Modern military medical operations frequently occur in environments where access to specialized procedural care is limited by distance, mobility requirements, and constrained infrastructure. In these settings, forward medical teams must often manage complex conditions with limited personnel and equipment. Physician associates represent a critical component of the military medical workforce and frequently serve as a senior medical provider within forward and austere environments. Because physician associates are already embedded within deployed medical teams and are trained to perform a range of invasive procedures, expanding their role in image-guided procedural care represents a potential pathway to strengthen forward medical capability without increasing personnel requirements. This article examines the potential role of physician associates as procedural extenders for image-guided care in expeditionary medical systems. Military medical literature, radiology workforce analyses, and global interventional radiology education initiatives were reviewed to evaluate how physician associates could safely perform selected image-guided procedures with appropriate training and oversight. Historical experience demonstrates that physician associates have long served as procedural leaders in deployed settings, routinely performing vascular access, thoracic drainage, and other invasive interventions within Role 1 and Role 2 medical elements. Civilian data further show that advanced practice providers safely perform procedures such as paracentesis, thoracentesis, venous access, drain placement, and lumbar puncture with outcomes comparable to physicians when structured training and supervision are present. These precedents suggest that physician associates may be well positioned to expand their scope to include selected image-guided procedures when supported by focused education and standardized credentialing. A training model emphasizing ultrasound proficiency, procedural decision-making, and complication management could enable physician associates to perform procedures such as vascular access, fluid drainage, and diagnostic aspiration in austere environments. Simulation-based training and tele-supervision networks may further support safe implementation while maintaining oversight from physician specialists. Positioning physician associates as procedural extenders aligns with broader military medical priorities that emphasize modular, capability-based care and efficient use of existing personnel. By leveraging an already deployed workforce, this model could expand access to minimally invasive procedures in combat, humanitarian, and prolonged casualty care environments while maintaining continuity with higher-echelon medical facilities. Prospective evaluation will be necessary to fully define appropriate procedural scope, training standards, and safety outcomes.
Beyond its efficacy on atrial fibrillation, pulsed field ablation (PFA) presents potential advantages in ventricular arrhythmia. This study sought to investigate the feasibility of PFA for ventricular tachycardia (VT) and premature ventricular complexes (PVC). A systematic search (Scopus, PubMed, and Science Direct) with citation searching was performed on 9 January 2026. Studies evaluating the feasibility of PFA in VT and PVC were included. This study included seven studies (74 patients with VT and 86 with PVC). Pooled acute procedural success rate in VT was 0.92 (95% CI: 0.86-0.99) and in the PVC was 0.93 (95% CI: 0.86-1.00). During follow-up, VT recurrence rates ranged from 20% to 54%. PVC ablation demonstrated a significant burden reduction (MD: 86.54%; 95% CI: 59.21-113.86; p = 0.005) with long-term success rates ranging from 50% to 85%. Safety evaluation demonstrated satisfactory outcomes, with major adverse cardiovascular events (MACE) during follow-up occurring in four patients with high-risk comorbidity. Major adverse events (AEs) occurred in 11 patients and were preventable; minor AEs consisted solely of vascular access site AEs. PFA was feasible for VT and PVC ablation. Larger long-term studies and standardized protocol were urgently necessary to ensure efficacy with minimal AEs. www.crd.york.ac.uk/prospero identifier is CRD420251272352. Pulsed field ablation (PFA) is a newer technology for abnormal heart rhythms. It uses electrical pulses to treat parts of the heart tissue that cause abnormal rhythms. Unlike older treatments, it does not use heat or freezing. In the world, doctors are already used to treating atrial fibrillation. However, less is known about its use for ventricular arrhythmias. These include ventricular tachycardia and premature ventricular complexes. This study reviewed data from seven studies involving 158 patients. The study found that new technology worked well during the procedure in most patients. However, some patients later had the abnormal heart rhythm return, especially those with ventricular tachycardia. In patients with premature ventricular complexes, the treatment lowered the number of extra heartbeats. Serious complications were rare and mostly happened in patients who already had severe health problems. We found that most complications are also preventable by the doctors, although more research needs to be done in this area. Overall, PFA appears to be a promising and feasible technology for these types of heart rhythm disorders.
Mast cells (MCs), as innate immune cells residing in cutaneous tissues, serve as critical mediators in the cross-talk between the neuroendocrine and immune systems. Upon activation by internal or external stimuli, MCs synthesize, accumulate, and secrete a variety of regulatory mediators, thereby exerting multifaceted effects through their secretory capacity and regulatory functions. Vitiligo, a complex disorder with a heterogeneous etiology encompassing genetic susceptibility, oxidative stress, autoimmunity, and neurogenic components, remains incompletely understood. Current pathogenetic models based solely on neural, humoral, or immunological frameworks fail to provide a comprehensive explanation for its development. Despite the incomplete characterization of mechanisms driving MC accumulation in vitiligo lesions, therapeutic agents targeting MCs and their signaling pathways (e.g., ketotifen, imatinib) have already been clinically implemented. Notably, MCs exhibit bidirectional interactions with neural and endocrine systems: they respond to neurotransmitter and hormonal signals while simultaneously releasing bioactive substances that reciprocally modulate neural activity, endocrine balance, and local immune responses, ultimately impacting melanocyte function. Consequently, targeting MCs and their key signaling pathways(e.g., the MrgX2-PAR2 axis and chymase-TLR4 pathway) represents a promising novel approach for vitiligo management, with potential applications in controlling disease progression, preventing relapse, and advancing therapeutic development.
ObjectiveTo examine longitudinal changes in depressive symptoms during a 30-session course of repetitive transcranial magnetic stimulation (rTMS) in routine clinical practice, with particular attention to symptom change by mid-treatment.MethodsIn this single-center, naturalistic, retrospective observational study, 24 patients with unipolar depressive disorder diagnosed in routine clinical practice according to the International Classification of Diseases, 10th or 11th revision, were included. The primary outcome was change in 17-item Hamilton Depression Rating Scale (HAMD-17) total score at baseline, after 15 sessions, and after 30 sessions, analyzed using a linear mixed-effects model. Secondary analyses examined the 6-item Hamilton Depression Rating Scale (HAMD-6) and the insomnia 3-item score.ResultsHAMD-17 total scores decreased significantly over time. Estimated reductions from baseline were 8.58 points at mid-treatment and 12.99 points at end-of-treatment, corresponding to reductions of 37.9% and 57.4%, respectively. A further 4.41-point reduction was observed from mid-treatment to end-of-treatment. HAMD-6 also decreased significantly across treatment, whereas the insomnia 3-item score improved mainly between baseline and mid-treatment.ConclusionsIn this small real-world cohort, depressive symptom scores decreased during rTMS, with substantial reduction already evident by 15 sessions. Mid-treatment assessment may provide clinically useful information during treatment, although these findings should be interpreted as hypothesis-generating.
Prostate cancer survivorship is becoming an increasingly important issue in Tanzania, especially because follow-up care is still heavily centralised in a few specialised centres. This model is difficult to sustain in a country with a limited number of oncologists and specialised facilities. At the same time, there is growing recognition both globally and locally that primary healthcare (PHC) should play a major role in supporting cancer survivors. With this in mind, the present study set out to determine the proportion of prostate cancer survivors who actually use PHC services after completing active treatment, and to identify the factors that influence this pattern of care. A cross-sectional study was conducted at Besta Super Specialised Polyclinic in Dar es Salaam, recruiting 213 survivors who completed radiotherapy between January 2021 and December 2023. Data were collected via medical record reviews and telephone interviews using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Prostate Cancer Module to assess symptom burden. The study found that 69.0% of survivors utilised PHC services, primarily at district hospitals (82.3%). Rural residence was the strongest predictor, with rural survivors over ten times more likely to access care than their urban counterparts. Higher education, early-stage diagnosis and severe treatment or sexual side effects also significantly increased utilisation. Interestingly, mild urinary symptoms were associated with higher PHC use compared to severe cases. These results suggest that a significant proportion of prostate cancer survivors in Tanzania are already engaged with PHC as a source for addressing survivorship issues, particularly those in rural settings with high symptom burdens. Given the persistent gaps and challenges in accessing specialised cancer services, it becomes even more important to recognise, understand and strengthen the role of PHC facilities as an essential part of the country's cancer care system.
In March 2026, a two-days' international workshop entitled "Hox- and TALE transcription factors: From developmental regulatory networks to disease states" took place in the historical guest house of the University of Heidelberg. The workshop recalled previous workshops organized under the European COST action between 2008 and 2013 and explored new advances in Hox/TALE biology in the context of congenital conditions. Hox- and TALE-homeodomain (HD) family proteins are highly conserved developmental transcription factors (TFs) that were originally characterized as major instructors providing spatial-temporal coordinates along the antero-posterior axis in bilaterian embryos. Hox and TALE proteins are also known to play numerous additional functions during embryogenesis, as well as during the adult life. Not surprisingly, several diseases and congenital malformations result from the aberrant expression or function of Hox- and/or TALE-encoding genes in human. Disorders that are attributable to already known mutations in Hox- and TALE-genes are expected to manifest themselves overtly. However, other mutations or allelic variants affecting Hox- and TALE-genes, or genes that encode for proteins they associate with, may produce more subtle effects. A central question of the workshop was therefore to explore whether the existence of such mutations or variants can be predicted based on research findings in model organisms. Against this backdrop, the workshop revealed novel functional and molecular aspects of Hox and TALE in the context of different animal model systems and regulatory pathways (Figure 1). It also illustrated the power of most recent technologies associated with dedicated bioinformatics tools in deciphering Hox/TALE molecular complexity at an unprecedented level in vivo. Time was dedicated for stimulating discussions and the workshop was also a good opportunity to bring together seniors and more junior colleagues in the Hox/TALE field. Over these two days, the Hox/TALE community not only demonstrated its remarkable dynamism but also raised key questions that are sure to inspire exciting research for years to come.
To develop and internally evaluate an age-assisted dual-input model for bone age assessment in late adolescence using paired hand-wrist and knee radiographs. This single-center retrospective study included 547 adolescents aged 13-19 years with paired left hand-wrist and left knee radiographs (1094 images) acquired during routine clinical care. Data were split at the subject level into training, validation, and internal held-out test sets (70%/10%/20%; 382/55/110 subjects), keeping paired images from each subject in the same subset. A ShuffleNet v2-based model used hand and knee radiographs as visual inputs and incorporated chronological age and sex as auxiliary variables. The validation set was used for model selection, and final performance was evaluated on the internal held-out test set using mean absolute error, root mean square error, and intraclass correlation coefficient. The final model achieved a mean absolute error of 3.77 months, root mean square error of 4.58 months, and intraclass correlation coefficient of 0.984, with 98.18% of predictions within 12 months of the reference standard. Internal ablation comparisons showed lower errors with paired hand-knee inputs and demographic variables than with single-site inputs. In this single-center retrospective cohort, the age-assisted dual-input framework showed promising internal performance for late-adolescent bone age assessment. Independent multicenter external validation is required before clinical deployment, forensic/disputed-age use, or legal decision-making. Knee radiographs should be used only when already available or medically justified, not as routine additional imaging.
Process engineering often requires continuous monitoring of structural health in components exposed to chemically aggressive environments or high temperatures. Examples include thermal solar power plants, where liquid-metal heat-transfer fluids must be monitored to ensure safe and efficient operation, and lithium or next-generation batteries, where liquid-metal electrodes or electrolytes may develop uneven flow, instabilities, or hotspots detectable in real time using ultrasound. Conventional contact ultrasound imaging, however, is limited in these applications because transducers are highly sensitive to harsh conditions, since harsh environment already include elevated temperatures, often resulting in device failure. Waveguides provide a promising alternative by shielding transducers from aggressive environments. Single-mode waveguides (SMWGs) have been widely studied for ultrasound testing, offering protection from thermal damage but requiring slow point-by-point scanning for imaging. Multimode waveguides (MMWGs) have therefore been proposed for ultrasound imaging at high temperatures, though challenges remain regarding wettability, geometry, boundary conditions and the development of aberration correction algorithms to address wavefront distortion. This paper presents a systematic review of ultrasound waveguide transducers for structural health monitoring under high-temperature conditions. It evaluates key designs, highlighting their benefits, drawbacks and contributions to knowledge and surveys aberration correction methods and modelling approaches applicable in harsh environments. The review also traces the evolution from SMWGs to advanced MMWGs that exploit multiple wave modes, discusses opportunities in computational ultrasound imaging, and outlines future research directions. These findings support the optimization of waveguide-based ultrasound imaging for high-temperature liquids in solar power and battery applications, with potential transferability to improve medical ultrasound imaging through aberrative medium (e.g skull).
Despite substantial disability-related costs, participation in public disability benefit programs remains incomplete in many countries. This is particularly the case in low- and middle-income countries where disability programs are relatively new and awareness of eligibility rules may be limited. This paper evaluates whether reducing information frictions can increase enrolment in Vietnam's national disability benefits program. In a randomised controlled trial across 70 rural communes, standardised information about disability benefits was embedded within routine government loudspeaker broadcasts over a five-week period. Using commune-level administrative data observed approximately two years after the intervention, the results show that program enrolment was 9 percent higher in treated communes. The effects are larger among individuals classified with severe disabilities, for whom enrolment increased by 12 percent. Smaller effects are observed among persons with the most severe disabilities, who were likely already well covered by the program. Larger effects are also observed among children who are eligible for higher monthly disability pension amounts. These findings demonstrate that a low-cost and scalable information campaign delivered through existing government communication infrastructure can substantially increase participation in disability benefit programs.
Rapidly decreasing costs of sequencing whole genomes has caused a boom in genomic resources for many species. However, many key nonmodel systems that were sequenced early in the genomic revolution lack assemblies that reflect the quality and contiguity that are routine with current technology. Some of these "early for assembly, late for contiguity" genomes belong to the butterfly genus Heliconius, a remarkably fruitful clade for exploring questions of phenotypic mimicry, speciation dynamics, and population genetics. We de novo assembled five new reference genomes of Heliconius butterflies based on PacBio HiFi sequencing: two subspecies of H. erato, two subspecies of H. melpomene, and a closely related species, H. numata. While independent assemblies of multiple subspecies are already a valuable resource, these specific genomes are important for exploration of the genomic basis of mimicry, because the four H. erato and H. melpomene genomes represent two pairs of H. erato/H. melpomene local comimics. These genomes prove to be high quality (merqury quality score 51-58) and approach completeness (>98% BUSCO complete genes) over a lower number of longer contigs than earlier Heliconius genomes, illustrating how PacBio long-read technology alone can unlock untapped genomic resources. This set of high-quality, uniformly processed genomes represents an important resource for exploring the genomics of adaptation, hybridization, and speciation. Although a Heliconius butterfly was among the first animal genomes to be sequenced, the genus lacks high-quality, publicly accessible, de novo reference genomes for most of its species. This is particularly important for Heliconius because independent and complete genomes are necessary to unambiguously determine the history of introgression and phenotypic innovation that makes this system so relevant for evolutionary research. We address this gap by generating deep-coverage PacBio long-read data from 5 Heliconius subspecies, assembling genomes de novo with a uniform and reproducible Snakemake processing pipeline. We recover excellent genome contiguity, quality, and completeness scores using only long-read data. We further annotate these genomes with subspecies-specific RNA-seq data to produce annotations with >97% BUSCO completeness. This group of Heliconius genomes represent an important contribution of identically processed, high-quality genomes for comparative genomic investigation into the evolution and innovation of ecologically relevant phenotypes.
High-impact sports participation may exacerbate pelvic floor dysfunctions (PFDs), a condition already common among women, in the female athletic population. In this population, pelvic floor health knowledge (PFHK) is key to preventing dysfunctions and sustaining performance. It was hypothesized that PFHK and dysfunctions in female athletes would differ according to age, education level, marital status, sport type, years of sports participation, and physical activity level. A total of 127 female athletes aged 16-40 years were recruited from various sports disciplines. Pelvic floor health knowledge (Pelvic Floor Health Knowledge Quiz), pelvic floor dysfunctions (Pelvic Floor Distress Inventory-20, PFDI-20), and physical activity levels (International Physical Activity Questionnaire-Short Form) were measured. The Mann-Whitney U test and Spearman correlation were used for statistical analysis. The mean age of participants was 21.1 ± 5.3 years, with 10.2 ± 5.3 years of sports participation. While 91.3% correctly identified the pelvic floor location, awareness of pelvic floor muscle training was limited. Athletes > 20 years and those with bachelor's or postgraduate education had significantly higher pelvic floor health knowledge (p < 0.05). Sports participation (> 10 years) was associated with higher risk/etiology and total scores (p < 0.05). PFDI-20 scores showed no significant correlations with demographic or sport-related variables (p > 0.05). While female athletes identify the pelvic floor's location, their knowledge of its function and treatment remains limited; therefore, integrating targeted education into athletic programs is essential to mitigate dysfunction risks and optimize long-term performance.
The phase 3 NIMBLE trial demonstrated the efficacy of cemdisiran, an siRNA inhibitor of hepatic C5 synthesis, in patients with myasthenia gravis, making it the first complement inhibitor in the disease to employ this novel mechanism of action. These results expand the growing therapeutic landscape that already includes three FDA-approved complement inhibitors for myasthenia gravis.
As the future of the dairy herd, heifers represent a large investment, however compromised claw health poses a significant risk to their productivity and longevity. Issues with mobility can be influenced by foot growth and shape, with corkscrew claw (CC) conformations now reported in heifers. This study aimed to assess claw growth of pre-calving heifers, along with claw shape observations. A convenience sample of 20 pre-conception heifers from a single fully housed dairy herd in the UK milking 2,500 cows were recruited, aged between 249 and 265. They were restrained in a crush and had their feet measured, with the horn marked at the dorsal and lateral heel wall to allow growth and wear measurements to be taken every 90 d. An additional 250 heifers aged between 267 and 437 d old were recruited for visual claw shape observations. All 8 claws of each heifer were scored every 90 d for claw shape following a visual guide based around dorsal and axial wall positions, over a total of 5 visits. In the heifer cohort having their feet measured, the dorsal wall was always longer than the heel wall (mean 67.6mm (SD 9.9mm) compared with 43.7mm (SD 9.2mm) respectively). Length of the claws and rate of growth at both the dorsal and heel positions reduced between visit 4 and 5 when heifers were about to or had already calved and entered the milking herd, with increased wear (0.25mm/ day) and reduced growth (0.13mm/ day). Shape score 1 claws (scissor claw) had longer dorsal walls 68.9mm (95% CI 64.2-73.6mm) than other claw shapes. Although only 10% (2/20) of the heifers developed score 2 corkscrew claw shapes, they did have higher rates of growth (2.1-2.2mm/ 90 d more), and reduced wear (2.2-10.1mm/ 90 d less) compared with shape scores 0 and 1. With regard to observed foot shape, only 24.4% of heifers maintained a score 0 foot shape throughout the whole study period, suggesting more attention should be paid to maintaining an optimal heifer foot shape before them entering the lactating herd. The foot shape of the heifers was dynamic with individual claws able to transition from one shape score to another between visits. The main transitions were from a score 0 to a score 1 scissor claw, with an increase in transitions to score 2 corkscrew claws over time, suggesting a cumulative deterioration in claw shape. Twenty-one heifers transitioned from a score 2 corkscrew claw shape back to a score 1 or 0, suggesting some mild to moderate dorsal wall deviations can rotate back to a more anatomically normal state. Overall, we found that minor changes to dorsal wall alignment of claws (scissor claws) did not necessarily lead to development of corkscrew claw foot shape in heifers, but use of early pregnancy foot inspections before calving, particularly focusing on the medial claws of heifers, may be of benefit in maintaining good claw conformation in pre-calving heifers.
Immediate patient access to cancer-related results through digital portals has transformed the timing and nature of cancer communication. Although open records promote transparency, autonomy and engagement, they may expose patients to complex terminology before clinical interpretation is available. This creates a gap between information access and meaningful understanding, particularly when radiology, pathology or genomic reports contain terms such as "possible malignancy", "suspicious", "progression" or "cannot exclude". This article argues for digital result literacy as an essential component of cancer education. Patients require calibrated support to interpret results safely, avoid panic or false reassurance, and understand who is responsible for next steps. Clinicians also need training to respond when patients have already formed interpretations before consultation. Educational safeguards should include anticipatory guidance, plain-language summaries, safety-netting, named responsibility, equitable non-digital communication routes and preparation for AI-assisted result explanations. Immediate access should therefore become informed access, not isolated access.
Transitional care after a hospital stay remains a challenge in Germany. Despite the legal obligation for structured discharge management that has been in place since 2017, seamless transition to post-acute care is still not consistently available. This scoping review aims to compile available studies on discharge management in Germany, identify key challenges for patients and stakeholders, and present measures that have already been implemented. This scoping review followed the methodology of the Joanna Briggs Institute and the PRISMA-ScR guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). A systematic search was conducted in four bibliographic databases (CareLit, Cochrane Library, MEDLINE via PubMed, Web of Science Core Collection), supplemented by reference screening and hand searching. Using predefined criteria, German-and English-language primary and secondary studies, as well as gray literature from 2015 onwards, were included, focusing on hospitalized patients in Germany and those involved in discharge management. Thirty studies were included. Interventional studies demonstrated limited effectiveness, particularly in preventing hospital readmissions. Non-interventional research identified barriers such as inconsistent implementation, absence of standardized procedures, shortages of resources, and poor communication between care sectors. Structured assessments, standardized discharge summaries, and case managers showed potential to strengthen the continuity of care and improve patient outcomes. Cross-sectoral care in Germany requires stronger interprofessional collaboration, binding standards, and flexible models adaptable to local conditions. Despite useful insights, further research is urgently needed to evaluate, implement, and compare existing strategies and pilot programs.
The loss of intraspecific diversity is a hidden crisis that threatens to disrupt ecological processes and ecosystem services, diminishing economic, subsistence, and cultural benefits to human communities. Conserving this diversity requires a deeper understanding of its evolutionary underpinnings and the ecological conditions necessary for its persistence amid rapid environmental change. Here, we integrate evolutionary principles and empirical evidence from recently developed genetic assays to examine the maintenance of run timing diversity within steelhead (Oncorhynchus mykiss), a widely distributed anadromous salmonid with distinct summer and winter adult migration timings. Using a GREB1L-based genetic assay, we analyzed nearly 2000 juvenile samples from the North Umpqua River, Oregon, USA to map watershed-scale distributions of run timing genotypes alongside climate-driven stream warming patterns. We found that summer-run genotypes dominate only in habitats located above seasonally passable barriers, such as natural waterfalls, that restrict or prevent passage by adult winter-run steelhead. This pattern supports the hypothesis that exclusive access to habitat provides a critical fitness advantage that compensates for the costs associated with summer run timing. Temperature modeling further revealed that habitats currently exclusive to summer-run steelhead are already thermally stressful and are projected to become increasingly so under end-of-century climate scenarios, reducing the quality of critical summer-run steelhead habitat. Because the persistence of summer-run steelhead under climate change depends on access to exclusive habitat of sufficient quality, we propose strategies to establish or maintain habitat exclusivity in more climate-resilient areas within the basin while minimizing impacts on winter-run steelhead and other anadromous species. More broadly, our study demonstrates how understanding the genetic basis of run timing and the fitness trade-offs associated with different life histories can inform the conservation of intraspecific diversity in migratory fish.
Systemic antifungals are frequently prescribed off-label, raising concerns regarding safety, equitable access to health care, and control of health expenditure. The aim of this study was to analyze off-label prescriptions of systemic antifungals in order to update the off-label indications thesaurus and ensure appropriate patient management. Off-label prescriptions of liposomal amphotericin B, voriconazole, isavuconazole, and micafungin reported by healthcare institutions in the Auvergne-Rhône-Alpes (ARA) region as part of prospective monitoring of indications, along with their bibliographic justifications, were analyzed by the Regional Group for the Appropriate Use of Antifungals (GréBA). One hundred eighty-one (n=181) off-label treatment initiations were reported in the ARA region that represents 20.9% (181/868) of systemic antifungal prescriptions. The majority, 66% (n=119), corresponded to a positioning listed in the thesaurus, including a reference from it. In 18% of cases (n=32), the positioning was justified, but the references used were not derived from the thesaurus. The remaining prescriptions concerned insufficiently documented situations, unjustified cases, or indications already covered by an existing marketing authorization. Finally, 1% (n=2) of prescriptions corresponded to a justified positioning including a reference that enabled an update of the thesaurus. The analysis of off-label prescriptions in the ARA region highlights a high rate of bibliographic justification in off-label prescribing. The off-label indications thesaurus was updated based on the analysis of these prescriptions.
Arsenic (As) contamination in riverine sediments within global gold mining regions poses persistent ecological risks due to its easy release into the overlying water especially under anaerobic conditions. To ensure long-term stability of As in the sediment, we developed a composite material consisting of ferrous iron, schwertmannite, and calcium carbonate (FSC) for synergistic As sequestration. It was found that FSC exhibited high adsorption capacities of 107.3 mg/g for As(III) and 116.6 mg/g for As(V). Applying FSC at 3% in the contaminated sediment with total As of 317-4200 mg/kg drastically reduced acetic acid extractable As (aeAs) by 75.2% - 84.7% and maintained long-term structural stability even under flooded conditions since As partitioned toward residual and crystalline Fe-oxide fractions. Synchrotron XAFS reveals two distinct valence-dependent As immobilization pathways. As(V) forms rigid bidentate-edge-sharing (2E) complexes with Fe and exhibits As-Ca coordination as johnbaumite precursors. In contrast, As(III) undergoes Fe(II)-mediated electron transfer and is ultimately sequestered into goethite templates. Corroborating these atomic insights, dynamic flume-scale simulation trial over 720 days confirmed the robustness of the surface layer of the sediment amended with FSC, through which a 96.2% decrease of As concentrations in overlying water was observed. Furthermore, in-situ real application of FSC in the remediation engineering project of the Jiehe River ultimately validated the superior comprehensive performance of this technology with comparison to already-reported materials. This strategy of altering As geochemical fate via anthropogenically regulated iron (oxyhydr)oxide formation offers a theoretical foundation and operable template for the global remediation of metalloid-contaminated sediments.
Primary care is becoming increasingly complex, with primary care physicians (PCPs) facing rising workloads driven by workforce shortages, growing administrative demands, and expanding clinical responsibilities. Recent advances in large language models (LLMs) offer new opportunities to support PCPs across clinical, administrative, and communication-related tasks within their workflows. Understanding how these technologies are perceived and used in primary care practice is, therefore, critical to inform their safe, effective, and human-centered implementation. This study aimed to explore Dutch and US PCPs' perceptions and experiences regarding the use of LLMs in clinical practice, with particular attention to clinical usability, communication and teamwork, and implications for everyday workflows. We conducted a qualitative study using semistructured interviews with 15 PCPs from the United States and the Netherlands. Data were collected between February and June 2025 and analyzed using reflexive inductive thematic analysis. Ten themes emerged related to the use of LLMs in primary care clinical practice, each theme consisting of a set of subthemes. We found that LLMs are being integrated into primary care as both clinical and communication support tools, assisting with diagnostic reasoning, administrative tasks, workload management, and interprofessional and patient communication. While PCPs reported perceived benefits, they also expressed concerns related to safety, efficiency, authenticity, and the preservation of the therapeutic relationship, highlighting the need for careful and context-sensitive use. Our findings suggest that LLMs are already being integrated into primary care in diverse ways, with their value shaped by both contextual factors and clinician judgment. Understanding how clinicians navigate LLM use in everyday practice is essential to ensuring that LLMs support high-quality, patient-centered primary care and inform organizational policy and LLM design.
The European Thoracic Oncology Platform (ETOP) International Breast Cancer Study Group (IBCSG) Partners Foundation initiated a series of workshops for experts to review current evidence and offer recommendations to guide future antibody-drug conjugate (ADC) research. Here, we summarise key findings from the third workshop, which included experts in various solid tumours, basic/translational research scientists and pharmaceutical industry representatives. Recent positive phase III trial data have further incorporated ADCs into the standard of care [e.g. lung: sacituzumab tirumotecan; breast: trastuzumab deruxtecan (T-DXd), sacituzumab govitecan, datopotamab deruxtecan; muscle-invasive bladder cancer: enfortumab vedotin; ovarian cancer: mirvetuximab soravastine; cervical cancer: tisotumab vedotin]. Thus, research priorities must be tailored according to tumour type, potentially focussing initially on settings where ADCs could replace chemotherapy. Many phase III ADC trials have been initiated based on positive phase I data and although these trials are larger than those conducted historically, prespecified criteria (e.g. patient numbers and magnitude of efficacy) should be met to justify proceeding directly to phase III. Importantly, although several ADCs have been successfully developed without mandatory biomarker selection, biomarker-driven ADC development enables rational patient selection, as illustrated by multiple ADCs (e.g. T-DXd, mirvetuximab soravtansine and telisotuzumab vedotin). The identification, development and validation of predictive biomarkers are therefore essential, particularly given several critical nuances, including the algorithms used to assess biomarker status and the type of specimen analysed, all of which may be influenced by temporal and spatial heterogeneity. Additional ADC research priorities include the optimisation of ADC constructs to enhance efficacy/tolerability and the identification of reliable ADC targets, including work to elucidate attributes of already-identified targets. Finally, considering the vast amount of ADC-related data being generated, artificial intelligence could be leveraged to analyse combined datasets and generate composite biomarkers, including tumour histology, optimal target expression thresholds, molecular alterations and activated pathways affecting payload activity and target function, to accelerate research.