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Climate change is increasing the risk of sea level rise globally, however, exposure varies, and certain places are more likely to be affected than others. The municipality of Örnsköldsvik experiences post-glacial rebound and is expected to have minimal exposure to the sea level rise. This study assesses the spatial vulnerabilities posed by an RCP8.5 flood scenario and a hypothetical 69-meter sea level rise to Örnsköldsvik’s land use and transportation infrastructure. The assessment was created from high-resolution digital elevation data using a static inundation approach in ArcGIS. The RCP8.5 flood resulted in minor exposure on the municipality’s land use and infrastructure, whereas the extreme scenario completely transformed the landscape, with 80% of the urban localities being submerged. Investigating worst-case scenarios can provide valuable insights into the potential impacts of sea level rise in Örnsköldsvik, contributing to discussions on climate adaptation and spatial planning.

Variation in flood duration is a dominant factor governing plant species distribution along the riparian elevation gradient, and long evolutionary histories in these dynamic environments give species distinct coping mechanisms. Despite providing critical ecosystem services at a disproportionally high amount, relative to their size, riparian ecosystems face intense anthropogenic pressure. Pressure from activities such as hydropower, mining and deforestation has contributed to an 80% loss of natural riparian habitats over the past 200 years. This project investiated the long-term effects of simulated altered hydrological conditions on plant species community resistance and species turnover. In a field experiment in the floodplains of the Vindel River near Strycksele, the riparian vegetation was transplanted between three elevation levels, effectively simulating both increased and decreased flooding. Vegetation changes were recorded regularly over a 25-year long period. Statistical analysis revealed that the river's natural flood regime has not significantly changed over the 25-year study period. However, the spring flood occured earlier every year only for the level furthest from the water, possibly due to an increased magnitude. Transplantation of riparian vegetation across elevation gradients resulted in a species turnover similar to the community species composition of the level it was transplanted to within 25 years. The effect of transplantation on the communities resistance differed for the most extreme transplant types. This indicates that riparian plant communities are sensitive to shifts in hydrological conditions in different ways. It is unclear what affects community resistance to change, as it is not solely dependent on the total number of flooded days.

Endolysosomal compartments act as critical sorting hubs for viral entry, trafficking, and uncoating, yet the contribution of lipid-modifying enzymes to these processes remains incompletely understood. Acid sphingomyelinase (ASM), a key regulator of endolysosomal membrane composition, has been implicated in host-pathogen interactions, and is actively engaged in human adenovirus (HAdV) infection. Here, we confirm ASM activity as an essential host determinant of efficient HAdV infection and demonstrate that its pharmacological inhibition synergizes with direct-acting antiviral therapy. Analysis of publicly available human datasets revealed age-associated changes in expression of host cell determinants for HAdV entry like ASM expression in respiratory epithelial tissues and colonic tissue, suggesting that ASM-dependent endolysosomal functions are modulated across the human lifespan. Using epithelial cell models of HAdV infection, we show that viral entry and replication critically depend on ASM activity. Pharmacological inhibition of ASM by functional inhibitors such as fluoxetine resulted in a dose-dependent suppression of viral replication and significantly reduced infection rates in single-cycle infection assays, indicating disruption of early stages of the viral life cycle. Mechanistically, ASM inhibition impaired HAdV uptake and trafficking by reducing viral internalization and co-localization with early endosomes. Importantly, combined treatment with fluoxetine and the viral DNA polymerase inhibitor brincidofovir acts synergistically in reducing HAdV titer. These findings demonstrate that targeting host-controlled endosomal entry pathways can potentiate the antiviral efficacy of direct-acting agents. Together, our study validates ASM as a central regulator of HAdV entry and identifies combined host- and virus-directed therapy as a promising strategy to suppress HAdV infection.

Boreal forests mitigate climate change by sequestering atmospheric carbon. Recent declines in the boreal carbon sink and tree growth suggest that this mitigating influence is weakening, yet the underlying drivers remain unresolved. Increasing drought frequency is one likely driver. Yet most studies have focused on managed forests, overlooking the significant but shrinking areas of old-growth forests, which recent evidence suggests exhibit greater drought resistance. We analysed tree rings from Norway spruce, Scots pine, and Birch across soil-moisture gradients in 12 Swedish old-growth forests to evaluate temporal trends and climatic drivers of tree stem growth during 2012–2021. Contrary to previous studies, we found no overall recent forest growth decline, only a species-specific decline for Norway spruce in the warmest region. Following the extreme 2018 drought, Norway spruce showed pronounced growth reductions that peaked one year after the event (a lagged response) and persisted for at least three years (a legacy effect) in warm, dry areas. In contrast, Scots pine and Birch were less affected. Warming and drought (i.e. periods when evaporative demand exceeds water availability) jointly affected growth, particularly in warmer climates, but with differences among species in timing and magnitude. Tree growth in old-growth forest appeared relatively resistant to warming and drought, especially in wetter locations, although Norway spruce appears increasingly vulnerable in already warm regions. We further found that to avoid misleading interpretations of climatic effects, statistical models had to account for both the diminishing legacy effect (by including an autocorrelation structure), and the lagged drought response (by including a lagged hydroclimatic variable). Together, our findings emphasise the critical role of tree species composition and landscape-level hydrological conditions in shaping climate sensitivity of tree growth, and suggest that old-growth forests may sustain C sequestration into long-lived pools under climate change and thereby be valuable models for climate-adapted forestry.

Ash transformation processes during the entrained flow combustion of brewer's spent grains (BSG), a P-rich grain- and seed-based agricultural biomass, were investigated in a 150 kW horizontal powder burner operating at ∼1400 °C. Coarse ash particles (> 1 μm) were obtained from several locations within the furnace and heat exchanger zone. The collected ash samples were characterized using energy-dispersive X-ray fluorescence (ED-XRF), scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD). Complementary thermodynamic equilibrium calculations were conducted to interpret experimental findings. The results showed that the majority of P was retained in the residual coarse ash fractions (> 1 μm) as Ca-Mg-rich phosphosilicate melt. Coarse ash samples collected near the flame zone exhibited intensified interaction between partially molten Ca-Mg-phosphates and Si-rich particles, promoting an increased melt fraction in the condensed phases. These insights deepen the understanding of ash transformation during entrained flow combustion of P-rich grain- and seed-based agricultural biomasses. They also carry practical implications for slag mitigation, system design, and phosphorus recovery from residual ash fractions.

Background: Reliable access to the olfactory epithelium is important for clinical and translational research; however, data on bilateral biopsy performed in an outpatient setting are limited.

Objectives: To evaluate the feasibility and procedural outcomes of endoscopy-guided bilateral olfactory epithelium biopsy performed under local anaesthesia in an outpatient setting following controlled exposure sessions.

Methods: Healthy adults participated in a randomized, double-blind, crossover exposure study. Endoscopy-guided biopsies were obtained in an outpatient setting. Primary outcomes included bilateral biopsy success, tolerability, adverse events, and nucleic acid yield.

Results: Twenty-nine subjects were enrolled; 26 completed the study. Bilateral biopsies were obtained more frequently after implementation of pre-endoscopic screening than without screening (75.0% vs 30.0%; odds ratio 7.0, 95% CI 1.20–40.83). No serious procedural complications were observed. One self-limiting episode of delayed epistaxis. No participant reported postoperative olfactory dysfunction. All samples yielded RNA and DNA of sufficient quantity and purity for downstream analyses.

Conclusion: Endoscopy-guided bilateral olfactory epithelium biopsy appears feasible in a carefully screened outpatient cohort. Pre-endoscopic anatomical assessment was associated with improved procedural success. Although objective olfactory testing was not performed, and subtle functional changes cannot be excluded, this technique provides a reproducible methodological framework for future studies involving the olfactory cleft.

• Leaf pavement cells of many plant species develop jigsaw puzzle-like shapes in which neighboring cells interdigitate, providing an ideal model for the study of cell shape regulation. Such shapes are likely to reduce tissue-wide mechanical stress, which is influenced by environmental conditions, such as drought stress.
• We analyzed pavement cell shape complexity in a natural population of European aspen (Populus tremula) genotypes and used a genome-wide association study (GWAS) to identify a candidate gene in cell shape regulation, Potra2n8c18226, encoding the transcription factor MYB305a. We subsequently validated a role for MYB305a in regulating aspen leaf pavement cell shape.
• We then demonstrated that drought stress strongly induces MYB305a promoter expression in these cells and provided evidence that MYB305a plays a role in regulating pavement cell shape in response to drought. Finally, we observed correlations of pavement cell shape complexity with water-use efficiency and average precipitation at the original sampling sites, in the natural aspen population.
• Taken together, our results suggest climatic variables affect shape complexity of pavement cells in aspen leaf and provide a foundation for future mechanistic studies on this process, by implicating the involvement of the transcription factor MY305a.

Climate-induced permafrost thaw unlocks large stores of organic carbon that are mineralized and emitted as carbon dioxide (CO2) from rivers to the atmosphere1. Concurrently, warming and permafrost thaw can increase mineral weathering rates, thus affecting the release and sequestration of inorganic carbon2, 3–4. Yet how these biological and geological carbon cycles interact and jointly affect CO2 dynamics (emission compared with drawdown) in permafrost rivers remains unknown5. Here we combine CO2 emissions, organic and inorganic solute concentrations, dual carbon isotopes (δ13C–Δ14C) and geochemical modelling to infer how permafrost thaw may affect river biogeochemistry over decades to centuries across the Qinghai–Tibet Plateau. Leveraging a gradient of thermal permafrost degradation, we find that river CO2 emissions decline, whereas solute fluxes from rock weathering increase with decreasing permafrost cover. Across this region, net CO2 drawdown fluxes from rock weathering are about 35% of river CO2 emissions, varying from around 15% in catchments with continuous permafrost to more than 100% in catchments with discontinuous or isolated permafrost. Thus, carbon fluxes from chemical weathering may become increasingly important with ongoing permafrost thaw, potentially even outpacing river CO2 emissions. Our findings disentangle the interplay between biological and geological carbon fluxes that are important for the cryosphere and the global carbon cycle.

Purpose: The risk of re-fracture after implant removal in healed hip fractures remains a clinical concern. This study aimed to determine the incidence of re-fracture following implant removal after osteosynthesis of a hip fracture.

Methods: We conducted a retrospective multicenter cohort study including patients aged ≥ 50 years who underwent implant removal between 2003 and 2023 after radiologically confirmed consolidation of a hip fracture. Patients were identified using procedural codes. Baseline variables included age, sex, ASA classification, fracture type (femoral neck or trochanteric), and implant type (pins/screws, sliding hip device [SHD], or short/long cephalomedullary nail [CMN]). Patients were followed from implant removal until re-fracture, conversion to arthroplasty, death, or end of follow-up, with a minimum follow-up of 1 year. Cox proportional hazards regression was used to assess associations between implant type and re-fracture risk, adjusting for age and sex. Because the proportional hazards assumption was violated, a time-stratified Cox regression and restricted mean survival time analyses were applied.

Results: A total of 575 patients (median age 73 years, IQR 65–81) were included, with a median follow-up of 53 months (IQR 18–100). Lateral hip pain was the most common indication for implant removal (72.5%). The overall re-fracture incidence was 10.4%. Risk varied by implant type: 7.1% after pins/screws, 10.5% after SHD, 18.3% after short CMN, and 15.8% after long CMN removal. Median time to re-fracture was 1.5 months, and 52% occurred after minimal or no trauma. Most re-fractures (85%) occurred within 90 months. Removal of CMNs was associated with a higher re-fracture risk compared with pins/screws (HR 2.79; 95% CI 1.52–5.13), whereas SHD removal was not.

Conclusion: Implant removal after consolidated hip fractures carries a measurable risk of re-fracture, most pronounced after CMN removal. These findings highlight the importance of careful patient selection and could aid in decision-making when considering implant exchange or removal following osteosynthesis.

Levels of evidence: IV, retrospective observational cohort study.

The plasma environment of our neighboring planets, Venus and Mars, differs significantly from Earth’s. Although neither of them possesses a dominant intrinsic dipolar magnetic field, there are still induced magnetospheres forming around the two planets, due to the interaction of the solar wind and the interplanetary magnetic field (IMF) with their conductive ionospheres, exospheres, and the localized crustal magnetic fields in the case of Mars. Induced magnetospheres, their associated plasma environments, and the physical processes within them are particularly susceptible to the changing upstream conditions. The increasing number of successful and long-lived missions during the last few decades has been key for describing the fundamental structures and processes comprising the induced magnetospheres of the two planets. Nevertheless, their induced magnetotails have been more challenging to probe, due to the restrictions of the orbital geometry of planetary missions. Here, we present the latest discoveries and a comprehensive comparison between the Venusian and Martian induced magnetotails, and we highlight the need for further exploration of these regions. Atmospheric escape and energy transfer processes and paths are inextricably linked with the climate history and the disappearance of water at Mars, though there are many unknowns still in the case of Venus. Past and current missions utilizing particle and fields instruments have explored a great part of the plasma environments of Venus and Mars. Several plasma boundaries, shaped by both internal and external factors, divide the planetary environments and magnetospheres into different plasma regimes and have been described by observations and models. Simulations and observations have also been utilized to investigate the magnetotail structure of the two planets, which appears to be governed mainly by the IMF, the solar wind dynamic pressure, and the crustal magnetic fields in the case of Mars. At Mars, the presence of the crustal magnetic fields, which are regions of crustal magnetization on the surface of the planet clustered mostly in the southern hemisphere, further complicates the interaction of the solar wind and the IMF with the planet’s plasma environment, thus justifying the term ‘hybrid’ – instead of induced – that is often used to describe the Martian magnetosphere. The existence of a magnetotail twist, as well as a first approach on mapping the structure of the current systems, has been reported at Mars, whereas different types of magnetotail current sheet flapping motion have been observed at both Mars and Venus. The magnetic topology, which describes the morphology of closed, open, and draped magnetic field lines over a planet, has also been inferred and explained for both planets. Escape processes, escape rates and their response to space weather have been reported, and we now have a better idea of the differences between the two planets. Escaping structures, contributing with a bulk removal of plasma, have also been observed in their magnetotails. Nevertheless, much still remains unknown, for example the specifics of how individual processes respond to solar drivers. Mars and Venus are not the only solar system bodies with no global intrinsic magnetic field. Induced magnetotails are formed around Saturn’s moon Titan and comets too. A comparison between those bodies and Venus and Mars will provide a broader and general picture of induced and hybrid magnetotails, which could help future investigations of the plasma environments and tails of exoplanets. Lastly, in this review paper, we also summarize the questions that remain unanswered, emphasizing the need for future missions.

Background: Longitudinal data on weight change, its timing, and the age of obesity onset in relation to cause-specific mortality are limited.

Methods: From ODDS, a nationwide pooled cohort study in Sweden, we included 258,269 men and 361,784 women with at least three weight assessments between ages 17 and 60, collected in 1963–2015. We applied linear mixed-effects models to estimate weight trajectories, age of obesity onset, and age-specific weight changes between ages 17 and 60. Outcomes were all-cause and cause-specific mortality, assessed from 5 years after the last weight assessment until death, emigration, or 31 December 2020. Associations with mortality were calculated using multivariable Cox regression models.

Findings: Over a median follow-up of 23.3 years in men and 11.7 years in women, 86,673 men and 29,076 women died. The median weight change between ages 17 and 60 was 0.42 kg/year in both sexes. A steep weight gain trajectory over this period, early obesity onset, and high weight gain between ages 17 and 29 were associated with higher all-cause mortality and with 13 of 23 specific causes of death investigated in men and 12 of 19 in women. Affected causes included cardiovascular diseases (including most subtypes), cancer (including specific types), type 2 diabetes, and digestive and genitourinary diseases. Hazard ratios (95% confidence intervals) of all-cause mortality associated with obesity onset at ages 17–29 vs. never by age 60 were 1.69 (1.60–1.79) in men and 1.71 (1.55–1.88) in women; and per 0.5 kg/year weight change at ages 17–29, 1.18 (1.17–1.19) and 1.16 (1.14–1.18), respectively. Weight gain later in adulthood generally showed weaker associations, except for cancer mortality in women, where the association was similar to that observed with earlier weight gain.

Interpretation: Weight gain in adulthood, especially in young adulthood, and obesity onset before age 30 are strong risk factors for mortality from multiple non-communicable diseases, underscoring the importance of early obesity prevention. Future studies should incorporate richer confounding data and, ideally, measures of changes in central adiposity and muscle mass. 

The Paleocene–Eocene Thermal Maximum (PETM; ∼55.9 Ma) was a rapid global warming event marked by intensified hydrological cycling, enhanced continental weathering, and widespread ocean deoxygenation. Although the extent of anoxic basins during the PETM is relatively well documented, the contribution of high-latitude continental weathering to regional ocean redox dynamics remains unclear, leaving the spatial impact of weathering on ocean biogeochemistry poorly constrained. Here, we use elemental geochemical data from sediments recovered from the Vøring Basin, North Atlantic during International Ocean Discovery Program (IODP) Expedition 396, to reconstruct variations in continental weathering intensity and redox conditions across the PETM. Our results show that high accumulation rates during the PETM coincided with low chemical weathering relative to underlying pre-PETM strata, indicating that rapid burial limited chemical alteration, although accumulation rates in the pre-PETM interval are not well constrained. This pattern likely reflects intensified rainfall, which primarily enhanced physical erosion and delivered large amounts of detrital material to the basin while limiting chemical weathering. The influx of fresh, reactive detrital material from the North Atlantic Igneous Province (NAIP) increased the supply of bioavailable nutrients, likely stimulating elevated primary productivity and contributing to the development of euxinic bottom waters during the onset of the PETM. On the boreal mid-Norwegian margin, our data suggest that enhanced physical erosion, rather than chemical weathering, dominated continental responses to extreme greenhouse forcing, promoting nutrient enrichment, transient euxinia, and organic carbon burial.

Phaeocystis globosa is a widespread phytoplankton species characterized by a complex polymorphic life cycle including a colonial phase. Due to its high ecological importance and capacity to produce Harmful Algal Blooms (HABs), understanding its population dynamics under increasing anthropogenic influences is essential. This study examined the seasonal dynamics of colonies of Phaeocystis globosa in the Marsdiep, the westernmost tidal inlet of the southern North Sea to the coastal Wadden Sea. Between 1994 and 2021, densities of different morphotypes of P. globosa and environmental conditions were measured ca. 40x per year. Between 1994 and 2009, the timing of the peak in densities of colony cells was highly variable (ranging from mid-March to mid-July), and the peak in colony cells was followed by one in flagellates (the sum of diploids and haploids). Between 1994 and 2021, variations in colony-cell densities were significantly and non-linearly correlated with those in phosphate concentrations, water temperature and light conditions. These three factors most likely co-limited the growth of this species. Although long-term increases or decreases were observed in these three factors, no phenological shift in Phaeocystis blooms was observed. The power of our analysis, however, was decreased due to a change in the assignment of cell types within ‘solitary’ and ‘colony’ categories in 2009/2010, and a longer time series may be needed to reveal causal factors influencing Phaeocystis blooms. As warming and de-eutrophication will progress, continuation of these time series is of utmost importance for monitoring the species, and for understanding impacts on coastal food webs.

Background: Community treatment orders (CTOs) permit compulsory mental healthcare outside hospital. Such orders have become part of an increasing number of mental health laws, even if there is a lack of consensus on their effects, negative personal experiences, diverging ethical positions and expectations that governments should reduce or abandon coercive practices. It is therefore surprising that there is limited research describing the availability and restrictiveness of CTO legislation, and we found no comprehensive European study. Such studies could contribute to clarification of differing positions and, through that, informing further research and discussions of how to promote voluntary options in clinical practice.

Aims: To establish the availability of CTO legislation across Europe, and how regimes in different ways restrict the person.

Method: Data were collected from 33 European countries through a network of researchers and practitioners, and links to relevant legislation were provided.

Results: We found 13 CTO regimes across the 33 countries: two-thirds therefore managed without them. Despite some variation, most law texts specified restrictions related to legal criteria, enforcement mechanisms and safeguards. Restrictions on the person were often specified in separate tailored plans, and most regimes permitted indefinite renewals, which means that the duration of restrictions can be ascertained only in retrospect.

Conclusions: CTO law texts preclude scrutiny of overall restrictiveness, which might add to current uncertainties regarding the proportionality of CTOs and their role in balancing individuals’ rights to both autonomy and care. The current policy drive towards community care should not automatically lead to new CTO regimes until their effectiveness and de facto restrictiveness are established.

Prostate cancer (PCa) is common world-wide. Current diagnostics based on testing for circulating levels of prostate specific antigen (PSA) is unspecific, and novel prognostic markers are needed for personalized therapeutic strategies. Pro-neuropeptide Y (pro-NPY) has been reported as a tissue marker for PCa related to poor prognosis. This study explored the prognostic value of circulating pro-NPY in PCa. Plasma samples were obtained from two patient cohorts: (1) men examined due to increased PSA levels in 2003–2011 (n = 796) and (2) patients treated for PCa in 2013–2016 (n = 92). Cohort 2 also provided plasma samples collected ~ 3 months after therapy. For plasma pro-NPY assessment, a sandwich immunoassay was developed. In cohort 1, 315 patients were diagnosed with PCa at the time for blood sampling, 137 were diagnosed during follow-up, and 344 remained disease-free. Plasma pro-NPY provided independent prognostic information from PSA regarding time to metastasis and PCa death. In cohort 2, high plasma pro-NPY levels were confirmed associated with metastatic disease and poor survival. Plasma pro-NPY levels were normalized after androgen-deprivation therapy, suggesting androgen-regulation. In conclusion, high circulating pro-NPY levels are associated with metastasis and poor outcome in PCa. Prospective validation is needed before suggesting pro-NPY for clinical use. The underlying biology and consequences of pro-NPY overexpression remain to be understood.

Background: Venous thromboembolism (VTE) is a well-recognised complication of cancer, but reported incidence rates vary due to differences in population characteristics and study design. Objective To estimate incidence rates of VTE among persons with cancer and to assess the association between cancer and first-ever VTE in a population-based Swedish cohort.

Methods: This cohort study was based on participants in the Västerbotten Intervention Programme who underwent health examinations between 1985 and 2014. Individuals with prior cancer or VTE were excluded. Cancer and VTE diagnoses were identified through Swedish national registers, and all potential VTE events were manually validated. Participants were followed prospectively from health examination until incident VTE, death, emigration, or end of follow-up. Incidence rates were calculated by time since diagnosis. Cox proportional hazards models with cancer as a time-varying exposure were used to estimate HRs for first-ever VTE.

Results: Among 105,997 participants, 9,643 developed cancer during follow-up, and 677 experienced a first-ever VTE after cancer diagnosis. The VTE incidence in individuals with cancer was 13.2 per 1000 person-years (95% CI 12.3–14.3). Incidence was highest during the first six months after diagnosis (60.2 per 1000 person-years). The incidence varied across cancer types (4.9–201.1 per 1000 person-years). Cancer was significantly associated with VTE, with an adjusted hazard ratio of 8.3 (95% CI 7.5–9.2).

Conclusion: In a population-based cohort we found a high incidence of VTE after cancer diagnosis. The incidence declined rapidly over time and varied across cancer types. Our study confirms the association between cancer and VTE.

Most genetic variants associated with complex heritability phenotypes lie in non-coding regions and are thought to influence disease risk by regulating gene expression. However, most transcriptome-wide association approaches primarily model local (cis) genetic effects, leaving much of gene regulation unexplained. Here, we show that incorporating distal (trans) regulatory effects improves the prediction of gene expression and the identification of disease-associated genes. Using RNA sequencing data from six human post-mortem brain regions, we developed INGENE and MODULE, two models capturing the combined influence of candidate trans-acting variants within gene coexpression networks. Integrating these models with conventional cis-based predictors improved gene expression imputation (maximum likelihood estimation, α = 0.05) for 18,744 genes across regions. Applying this framework to Psychiatric Genomics Consortium wave 3 genotypes identified 766 genes associated with schizophrenia (PFDR < 0.01), including 641 not previously reported by transcriptome-wide analyses. These findings highlight the contribution of distal regulatory mechanisms and gene network interactions to schizophrenia risk.

Frailty is a multifactorial geriatric condition linked to increased mortality and adverse health outcomes and is associated with gut microbiome features that differ from those observed in healthy ageing. We analyze gut metagenomic profiles in relation to estimated frailty severity and frailty-related clinical outcomes assessed with an internally developed and validated Frailty Mortality Index (FMI) in the SUPERB cohort, comprising 2,081 Swedish women aged 75–80 years. The FMI is a composite measure that integrates functional, physiological and psychological dimensions associated with frailty and mortality risk, and shows stronger associations with mortality compared to the Charlson Comorbidity Index in the SUPERB cohort. The FMI is inversely associated with microbial diversity, gene richness, and predicted functional capacity, which are linked to physical function, mortality and fall-related injuries. A total of 404 bacterial species are significantly associated with FMI, and most show concordant associations in a Chinese cohort of 1,448 older adults. Here we show microbial signatures linked to frailty and mortality across different continents.

Introduction: The short-term benefits of endovascular aortic repair (EVAR) compared with open repair for the treatment of abdominal aortic aneurysm (AAA) patients are well established. However, concerns have been raised regarding a potential increased long-term cancer risk associated with EVAR, related to procedural and surveillance-related radiation exposure. The aim of this nationwide population-based cohort study was to evaluate whether EVAR is associated with an increased long-term cancer risk compared with open repair.

Methods: All patients undergoing primary AAA repair for an intact AAA (ICD-10: I71.4) from January 2005 to February 2024 were identified from the Swedish National Patient Register. Previous and subsequent cancer diagnoses, as well as previous co-morbidities, for this cohort were recorded. Cause of death was retrieved from the Cause of Death Register. Inverse probability of treatment weighting (IPTW) was applied using propensity scores derived from baseline characteristics and co-morbidities. Weighted Cox regression models, with EVAR as the sole regressor, were then fitted for the event of a new cancer diagnosis and cancer related death.

Results: Some 15 509 patients were identified (mean age of 73 years, 16.8% female, and 23.7% with a previous cancer diagnosis). After weighting, standardized mean differences for co-morbidities, age, sex, and recent hospital admissions were all within ±0.1. The median survival was 8.7 (95% c.i. 8.4 to 8.9) years for EVAR patients and 9.4 (95% c.i. 9.1 to 9.6) years for open repair patients. The median follow-up time was 4.9 (interquartile range (i.q.r.) 2.3 to 8.4) years for new cancer and 5.9 (i.q.r. 3.0 to 9.4) years for cancer-related death. Freedom from new cancer was lower in EVAR patients (HR 0.92 (95% c.i. 0.86 to 0.98)), whereas cancer-related survival was similar (HR 0.93 (95% c.i. 0.85 to 1.02)).

Conclusion: EVAR was not associated with an increased risk of dying of cancer, but with an increased risk of being diagnosed with a new cancer. This should be interpreted carefully, as there is a clear risk of detection bias of otherwise unknown tumours due to routine imaging during EVAR surveillance.

Background: Perinatal depression affects up to 30% of women in Kenya, yet many contributing factors remain poorly understood. We explored mental health problems, social needs, and associated risk factors among women ante- and postnatally in Kajiado County, southern Kenya, from the perspectives of women and health-care workers (HCWs).

Methods: We conducted a qualitative study based on dual-perspective focus group interviews with mothers (ante- and postnatal) and HCWs in five health-care facilities (two urban and three rural) across Kajiado County (5–11 March 2025). Interviews were recorded, transcribed verbatim, translated into English when needed, and analysed using qualitative content analysis with an explorative and inductive approach. The text was divided into meaning units and manually coded in Atlas.ti (https://atlasti.com). Themes, subthemes and categories were articulated following a stepwise, iterative and reflexive process of abstraction and interpretation.

Results: Across five sites, 51 mothers and 39 HCWs participated. Three themes were developed relating to stress, distress and affecting mental wellbeing, (a) Women’s autonomy and self-determination – mothers lacked control over resources or decision-making, while shouldering most household responsibilities, and HCWs highlighted the vulnerability of girls subjected to early marriage and female genital mutilation, often unprepared for motherhood, (b) Responsive maternal and mental health care – distance, costs, and low expectations limited access, while women feared traumatic births, miscarriage, and caesarean sections, and (c) Community knowledge and acceptance of mental health problems – mental health problems were often seen as irrationality or spiritual possession, delaying care. Stigma was particularly associated with caesarean sections, mental health problems, and HIV.

Conclusions: Our findings describe how maternal mental health is closely intertwined with gender norms and prevailing perceptions of mental illness including stigma. Expanding maternal mental health services may be important but it is unlikely to be sufficient in isolation. Sustainable change may depend on the promotion of women’s rights, increased mental health literacy at the community level, and the engagement of men. In addition, fear of traumatic birth and stigma associated with CS may need to be addressed not only at the individual level but also within the broader community context.

Omics profiling of saliva is an emerging research area with potential to uncover molecular signatures associated with oral and systemic health. We conducted a comprehensive multi-omics analysis of saliva to investigate associations between host demographics (age, sex, body mass index (BMI)) and molecular profiles. Saliva from 423 participants (16–79-years-old) were analyzed using LC-MS metabolomics (9,380 metabolite features for 416 participants), GC×GC-MS sugar profiling (69 sugars for 200 participants), and full-length 16S rDNA sequencing (500 microbial species for 420 participants). We used random forest modeling, multivariate OPLS analysis, and partial correlation networks for data integration. Age emerged as the strongest demographic factor, explaining up to 30% of variance in metabolite features, 17% in sugars, and 25% in microbial species, while sex showed moderate and BMI minimal associations. Age-associated metabolites included caffeine and trigonelline (higher in older participants) and urocanic acid (higher in younger participants). Younger participants had greater abundance of saccharolytic, facultative anaerobic bacteria while older participants had more anaerobic species. Species in the Streptococcus, Prevotella, and Veillonella genera correlated strongly with salivary sugars. These findings demonstrate that saliva provides a rich source of molecular information related to the individual, and that demographic factors must be considered in saliva-based biomarker-discovery studies.

Introduction: Psychological safety enables team members to take interpersonal risks without fear of negative consequences. Low psychological safety could be related to psychological distress among primary care physicians, but evidence in this setting remains limited. We assessed anxiety symptoms, perceived stress, psychological safety, and their interrelations in this group.

Methods: A cross-sectional survey was administered to 231 physicians (63.2% women; 131 general practitioners [GPs] and 100 residents). The survey included the Team Psychological Safety Survey, the two-item Generalized Anxiety Disorder scale, the four-item Perceived Stress Scale, and sociodemographic items. Data were analyzed using hierarchical multiple regression models for anxiety and stress, adjusting for gender, training level, and age. Group comparisons by gender and training level were examined as secondary analyses.

Results: Of the 231 physicians invited, 111 responded (67.6% women; 62 GPs and 49 residents), yielding a 48% response rate. Among participants, 18.9% screened positive for clinically relevant anxiety symptoms on the GAD-2. Women reported higher levels of anxiety symptoms and lower psychological safety compared with men. Psychological safety was inversely associated with anxiety symptoms and perceived stress, and these associations remained significant after adjusting for demographic factors.

Conclusions: Low psychological safety is associated with more anxiety symptoms and greater perceived stress among primary care physicians. Compared with men, women reported more anxiety symptoms and lower psychological safety. These findings suggest that perceived psychological safety is a relevant correlate of psychological distress among primary care physicians. Longitudinal and qualitative studies are needed to better understand the relationship between psychological safety and psychological distress, and to explore gender-related differences.

Background: The World Health Organization recommends models with midwifery continuity of care for pregnant women, as they have been shown to result in positive outcomes. While some initiatives have been taken to introduce such models into Swedish maternity care, they have not been fully implemented. Therefore, this study aimed to investigate midwifery students' views on implementing midwifery continuity of care within the current maternity healthcare organization in Sweden.

Methods: A Swedish national interview study involving 16 midwifery students was conducted in 2023. The data were analyzed using Reflexive Thematic Analysis following Braun and Clarke's method.

Results: The midwifery students ranged in age between 27 and 45 years and were in their second or third semester. Their views on implementing midwifery continuity of care within the current Swedish maternity healthcare organization were described by the following themes: Integrating evidence-based midwifery continuity into maternity care; Providing maternity care that respects women's needs for quality care; and Societal and financial prioritization of midwifery continuity of care is crucial.

Conclusion: Although the midwifery students held a positive attitude towards implementing midwifery continuity of care within the current Swedish maternity healthcare organization, they also highlighted essential factors that need to be addressed to support increased implementation.

Introduction: Several mechanisms are thought to contribute to hyponatremia in patients with anorexia nervosa (AN). The aims of this descriptive, cross-sectional study among patients admitted to a specialized somatic unit for eating disorders (ED) were to determine the frequency of hyponatremia and to compare medical findings between patients with normonatremia and hyponatremia.

Methods: This retrospective, descriptive cross-sectional study included patients admitted to the unit between December 2016 and October 2021. Demographic, medical history, and clinical data were extracted from medical records. Patients were categorized according to plasma sodium concentration (<135 mmol/L vs. ≥135 mmol/L).

Results: Among 131 patients, 17 (13%) had hyponatremia at admission. Hyponatremia was associated with lower BMI, lower nadir BMI, longer disease duration, and an adverse biochemical profile (lower albumin, higher creatinine, higher platelet counts, and higher bicarbonate levels). Thirteen patients (10%) were deceased at follow-up; hyponatremia was associated with mortality in unadjusted analysis (OR 8.03, 95% CI 2.29–28.16) but not after multivariable adjustment.

Discussion: The study found that 13% of patients admitted to a specialized somatic unit for ED had hyponatremia, which clustered with indicators of more severe and longstanding AN (lower BMI, lower nadir BMI, longer disease duration). Hyponatremia was associated with mortality in unadjusted analyses, but this association was attenuated after adjustment for age and illness severity. Despite the established potential of purging to induce hyponatremia, our findings suggest that, in this severely ill inpatient population, overall illness severity and chronic medical deterioration may be more important determinants of both hyponatremia and mortality risk than purging per se.

High-throughput sequencing has transformed clinical diagnostics of rare diseases (RD), cancer and infectious diseases by enabling the identification of disease-causing genetic alterations and facilitating individualised treatment and care. In response to these advances, Genomic Medicine Sweden (GMS) was established in 2017 as a national collaborative effort to accelerate implementation of genomics-based precision medicine within Sweden's regionally organized, publicly funded healthcare system. GMS brings together the seven university healthcare regions and their associated medical faculties, in collaboration with healthcare regions across Sweden, Science for Life Laboratory, patient organizations, industry and governmental agencies. Activities are coordinated through national disease-specific expert groups, supported by cross-cutting functions in bioinformatics, health economics, ethics, education and patient engagement. At the operational level, seven Genomic Medicine Centres, embedded at university hospitals, develop and deliver harmonised genomic diagnostics nationwide. The National Genomics Platform provides secure infrastructure for large-scale data storage, analysis, and national and international data sharing. Following initial project-based funding, GMS now receives long-term governmental support. This review describes the national implementation of genomic-based precision diagnostics, discusses challenges and lessons learnt, and highlights key milestones across disease areas, including whole-genome sequencing in RD and paediatric cancer, comprehensive genomic profiling of haematological malignancies and solid tumours, pathogen genomics in microbiology, pharmacogenomic testing and emerging applications of polygenic risk scores in complex diseases. Collectively, these efforts have contributed to more than 500,000 genomic tests being performed within Swedish healthcare between 2017 and 2025. Finally, we outline future diagnostic needs and priority areas to ensure sustainable, scalable and equitable access to precision medicine.

Background: As a surrogate for eosinophilic activation, eosinophil-derived neurotoxin (EDN) is a potential clinical biomarker. However, EDN levels and discriminatory ability in different asthma phenotypes are unknown. We quantified serum and nasal lavage fluid (NLF) EDN levels and assessed the potential to differentiate clinically defined asthma phenotypes in an adult-representative sample.

Methods: A total of 1499 serum and 386 NLF samples from individuals with current asthma obtained from the West Sweden Asthma Study were analyzed for EDN. Eosinophilic asthma was defined as blood eosinophil count of ≥ 300 cells/mm3, T2-high asthma was defined as blood eosinophil count of ≥ 300 cells/mm3 or fractional exhaled nitric oxide (FeNO) levels of ≥ 25 ppb. Other asthma phenotypes were defined based on presence of atopy, chronic rhinosinusitis (CRS), nasal polyposis, and obesity.

Results: Subjects with eosinophilic asthma had higher serum and NLF EDN levels than those with non-eosinophilic asthma. In ROC analyses, serum EDN provided excellent discrimination between eosinophilic and non-eosinophilic asthma (area under curve [AUC] = 0.84, 95% CI = 0.82–0.86); the corresponding AUC for NLF EDN was 0.67 (95% CI = 0.62–0.73). Serum and NLF EDN were higher in atopic asthma, T2-high asthma, and asthma with nasal polyposis compared to their counterparts, but not in asthma with CRS. The highest absolute values of serum and NLF EDN were observed in the high eosinophil + FeNO group, followed by the high-eosinophil-only and high-FeNO-only groups.

Conclusion: Both serum and NLF EDN were higher in those with eosinophilic compared to non-eosinophilic asthma. However, only serum EDN appears to distinguish eosinophilic asthma in ROC analyses.

Low-kaolinite clays represent a globally abundant resource for reducing clinker content, yet their durability remains poorly understood. This study examines the carbonation behavior of a clay blended binder incorporating 30 wt% of a thermally-mechanochemically activated 2:1 mixed-layer clay, with emphasis on hydrate assemblage evolution, C-A-S-H chemistry, and pore structure. Drying was decoupled from CO₂ exposure to distinguish physical conditioning from chemically driven carbonation damage, and curing duration was varied to access different hydrate states in this slow-reacting system. Carbonation proceeds through CH depletion, AFm/AFt destabilisation, and C-A-S-H decalcification; however, the extent of degradation depends strongly on the chemical maturity of the gel at the time of exposure. Binders carbonated after extended curing show markedly reduced decalcification (Ld ≈ 34% versus 92% in short-cured samples) and limited pore coarsening. Drying induces gel contraction and pore restructuring, but severe degradation occurs only when carbonation chemically decalcifies the gel. These results demonstrate that carbonation resistance in low-kaolinite binders is governed by hydrate assemblage evolution and chemical maturity of C-A-S-H, reflecting carbonation pathways distinct from those assumed for OPC and LC3 systems.

Background: New sophisticated deep brain stimulation (DBS) systems enabling steering of current and aiming at improving further motor outcome and decreasing side effects have virtually replaced old omnidirectional systems, despite being more labor-intensive and expensive.

Objectives: The objective was to evaluate whether modern directional DBS resulted in better motor improvement compared to “old” omnidirectional DBS.

Methods: Publications on subthalamic nucleus (STN)-DBS from the “old” period were compared to modern publications, focusing on severity of motor symptoms at baseline and motor outcome at various intervals after surgery.

Results: Although patients from old DBS era had a more advanced disease at baseline than those treated with modern DBS hardware, they benefitted more from STN-DBS and showed a higher percentage decrease in dopaminergic medication.

Conclusions: The new directional DBS does not result in better motor outcome compared to the older omnidirectional DBS. However, it may, in some cases, contribute to decreasing some side effects of stimulation such as dysarthria.

LWFA experiments are pioneering new developments in industry and medicine by aiming to generate and control high-energy electrons through plasma waves with accelerating gradients of approximately 10–100 GV/m in an underdense plasma. The properties of these electrons can be determined from their positions on scintillating screens after deflection by an electron spectrometer. In this work, the magnetic field of the permanent magnet was characterized and found to be in good agreement with the three-dimensional field-mapping simulation, enabling the position– energy calibration of an electron spectrometer. The directional characteristics of the KODAK Biomax MS scintillating screen were also investigated using a 520 nm, (4.76 ± 0.02) mW laser source and a CCD camera. The measured laser-induced angular response contained a broad cosine-like component together with a narrower Gaussian component and was represented by a Gaussian–cosine composite function. The detected signal along the screen was strongly influenced by the directional optical response, while the variation in solid angle produced a smaller effect. The minimum-to-maximum increase of the measured ROI signal was reduced from 209.8% to 43.0% after the Gaussian angular-response correction and to 32.4% after the combined Gaussian and solid-angle correction. The position– energy calibration, CCD photon-to-count calibration, and optical characterization of the scintillating-screen imaging system provide a basis for reconstructing the electron energy distribution and estimating the corresponding absolute charge in future LWFA experiments.

The EURO-PROBE dataset provides manually created segmentations of the prostate and intraprostatic urethra on axial T2-weighted MRI volumes, complementing the existing LUND-PROBE (LUND Prostate Radiotherapy Open Benchmarking and Evaluation) dataset for prostate radiotherapy research. Delineations were performed by delineators with varying levels of experience, including radiologists, radiology and urology residents, and medical students, which enables both inter-reader variability analysis and stratification by reader experience. Across all 467 cases in the LUND-PROBE dataset, at least one paired segmentation of the prostate and intraprostatic urethra was created for each case, yielding 1,227 paired segmentations in total. By expanding the LUND-PROBE dataset, EURO-PROBE supports the development of automated segmentation tools, including for the urethra, which is a highly relevant organ at risk in focal dose escalated prostate radiotherapy.

Many key ecosystem functions are affected by plant roots and their traits. However, understanding of the patterns in, and drivers of, root traits lags far behind equivalent knowledge of above-ground tissues, particularly in boreal old growth forests. We surveyed community-level root traits across 11 old growth forests spanning a wide latitudinal range in Sweden, encompassing a ~7oC range in mean annual temperature. In each forest, three plots were selected in locations with low, intermediate and high soil moisture index (SMI). We then applied principal components, redundancy analysis and linear regression to quantify how root traits co-varied with stand abiotic and biotic properties, including plant foliar area in the same stands. Stand hydrology did not affect overall mass based root trait values (tissue density, nitrogen content, carbon:nitrogen ratio, root tips, length and area per unit dry root mass), but appeared to strongly mediate the responses of these traits to environmental drivers across forests. Overall, measured root and leaf area per unit ground area were not clearly related to each other or to tree biomass across plots and forests. Measured root surface area per unit ground area was much greater than literature estimates from similar forests, and ~3 times greater than leaf area per unit ground area recorded from the same forests. Our results provide a valuable baseline for root traits in old growth boreal forests, redefining what are considered typical or natural root properties for the biome and highlighting key environmental controls.

Generalised Monge–Ampère (gMA) equations form a large class of PDE including Donaldson's J-equation, inverse Hessian equations, some supercritical deformed Hermitian–Yang–Mills (dHYM) equations and some Z-critical equations. Solvability of these equations is characterised by numerical criteria involving intersection numbers over all subvarieties, and in this paper, we aim to characterise algebraically what happens when these non-linear Nakai–Moishezon type criteria fail. As a main result, we show that under mild positivity assumptions, there is a finite number of subvarieties violating the Nakai-Moishezon type criterion, and such subvarieties are rigid in a suitable sense. This gives the first effective solvability criteria for these families of PDE, thus improving on work of Chen, Datar–Pingali, Song and Fang–Ma, and provides the first existence results in higher dimensions of a natural PDE analogue of Bridgeland's locally finite wall–chamber decomposition.

European ash (Fraxinus excelsior) is a keystone broadleaved tree species in northern Europe, valued for its ecological functions, cultural heritage, timber and biodiversity support. Since the early 2000s, ash populations have declined dramatically due to ash dieback caused by the invasive fungus Hymenoscyphus fraxineus, raising questions about whether and how the species can be restored. While substantial research has focused on genetic resistance of ash, less is known about how stakeholders perceive the feasibility, risks, and responsibilities associated with restoration. This study explores the willingness to engage in and support ash restoration among forestry stakeholders in regions of Sweden where ash has historically been common. Interviews with forest owners, managers, and other forestry actors were analysed within a social-ecological framework integrating societal, technological, and ecological dimensions. Respondents expressed attachment to ash and broad support for its restoration in principle. However, willingness to act was conditional on several factors. Key barriers included uncertainty about resistance durability, financial risk for landowners, limited suitable planting sites, availability of commercially viable seedlings, and fragmented governance responsibilities. The respondents showed high confidence in conventional breeding approaches but were sceptical toward biotechnological solutions. Existing policy, particularly Sweden's Noble Broadleaves Policy, was viewed as promising but requiring adaptation to explicitly support ash restoration. The findings highlight that ash restoration is not solely a biological or technical challenge, but also a social and governance venture. Aligning national policy with the EU Nature Restoration Law could help reduce uncertainty, mobilize stakeholder engagement and create enabling conditions for future restoration efforts.

We evaluated the magnitude and function of antibody responses to seasonal influenza vaccination in individuals with HIV receiving ART compared with individuals without HIV. In a prospective cohort of 78 adults, influenza strain-specific IgG levels were measured up to one-year post-vaccination. Linear mixed-effects models assessed longitudinal trends. IgG levels peaked at two weeks and declined gradually in both groups. HIV status did not significantly influence antibody magnitude or neutralizing activity, and H1N1 antibody levels correlated with neutralization titers. These findings demonstrate robust, durable, and functional humoral response in well-controlled HIV, supporting the effectiveness of annual influenza vaccination in this population.

OBJECTIVES: To evaluate the pilot implementation of Parwarish (Parenting for Lifelong Health-Teens) programme on reducing violence against adolescents and improving parenting practices, mental health, gender attitudes, resilience and financial coping among families in disadvantaged communities in North India.

DESIGN: Pilot implementation study using a pre-post study design.

SETTING: Community-based implementation in three disadvantaged settings in North India, including urban informal settlements, rural agricultural areas and remote tribal communities.

PARTICIPANTS: A total of 239 adolescents (aged 12-18 years) and 478 parents from 239 families were recruited using purposive and snowball sampling; all participants completed baseline assessment, with follow-up conducted within 6 weeks after intervention completion.

INTERVENTIONS: A 14-week group-based parenting intervention delivered weekly in community settings, focusing on communication, problem-solving, non-violent discipline and financial management, facilitated by trained community members.

PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcomes were parent and youth-reported maltreatment. Secondary outcomes included parenting practices, adolescent behaviour, mental health, resilience, gender-equitable attitudes and financial coping.

RESULTS: Significant improvements were observed across all outcomes. Among adolescents, positive parenting increased (β=13.7; 95% CI 12.43 to 14.98), youth behaviour improved (β=9.12; 95% CI 8.11 to 10.13), resilience increased (β=9.53; 95% CI 8.19 to 10.86) and harsh discipline decreased (β=-8.69; 95% CI -10.45 to -6.94). Among parents, positive parenting improved (β=10.6; 95% CI 9.43 to 11.85), youth behaviour improved (β=11.11; 95% CI 10.20 to 12.02), harsh discipline decreased (β=-10.60; 95% CI -12.23 to -8.96) and financial coping improved (β=-4.97; 95% CI -5.98 to -3.97).

CONCLUSIONS: This low-cost, community-delivered pilot implementation of the Parwarish intervention was associated with improvements in parenting practices and in mental health and resilience among adolescents and parents. While causal inference is limited by the study design, the findings support further evaluation using controlled designs. It suggests potential for scale-up in similar low-resource settings.

TRIAL REGISTRATION NUMBER: ACTRN12622000858796.

Highly purified adenovirus preparations are essential for fundamental research and therapeutic use. However, the impact of viral concentration during CsCl gradient ultracentrifugation on virion integrity is poorly understood, and this incomplete mechanistic understanding may adversely affect product quality and constrain further advances in research. In this study, we examined how viral input affects adenovirus infectivity, cytotoxicity, yield, and structural integrity using transmission electron microscopy and analysis tools. High-concentration preparations (AdV-HC) showed significant aggregation, capsid damage, and considerably lower TCID₅₀ values, while optimally concentrated preparations (AdV-OC) preserved intact icosahedral structures and high infectivity. Efforts to reverse aggregation failed, showing that excessive viral concentration during purification causes irreversible structural harm. These findings indicate that overloading during CsCl ultracentrifugation promotes vector aggregation, thereby compromising virion stability and biological activity. To preserve structural integrity and ensure consistent performance, we recommend maintaining the final purified vector concentration at or below 2 mg/mL. Based on this threshold, we defined theoretical optimal optical density (OD) ranges for adenovirus concentration in cell lysates prior to ultracentrifugation to minimize vector aggregation during purification. Therefore, this study provides a simple and effective strategy for improving the consistency, purity, and infectivity of adenovirus preparations for both research and clinical applications.

Background: IgE-mediated food allergy prevention guidelines are now established in many countries, but their implementation in routine clinical practice globally remains unclear.

Methods: An anonymous online survey was distributed to healthcare professionals (HCPs) through the World Allergy Organization network between December 2024 and April 2025, collecting data on food allergy prevention recommendations in daily clinical practice.

Results: The analysis included 731 healthcare professionals from 80 countries worldwide: Asia (36.7%), Europe (27.1%), North America (15.9%), and Rest of the World (20.0%; Russia, South America, Africa, Oceania). Unsupervised clustering revealed two distinct practice patterns—one favoring early allergen introduction and one favoring later introduction—with timing varying by allergen type. For peanuts, clusters diverged between early (median 6 months of age) and late (median 18 months of age) introduction recommendations for high-risk infants. Allergen introduction timing was independently driven by region and specialty: North American HCPs recommend peanut introduction 6.7 months earlier than those in Asia (5.48 (Formula presented.) 3.32 vs. 12.18 (Formula presented.) 7.27 months; p < 0.001), and pediatric allergists globally advocate for introduction 2.37 months earlier than non-allergists (8.72 (Formula presented.) 5.85 vs. 11.09 (Formula presented.) 7.14 months, p = 0.024). This disparity is more pronounced in high-risk infants than in normal-risk infants.

Conclusions: The variability in allergen introduction practices, driven by geography and medical specialty, highlights a persistent gap in prevention guidelines adoption. This divergence likely reflects both suboptimal implementation of existing recommendations and regional differences in food allergy epidemiology. These findings underscore the need for population-tailored allergen introduction strategies across diverse healthcare settings.

Introduction: Persistent spinal pain syndrome (PSPS) with predominant low-back pain (LBP) is difficult to manage when conservative and surgical treatments fail. Dorsal root ganglion stimulation (DRG-S) offers segmental, focal neuromodulation that may be particularly suited for managing axial LBP, yet long-term evidence from real-world practice remains limited. This study evaluated the effectiveness, safety, and impact on medication use of bilateral T12 DRG-S in patients with intractable LBP, using prospectively collected registry data.

Methods: Of 33 consecutive patients with chronic LBP assessed for DRG-S, 20 underwent trial stimulation after multidisciplinary evaluation. Eighteen (90%) proceeded to permanent implantation following ≥ 50% pain reduction during trial. Patients were followed via a digital platform at 3, 6, 12, and 24 months. Outcomes included pain intensity (NRS), quality of life (PROMIS-29), pain catastrophizing (PCS), satisfaction, medication use, and adverse events. Statistical comparisons were made between baseline and follow-up time points using paired tests.

Results: Pain intensity decreased substantially and significantly across all follow-up assessments: mean NRS declined from 8.0 ± 1.8 at baseline to 3.6 ± 1.6 at 3 months, 3.2 ± 1.8 at 6 months, 3.6 ± 1.7 at 12 months, and 2.9 ± 1.6 at 24 months (all p < 0.001). At 24 months, 100% of patients achieved ≥ 30% pain reduction and 70% achieved ≥ 50% reduction. Patient-reported outcomes demonstrated broad improvements. PROMIS-29 domains showed significant gains in physical function, pain interference, fatigue, and sleep disturbance, with consistent improvements also observed in anxiety and depression. Pain catastrophizing (PCS) scores decreased markedly, with total scores reduced by 47%–62% across follow-ups (all p < 0.001), reflecting improvements across helplessness, magnification, and rumination subdomains. Medication use declined over time. Mean opioid dose fell from 27 mg/day at baseline to 11.25 mg/day at 1 year and 4.44 mg/day at 2 years (p = 0.019 and 0.011, respectively). Paracetamol use also decreased significantly, whereas gabapentinoid use remained variable. Seven hardware-related complications were recorded (lead migration n = 3, lead fracture/damage n = 4), all successfully managed with revision surgery. Kaplan–Meier analysis estimated mean time to complication at 1080 days. Two patients discontinued therapy (EOT), both for reasons unrelated to device failure.

Conclusions: In this prospective registry, bilateral T12 DRG-S provided durable reduction in pain intensity, improved physical, psychosocial, and cognitive outcomes, and facilitated meaningful opioid-sparing effects over 2 years. Complications were limited to correctable hardware issues, and therapy discontinuation was rare. Although larger multicentre studies are warranted, these findings add important real-world evidence supporting DRG-S as a valuable therapeutic option for refractory axial LBP.

Background: People with Parkinson's (PwP) who lose independence may need care in nursing homes or similar institutions if home care is insufficient. Institutionalisation has major social and financial implications. Better understanding of which PwP are most likely to be institutionalised would improve information provision, clinical risk stratification, and healthcare planning.

Objectives: To identify risk factors for institutionalisation in PwP and develop models predicting individual institutionalisation risk.

Methods: We described institutionalisation in the Parkinson's Incidence Cohorts Collaboration, comprising 6 European incidence cohorts. We identified prognostic factors by two-stage individual-participant-data meta-analysis. Prognostic models predicting risk of institutionalisation within 7 years and 10 years were developed using the Royston-Parmar model. Heterogeneity in model performance was assessed using internal-external cross validation (IECV).

Results: In 1046 PwP, the cumulative incidence of institutionalisation by 10 years was 37.2%. The incidence rate ranged from 1.7 to 6.2 per 100 person-years. Older age, higher MDS-UPDRS part 3 and lower MMSE at baseline independently predicted higher institutionalisation risk. IECV showed good discrimination in the 10-year (C-statistics 0.73-0.81) and 7-year (0.71-0.84) models. However, calibration (agreement between predictions and observed outcomes) showed under- and over-prediction across studies. After updating model intercept and coefficients (recalibration), the calibration improved.

Conclusion: 37% of PwP entered institutional care within ten years from diagnosis. Older age, higher MDS-UPDRS part 3 and lower MMSE predicted institutionalisation. The prognostic models discriminated well, but calibration varied between cohorts. We recommend further validation before applying the models in other settings.

The biodiversity hypothesis links urban species richness to human immunity, yet overlooks habitat heterogeneity that can quarantine pathogenic microbiota. We propose the β-diversity hypothesis: increased tree heterogeneity promotes urban microbial heterogeneity and improve human health. Using plant surveys and paired data of soil, phyllosphere and airborne microbiota transferred indoors (AMTI) across 72 Shanghai neighborhoods, we showed that elevated tree heterogeneity corresponds to higher β-diversity in both AMTI and soil communities. The spatial patterning of respiratory diseases (RDs) was driven by AMTI β-heterogeneity, revealing that homogenization of airborne microbiota affects human respiratory health. We further developed the urban tree βdis model and identified a threshold value of 0.661. Selecting phylogenetically distant tree families, e.g. Arecaceae, Oleaceae and Magnoliaceae at or above this threshold yields ready-to-use planting templates that maintains AMTI β-diversity and a scalable protocol for city-wide greening. Given microbial heterogeneity’s emerging health links, our findings call for embedding the β-diversity hypothesis into biodiversity–health frameworks and for cross-biome validation.

Background: Optimal reconstruction of the perineal defect after extended abdominoperineal excision remains uncertain, and randomized comparisons between biological mesh and myocutaneous flaps are lacking. This trial assessed whether an acellular porcine collagen implant (APCI) is non-inferior to a gluteus maximus myocutaneous flap (GMF) for pelvic floor reconstruction.

Methods: NEAPE was a multicentre, randomized, non-inferiority trial conducted in eight Nordic referral centres. Adults undergoing extended abdominoperineal excision for rectal cancer were randomized to reconstruction with an APCI or unilateral GMF. The primary outcome was the proportion of patients underperforming in the timed-stands test at 6 months, defined relative to age- and sex-matched reference values. The non-inferiority margin was −10%.

Results: Eighty-three patients were included in the modified intention-to-treat population (mean(standard deviation) age 68(10) years; 31% female). At 6 months, 71% of patients (25 of 35) in the implant group and 60% of patients (20 of 33) in the flap group underperformed. The risk difference was −11% (one-sided 95% confidence interval −30% to ∞), and non-inferiority was not demonstrated.

Conclusion: The APCI did not demonstrate non-inferiority compared with the GMF. The direction of the effect favoured the flap, with results compatible with worse functional outcomes in the implant group. Registration number: ClinicalTrials.gov NCT01347697.

Background: Exercise capacity (EC) is a key prognostic indicator in adults with congenital heart disease (ACHD), closely associated with all-cause mortality. Thus, EC may serve a valuable tool for risk-stratification in ACHD. We propose a novel risk score incorporating EC, age, and lesion complexity to improve mortality risk prediction in ACHD.

Methods: This observational study utilized data from the Swedish National Register of Congenital Heart Disease. Adults aged 18 to 60 years who had completed at least one bicycle ergometer exercise test were included. EC was classified according to percentage of predicted capacity (% ECpred): normal (>70%), moderately impaired (50–70%), severely impaired (<50%). Patients were followed for ten years or until death. Odds ratios for mortality were used to derive a 5-point risk-score to estimate 10-year mortality, with the following point allocation: % ECpred 50–70 = 1 point, <50% = 2 points; age 25–40 years = 1 point, 40–60 years = 2 points; moderate/severe lesion complexity = 1 point. Internal validation of risk score resulted in a median AUC of 0.72 for training data, and 0.70 for test data.

Results: In total, 1,525 patients (mean age 31.1 ± 11.8 years; 44% women) were included, where 104 deaths occurred during follow-up. Risk scores ranged from 0 to 5, corresponding to 10-year mortality rates of 1%, 3%, 5%, 10%, 18%, and 34%, respectively.

Conclusion: A simple risk score incorporating exercise capacity, age, and congenital heart lesion complexity can effectively stratify ACHD patients to 10-year risk of all-cause mortality following an exercise test.

Pulmonary embolism (PE) is a life-threatening condition for which accurate risk stratification is essential for clinical decision-making. Most existing prognostic models rely on a single data modality, typically structured electronic health records (EHR), limiting their ability to capture the heterogeneous nature of the disease. Multimodal approaches combining EHR, computed tomography (CT) imaging, and free-text clinical reports provide complementary information, but the optimal fusion strategy for prognosis prediction remains unclear. In this study, we present a comprehensive comparative study of multimodal fusion strategies for PE prognosis using the INSPECT dataset, which includes structured EHR, CT images, and clinical text with mortality labels. We develop unimodal baselines and multiple bimodal and trimodal models using early, intermediate, late, and cross-fusion strategies within a unified framework. Models are evaluated for 1-, 6-, and 12-month mortality prediction. Multimodal models consistently outperform unimodal baselines across all prediction horizons, with MCC improvements up to +0.13 for 1-month mortality (0.399 vs 0.269) and +0.11 for 6-month mortality (0.479 vs 0.367). The best overall performance is achieved by late fusion models, reaching an MCC of 0.497 for 12-month prediction, compared to 0.454 for the best unimodal model. Interestingly, bimodal combinations often outperform trimodal fusion in short-term prediction, suggesting that improper integration of multiple modalities may introduce noise and reduce effectiveness. These results highlight the importance of fusion design in multimodal clinical AI and provide practical guidance for developing robust prognosis models for pulmonary embolism. Code is publicly available at https://github.com/arco-group/INSPECT-CS.

Bridge infrastructure worldwide is aging, while demands for safety, sustainability, and cost-efficiency intensify challenges in bridge management (BM). This study develops a comprehensive knowledge map of BM through scientometric analysis, clarifying its intellectual structure, technological frontiers, and emerging themes. Using CiteSpace, 1582 peer-reviewed articles (2003–2024) from the Web of Science Core Collection were analyzed, with keywords and gaps refined via a Delphi process involving five senior experts. Scientometric techniques—including co-citation, cluster mapping, citation bursts, and keyword time-zone analysis—were employed to trace field evolution. Results reveal three stages: exploratory (2003–2009), steady growth (2010–2016), and digital transformation (2017–2024). Ten thematic clusters emerged, spanning intelligent management, hybrid decision-making, inspection technologies, and life-cycle sustainability. Research hotspots highlight digital twins, machine learning, condition assessment, and structural health monitoring. Five evidence-informed future priorities were identified: integrated AI-driven frameworks, hybrid decision models, network-level inspection planning, sustainability-oriented life-cycle assessment, and robust resilience modeling. Co-authorship and institutional collaboration networks further reveal global hubs shaping BM knowledge exchange. This study provides an updated mapping of BM, offering a structured agenda that links quantitative evidence with practical directions for advancing intelligent, sustainable, and risk-resilient BM.

Urinary metabolites and their concentrations serve as biomarkers for identification of metabolic pathways that relate to specific diseases; therefore, fast and accurate quantification of the metabolites in urine is essential in health assessment and diagnosis. As many urinary metabolites are of polar nature, hydrophilic interaction liquid chromatography (HILIC) has been used over the last several years because it offers faster and more reproducible analyses compared to traditional techniques such as reversed-phase chromatography or capillary electrophoresis. In our study, we developed a HILIC method by using a 3 cm analytical column in connection with tandem mass spectrometry detection for quantification of 10 urinary metabolites including creatinine as the reference for normalization. As all tested metabolites contain ionizable functional groups, pH of the mobile phase was optimized to achieve baseline separation of 2 isomeric pairs (1-methyl-4-imidazoleacetic acid/1-methyl-5-imidazoleacetic acid and 1-methylhistidine/3-methylhistidine) and to obtain overall better separation efficiency resulting in a 7 min analysis. The developed method was validated in terms of sensitivity, carry-over, linearity, matrix effects, accuracy, and precision. The metabolite concentrations in healthy subjects determined by the developed method correspond well with the normal reference values found in the literature. Moreover, the method was tested on a small cohort of COVID-19 patients, where it enabled identification of differences in metabolite levels. Thus, the developed method has potential to be used routinely in a diagnostic field for high-throughput analysis of urine samples.

The role of pets in supporting children's mental health and well-being has attracted growing attention. Although pets are often described as emotionally significant companions—offering comfort, security and stability—the effects of pet ownership are not universally positive or consistent. This scoping review maps existing research on the significance of pets for children's well-being, particularly those experiencing mental health challenges. Drawing on 20 studies—quantitative, qualitative and mixed-methods—published across diverse cultural contexts, the review identifies three central themes: emotional support and friendship; responsibility, routine and family; and psychosocial well-being. Findings suggest that the emotional quality of the child-pet relationship, rather than pet ownership alone, is key to potential benefits such as reduced stress and enhanced resilience. The review underscores the importance of context-sensitive understandings of well-being. Pets may be valuable allies in children's mental health, but their role should be understood as part of broader social contexts. Contextual factors including age, gender, species of pet and socio-economic environment may influence the outcomes. However, strong reliance on pets can also reflect or reinforce social isolation. Limitations include a small evidence base focused largely on high-income countries and a lack of studies centring children's own perspectives. Further research is needed to explore how children across varied settings experience relationships with pets, and how these connections might inform support strategies in social work and mental health care.

RNA modification pathways are often misregulated in various cancers, with N6-methyladenosine (m6A) having a pivotal role in cancer progression and metastasis. Methyltransferase-like 3 (METTL3), a core component of the m6A methyltransferase complex, not only functions as an m6A writer but also promotes tumorigenesis through m6A-independent mechanisms. Here, we show that METTL3 is mislocalized to the cytoplasm in breast cancer tumors from patients, contributing to the oncogenic phenotype. Cytoplasmic METTL3 interacts with EXOC7, a key regulator of exocytosis, promoting its stabilization. In addition, METTL3 regulates m6A-dependent alternative splicing of EXOC7. Silencing METTL3 impairs vesicle trafficking and the breast cancer secretome-effects that do not rely on its enzymatic activity but instead involve METTL3-mediated stabilization of EXOC7 and potentially other exocyst components. Furthermore, METTL3 knockdown impairs invadopodia formation, collagen matrix invasion, and focal adhesion morphology in vitro, while inhibition of METTL3 catalytic activity does not. Our findings uncover noncatalytic roles of METTL3 in regulating exocytosis and the cancer secretome.

Atherosclerosis, manifesting as acute myocardial infarction, stroke and peripheral artery disease, is the main cause of death worldwide. Conventional risk factors contributing to the development and progression of atherosclerosis are well established, including diabetes mellitus, hypertension, hypercholesterolemia, smoking and obesity. In recent decades, other lipid molecules have been identified as risk factors for atherosclerosis and arterial calcification, including lipoprotein (a) and apolipoproteins. Despite the available evidence for the association between those biomarkers and atherosclerosis in the general population, their impact on diabetic patients is incompletely characterized. This review aims to summarize the current evidence on the relationship between lipoprotein (a), apolipoproteins and atherosclerotic cardiovascular disease in diabetic patients. By integrating genetic, epidemiological, and mechanistic data, this review highlights the dual and context-dependent associations of lipoprotein (a) with incident type 2 diabetes and atherosclerotic cardiovascular risk, supporting more nuanced interpretation of Lp(a) in diabetes-related risk assessment.

Introduction – Trans-cranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique with increasing evidence of efficacy in treating neuropsychiatric conditions. There is a need for biomarkers to predict and monitor tDCS efficacy. We aimed to conduct a systematic scoping review to assess the evidence regarding the ability of biomarkers to predict response to tDCS and identify promising candidate biomarkers in neuropsychiatric patient populations.

Methods – Comprehensive searches were conducted in the MEDLINE and EMBASE databases on 24/09/2023. Articles were screened at the title and abstract level and then at full text, and inclusion/exclusion criteria applies. Data was extracted and the quality of the studies assessed with the JADAD, MINORS and Ottawa rating scales. 154 including 154 studies in the review. Disorders studied weredivided into 10 categories, Stroke/Aphasia, Psychotic Disorders, Affective Disorders, Neurocognitive Disorders, Pain Disorders, Addiction Disorders, Disorders of Consciousness, Multiple Sclerosis, Neurodevelopmental Disorders and Traumatic Brain Injury. Biomarkers with positive results in at least 2 studies in each group were identified.

Results – The most common biomarker across groups was functional connectivity, appearing in 7 of 10 groups. This was followed by EEG features and Cortical Activation. The biomarkers with most evidence have plausible mechanisms of action and have been previously proposed as candidate biomarkers in similar research. Other biomarkers included anatomical and clinical features, and levels of neurotransmitters in the brain.

Conclusion – This review identified the most promising candidate biomarkers in predicting and monitoring tDCS response in neuropsychiatric disorders and this may provide a focus for future research.

Systematic review registration – https://osf.io/r6mkp/?view_only=64ec4811e21f43ba84fe31496f403ec2.