Inverse planning is often used for Gamma Knife radiosurgery, allowing clinicians to mathematically specify desired clinical objectives and dose limits. The objectives are controlled by weights that are manually tuned to find the desired trade-off, which varies from case to case. Automation of this process can reduce clinical workload and improve consistency in plan quality. To train a deep reinforcement learning agent using a reward function that incorporates the clinical metrics from past plans into its scoring criteria. The metric trade-off from the clinical plan is scored higher than all others, guiding the agent to produce plans with similar trade-offs. An agent was trained to adjust the two priority weights (i.e., digital slider bars) in the clinical inverse planner. The agent consists of a neural network that receives the metrics and dose distribution of the current plan and the target and organ-at-risk masks as inputs. These methods were demonstrated on a dataset of 204 single-target metastases and a dataset of 71 acoustic neuroma cases. The cases were split into training, validation, and testing sets of size 123/41/40 and 42/14/15 for the metastases and acoustic neuromas, respectively. On the metastases test dataset, the agent achieved a significantly higher (p=0.0136) average plan score (3.925±0.130) compared to the default slider plans (3.874±0.147). On the acoustic neuromas test dataset, the agent achieved a higher (p=0.4493) average plan score (4.035±0.177) compared to the default slider plans (3.995±0.365). The higher plan scores are reflected in the four plan quality metrics: the agent's plans, on average, had metrics more similar to the clinical plans, compared to the default slider plans, for both test datasets. The proposed reward function enabled the agent to learn to find plans that aligned with historical planning decisions. Future work will investigate providing the agent with additional inputs that can explain the variability in planning decisions, which would further improve its performance.

Time-resolved X-ray solution scattering (TR-XSS) enables tracking of protein structural dynamics but can suffer from radiation damage when performed with continuous X-ray beam exposure at multipurpose small-angle X-ray scattering (SAXS) beamlines. Here, we systematically assess how protein concentration, exposure time, X-ray dose and beam focusing influence the stability of adenylate kinase (AdK) during TR-XSS at CoSAXS at the MAX IV Laboratory. Static SAXS measurements from 2.5 to 21 mg ml-1 showed only minor interparticle effects, establishing suitable concentrations for TR-XSS. Under detector-focused conditions, AdK irradiated at room temperature remained stable up to 3.13 kGy, with consistent absolute and difference scattering profiles over 50 ms. In contrast, focusing the beam directly on the sample increased the absorbed dose to 21.3 kGy and produced clear signatures of radiation damage, which included low-q intensity loss and increasing deviation from the low-dose condition. These results identify practical system-specific dose limits and highlight beam focusing as a key determinant of sample integrity. The workflow presented here provides general guidelines for minimizing radiation artifacts in TR-XSS on multipurpose SAXS beamlines.

To evaluate the radiation protection requirements for a UK first specimen PET-CT scanner, the AURA10 (Xeos, Ghent), as assessed through a clinical trial investigating its use for intra-operative surgical margin assessment in urology and head and neck (H&N) tumour removal. A radiation risk assessment was performed to inform radiation protection requirements and training. 0.8 MBq/kg of 18Fluorine fluorodeoxyglucose and 50 MBq of 68Gallium prostate-specific membrane antigen were administered for H&N and urology cases respectively. Whole body optically stimulated luminescence dosimeters, finger and eye ThermoLuminescent dosimeters and electronic personal dosimeters were issued to staff in theatres, recovery, and histopathology. Dose rate measurements were recorded at the position of staff members in theatres. Measured counts and dose rate from the resected specimen and swabs were obtained and contamination monitoring of the room were performed following removal of the patient. Training sessions and dry runs with surgical staff helped identify radiation risks and optimise workflow. Occupational doses from surgeons and scrub nurses were the highest for both modalities. Doses to other theatre staff were below dose limits for members of the public in the UK. Doses to staff outside theatres, including recovery and histopathology, were found to be below threshold values. Low level contamination was present in swabs (< 6kBq and < 250kBq for H&N and urology cases respectively). Thorough staff training, systems of work and shielding are required to ensure radiation doses to staff are minimised and contamination and radioactive waste are contained. There were difficult occasions during shift changes and untrained staff rota-ed in, but nuclear medicine supervision and then the introduction of theatre-based cascade trainers helped solidify learning and provide assurance to theatre staff and staff showed good compliance with the systems of work in place. Annual doses to theatre staff are heavily dependent on workload, with surgeons and scrub nurses closest to the patient receiving whole body doses of 39 µSv and 12 µSv, and finger doses of 88 µSv and 48 µSv respectively per case for H&N. Corresponding urology doses per case were measured as 7.2 µSv and 2.5 µSv for whole body and 16 µSv and below threshold values for the assisting surgeon and scrub nurse respectively. www. gov. URL trail registry record: Study Details | NCT06676943 | Investigating the Diagnostic Performance of High-resolution Specimen PET-CT in Determining Margin Status in Cancer Resection | ClinicalTrials.gov.

Objective.To develop and illustrate the potential of a new, flexible, open-source software engine for task-based optimisation of exposure parameter settings in x-ray projection imaging.Approach.The engine was built from several Python-scripted modules to automate exposure parameter optimization. Input is taken from a set of pre-calculated tables containing image quality and dose data, and system parameters defined by the user. Modular code is employed, with classes responsible for image quality and dose calculations. For this study, the image quality (IQ) module incorporated the standard signal-to-noise ratio (SNR) and a version ofSNR(SNRw) that is weighted for the influence of the x-ray focus size and finite x-ray pulse width on the task. Optimal x-ray factors for a specified task are established by the Optimizer class that maximizes a figure-of-merit defined asSNR2orSNRw2divided by dose. A set of six experiments with different degrees of complexity was performed to illustrate the engine and the influence of x-ray factor selection for a cardiac imaging task.Main results. A full parameter search covering 2400 different combinations of tube potential, additional copper filtration and focal spot size for 11 distinct patient thicknesses took approximately 30 min. The six experiments demonstrated that it is essential to consider x-ray tube power limitations and, when applicable, object motion and dose limits when determining the optimal exposure parameters.Significance. The proposed engine automates optimal exposure parameter selection for user-defined image quality metrics and dose estimates. The influence of x-ray system parameters on system performance can be explored systematically. The engine is provided as an open-source resource with a modular structure that can be extended to include different figures of merit, and different image quality and dose metrics. The repository containing the engine is available athttps://gitlab.kuleuven.be/medphysqa/deploy/flexpose/flexpose.

Pancreatic cancer carries a disproportionate burden of mortality and highlights a need to identify therapies that improve local control and survival outcomes. Radiotherapy is an option for the large proportion of patients who are surgically unresectable but has previously been restricted by surrounding dose-limiting organs. The use of stereotactic body radiotherapy (SBRT) can overcome these limitations and deliver a higher biologically equivalent dose to improve local control. Eighty-seven patients with locally advanced, unresectable and histologically confirmed pancreatic adenocarcinoma treated with SBRT were enrolled. Patients underwent SBRT with endoscopic fiducial seed guidance, with either concurrent chemotherapy or dose-escalated radiotherapy alone. Fractionation regimens ranged from 3 to 5 fractions. With a median follow up of 8 months (range 8-51), the median overall survival was 8 months. The local control in those alive at 1 year was 75%. Five patients had Grade 3 toxicity and 5 had moderate (Grade 2) toxicity, with the remaining patients having mild or no toxicity. There were no Grade 4 or greater toxicities. SBRT potentially bypasses the dose limitations of adjacent organs compared with conventional radiotherapy, allowing for improved local control and shorter treatment times. The additional benefit of manageable toxicities makes this an appealing therapy for patients with unresectable pancreatic cancer.

ABSTRACT Introduction Model-Informed Precision Dosing (MIPD) has improved individualized therapy, but in critical illness its reliance on intermittently updated data creates a temporal mismatch between pharmacokinetic (PK) models and rapidly evolving physiology. Areas covered Synthesizing population pharmacokinetic (popPK) and data science literature, we examine the limitations of snapshot-based dosing, using vancomycin as example. We propose the Dynamic Living Digital Twin (DLDT) framework, which integrates high-frequency electronic health record data into adaptive state-space models such as Kalman filtering. Rather than adding more covariates, the DLDT reframes patient physiology as a continuously evolving latent state that can be updated using temporally dense clinical data. Methodological, infrastructural, and regulatory Software as Medical Device (SaMD) barriers are also evaluated. A non-systematic PubMed search identified relevant publications available up to March 2026. Expert opinion The next advance in precision dosing will come from temporally adaptive PK reasoning. In this paradigm, patient physiology is treated as an evolving latent state, and clinical pharmacists may increasingly interpret exposure trajectories rather than isolated dose recommendations. Although technically feasible, implementation remains constrained by data interoperability and workflow integration challenges. Clinical pharmacists may therefore increasingly act as stewards of dynamic model outputs, using anticipated exposure trajectories to preempt PK shifts.

Occupational radiation exposure and radiation protection practices in interventional radiology and cardiology: A multicenter study in France.

To establish an objective discard framework for lead aprons, defect areas quantified from X-ray fluoroscopy videos were linked to their corresponding dosimetric impacts. A fine-tuned YOLOv8 instance segmentation model, achieving an average precision at an intersection-over-union threshold of 0.5 (AP@0.5) of 0.457, was employed to analyze fluoroscopic videos of 18 aprons with 0.25 mmPb equivalence. The model enabled automated defect detection and area estimation with a video processing time of 15s. Dosimetry experiments mimicking endoscopic retrograde cholangiopancreatography (ERCP) conditions were conducted using an anthropomorphic phantom and apron samples with slit defects of varying widths. The results indicated that the transmitted dose increased linearly with defect area under all tested conditions. Based on weighted least-squares analysis of covariance (WLS-ANCOVA), slit widths of 1.0, 2.0, and 3.5mm were pooled for modeling, as they exhibited similar dosimetric behavior. A linear model was applied to relate defect area to the increase in transmitted dose, defining the discard threshold as the minimum area at which the upper one-sided 95% prediction limit reached a specified dose limit. Given a baseline dose of 2.38 mSv after transmission through the apron without defects and a regulatory dose limit of 5 mSv per 3 months, the discard threshold for slit-like defects was determined to be 2.87 cm2. The proposed framework enables automated and facility-tailorable discard decisions by linking quantified defects to radiation protection objectives using conservative, prediction-based criteria.

The use of fluoroscopy in orthopedic interventional procedures has become increasingly common. Although it offers significant clinical advantages by reducing procedural invasiveness, it also exposes both patients and medical staff to ionizing radiation. This study reports occupational dose measurements for surgeons during 40 proximal femur fracture (PFF) procedures conducted at a reference hospital in Recife, Brazil. The estimated annual effective doses for the leading and auxiliary surgeons were approximately 1.3-1.5 mSv, corresponding to about 7.5% of the annual dose limit (n=325 procedures.yr-1). The estimated annual eye lens exposures for both surgeons ranged from 4.7-5.8 mSv yr⁻¹, approaching 30% the current eye lens dose limit. For these procedures, the glabella (forehead) position was identified as the most appropriate location for the eye lens dosimeter. A correlation between Hp(10) values measured externally on the thyroid shield and Hp(3) doses at the glabella suggests that eye lens dose measurements can serve as a preliminary indicator-within ±15%-for determining the need for dedicated eye lens monitoring when annual lens doses may exceed 15 mSv. Dose measurements to the hands varied according to the procedure type and the equipment used. The highest values were observed during complex surgeries, such as complex subtrochanteric fractures with multiple fragments. The frequency of outliers in the hand dose data, observed in approximately 15% of the procedures, is associated with cases in which at least one of the surgeon's hands was exposed to the primary beam. For the leading surgeon, the doses from outliers to the left hand accounted for 58% of the total dose to that hand, whereas for the auxiliary surgeon, 16% of procedures classified as high outliers contributed 75% of the total dose. These findings emphasize the importance of keeping hands outside the primary beam, as even brief direct exposures can significantly increase occupational hand doses.

Atomic electron tomography (AET) is a powerful technique for determining the three-dimensional atomic structure of matter in real space. However, conventional AET requires numerous projections across a wide angular range. The high dose and prolonged acquisition severely limit its application. Here, we propose an interpretable and universal algorithm for low-dose, fast and tilt-constrained AET: null-space iterative reconstruction (NSIRE), which uses an unsupervised diffusion model to iteratively compute null-space solutions of projection equations, thereby generating tomograms consistent with both projection constraints and atomic potential prior. NSIRE can resolve a wide range of complex materials under 6-12° sparse projection or within ±29° small tilt-range without retraining. Using the NSIRE, we determine the three-dimensional atomic structures of a 4-nm Pt nanoparticle with grain boundaries and a 3-nm PtCo nanoalloy (the smallest one resolved so far), achieving a root-mean-square displacement of <20 pm and high projection consistency, overcoming the scale, dose and time limitations of AET.

Radiological dose assessment of waterborne radon and Monte Carlo-based evaluation of lifetime excess cancer risk in uranium mining regions of South Africa.

American cranberry (Vaccinium macrocarpon) is consumed as juice, fruit, or standardized supplements and is widely promoted for urinary tract health. Evidence suggests cranberry preparations may help prevent urinary tract infections (UTIs), yet pharmacists' knowledge and counseling practices may vary. This study assessed knowledge, attitudes, and practices (KAP) regarding cranberry extract among registered pharmacists in Jordan. A self-administered online questionnaire, developed from the literature and assessed for face/content validity and internal consistency, was distributed to registered pharmacists in Jordan. Knowledge was assessed using 14 true/false/I do not know items, while attitudes and practices were assessed using Likert-type scales. Descriptive analyses were supplemented with bivariate testing, multivariable regression models, correlation analyses, and a comparison of participants who did and did not complete the practice section. A total of 409 responses were analyzed. Participants were predominantly aged < = 35 years (82.6%), resided in central Jordan (89.2%), and worked in community pharmacies (52.6%). Overall knowledge was moderate/neutral (mean 7.65 ± 3.07 out of 14), and 57.9% had low knowledge scores using Bloom's < 60% cut-off. Attitudes were neutral overall (mean 3.21 ± 0.41 out of 5). Among 268 participants who completed the practice section, the mean practice score was 3.14 ± 0.70 out of 5. In multivariable analysis, working in community pharmacy (β = 1.16, 95% CI 0.53 to 1.79; p < 0.001) and using research/books/university sources of information (β = 1.18, 95% CI 0.43 to 1.92; p = 0.002) independently predicted higher knowledge. Among practice-section respondents, higher knowledge (β = 0.05, 95% CI 0.02 to 0.08; p < 0.001) and more positive attitudes (β = 0.44, 95% CI 0.26 to 0.63; p < 0.001) independently predicted safer practice scores. Jordanian pharmacists recognized cranberry's role in UTI prevention, but clinically relevant gaps were identified regarding safety, interactions, dose limits, pregnancy/lactation uncertainty, and appropriate counselling. The inferential analyses suggest that evidence-based information sources and KAP interrelationships are important targets for continuing professional development. Findings should be interpreted cautiously because recruitment was online and the practice section was completed mainly by pharmacists for whom cranberry dispensing was applicable.

Biologics, protein- and peptide-based drugs derived from living organisms or cell lines have emerged as effective therapies across a broad range of indications. However, parenteral administration and the need for frequent dosing increase costs and limit compliance, creating an urgent need for innovative platforms capable of continuously, safely, and efficiently delivering sustained biologics in situ within the host. Here, we describe a bioengineered hookworm platform to manufacture and deliver biologic therapeutics in vivo. As proof of concept, we engineer the Ancylostoma ceylanicum secretome by inserting a human single-chain variable fragment antibody (s16-HuScFv) into its genome. Transgene expression does not perturb surrounding gene expression, and heritable transgenesis is confirmed. The s16-HuScFv transgene product is secreted into host circulation and partially neutralizes tetrodotoxin. Given the availability of controlled human infections, our disease-agnostic bioengineered hookworm platform offers a next-generation approach to address a suite of chronic human diseases, and with a single-dose administration, could potentially produce and deliver biologic medicines within the human host for years.

Stroke is increasingly understood as a systemic disorder rather than a brain-only lesion. Beyond the initial cerebral ischemic insult, rapid autonomic and neuroendocrine stress responses destabilize peripheral organ homeostasis and promote widespread immune and metabolic remodeling. Subsequent barrier failure and peripheral immune dysregulation can generate a sustained "second hit" in which circulating microbial products, damage-associated signals, and inflammatory mediators feedback to amplify neuroinflammation in a blood-brain barrier-vulnerable state. Meanwhile, post-stroke immunity is temporally plastic: inflammatory programs that worsen acute injury can later support resolution and repair, indicating that outcomes depend on immune balance and timing, not simply inflammatory magnitude. Stem cell-derived extracellular vesicles (EVs) are emerging as multi-cargo biologics with consistent preclinical benefit across functional, histological, and inflammatory endpoints. However, clinical translation has progressed slowly, in part because development has largely prioritized strategies to enhance central nervous system delivery even though systemically administered vesicles typically show low exposure in brain parenchyma. Here, we propose a "periphery-first" therapeutic strategy that reframes this pharmacokinetic profile as an advantage. By leveraging the natural sequestration of systemically delivered vesicles by reticuloendothelial and barrier-associated organs-particularly the liver, spleen, and gut-this approach aims to reprogram peripheral immune trajectories, strengthen barrier integrity, and suppress humoral amplification loops that sustain secondary brain injury. We synthesize evidence for stroke-driven multi-organ dysfunction and phase-dependent immune remodeling and integrate mechanistic plausibility for EVs acting through complementary routes: peripheral immune and metabolic rebalancing, actions at the blood-brain barrier interface and limited but potentially meaningful effects within central nervous system immune niches. We also summarize the emerging clinical landscape of EV interventions in stroke and highlight key translational constraints, including product heterogeneity and potency-linked quality control, comorbidity-relevant modeling aligned with systemic pathology, dosing and safety limitations imposed by hepatic clearance, and the need for artifact-resistant biodistribution methods and causal necessity/sufficiency study designs to quantify route-to-efficacy. A periphery-first framework positions EV therapy as a systems-level intervention that targets peripheral drivers of secondary brain injury. Establishing quantitative causal mechanisms and translation-ready manufacturing and dosing principles will be essential to accelerate clinical development beyond a primarily brain-delivery paradigm.

Aerosolized adenoviral IL4/IL10 delivery alleviates LPS-induced acute lung injury.

Reproductive toxicity of Fructus Psoraleae in zebrafish: material basis and implications for clinical safety dosing.

BackgroundWhile transforaminal full-endoscopic spine surgery (TF-FESS) under local anesthesia offers the advantages of real-time neurological feedback and minimized physiological stress, concerns persist regarding whether the procedure can be consistently completed within safe local anesthetic dosage limits in all patient populations. This study evaluated the feasibility and safety of TF-FESS under local anesthesia independent of frailty status using body weight-based safety thresholds for lidocaine.MethodsWe retrospectively identified 108 patients who underwent single-level TF-FESS under local anesthesia and categorized them into a non-frail group (modified Frailty Index-5 [mFI-5] < 2, n = 80) and a frail group (mFI-5 ≥ 2, n = 28). Weight-based thresholds, calculated using actual body weight, were set at 7 mg/kg for non-frail patients and 5 mg/kg for frail patients. The anesthesia protocol consisted of sequential 1% lidocaine injection and conscious sedation. Complications were defined as clinically significant local anesthetic systemic toxicity, postoperative delirium, and permanent nerve root injury, with exclusion of transient intraoperative feedback.ResultsSurgery was successfully completed under local anesthesia in all 108 cases (100%), with continuous verbal communication maintained throughout the procedure. The mean lidocaine dose was 218 ± 40 mg, with no significant difference between groups (p = 0.722). In the frail group, 92.9% of patients remained within the stricter 5 mg/kg threshold. No documented cases of clinically significant local anesthetic systemic toxicity, permanent nerve root injury, or postoperative delirium were observed in either group.ConclusionsTF-FESS under local anesthesia appears feasible, with no clinically significant complications observed in this cohort, irrespective of frailty status. Although the dosing thresholds were well-tolerated, they should be interpreted with caution given the study’s retrospective nature. Adherence to weight-based dosing and a standardized conscious sedation protocol is associated with a favorable safety profile while preserving real-time neurological feedback. This strategy may minimize perioperative physiological stress and cognitive risks in an increasingly aging population.

Post-liver transplant (LT) weight gain and metabolic dysfunction predispose to cardiovascular (CV) morbidity, allograft steatosis, and reduced long-term survival. Glucagon-like peptide-1 receptor agonists (GLP-1 RA) promote weight loss and improve cardiometabolic health, yet evidence in liver transplant recipients (LTR) is limited. We aimed to evaluate the safety, tolerability, and efficacy of GLP-1 RAs in post-LT weight management. We performed a multicenter retrospective cohort study of adult LTRs treated with GLP-1 RAs across four international centers (January 1, 2010-June 30, 2025). Regular GLP-1 RA users were compared with matched non-users by age, sex, obesity and diabetes status, transplant year, and center. Primary outcome was change in body weight 1-year post-exposure. Secondary outcomes included glycemic and lipid profiles, kidney and allograft function, immunosuppression effects, major adverse cardiovascular events (MACE), and adverse effects. Longitudinal analyses used linear mixed models with multiple imputation. Among 104 GLP-1 RA users, 68.3% initiated therapy for diabetes; subcutaneous semaglutide was most used at a median dose of 0.82±0.46mg weekly. Treatment led to significant reductions in body weight (-3.8kg; -3.9%, p<0.001), body mass index (BMI) (-1.6kg/m2; -5.0%, p<0.001), and glycated hemoglobin (HbA1c) (-0.48%, p=0.002), with modest lipid improvement. Liver function tests and immunosuppression trough levels remained stable, and no treatment-limiting adverse events occurred. In matched analyses (80 GLP-1 RA users vs. 116 non-users), GLP-1 RAs facilitated greater weight loss (-3.4kg difference, p=0.009) and HbA1c reduction (-0.43% difference in HbA1c, p=0.042) without increased risk of allograft dysfunction, T-cell-mediated rejection (TCMR) or MACE. This multicenter, international study demonstrates GLP-1 RAs are safe and moderately effective in reducing weight and improving metabolic parameters post-LT, without adverse effects on allograft function or immunosuppression, despite limitations of low dosing. Prospective, randomized trials of GLP-1 RAs in LTRs are thus warranted.

Classification of harmful radiation-induced effects on human health for radiological protection purposes: history and concepts.

Optimal radiotherapy dose scheduling with variable fraction sizes and breaks via sequential mixed-integer convex programming