Treatment decisions for lower-grade gliomas (WHO grades 2-3) rest on trial averages, which lack temporal resolution. We applied Causal Analysis of Survival Trajectories (CAST), a causal-machine-learning method that builds treatment-effect trajectories from horizon-specific estimates, to 776 adults from The Cancer Genome Atlas (TCGA, n = 512) and the Chinese Glioma Genome Atlas (CGGA, n = 264) across six radiotherapy and alkylating-chemotherapy scenarios on overall (OS) and progression-free survival (PFS). Elastic-net propensity scores with overlap weighting (target: average treatment effect on the overlap population, ATO) balanced age, sex, grade, IDH, 1p/19q, and extent of resection. Chemotherapy showed adjusted survival-probability gains peaking at 0.34 (95% CI -0.32 to 1.00) at 84 months (TCGA OS) and 0.48 (0.04 to 0.92) at 108 months (CGGA OS); E-values of 5.1-27.6 indicate robustness to unmeasured confounding. Radiotherapy estimates were mixed (E-values 1.1-5.1) and are reported as adjusted associations sensitive to residual confounding from missing extent-of-resection and performance-status data, not as evidence of treatment-induced effect. Age drove most heterogeneity (46-52% of splits); refutation tests supported the chemotherapy findings.

Within the ultraviolet C (UVC) spectrum, the wavelengths in the 200-235 nm range, here named far-UVC, have been shown to effectively inactivate a variety of pathogens. Because of their limited penetration in biological materials, far-UVC wavelengths are anticipated to be minimally damaging to human skin and eyes. The germicidal efficacy of these wavelengths combined with a predicted low health hazard for humans suggests that far-UVC sources could operate continuously in indoor locations to reduce the risk of transmission of airborne diseases among occupants. While it is well-established that exposure to far-UVC light is minimally damaging to skin, concerns remain on the safety of exposed eyes. Scientific bodies overseeing UV radiation protection recommend eye safety limits based on published peer-reviewed data. To support this goal, our previous work used a 3D model of the human cornea to assess the wavelength dependence of corneal damage induced by UVC radiation; unlike relatively longer wavelengths, far-UVC wavelengths induced DNA dimers only in the uppermost layers of the corneal epithelium. Here, similar eye safety studies were extended to excised human corneas. The depth of DNA photodamage into the corneal epithelium was evaluated after exposure of the anterior surface to 50 mJ/cm2 or 100 mJ/cm2 from 222 nm or 254 nm light.

Radiochromic films are a reliable tool for quantifying ultraviolet exposure dose. When used without modification, these films enable a simple, low-cost measurement of accumulated dose over time which is amenable to personal exposure monitoring. This study presents two methods to expand the utility of these films for dosimetry applications. One approach utilized an ultraviolet radiation attenuator to effectively extend the usable dose range of radiochromic films. The attenuators have the added advantage of obscuring the film from view so the color change of the film due to increasing exposure dose is not visible. The practical use of these films with attenuators over prolonged exposure periods is highlighted as a case study in this manuscript. A second modification is the addition of a structure to limit the dose received by the film to an 80° field of view. Limiting the field of view of the film dosemeter provides for an estimate of the dose received by the eyes, accounting for protection provided by the ocular cavity, and the use of a dosemeter with a restricted field of view is included in recommendations for commissioning of ultraviolet lighting installations. Radiochromic films, when used in conjunction with these tools, offer an effective solution for extended dose ranges and eye-specific ultraviolet dose measurement in indoor spaces utilizing germicidal ultraviolet technologies.

Lower-grade gliomas (World Health Organization [WHO] grades 2-3) exhibit variable treatment responses, yet clinical decisions remain guided by population-level trial results. Standard causal survival forests estimate treatment effects at individual time horizons but lack methodology to synthesize these into interpretable temporal trajectories. Here, we apply the Causal Analysis of Survival Trajectories (CAST) framework, a recently developed extension of causal survival forests that synthesizes horizon-specific causal effect estimates into smooth temporal curves while accounting for between-horizon covariances via bootstrap estimation and Ledoit-Wolf shrinkage. We apply CAST to estimate time-varying, heterogeneous effects of radiotherapy and chemotherapy in 776 patients with lower-grade gliomas from The Cancer Genome Atlas (TCGA; n=512) and the Chinese Glioma Genome Atlas (CGGA; n=264), analyzing six treatment-outcome scenarios and adjusting for age, sex, WHO grade, isocitrate dehydrogenase (IDH) mutation status, 1p/19q codeletion, and extent of resection using elastic net propensity scores with overlap weighting. CAST curves reveal that chemotherapy provides consistent, sustained benefits across both cohorts; survival probability gains peak at 0.31 at 72-84 months for TCGA overall survival and 0.46 at 48 months for progression-free survival, with restricted mean survival time gains of 18.4 and 32.5 months at 10 years, respectively. CGGA chemotherapy shows delayed but large positive effects (survival probability peak 0.48 at 108 months). Radiotherapy effects are mixed, with modest E-values indicating sensitivity to residual confounding by indication. Subgroup CAST curves identify age at diagnosis as the dominant driver of treatment effect heterogeneity (46-56% of splits). All findings are robust to placebo permutation, simulated unobserved confounder, and negative control refutation tests. The CAST framework provides a general-purpose tool for temporal treatment effect visualization applicable beyond neuro-oncology. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement There was no outside funding for this project. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The TCGA lower-grade glioma and glioblastoma datasets are publicly available through the Genomic Data Commons (GDC) Data Portal (https://portal.gdc.cancer.gov/). The CGGA dataset is publicly available through the Chinese Glioma Genome Atlas website (http://www.cgga.org.cn/). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The TCGA lower-grade glioma and glioblastoma datasets are publicly available through the Genomic Data Commons (GDC) Data Portal (https://portal.gdc.cancer.gov/). The CGGA dataset is publicly available through the Chinese Glioma Genome Atlas website (http://www.cgga.org.cn/).

The anti-microbial capacity of far-ultraviolet C (UVC) light (200-235 nm) has been shown for a variety of pathogens. There is evidence that far-UVC has limited ability to damage human skin and eyes; therefore, far-UVC fixtures could be used to continuously disinfect occupied indoor spaces and be a practical intervention for pandemic control. Our group has previously shown that 222 nm inactivated aerosolized viruses as well as drug-resistant bacteria when exposed on agar surfaces or in aerosol. This work extends those studies and presents novel findings from a series of experiments conducted over the past five years, all aimed at probing different aspects of the antimicrobial effectiveness of far-UVC light. Specifically, the study (1) describes the susceptibility of human coronavirus OC43 (HCoV OC43) exposed on a plastic surface to different sources of far-UVC; (2) describes the survival of clinical bacterial isolates exposed to 222 nm on agar surfaces; (3) evaluates a suitable surrogate of human viruses exposed to 222 nm in aerosol; (4) compares the inactivation of HCoV OC43 exposed to 222 nm on surfaces, aerosol, or in aqueous solution. By integrating complementary observations, the results contribute further evidence supporting the effectiveness of far-UVC against pathogens exposed under different laboratory conditions.

Reducing airborne disease transmission is a public health goal. Far‐UVC light, defined as 200–235 nm, is a promising technology to inactivate viruses within occupied spaces. This work examines state of the art far‐UVC emitting LEDs, with a center emission wavelength of 233 nm, for virus inactivation efficacy and for DNA damage to skin models. The LEDs were used to expose an aerosolized surrogate of SARS‐CoV2, the human coronavirus OC43, and survival results estimated a susceptibility constant of k 233‐aerosol = 4.0 ± 0.2 cm 2 /mJ, which corresponds to a D 90 of 0.58 mJ/cm 2 . HCoV‐OC43 was also exposed after drying on a plastic or glass surface, and inactivation results estimated susceptibility values of k 1_233‐plastic = 6.7 ± 3.8 cm 2 /mJ and k 1_233‐glass = 7.2 ± 3.0 cm 2 /mJ which were not significantly different. For safety evaluation, human skin biopsies exposed to 100 mJ/cm 2 from the 233 nm LEDs indicated only 8% of the epidermal cells were positive for DNA damage, whereas the same dose from a 254 nm lamp showed damage in 45% of epidermal cells. A radiant exposure of 100 mJ/cm 2 from the 233 nm LEDs did not produce DNA double strand breaks within the skin biopsies. These tests for the safety and efficacy of a 233 nm far‐UVC LED system provide support for the continued development of far‐UVC LED sources.

Due to a limited penetration into skin and eyes combined with a broad germicidal effectiveness, far‐UVC light (200–235 nm) has been proposed as an effective intervention for airborne pandemic control. Specifically, 222 nm light is not predicted to damage skin because it is primarily absorbed by the proteins in the superficial stratum corneum of the epidermis. Thus, it is hypothesized that the thickness of the stratum corneum is one of the most significant contributing factors to the risk of skin damage from exposure to far‐UVC. From measurements of the stratum corneum thickness in live human skin biopsies, it was found that none of the donor demographics studied had an impact on the thickness of the stratum corneum. While multiple studies suggest that exposure to 222 nm is minimally damaging to skin, a few studies to date have investigated effects as a function of skin characteristics (e.g., individual's age and sex). In selected tissues, the induction of DNA damage following an acute exposure to 100 or 500 mJ/cm 2 from 222 nm light was analyzed as a function of donor demographics. The results agree with previous studies using other models of human skin and show that in human skin biopsies, 222 nm induces minor DNA damage only at high doses, especially in skin with low melanin content (phototype).

The application of 222 nm light from KrCl excimer lamps (GUV222 or Far-UVC) is a promising approach to reduce the indoor transmission of airborne pathogens, including the SARS-CoV-2 virus. GUV222 inactivates airborne pathogens and is believed to be relatively safe for human skin and eye exposure. However, UV light initiates photochemical reactions which may negatively impact indoor air quality. We conducted a series of experiments to assess the formation of ozone (O3), and resulting formation of secondary organic aerosols (SOA), induced by commercial far-UVC devices in an office environment (small conference room) with an air exchange rate of 1.3 h-1. We studied scenarios with a single far-UVC lamp, corresponding to the manufacturer’s recommendations for disinfection of a space that size, and with four far-UVC lamps, to test conditions of greater far-UVC fluence. The single lamp did not significantly impact O3 or fine particulate matter levels in the room. Consistent with previous studies in the literature, the higher far-UVC fluences lead to increases in O3 of 5 to 10 ppb above background, and minor increases in particulate matter (16% ± 10 % increase in particle number count). The use of far-UVC at minimum intensities required for disinfection, and in conjunction with adequate ventilation rates (e.g. ANSI/ASHRAE recommendations), may allow the reduction of airborne pathogen levels while minimizing the formation of air pollutants in furnished indoor environments.

BACKGROUND:Methods for cleaning the air can play an important role in decreasing the airborne transmission of diseases. The implementation of far-ultraviolet C (UVC) fixtures emitting at 222 nm is a promising engineering control to directly inactivate airborne microbes within an occupied space. AIM:To examine the efficacy of a far-UVC installation in a large dental clinic containing 24 treatment chairs. METHODS:Air samples were collected using two different methods and the number of culturable bacteria was determined for conditions with the lamps on and lamps off. FINDINGS:The estimated reduction using results pooled from both air sampling methods was 39.5% (95% confidence interval: 19%, 60%). Given the 10 air changes per hour from the ventilation system, the operation of far-UVC lighting provided 6.5 additional air changes per hour for the dental clinic. CONCLUSION:These results show the efficacy of far-UVC lighting for the inactivation of airborne bacteria. Far-UVC lighting is a promising intervention technology for preventing disease transmission in a clinic.

Causal machine learning (CML) enables individualized estimation of treatment effects, offering critical advantages over traditional correlation-based methods. However, existing approaches for medical survival data with censoring such as causal survival forests estimate effects at fixed time points, limiting their ability to capture dynamic changes over time. We introduce Causal Analysis for Survival Trajectories (CAST), a novel framework that models treatment effects as continuous functions of time following treatment. By combining parametric and non-parametric methods, CAST overcomes the limitations of discrete time-point analysis to estimate continuous effect trajectories. Using the RADCURE dataset [1] of 2,651 patients with head and neck squamous cell carcinoma (HNSCC) as a clinically relevant example, CAST models how chemotherapy and radiotherapy effects evolve over time at the population and individual levels. By capturing the temporal dynamics of treatment response, CAST reveals how treatment effects rise, peak, and decline over the follow-up period, helping clinicians determine when and for whom treatment benefits are maximized. This framework advances the application of CML to personalized care in HNSCC and other life-threatening medical conditions. Source code/data available at: https://github.com/CAST-FW/HNSCC

Objective. The FLASH effect has gained significant attention in radiobiology and radiation oncology due to its potential to improve therapeutic outcomes by delivering ultra-high dose-rate (UHDR) irradiations. Understanding UHDR biological mechanisms can also contribute to the development of biodosimetry and radiological medical countermeasures. However, achieving stable and reproducible high-current UHDR electron beams has been reported to be challenging with modified clinical linear accelerator (Linac) systems, and has not been systematically studied. Approach. We investigated how key standing-wave linear accelerator parameters, including electron gun current, pulse-forming network voltage, and auto-frequency control, affect the stability of electron beam intensity on a modified Varian Clinac 2100 C. We also developed a parameter-tuning method to adjust beam intensity and improve beam stability. Main results. This approach enabled (1) fine-tuning of dose-per-pulse without modifying the physical setup and (2) reduction of beam fluctuations, particularly during cold starts. These improvements enhanced both pulse-by-pulse stability and trial-by-trial reproducibility. The resulting stability was validated through multiple biological experiments. Significance. This work offers practical guidance for improving UHDR beam stability and reproducibility, as well as enabling intensity tuning in modified clinical linear accelerators. It can support the development of more reliable preclinical FLASH irradiators, thereby contributing to the advancement of FLASH research.

Scientific bodies overseeing UV radiation protection recommend safety limits for exposure to ultraviolet radiation in the workplace based on published peer-reviewed data. To support this goal, a 3D model of the human cornea was used to assess the wavelength dependence of corneal damage induced by UV-C radiation. In the first set of experiments the models were exposed with or without simulated tears; at each wavelength (215–255 nm) cells with DNA dimers and their distribution within the epithelium were measured. Simulated tears reduced the fraction of damaged cells to an extent dependent on the wavelength and tissue layer. Subsequent experiments were performed with models exposed without simulated tears; yields of DNA-damaged cells and their distribution within the corneal epithelium were evaluated at each wavelength, together with other markers of cell and tissue integrity. Unlike relatively longer wavelengths, the range of wavelengths commonly referred to as far-UV-C (215–235 nm) only induced dimers in the uppermost layers of the epithelium and did not result in lasting damage or halt proliferation of the germinative cells. These results provide evidence for the recommended exposure limits for far-UV-C wavelengths, which have been proposed as a practical technology to reduce the risk of transmission of airborne diseases in occupied locations.

Chronic wounds are a major healthcare issue affecting more than 10 million Americans each year, with a 5‐year survival similar to cancer and costing the healthcare system billions of dollars annually. Current solutions, such as antiseptics and antibiotics, can be toxic to cells or contribute to the development of antibiotic‐resistant strains of bacteria. Exposure to germicidal ultraviolet radiation (GUV) at 254 nm has been reported as an effective method for chronic wound management. However, concerns about the health hazards from exposure to 254 nm radiation have limited its use for wound management applications. In contrast, wavelengths of ultraviolet radiation in the range of 200–235 nm have exhibited similar germicidal ability but with a lower penetration range in tissue, potentially making those wavelengths better suited for chronic wound disinfection. In this study, a novel phototherapy device emitting principally at 234 nm was used to assess the killing efficacy against Methicillin‐resistant Staphylococcus aureus (MRSA) . Potential health hazards from exposure using the device were evaluated using a 3D human skin model. The ultraviolet exposure device tested in this study shows promise for effective decontamination of chronic nonhealing wounds without associated health hazards.

The Centers for Medical Countermeasures against Radiation Consortium (CMCRC) has provided a strong research foundation for the radiobiology science that will follow. After 20 years, however, the CMCRC will continue to conduct research on preparedness in niche areas of radiobiology and advanced product development, many of which were initiated by the CMCRC. This manuscript offers a review of past and current strategies and advancements in medical countermeasures to address radiation injuries, carried out by the CMCRC and funded by the National Institute of Allergy and Infectious Diseases Radiation and Nuclear Countermeasures Program. It also explores the mechanisms of radiation-induced injuries, discusses existing medical countermeasures, and highlights emerging technologies and potential future directions for radiobiology researchers. This review aims to enhance our understanding of current medical countermeasures against radiation and contribute to the future development of more efficient and innovative approaches to mitigate and treat radiation-induced damage.

Purpose: We aimed to analyze the effects of age on human tear film (TF) using a novel nanometer resolution TF imaging device (Tear Film Imager, TFI, AdOM, Israel). Methods: 44 healthy adult subjects (≥18 years of age) without ocular or systemic diseases or prior eye treatments with ages spanning seven decades were enrolled in this prospective cross-sectional study. Subjects underwent a comprehensive ophthalmic examination and completed the Ocular Surface Disease Index questionnaire (OSDI). All study participants underwent TF imaging using the TFI, including assessment of muco-aqueous layer thickness (MALT), lipid-layer thickness (LLT), inter-blink interval, and lipid map uniformity. Associations between TFI parameters and age were tested using linear regression (accounting for multiple eyes). Results: A total of 80 eyes (44 subjects) were imaged: 19 eyes from 10 subjects in the 3rd decade of life (aged 20–29); 10 eyes from 5 subjects in the 4th decade of life (aged 30–39); 5 eyes from 3 subjects in the 5th decade of life (40–49); 12 eyes from 7 subjects in the 6th decade of life (50–59), 19 eyes from 11 subjects in the 7th decade of life (60–69); 11 eyes from 6 subjects in the 8th decade of life (70–79); and 4 eyes from 2 subjects in the 9th decade of life (80–89). With increasing age, MALT significantly decreased (p = 0.024), and LLT significantly increased (p = 0.001). No statistically significant linear age effects were found for the other TFI parameters (p > 0.05) or the OSDI scores of study participants of different ages (p = 0.786). Conclusions: Quantitative TF biomarkers varied significantly with advancing age in healthy individuals, highlighting the importance of accounting for age in TF assessments.

The SKH-1 mouse model is commonly used to assess the effects of ultraviolet light exposure on skin using visual and biological endpoints. Although skin bi-fold thickness is a well-established quantitative measure of edema, evidence characterizing its use to evaluate skin responses in the UVC range remains limited. This study evaluated skin bi-fold thickness measurements made using a digital caliper. Hairless SKH-1 mice were exposed using the narrow bandwidth output from a monochromator with wavelengths from 200 to 270 nm. Post-exposure thickness measurements were normalized against pre-exposure thickness measurements to determine the fold change. These findings were compared with qualitative visual assessments of changes to the skin. The results indicate that quantitative measures of increases in skin thickness are correlated with subjective visual scoring measures. The observed magnitude of the bi-fold change following UVC exposures was limited in this study because exposures were at doses close to the threshold dose for causing a visually observed change to the skin. The results support using skin bi-fold measurements for quantifying skin responses to ultraviolet light exposure.

This study employed state-of-the-art machine learning to evaluate the mortality effects of alpha-emitting radionuclides (241Am, 249Cf, 252Cf, 238Pu, 239Pu, 224Ra, 226Ra, 228Th) on 2,576 dogs, factoring in radioactivity levels, composition, administration method (injection or inhalation), and age at exposure. There were 972 cancer deaths, 599 non-cancer deaths, 789 deaths from many diseases (involving several diagnoses, including both cancer and non-cancer pathologies), and 216 deaths with uncertain causes. A Random Survival Forest model for overall mortality achieved concordance scores of 0.763 and 0.745 on training and testing data subsets, respectively. A model variant with competing risks was used to investigate mortality trends over time for different disease categories. It achieved concordances of 0.814 for cancer, 0.652 for non-cancer, and 0.778 for many diseases on training data, and 0.817 for cancer, 0.651 for non-cancer, and 0.780 for many diseases on testing data. All radionuclides exhibited radiation responses for cancer, with 226Ra and 239Pu showing the strongest effects. Some responses were non-linear, with indications of saturation or downturn at high treatment quantities. For non-cancer diseases, radiation responses were generally weaker and more variable. For the many diseases endpoint, 238Pu and 239Pu demonstrated the strongest response patterns, with 239Pu exhibiting greater lethality via inhalation compared to injection.. Using a Causal Forest model, which is designed to detect causal relationships rather than just associations, we investigated the causal impact of radioactivity on dog mortality, accounting for other variables. We found a significant (p < 2 × 10-16) negative average causal effect of -1,375 days per log10 radioactivity unit on survival time. This study improves current knowledge of cancer and non-cancer mortality patterns from densely-ionizing radiation in mammals by using machine learning to analyze combined historical data on dogs exposed to different radionuclides, modeling multiple variables, nonlinear dependencies, and causal relationships.

In the event of a large-scale radiological emergency, delivering timely medical aid to individuals receiving potentially lethal doses of radiation will result in improved survival and decreased severity of injuries. While it may be possible to reconstruct a dose estimate based on a location during the event and/or early symptoms presenting after the event, limitations with readily available information and inaccuracy of that estimate may not provide enough certainty for successful medical triage. Thus, individual biodosimetry assessments would assist medical professionals in providing prompt care to those who would benefit the most. In this study, a variety of accessible biospecimens (blood, plasma, serum, feces, saliva, and urine) from eight rhesus macaques irradiated with a single total body sublethal dose of 4 Gy of 60Co γ rays were collected before and up to 60 days after exposure for distribution to 10 different investigators' work sites for site-specific analyses. Results showing statistically significant changes in hematology parameters as well as gene, protein, and metabolite expression have since been published. Here, these results are combined and integrated with new data from microRNA (miRNA) expression in plasma samples as well as 16S rRNA sequencing and metabolomics data from fecal samples. A total of 40 unique miRNAs were significantly expressed on days 3, 6, 30, or 60. Metabolomic analysis of fecal samples found changes in multiple pathways, including steroid hormones, C18 (sex) hormones, and bile acid synthesis. Temporal changes were found in the gut microbiome for microbial abundance and richness. Finally, a retrospective view of the collective results demonstrated common overlapping pathways that were enriched from significantly altered biomarkers. This large, collaborative study from a single irradiated cohort demonstrates the utility of multiple timepoints, biospecimen types, and omics technologies that collectively identified 61 common biomarkers across 4 omics platforms that were enriched for pathways relevant to an acute radiation injury to the hematopoietic system that may aid future radiation biodosimetry efforts.