Peptide cancer vaccines often suffer from poor lymphatic drainage, limited antigen-presenting cell uptake, and weak innate immune activation. To overcome these barriers, we engineered the Self-Assembling Peptide-Adjuvant Conjugate (SaPAC) platform, which covalently links neoantigen epitopes to the TLR7 agonist 1V209 through site-selective lysine conjugation. Synthesized by Fmoc solid-phase peptide synthesis, SaPAC conjugates self-assemble into cationic nanoparticles with hydrodynamic diameters of approximately 100-200 nm. Compared with unconjugated self-assembling peptide nanoparticles mixed with soluble adjuvant, SaPAC nanoparticles enhanced lymphatic drainage and antigen persistence in draining lymph nodes. Mechanistically, SaPAC activated the TLR7-MyD88 axis, promoted plasmacytoid dendritic cell and macrophage recruitment, drove APC maturation (CD80+CD86+), and enhanced MHC-I cross-presentation to amplify antigen-specific CD8+ T-cell priming. Therapeutically, SaPAC monotherapy suppressed tumor growth in B16-OVA melanoma and MB49 bladder carcinoma models by increasing intratumoral infiltration of activated CD8+ T cells and NK cells. In an orthotopic 4T1 triple-negative breast cancer model, multivalent SaPAC vaccination synergized with anti-PD-1 blockade and achieved durable tumor suppression comparable to the Poly(I:C)-adjuvanted benchmark without detectable systemic toxicity. Collectively, SaPAC represents a chemically defined platform that bridges innate and adaptive anti-tumor immunity.

Heavy metal contamination remains a persistent threat to water quality and ecological safety. Although electroactive microorganism (EAM)-based sensing technologies have shown promise for toxicity monitoring, their practical application is constrained by limited sensitivity. Here, we developed a strategy to improve monitoring performance by identifying and exploiting heavy metal-sensitive EAMs from mixed microbial communities. We successfully identified and isolated Acinetobacter baylyi C8 as a highly sensitive strain by integrating metagenomic analysis of mixed EAM communities under metal stress with electrochemical plate-based isolation. In bioelectrochemical sensing systems, C8 showed current-inhibition responses to eight representative heavy metals that were approximately one order of magnitude higher than those of mixed EAMs. For Cd2+ and Pb2+, good linear responses were obtained, with detection limits of 0.0157 and 0.0205 mg/L, respectively. C8 also responded consistently to binary and ternary heavy metal mixtures, while common coexisting ions caused little interference with Cd2+ and Pb2+ responses. Stable performance was maintained in drinking water, river water, and lake water, with deviations below 5 %. Further analyses showed that the high sensitivity of C8 was associated with low protein content in extracellular polymeric substances (EPS), greater intracellular metal accumulation, and stronger oxidative, metabolic, and electron-transfer disturbances. Overall, this study provides a practical route for identifying heavy metal-sensitive EAMs from mixed communities and highlights their potential for improving bioelectrochemical monitoring of heavy metal toxicity in water environments.

Cachexia is a multifactorial syndrome characterized by systemic inflammation, weight loss, and muscle wasting, affecting over 80% of patients with pancreatic cancer. It decreases treatment tolerance, quality of life, and survival. Yet, despite its well-recognized detrimental impact, cachexia remains underdiagnosed and undertreated in oncology clinics. This review synthesizes current understanding of pancreatic cancer cachexia with an emphasis on its complex pathophysiology involving inflammatory cytokines, tumor-derived catabolic factors, neuroendocrine disruption, and pancreatic insufficiency as advancing insight into these underlying mechanisms is driving the development of targeted therapies for cachexia. A narrative review of the literature was performed using PubMed, Embase, and Google Scholar to identify studies related to pancreatic cancer cachexia. Relevant peer-reviewed clinical trials, translational studies, and review articles focusing on pathophysiology, nutritional assessment, and management strategies were prioritized. Emerging therapeutic strategies targeting the underlying biology of cachexia, including growth differentiation factor-15 inhibition, inflammatory pathway blockade, and ghrelin receptor agonism, have demonstrated encouraging effects on weight, muscle preservation, appetite, and functional measures. Advances in nutritional assessment, body composition analysis, and biomarker development may further improve early detection and management. Pancreatic cancer cachexia should be recognized as an active and potentially modifiable process rather than an inevitable consequence of advanced disease. Earlier identification, multidisciplinary management, and emerging mechanism-based therapies may improve clinical outcomes and quality of life for patients with pancreatic cancer.

Achondroplasia is the most common skeletal dysplasia and presents as a lifelong, multi-system condition characterized by disproportionate short stature, rhizomelic limb shortening, macrocephaly with frontal bossing, and a spectrum of neurological, respiratory, orthopedic, and psychosocial complications. Effective management requires anticipatory surveillance, coordinated multidisciplinary care, and early recognition of life-threatening complications. Therapeutic options have expanded in recent years with the introduction of vosoritide, a C-type natriuretic peptide analog that targets the underlying pathophysiology and has demonstrated significant improvements in linear growth and body proportionality in eligible children. However, global advances have not been uniformly translated into clinical practice across the Middle East, where challenges such as delayed diagnosis, inconsistent access to genetic testing, limited multidisciplinary infrastructure, and inequities in treatment availability continue to impact patient outcomes. In this document, a panel of pediatric endocrinologists and clinical geneticists from the Middle East convened to develop a set of regionally relevant, evidence-informed consensus statements on the diagnosis and management of achondroplasia in light of novel advances in the management of this condition. Using a modified Delphi process, the panel achieved consensus on 25 statements covering diagnosis, surveillance, multidisciplinary management, psychosocial support, pharmacologic interventions, transition to adult care, and research priorities. This consensus, endorsed by the Arab Society for Pediatric Endocrinology and Diabetes (ASPED) and the MENA Medical Genetics Association, aims to standardize and enhance the quality of care for individuals with achondroplasia across the region by integrating international best practices with local healthcare realities. The author panel believes that the implementation of these recommendations has the potential to improve early detection, optimize long-term outcomes, strengthen family support, and expand equitable access to emerging therapies.

Emerging imaging and computational technologies are reshaping how osteoporosis and low bone mass are assessed. Dual-energy X-ray absorptiometry (DXA) is key for the operational definition of osteoporosis, but advances in single-component tools such as finite element analysis, trabecular bone score, DXA-based 3D shape modelling, quantitative ultrasound, radiofrequency echographic multi-spectrometry and artificial-intelligence-driven interpretation of routine radiology offer complementary insights into bone strength, microarchitecture and fracture risk. Some of these approaches provide additional fracture-risk measures beyond areal bone mineral density, whereas others enable opportunistic identification of people with low bone density in populations who would otherwise be missed. Strong pre-clinical and encouraging observational data support the use of these technologies and, although their current use in clinical practice varies with the age of the technology, they all have a potential role in the assessment of fracture risk at a variety of points in the patient journey (from screening to monitoring response to therapy). As their use becomes more widespread, monitoring performance, assessing the equitability of implementation and evaluating the health-service benefits of these tools in clinical practice will be key.

Soil underpins food production, freshwater, carbon storage and biodiversity, yet over 40% of the world's soils are now degraded, eroding at rates up to 1000 times their formation rate. Microbial technologies have matured and can now aid soil recovery, but deployment has lagged due to absent shared targets, harmonized metrics, and coherent reward structures to mobilize solvers across academia, industry, philanthropy, and government. Building on major initiatives (e.g. A Soil Deal for Europe, the FAO Global Soil Partnership, etc.) a consensus has emerged on the need for actionable, transformative advances in soil health. To translate that consensus into coordinated action, The Soil Stars, a multidisciplinary coalition of scientists, communicators, investors, policymakers, and farming-systems leaders, convened the inaugural Soil Stars Heligan Summit in March 2026 at The Lost Gardens of Heligan, Cornwall, United Kingdom, with a public launch at the Eden Project's Anthropy 2026 forum. The summit combined a grand-missions hack-a-thon with roundtables on the climate-society interface, the soil carbon-fertility-microbiome nexus, and deployment hurdles. The primary outcome is the first draft of the Heligan Grand Challenges; seven XPRIZE-inspired challenges with concrete performance thresholds achievable within 24-36 months, alongside a path toward a formal Grand Challenges paper and five-year implementation roadmap.

It remains unclear how awareness-of and planning-for eventual neurodegenerative disorder (NDD) diagnosis and care is influenced by age, gender, and culture across worldwide societies.

This report summarizes expert and patient-representative perspectives from the meeting entitled 'Standalone NF1: guiding the transition from paediatric to adult care', held in Madrid on October 2, 2025. Its primary objective was to examine clinical, organizational and patient-related challenges during transition and identify practical measures to improve continuity of care. Discussions focused on multidisciplinary co-ordination, case management, patient autonomy and structured transition pathways. NF1 characteristics, plexiform neurofibroma burden, surgery, and the currently approved MEK inhibitors selumetinib and mirdametinib, are summarized only for clinical context; selumetinib is discussed in greater detail because it was the treatment available at that time and the one addressed during the meeting.

Background Do-not-resuscitate (DNR) orders in pediatrics are frequently analyzed as static outcomes, although they emerge through a longitudinal process shaped by evolving illness trajectories and repeated clinical encounters. Our primary objectives were to characterize the time from the first pediatric palliative care (PPC) consultation to formal DNR order establishment and to identify associated clinical factors. Secondary objectives were to describe longitudinal changes in DNR status and withdrawal of life-sustaining therapy. Methodology We conducted a retrospective cohort study of 371 children who received hospital-based PPC consultation at a quaternary children's hospital in the United States between December 2011 and December 2016. The descriptive cohort included all 371 patients. Time-to-event analyses included 351 patients with an ascertainable event time and no DNR order before the first PPC consultation. Kaplan-Meier methods and multivariable Cox proportional hazards models were used, with follow-up extending across subsequent hospitalizations. Results Among 371 patients (median age = 2.4 years; 49.1% female), 115 (31.0%) had a documented DNR order. In the time-to-event cohort, 95 patients established a DNR order. DNR-free survival differed by diagnosis category (log-rank p = 0.003). Life-limiting illness without a realistic hope of cure was associated with a higher hazard of DNR establishment (adjusted hazard ratio (adjHR) = 2.10, 95% confidence interval (CI) = 1.14-3.86, p = 0.017). Symptom management consultations were associated with a lower hazard (adjHR = 0.08, 95% CI = 0.02-0.35, p < 0.001). Other hospital-based settings were associated with a higher hazard than the pediatric intensive care unit (adjHR = 5.85, 95% CI = 1.74-19.69, p = 0.004), although this estimate was based on six patients and three events. Religious affiliation was not associated with time to DNR. Among patients with a DNR order, 54 of 115 (47.0%) underwent withdrawal of life-sustaining therapy. Conclusions Formal DNR order establishment among children receiving palliative care was longitudinal and associated with illness trajectory and consultation context. DNR order establishment and withdrawal of life-sustaining therapy were distinct outcomes. Estimates from sparse subgroups require cautious interpretation.