paper diaries were more frequently used (42.1% and 26.3%, respectively) and were perceived as useful (26.7% and 22.3%). In contrast, digital tools (e.g., mobile apps, SMS reminders, electronic pillboxes) were rarely recommended and often described as unfamiliar. Patient-related barriers emerged as the most commonly reported obstacles for both traditional and digital tools. Italian healthcare professionals show limited familiarity with and use of medication adherence tools, particularly digital solutions. Targeted training and system-level strategies are needed to increase awareness, address perceived barriers, and promote the integration of effective adherence-supporting tools into routine care.
Rising global life expectancy intensifies the health impact of female lower reproductive tract aging, particularly affecting the uterus, cervix, and vagina. This process is primarily driven by estrogen depletion triggering hormonal imbalance, chronic inflammation, cellular senescence through senescence-associated secretory phenotype mediators, and systemic oxidative stress. These interconnected mechanisms accelerate structural degeneration leading to uterine fibrosis with endometrial atrophy, pelvic organ prolapse, cervical susceptibility to persistent HPV infections and subsequent malignancy development, vaginal microbiome disruption, and genitourinary syndrome of menopause. Future advances will require addressing the pronounced research imbalance across anatomical sites, resolving the causal links between immune aging and tissue-specific pathologies, and integrating multi-omics and organoid technologies to enable personalized, site-specific interventions.
Age-related macular degeneration (AMD) represents the leading cause of irreversible vision loss in the elderly, affecting over 200 million individuals worldwide. Despite recent advances, therapeutic options remain severely limited, particularly for dry AMD characterized by progressive geographic atrophy. Emerging evidence implicates mitochondrial dysfunction and metabolic reprogramming of retinal pigment epithelium (RPE) cells as central pathogenic drivers. Under pathological conditions, RPE cells exhibit profound bioenergetic collapse marked by declining oxidative phosphorylation, compensatory glycolytic activation, and aberrant tricarboxylic acid cycle intermediate accumulation. This metabolic catastrophe is structurally underpinned by dysregulated mitochondrial dynamics. The resultant accumulation of fragmented, dysfunctional mitochondria perpetuates reactive oxygen species overproduction and mitochondrial DNA damage, establishing a self-amplifying vicious cycle driving RPE degeneration. Mechanistically, this involves dysregulation of the AMPK/mTOR energy-sensing axis, SIRT1/PGC-1α transcriptional control, and Nrf2/ARE antioxidant defenses. Multi-omics profiling reveals distinct metabolic signatures. These discoveries have catalyzed mechanism-based interventions. However, translational applications still face many challenges, and the combination of single-cell multi omics and multimodal therapies is expected to play a role.in restoring mitochondrial homeostasis and preserving vision in aging population in the future.
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Neurobehavioral development in offspring is shaped by multiple interacting determinants. As a critical organ during gestation and fetal development, the placenta exerts programming effects on offspring neurobehavioral outcomes through diverse mechanisms. This article systematically examines the programming role of placental factors from the following perspectives: placental barrier function, placental pathological alterations, neuroendocrine pathways, epigenetic regulation, and immunomodulatory mechanisms. In addition, it explores potential mechanisms underlying sex-specific influences on offspring neurodevelopment, providing a comprehensive perspective for understanding placenta-derived neurodevelopmental abnoramlities. 子代神经行为的发育受多种因素的调控，胎盘作为妊娠与胎儿发育的关键器官，可通过多种机制对子代神经行为发育产生影响。本文将从胎盘屏障功能、胎盘病理学改变、神经内分泌路径、表观遗传调控、免疫调节等方面探讨胎盘对子代神经行为发育的编程作用，以及阐明影响子代神经发育的性别特异性的可能机制，以期为理解子代胎盘源性神经发育异常提供更加全面的视角。.
Transposable elements (TEs) are ubiquitous, mobile DNA elements that often exist as multiple copies within host genomes. To persist despite ongoing mutational decay, these genomic parasites must continuously generate new insertions into the germline genome, a process that risks compromising host reproductive capacity by disrupting coding regions and regulatory sequences and by reshaping chromosomal architecture. Accordingly, hosts have evolved mechanisms to repress TE activity and reduce its fitness costs. In principle, however, such antagonism could lead to lineage-specific TE extinction, which may be suboptimal for hosts, as TEs possess aspects that confer beneficial functions to them. Therefore, hosts not only resist but also tolerate and even exploit the presence of TEs. In parallel, TEs themselves have acquired and deployed unique strategies that promote their own persistence while limiting harm to the host. This review explores how "peaceful" coexistence between hosts and TEs is achieved, focusing on resistance, tolerance, and the associated trade-offs from both host and TE perspectives.
Primary care professionals routinely discuss health issues with children and families, including difficult or taboo topics. Although clinicians want better resources to support these conversations, existing evidence largely reflects health professionals' perspectives. This study aimed to understand how parents/caregivers/whānau and children want common health messages communicated to them. A qualitative mixed-methods sequential design was used, comprising three stages: (1) an online survey of parents/caregivers of children aged 7-12 years living in Aotearoa New Zealand; (2) interviews with children whose parents opted in for participation; and (3) development of a health professional specific resource. Thematic analysis was applied to open-ended survey responses and interview transcripts. Eighty parents/caregivers completed the survey, and 25 children participated in interviews. Three themes were identified: (1) Speak to the child but… highlighting the importance of direct, respectful, and non-judgemental communication; (2) Connection, emphasising rapport, trust, and tailoring information to a child's developmental level; and (3) Give kids choice, reflecting children's desire for autonomy, honesty, and involvement in decisions about their care. These findings informed the design of a lanyard-based resource to support health professionals' communication practices. Children valued being spoken to directly in ways that respected their understanding and agency, and parents stressed the importance of trust, inclusion, and reinforcement through written or visual aids. The study highlights the need for child and whānau-centred approaches to communication in primary care. Future research will evaluate the resource's acceptability and effectiveness in real-world settings.
Inorganic non-metallic materials have garnered significant attention in biomedicine due to their structural tunability and multifunctional properties. The emergence of next-generation artificial intelligence (AI) technologies is transforming the conventional trial-and-error paradigm of materials research, supporting a more data-driven and predictive approach. This review highlights the frontier applications and key breakthroughs of AI in the design and development of inorganic non-metallic biomaterials. We first introduce the fundamental paradigm and workflow of AI4S, which integrates data acquisition, model construction, and material optimization. Based on this framework, we summarize recent advances in two major directions: forward prediction and inverse design. Forward prediction focuses on critical performance indicators such as drug release profiles, biological interactions, material stability, toxicity and biosafety, and biocatalytic activity. Simultaneously, AI-driven inverse design is accelerating the development of targeted materials, including drug delivery carriers, biomaterials for inflammatory disease treatment, antitumor, and tissue engineering. Finally, we discuss key breakthroughs in AI-assisted inorganic biomaterial design, emphasizing the emerging role of generative models in enabling inverse design. Future perspectives on integrating domain knowledge, high-throughput experiments, and interpretable models are also outlined, which may provide guidance for the intelligent development of next-generation biomaterials.
While surgery of single-suture sagittal craniosynostosis (SS) is effective for cranial shape correction, its role in preventing neurocognitive impairment or intracranial pressure (ICP)-related sequelae is uncertain. We conducted a mini-survey of experts and a narrative literature review to evaluate current perspectives and evidence guiding treatment indications for SS. A mini-survey was distributed to 25 pediatric neurosurgery experts following a debate at the 2025 Varna meeting. Respondents were presented with clinical scenarios of infants with moderate or severe SS and queried regarding counseling on non-cosmetic consequences of nonoperative management. In parallel, a narrative PubMed literature review (December 2025) examined neurocognitive outcomes, ICP prevalence, treatment timing, surgical technique, and methods of ICP assessment in SS. Survey responses demonstrated marked heterogeneity in expert opinion. While many surgeons viewed cosmetic correction as the primary indication for surgery, others recommended intervention to mitigate uncertain risks of neurodevelopmental delay or elevated ICP. The literature consistently shows that most children with SS achieve normal-range intellectual functioning and attend regular schools, though mild and heterogeneous vulnerabilities in language, attention, motor skills, and learning are described compared to the normal population. These differences are also detectable in infancy, suggesting a prenatal contribution to altered brain development, that may persist despite surgery. Evidence linking surgery, age at intervention, or surgical technique to improved long-term neurocognitive outcomes is inconsistent. Untreated SS carries a variable risk of elevated ICP, which is imperfectly detected by non-invasive surrogates; postoperative ICP elevation occurs in a minority of cases. SS is generally associated with favorable neurocognitive and developmental outcomes, though mild neurodevelopmental differences and ICP-related risks warrant careful long-term surveillance. Given limited and heterogeneous evidence, individualized counseling and shared decision-making remain essential.
Mytilus coruscus (M. coruscus) is a high-value marine aquaculture species with significant economic importance. Traditional semi-artificial seed collection methods in coastal waters are insufficient to meet current demands for improved M. coruscus varieties exhibiting desirable traits such as enhanced growth rates and larger body size. Long non-coding RNAs (lncRNAs) are known to regulate critical cellular processes, including proliferation, development, and the cell cycle. To investigate potential regulatory influences on M. coruscus growth, comparative transcriptomic analyses were performed on specimens exhibiting divergent growth phenotypes (fast-growing and slow-growing) reared under identical conditions. Foot tissue samples were aseptically collected from each group for full transcriptome sequencing. Sequencing analysis identified 91 differentially expressed long non-coding RNAs (DE-lncRNAs), comprising 55 upregulated and 36 downregulated transcripts. GO analysis showed that the target or source genes of these differentially expressed RNAs were mainly enriched in the categories of biological processes, cellular components, and molecular functions. KEGG pathway analysis revealed several signaling pathways potentially involved in growth regulation, notably TGF-beta, VEGF, Wnt, and mTOR signaling pathways. Among the identified DE-lncRNAs, MSTRG.10759.1 exhibited the highest expression levels and is predicted to regulate the BVES and RASV genes, as well as the ST13/HIP protein. Interaction network analysis of lncRNA-mRNA pairs highlighted two core target genes, PLOD1 and ANK, suggesting their potential regulatory roles in mussel growth. These findings offer new perspectives on the molecular mechanisms underlying growth in mytilids and provide foundational data for the development of molecular marker-assisted breeding strategies to produce fast-growing mussel strains.
Amidst growing concerns over research misconduct in academic institutions, this study examines the complex causal mechanisms that influence research integrity among university faculty. In this article, we explore how the interplay between personal attributes and institutional environments influences ethical research behavior, drawing on perspectives from both individual and organizational dimensions. We analyzed data from 109 university teachers across six key conditions, including factors related to individual endowment and the organizational environment, using fuzzy-set Qualitative Comparative Analysis (fsQCA). The results revealed that no single factor is a necessary condition for ensuring research integrity. Four distinct causal pathways were identified as sufficient to promote integrity, reflecting the principle of equifinality. These findings revealed the various combinations of internal and external factors that can yield similar positive outcomes. Based on the results, promoting research integrity requires a contextualized approach, where universities should tailor interventions and institutional policies to the specific characteristics and needs of their faculty members. This configurational understanding enhances theoretical insights into ethical behavior in academic settings and offers practical guidance for fostering a culture of integrity in higher education.