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Photochemistry and Photobiology

○ Wiley

Preprints posted in the last 30 days, ranked by how well they match Photochemistry and Photobiology's content profile, based on 10 papers previously published here. The average preprint has a 0.01% match score for this journal, so anything above that is already an above-average fit.

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10-Nitro-oleic acid improves survival following gamma irradiation and modulates hematopoietic and intestinal responses

Pereckova, J.; Vichova, R.; Toufar, J.; Chrenko, D.; Pospisil, J.; Perecko, T.

2026-10-01 pharmacology and toxicology 10.64898/2026.09.25.754470 medRxiv
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Acute radiation syndrome remains a major consequence of high-dose ionizing radiation exposure, and effective pharmacological countermeasures are limited. Nitro-fatty acids possess anti-inflammatory and cytoprotective properties, suggesting potential effectiveness in radiation injury. Here, we investigated the radioprotective effects of 10-nitro-oleic acid (10-NO2OA) in mouse models of total body irradiation (TBI). C57BL/6 mice were exposed to either sublethal (4 Gy) or LD50-level (7.5 Gy) gamma irradiation and treated with 10-NO2OA according to pre-irradiation, post-irradiation, or combined treatment regimens. Survival, hematological responses, bone marrow cells (BMCs)/colony-forming units (CFU), plasma granulocyte colony-stimulating factor (G-CSF), NRF2-responsive signaling, and intestinal responses were evaluated. Administration of 10-NO2OA before and after irradiation significantly improved 30-day survival following 7.5 Gy TBI (57% vs. 20% in vehicle-treated controls). In contrast, post-irradiation treatment alone was ineffective, whereas pre-irradiation treatment alone produced a non-significant trend toward improved survival. The protective effect was absent in BALB/c mice, indicating strain dependence. Although 10-NO2OA did not prevent long-term radiation-induced cytopenia, it increased neutrophil and platelet counts, elevated plasma G-CSF levels shortly after irradiation, and transiently enhanced BMC counts. In irradiated BMCs, 10-NO2OA activated NRF2-responsive gene expression in vitro and in vivo. Exploratory intestinal analyses revealed improved macroscopic appearance and partial restoration of irradiation-suppressed cytokine and growth factor production. In conclusion, 10-NO2OA improves survival following LD50-level gamma irradiation and is associated with modulation of hematopoietic, cytoprotective, and intestinal responses. These findings identify 10-NO2OA as a promising candidate radioprotective agent and support a multifactorial mechanism of action.

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Cross-validation of wearable light loggers across electric and natural light conditions: focus on illuminance, melanopic EDI, and CCT

Pilehchi-Ha, P.; Stefani, O.; Schweiker, M.; de Kort, Y.; Smolders, K.; Harmsen, J.-F.

2026-10-07 occupational and environmental health 10.64898/2026.10.06.26364836 medRxiv
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Wearable light loggers are increasingly used to assess light exposure in everyday environments in studies of circadian physiology and sleep, yet their accuracy under diverse lighting conditions remains insufficiently understood. This study evaluated three commonly used wearable light loggers (ActLumus, Lido and OcuWEAR) by comparing measurements of photopic illuminance, melanopic equivalent daylight illuminance (m-EDI), and correlated colour temperature (CCT) against a reference spectroradiometer under controlled laboratory conditions and in the field. Measurements were conducted across fluorescent, incandescent, and multiple LED sources, as well as under dynamic daylight exposure. Device performance depended strongly on both light source characteristics and metric type. Illuminance exhibited lower variability, whereas m-EDI and CCT showed substantial device- and condition-specific biases, particularly under spectrally atypical illumination conditions. These differences were consistent with spectral mismatch effects arising from standard photometric calibration practices. Importantly, the impact of measurement bias varied by exposure context: under dim light conditions, small absolute deviations led to substantial misclassification relative to currently recommended thresholds, whereas brighter electric light and daylight conditions were more robust. These findings highlight that device- and context-dependent biases can influence the interpretation of light exposure in circadian and sleep research, underscoring the need for careful device selection and data interpretation.

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Radiance-Invariance Evaluation of a Compact LED-Based Source for Imager Radiance Transfer

Ruiz, A. J.; Robledo, E. A.; Littler, E. A.

2026-09-28 bioengineering 10.64898/2026.09.27.754831 medRxiv
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Significance: Fluorescence imaging remains largely qualitative and device-specific, limiting reproducibility and intersystem comparisons. SI-traceable radiometric characterization requires calibrated sources suitable for transferring known radiance to imaging systems. Aim: Establish and evaluate a compact, calibrated solid-state radiometric emitter target (RET) for SI-traceable radiance transfer, and assess methods for evaluating radiance invariance, imager responsivity, and extension of radiance transfer to digitally defined regions of interest (ROIs). Approach: The radiance invariance of an LED-based RET was evaluated by measuring its radiance across varying source-to-aperture distances and collection apertures. A previously described radiance-transfer formalism based on calibrated source radiance and collection geometry was implemented to determine imager responsivity (R{lambda}), which was evaluated across varying working distances and lens apertures. Grubbs and MAD outlier tests and one-way ANOVA were used to assess radiance and responsivity invariance. Finally, responsivity obtained using digitally defined ROIs was compared with matched physical apertures to assess ROI-based radiance transfer. Results: The measured RET radiance remained invariant across the tested source-to-aperture distances and collection apertures, with no significant differences observed across distance (p = 0.88) or aperture (p = 0.15). Imager responsivity remained stable across working distances for both tested lens configurations (p = 0.48 and p > 0.99). Responsivity was also invariant across lens apertures, except for deviations at f/11 that were consistent with practical aperture tolerances. Digitally defined ROIs reproduced responsivity values obtained using matched physical apertures, demonstrating that the radiance-transfer approach can be extended to image-defined regions. Conclusions: The presented methods provide an approach for evaluating compact LED-based sources for invariant-radiance emission and suitability for SI-traceable radiance transfer. The characterized RET supported stable imager responsivity across changes in imaging geometry and extension to digitally defined ROIs. These methods can be adapted to other LED-based sources, with further angular characterization and uncertainty analysis needed to establish broader applicability.

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Inhalation exposure to methamphetamine in contaminated residences

Dennison, J.

2026-10-13 occupational and environmental health 10.64898/2026.10.02.26364615 medRxiv
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Current health risk assessments from thirdhand exposure to methamphetamine (meth) to occupants of contaminated residences when no cooking or use is still occurring assume that inhalation exposure is insignificant. After Wright et al. (2021) reported substantial meth concentrations in a contaminated residence, the present study was conducted to further test the hypothesis that concentrations were high enough to contribute to total occupant dose. Air sampling was conducted in contaminated residences that had been previously sampled for surface contamination. Samples were collected on personal sampling pumps in fixed locations on treated glass fiber filters is cassettes and analyzed by gas or liquid chromatography with mass spectroscopy. Sixty-nine samples were collected from eighteen residences for the study. Meth concentrations ranged from 0.02 to 15 ug/m3. Concentrations in supply air vents were significantly higher than in return vents or in ambient air. Residences with no HVAC systems (baseboard heat) had airborne concentrations similar to residences with HVAC systems turned off, and lower than when HVAC was on. Whether a residence was occupied or not did not show differences. All data from residences with HVAC had a significant correlation with surface concentrations (R2 = 0.61) but some factors that affected results were not determined in the study. In the context of the risk assessment and regulatory standard established by California and adopted in several other states, the inhalation exposure would approximately double total occupant dose for infants, and this population would exceed the California reference dose by approximately 100%. Further studies should be conducted to refine these estimates and determine the factors that influence airborne concentrations.

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Coumarin-based blue excitable probe for functional screening of dehalogenase activity

Mion, S.; Mallet, M.; Louis, Y.; Fontanay, S.; Ruaudel, F.; Bastian, F.; Jacolot, M.; Popowycz, F.; Oger, P. M.

2026-10-05 biochemistry 10.64898/2026.10.02.756220 medRxiv
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In the enzymatic toolbox of depollution, hydrolytic dehalogenases are of particular interest for the bioremediation of organohalogenated compounds. To better identify and characterize these enzymes, it is important to develop appropriate sensing methods. Fluorescent probes for dehalogenase detection have been developed in the past years, however, to this date none were available for application using the common FITC parameters (i.e. excitation laser at 488 nm). To address this limitation, we herein report a new fluorescent probe, COU4-Cl, excitable in the violet (405 nm) and blue (488 nm) wavelengths adapted for the detection and characterization of haloalkane dehalogenases. Its applicability is discussed and evaluated in comparison to the previously described COU2-Cl probe only excitable in the violet (405 nm). This study shows the advantages and complementarity of the two probes, and further demonstrate their application for the discrimination of dehalogenase activity in whole cell assays.

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In-Situ Disinfection of Hospital Privacy Curtains Using a Next-Generation Aerosolized Hydrogen Peroxide System

Navas, C. D.; Hawkins, B.; Lazarus, C.; Kulstad, E.; Warye, K.

2026-10-21 infectious diseases 10.64898/2026.10.21.26365806 medRxiv
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Background: Privacy curtains represent a uniquely difficult infection control surface because they are frequently touched by patients, visitors, and healthcare workers, yet are difficult to disinfect using routine environmental cleaning protocols. We sought to quantify the performance of a novel automated aerosolized hydrogen peroxide system against pathogens on privacy curtains. Methods: This study was performed in an enclosed office space ({approx} 65 m^3), approximating a patient exam room. Four Bacillus atrophaeus (ATCC 9372) biological indicators (BIs) were affixed to a standard polyester privacy curtain. A single one-minute fogging phase was followed by a ten-minute contact/aeration phase (total = 11 min). Four corresponding chemical indicators measured peak airborne aerosolized hydrogen peroxide concentration, and two control BIs were placed outside of the room. Results: All four BIs demonstrated complete inactivation (no growth after seven-day incubation), representing [≥] 4-log10 spore reduction. Peak dosages reached 42 ppm nearest the aerosolized hydrogen peroxide jet outlet, with the lowest value at the near point on the back side of the curtain reaching 27 ppm (exceeding the target dosage of 25 ppm). Control exposures failed to achieve sterilization. Conclusions: A next-generation aerosolized hydrogen peroxide dry-fogging disinfection system achieved full inactivation of resistant spores on both sides of privacy curtains within a short 11-minute automated cycle.

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Intra-Patient Comparison of a Minimally Invasive Lid Treatment and Traditional Blepharoplasty: Patient and Surgeon-Reported Outcomes

Victoria, A. C.; Roth, R. E.; Berkowitz, M. N.; Jindal, S.; Buehler, P.

2026-10-06 ophthalmology 10.64898/2026.10.02.26364300 medRxiv
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Abstract Purpose: To use a minimally invasive lid treatment (MILT) utilizing Compressive Skin Contouring (CoCo) technology to compare patient- and surgeon-reported ecchymosis, edema, and incision appearance following MILT and traditional upper eyelid blepharoplasty (tBULB). Methods: Prospective, single-surgeon intra-patient study comparing MILT and tBULB in patients seen for bilateral blepharoplasty. Patients and the operating surgeon rated MILT and tBULB outcomes post-operatively on the day of surgery (T1) and at 2 months (T2) using surveys. Patient photographs taken 3 and 9 days post-operatively were blindly assessed by 3 independent surgeons to compare ecchymosis, edema, and incision appearance on the MILT and tBULB sides. Results: Seven patients participated in the study. At T1, 6/7 patients reported [&le;] ecchymosis and edema, and all patients reported better or equivalent incision appearance on the MILT side compared to the tBULB side. At T2, 6/7 of patients reported [&le;] edema; 4/7 reported < ecchymosis and better incision appearance on the MILT side. The surgeon reported < ecchymosis and [&le;] edema for 7/7 patients and better or equivalent incision appearance for 6/7 patients at T1; [&le;] ecchymosis and better or equivalent incision appearance for 7/7 and [&le;] edema for 6/7 patients at T2 on the MILT side. In the blinded evaluation, mean ecchymosis scores were lower, edema scores were lower or equivalent, and incision appearance was better for MILT vs. tBULB at days 3 and 9. Conclusions: In this intra-patient study, MILT outcomes compared favorably with tBULB, especially for ecchymosis and edema; two important aesthetic measures of patient perception.

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Night-break photoperiod timing shapes growth trajectories, functional phenotype, and biomass partitioning in Cannabis sativa L. in a genotype-dependent manner

Rodriguez-Roncancio, M. P.; Castillo-Hernandez, L. C.; Love, N.; Melgarejo, L. M.; Sarmiento, F.

2026-09-30 plant biology 10.64898/2026.09.29.755452 medRxiv
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Cannabis sativa L. cultivation in tropical regions or under indoor conditions requires supplemental lighting to maintain plant yields. Night-break (NB) photoperiods offer a cost-effective alternative to conventional day extension, although genotypic responses have not been clearly described. This study evaluated the effects of continuous and pulsed NB treatments on the growth, phenology, physiology, productivity, and cannabinoid accumulation of three Cannabis sativa genotypes representing two chemotypes. Plants were exposed to a commercial 18-h photoperiod (T1), a continuous 1-h NB (T2), or four 15-min NB pulses (T3) with equal total duration. Continuous NB produced responses comparable to the commercial photoperiod. In contrast, pulsed NB accelerated phenological progression by two to three weeks and reduced final plant height by 15-28%, depending on genotype, without impairing photosynthetic performance or decreasing floral dry biomass. Harvest index increased under both NB treatments, indicating enhanced biomass allocation to reproductive structures, while cannabinoid accumulation remained primarily genotype-dependent with only minor treatment-specific modulation. These findings demonstrate that NB efficacy depends not only on the duration of nocturnal light but also on its temporal distribution, highlighting temporal organization of nocturnal light as a key regulator of photoperiodic responses and a promising strategy for optimizing cannabis cultivation.

9
Pyrrolocytosine as a Fluorescent Sensor of RNA-Small Molecule Interactions

Coulson, T. L.; Valdez, G. A.; Widom, J. R.

2026-09-30 biophysics 10.64898/2026.09.29.755477 medRxiv
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Fluorescent base analogues have proven to be valuable probes of RNA structure. Pyrrolocytosine (pC), an analogue of cytosine, exhibits highly environment-sensitive fluorescence within RNA and is strongly quenched in hydrogen-bonded contexts. In this work, we incorporated pC into the aptamer domain of the B. subtilis guanine riboswitch to determine if this quenching mechanism could allow for sensing of RNA-small molecule interactions. We utilized complementary fluorescence spectroscopy methods to under-stand the functional impacts and ligand-sensitivity of pC substitutions distal to and within the binding pocket. We found that pC substitution within a static structural region exhibits the expected ligand-independent fluorescence properties. When placed in the ligand binding pocket, pC exhibits a moderately decreased affinity for the ligands guanine (G) and hypoxanthine (Hx) while maintaining high specificity for G. We found that pC behaves as a turn-off sensor, with distinct changes in fluorescence upon G or Hx binding. These differences are dependent on the number of hydrogen bonds formed with pC and are resolvable in both time-dependent and steady-state fluorescence measurements. Our results show that pC can be used to study RNA-small molecule interactions and can discriminate between similar ligands even when they have identical binding modes.

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Volatile Metabolic Signatures Reveal Early Pulmonary Responses to PFAS Exposure

Agorsor, P.-I.; Lin, T.-C.; Huang, Y.-W.; Eze, M. O.

2026-09-24 biochemistry 10.64898/2026.09.23.753921 medRxiv
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Inhalation of airborne per- and polyfluoroalkyl substances (PFAS) represents an important yet understudied exposure route. While volatile organic compounds (VOCs) have been widely explored as biomarkers of toxicant exposure, their potential for early detection of PFAS-induced pulmonary toxicity remains largely unexplored. This study investigated VOC profiles in human alveolar (A549) and bronchial (BEAS-2B) epithelial cells following exposure to environmentally relevant PFAS concentrations (1, 5, and 10 ppb) for 12, 24, and 48 h. VOCs were analyzed using headspace solid-phase microextraction coupled with gas chromatography-Orbitrap mass spectrometry. We observed significant concentration- and time-dependent alterations in VOC profiles in both cell models. The principal VOCs associated with PFAS exposure include butanal, acetone, 2-butanone, 2-nonanone, (E)-2-nonenal, (E)-2-octenal, (E)-2-heptenal, 2,4-heptadienal, 2,4-nonadienal, 2,4-decadienal, 1-pentanol, and 1-hexanol. Cell type-specific regulations were observed, reflecting differential metabolic responses between transformed and non-transformed lung epithelial cells. Metabolite set enrichment analysis indicated perturbations in ketone body metabolism, consistent with altered cellular energy metabolism. Complementary qPCR analysis revealed altered expressions of CYP1A1, CYP2E1, ALDH1A1, and ALDH2, supporting a mechanistic link between PFAS exposure and oxidative stress, lipid peroxidation, and impaired aldehyde detoxification. These findings demonstrate that VOC profiling, combined with transcriptional analysis, can reveal PFAS-induced metabolic perturbations in pulmonary epithelial cells.

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AMMPER-2: A spatially explicit agent-based model of microbial radiobiology with redox dye simulation

Palacios, D.; Lee, J.; Sharma, P.; Marous, M.; Mejia, D.; Liddell, L.; Gentry, D.; Santa Maria, S.

2026-10-10 microbiology 10.64898/2026.10.08.757403 medRxiv
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To reduce health risks for human space exploration, it is important to model the effects of deep-space radiation on biological systems. The budding yeast Saccharomyces cerevisiae is a common model organism in space radiobiology, but little is known about how radiation damage to individual cells translates into the population-level effects that experiments measure. The Agent-Based Model for Microbial Populations Exposed to Radiation (AMMPER) is a spatially explicit agent-based model that simulates the effects of ionizing radiation on S. cerevisiae cells and produces population-level results. Its goal is to improve experiment design and data interpretation. AMMPER-1 demonstrated that agent-based simulations can qualitatively reproduce the effects of proton radiation on the growth rate of wild-type and DNA-repair mutant yeast. Here, we present AMMPER-2, which addresses limitations of the first model and expands its capabilities. AMMPER-2 incorporates the dynamics of the redox dye alamarBlue, a data type commonly generated in spaceflight microbiology experiments, and models the fate of reactive oxygen species in more detail. It also adds an improved graphical interface and runs faster. AMMPER-2 remains easy to execute in Python on a standard personal laptop, providing space biologists a tool to explore experimental conditions, generate hypotheses, and interpret data from microbial space radiation experiments.

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User-friendly software for high-throughput processing of chlorophyll fluorescence images to assess plant stress responses: fvfmPy and fvfmR packages

Garen, J. C.; Arnold, P. A.; Crous, K. Y.

2026-10-09 plant biology 10.64898/2026.10.06.757212 medRxiv
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Chlorophyll fluorescence imaging is a powerful tool used to characterize abiotic and biotic stress response of photosynthesis in plants. However, extracting metrics such as Fv/Fm (maximum quantum yield of photosystem II) from chlorophyll fluorescence images remains a substantial bottleneck in large measurement campaigns, often requiring significant manual effort. To resolve this issue, we developed fvfmPy, a user-friendly program which enables rapid analysis of chlorophyll fluorescence images of arrays of leaf discs. fvfmPy uses algorithmic image segmentation to identify regions of interest and extract fluorescence metrics from tens or hundreds of leaf samples per image with little to no manual input. fvfmPy is developed in Python and includes a graphical user interface enabling intuitive parameter adjustment and real-time quality control checking. We additionally developed fvfmR, an R wrapper package for fvfmPy. Fv/Fm values extracted with fvfmPy were indistinguishable from those obtained using manual methods (r2 > 0.99) but required 94% less time to complete (13 s vs. 200 s per 100 measurements). fvfmPy and fvfmR were built to directly integrate with existing fluorescence software packages and can greatly increase throughput of fluorescence measurements to help address key challenges in agriculture and ecology.

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A Single Suprachoroidal Injection of AXT107 (Gersizangitide), a Multimodal, Long-Acting Integrin-Disrupting Peptide, in Patients with Neovascular Age-Related Macular Degeneration: Results of the Phase 1/2a DISCOVER Trial

Pandey, N. B.; Mirando, A. C.; Almeida, D. R. P.; Dang, S.; Lally, D. R.; Bridges, W. Z.; Campochiaro, P. A.; Popel, A. S.; Green, J. J.

2026-09-24 ophthalmology 10.64898/2026.09.19.26363031 medRxiv
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Purpose To evaluate the safety, tolerability, and preliminary bioactivity of a single suprachoroidal injection of AXT107 (Gersizangitide), a multimodal integrin-disrupting peptide that acts on both the VEGFA pathway and angiopoietin-Tie2 pathway, in eyes with neovascular age-related macular degeneration (nAMD). Design Phase 1/2a, open-label, dose-escalation clinical trial. Participants Fifteen subjects with active nAMD, including 11 treatment-experienced partial responders to intravitreal anti-vascular endothelial growth factor (VEGF) therapy and 4 treatment-naive subjects; 14 eyes met the protocol-specified baseline imaging criterion and were included in efficacy analyses. Methods Study eyes received a single suprachoroidal injection of AXT107 microparticles at doses of 0.125, 0.25, or 0.5 mg and were followed for 40 weeks. Protocol-specified rescue intravitreal anti-VEGF treatment was permitted from week 12 based on protocol-specified best-corrected visual acuity (BCVA) or central subfield thickness (CST) criteria; anti-VEGF treatment before Week 12 was investigator-initiated. Primary outcomes were ocular and systemic safety through week 40; secondary outcomes included change in CST, change in BCVA, and time to first protocol-specified rescue injection. Main Outcome Measures Incidence of ocular and systemic adverse events, intraocular pressure (IOP), CST, BCVA, and time to first protocol-specified rescue injection. Results Twenty subjects were screened and 15 enrolled across 4 U.S. sites; 3 eyes received 0.125 mg, 3 received 0.25 mg, and 9 received 0.5 mg of AXT107. No serious adverse events related to AXT107 occurred, and no cases of endophthalmitis, retinal detachment, suprachoroidal hemorrhage, or clinically significant intraocular inflammation were observed through week 40. No clinically meaningful intraocular pressure (IOP) elevations occurred at any dose, and no subject required chronic IOP-lowering therapy. Among the 14 eligible eyes included in efficacy analyses, 2 eyes (01-04 and 01-05) completed 40 weeks without protocol-specified anti-VEGF rescue, and 1 eye (02-04) first received protocol-specified rescue at week 36. At the last on-treatment visit, BCVA changes ranged from +15 to -31 ETDRS letters; 3 eyes gained[&ge;]5 letters, 3 gained[&ge;]10 letters, and 1 gained[&ge;]15 letters. Among the 14 eligible eyes, anatomical improvements in CST were observed in at least 1 eye in each dose cohort. The most durable responses were seen in treatment-experienced eyes receiving 0.5 mg (median durability of 36 weeks), whereas treatment-naive 0.5-mg eyes showed more variable courses and generally earlier protocol-specified rescue in this small cohort. Conclusions In this first-in-human study, a single suprachoroidal injection of AXT107 up to 0.5 mg was well tolerated through Week 40, with no drug-related serious adverse events, no clinically significant intraocular inflammation, and no sustained IOP elevations. After a single suprachoroidal AXT107 injection, 2 eyes completed 40 weeks without protocol-specified rescue anti-VEGF treatment, and 1 additional eye received its first protocol-specified rescue treatment at Week 36. The exploratory observation that durability appeared greatest in treatment-experienced eyes supports further controlled study of AXT107, particularly in treatment-experienced nAMD populations.

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Beyond the Index: Association of AI-CO Central Image Area with Central Visual Field Damage in Glaucoma

KORA, Y.; Kora, H.; Kora, T.

2026-10-21 ophthalmology 10.64898/2026.10.18.26365818 medRxiv
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Purpose: To evaluate the associations of the numerical AI-CO center index and visually classified central dark-area extent with Humphrey 10-2 mean deviation (MD). Methods: This single-center retrospective study included 320 eyes of 169 patients with AI-CO imaging, broad-field 24-2F or 30-2 testing, and 10-2 testing. Both visual field examinations were performed within 365 days before or after AI-CO imaging. Two ophthalmologists independently classified central dark-area extent into five Levels (0-4). Analyses assessed Spearman correlations, areas under the receiver operating characteristic curve (AUCs), distributions across final central dark-area Levels, and interrater reliability. Patient-cluster bootstrap confidence intervals and a one-eye-per-patient sensitivity analysis addressed inclusion of both eyes. Results: AI-CO center correlated with 10-2 MD (rho=0.829; 95% CI, 0.773-0.873). AUCs for 10-2 MD below -2, -6, and -12 dB were 0.902, 0.939, and 0.961, respectively. The numbers of eyes in Levels 0-4 were 66, 57, 94, 53, and 50; median 10-2 MD values were -0.59, -1.48, -3.54, -6.24, and -18.15 dB, respectively. Quadratic-weighted kappa was 0.970 (95% CI, 0.958-0.981). Sensitivity analyses yielded broadly similar findings. Conclusions: The numerical AI-CO center index and visually classified central dark-area extent were associated with central visual field damage. Assessing the extent of dark regions in the central image alongside the numerical index may provide useful information for interpreting central visual field status from the AI-CO display.

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Clonogenic survival and relative biological effectiveness of pancreatic ductal adenocarcinoma under pristine and spread-out Bragg peak irradiation with protons and carbon ions.

Denbeigh, J. M.; Kneringer, A.; Radstake, W. E.; Parisi, A.; Barna, S.; Hartzell, S.; Kerschbaum-Gruber, S.; Dias, A. B.; Fischer, P.; Fuchs, H.; Slade, D. M.; Georg, D.; Beltran, C. J.

2026-10-01 cancer biology 10.64898/2026.09.30.754978 medRxiv
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Biological effectiveness in ion therapy varies with radiation quality and biological context, yet cancer cell response data acquired under well-characterized physical conditions remain limited. We investigated clonogenic survival and relative biological effectiveness (RBE) in PANC-1 and BxPC-3 pancreatic ductal adenocarcinoma (PDAC) cells irradiated at four positions along pristine 180.1 MeV proton and 352.4 MeV/u carbon ion Bragg curves, with 4 cm spread-out Bragg peak (SOBP) irradiation included as a clinically relevant comparison. Cell plane positioning and dose were verified in a water-tank system using an Advanced Markus ionization chamber, and Monte Carlo simulations using TOPAS provided dose-averaged linear energy transfer (LETD) and microdosimetric quantities. RBE was calculated relative to 200 kVp X-rays using the linear-quadratic survival model. Across the sampled pristine beam positions, spanning LETD values of approximately 1-9 keV/m for protons and 12-163 keV/m for carbon ions, RBE increased with LETD. Proton RBE10 exceeded the conventional clinical value of 1.1 at distal positions, whereas carbon ion RBE10 increased from 2.3 to 5.2 in PANC-1 and from 1.3 to 3.7 in BxPC-3, with larger differences between cell lines observed near the Bragg peak. SOBP measurements showed different biological responses across field conditions despite comparable LETD. These physically characterized survival data provide PDAC-relevant benchmarks for evaluating whether RBE models reproduce biological responses across pristine and SOBP irradiation conditions, supporting the future integration of radiation-quality-dependent effects into ion planning.

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Hiporfin (HpD) for fluorescence-guided resection of recurrent glioblastoma: diagnostic accuracy and feasibility of an integrated photodynamic strategy

He, Z.; Zhang, G.; Wang, C.; Wu, L.; Hu, W.; Duan, H.; Chen, Y.; Lu, J.; Yuan, Z.; Zhang, X.; Mou, Y.

2026-10-09 surgery 10.64898/2026.10.07.26364687 medRxiv
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Background. Hematoporphyrin derivative (HpD, Hiporfin) is used for photodynamic therapy (PDT) of solid tumors but had never been evaluated for fluorescence guided resection (FGR) in glioma. We assessed Hiporfin fluorescence accuracy against histopathology in recurrent glioblastoma (rGBM) and the feasibility of adding cavity PDT to FGR. Methods. In this prospective single arm series, adults with rGBM received a single preoperative intravenous Hiporfin dose of 5 mg/kg before FGR under blue light excitation and 630 nm cavity PDT. Intraoperative fluorescence assessment was the index test and histopathology the reference standard. Specimen level diagnostic accuracy was pooled with bivariate random-effects modeling. Results. Of 63 specimens, 35 were true positive, 7 false positive, 8 false negative and 13 true negative. Pooled sensitivity was 0.751 (95% confidence interval 0.600 to 0.858) and specificity 0.606 (0.407 to 0.775); the crude positive predictive value was 0.833 (0.694 to 0.917) and the negative predictive value 0.619 (0.409 to 0.792). All seven false positive specimens were peritumoral tissue and the eight false negatives were non fluorescent tumor. FGR combined with cavity PDT was completed in all six patients without new neurological deficits. Conclusions. Hiporfin fluorescence identified rGBM with moderate accuracy: fluorescent regions were likely tumor, while non fluorescent tissue often still contained tumor. The main source of error was peritumoral tissue of the treated cavity, and not the drug or the optics. Hiporfin is a new fluorescence agent for glioma. One drug provides both fluorescence guidance during resection and immediate cavity PDT.

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Four-State Hemodynamic Framework for Neovascular Age-Related Macular Degeneration: Mathematical Model Integrating Vascular Permeability, Lesion Transmural Pressure, Choroidal Excess Pressure, and Wall Stability

Yanagi, Y.; Inoda, S.; Azuma, K.; Takahashi, H.; Inoue, T.; Mayumura-Inoue, M.; Kadonosono, K.

2026-10-07 ophthalmology 10.64898/2026.10.05.26364815 medRxiv
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Abstract Purpose To apply a mathematical model integrating vascular permeability, lesion transmural pressure, choroidal excess pressure, and wall stability to incomplete fluid response and massive submacular hemorrhage in neovascular age-related macular degeneration. Methods Permeability was calculated from aqueous vascular endothelial growth factor (VEGF). Windkessel gave usual lesion pressure from choriocapillaris pressure and high inflow from an arterial-level puncture pressure used as a working value. Choroidal excess pressure was calculated from choroidal thickness and a pachy index as increased outflow resistance. Exudative change used a revised Starling equation scaled to early central-retinal-thickness reduction, with 40-m threshold. A relative rupture-hazard index was calculated from Laplace wall stress and wall stability. VEGF, pressures, and that reduction were from the literature. Pressure was isolated from permeability and choroidal excess. Results In the model, raising lesion pressure from choroidal-excess lesion pressure to high inflow increased untreated exudative change from 150 to 760 m. Residual under saturation was 64 m as a lower-end reference (Monte Carlo 69 - 286 m; median, 170) and 90 m with high-hazard choroidal excess; both above 40 m. Reducing choroidal thickness in the thickened choroidal-excess state added 13 - 14 m, smaller than that residual. Lowering lesion pressure from high inflow to usual lesion pressure (21 to 10 mmHg) reduced the index to 0.64 of the high-hazard reference, and to 0.34 with wall stabilization. Conclusion Lesion transmural pressure due to high inflow left residual exudation even after permeability suppression with anti-VEGF. Fluid resolution on optical coherence tomography may not parallel a reduction in the rupture-hazard index, depending on wall stability.

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Interpretable Automated Detection and Measurement of Dome-Shaped Macula on Optical Coherence Tomography

Yang, F.; Zhou, Y.; Zhang, B.; Yang, J.; Du, L.; Yu, C.; Chen, X.; Zhu, J.; Wang, Y.; He, X.

2026-09-29 ophthalmology 10.64898/2026.09.28.26356190 medRxiv
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Purpose: To develop an interpretable automated pipeline for dome-shaped macula (DSM) detection and measurement from optical coherence tomography (OCT) B-scans. Methods: We analyzed one eye from each of 300 children aged 4-18 years in the Shanghai Child and Adolescent Large-scale Eye Study High Myopia (SCALE-HM) cohort (50 DSM-positive; 100 test eyes). A U-Net pretrained on OCTA-500 and fine-tuned on the development set segmented the retinal pigment epithelium (RPE) boundary. A geometric module located the apex, fitted a tangent-line baseline, and computed perpendicular height in physical coordinates. An eye was DSM-positive if any gradable B-scan had height >= 50 um. Two masked graders evaluated the test set; a third adjudicated disagreements. Results: The area under the receiver operating characteristic curve was 0.927 (95% confidence interval [CI], 0.850-0.986), sensitivity was 82.1% (95% CI, 64.4%-92.1%), and specificity was 100% (95% CI, 94.9%-100%) against the adjudicated reference. In concordant-positive eyes, automated height agreed with manual measurements (intraclass correlation coefficient, 0.949; mean absolute error, 6.9 um; bias, -5.7 um, versus Doctor A). Mean RPE-boundary error on pediatric test scans was 1.54 um. Conclusions: The pipeline may be considered a reliable and reproducible tool for automated DSM detection and height measurement on radial OCT, with each value traceable to landmarks on the source B-scan. External validation across populations, devices, and acquisition protocols is needed. Translational Relevance: The pipeline provides an objective and reproducible method to detect DSM and quantify dome height, width, and orientation across OCT meridians. Because each measurement can be verified on the source B-scan, it enables standardized DSM assessment.

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Normative Temperature, Demographic Categories, and the Limits of Infrared Thermometry

Lohier, A.; Campbell, A. G.; Chartash, D.

2026-10-21 health informatics 10.64898/2026.10.19.26365925 medRxiv
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Objective. Temperature readings are routinely stratified by race and ethnicity, though significant group differences may reflect physiology, instrument noise, or categorization rather than biology. This study tests whether these categories partition facial infrared thermography measurements beyond individual variation and baseline device noise. Approach. A secondary analysis of thermography data (n = 951 adults) compares inner-canthus maximum (TCEmax) and full-face maximum (Tmax) temperatures across five administrative categories via one-way analysis of variance (ANOVA), mixed-effects modeling, Bland-Altman analysis against oral reference, and Monte Carlo sensitivity analysis. Main results. ANOVA returns significant group differences (p < 0.001; eta-squared = 0.04 for TCEmax, 0.03 for Tmax), but the total spread (0.2 to 0.3 degrees Celsius) is comparable to device accuracy and within-subject variability. Individual variation accounts for 95% of TCEmax variance, and adding simulated Gaussian noise to participant-level temperatures (sigma = 0.10 to 0.30 degrees Celsius) preserves the complete group-mean rank order in as few as 37.5% of iterations. Significance. Testing whether a group difference survives perturbation at the scale of instrument accuracy offers a check against treating significance alone as evidence of physiology. Here, observed group differences are small relative to measurement variability, and their physiological interpretation remains uncertain, with implications for clinical tools that treat administrative categories as biologically meaningful.

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Cytotoxic Effects of Multiple Pesticides and their Mixtures on Caco-2 Cells Evaluated by Using MTT and Trypan Blue Assays

Truzzi, F.; Tibaldi, E.; Dilloo, S.; Noferini, R.; Sgargi, D.; Panzacchi, S.; D'Amen, E.; Gnudi, F.; Dinelli, G.; Scheepers, P. T. J.; Mandrioli, D.

2026-09-29 pharmacology and toxicology 10.64898/2026.09.23.753704 medRxiv
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BACKGROUND: Pesticides are extensively used in agriculture, raising concerns about their potential impact on human health through dietary and environmental exposure. OBJECTIVES: This study evaluated the in vitro cytotoxicity of ten commonly used pesticides and their mixtures (lambda-cyhalothrin, cypermethrin, deltamethrin, tebuconazole, glyphosate, acetamiprid, cyprodinil, piperonyl butoxide, fluopyram, and imazalil) on human intestinal Caco-2 cells. METHODS: Cytotoxicity was assessed using the MTT assay, as a measure of metabolic activity, and the trypan blue exclusion test, as an indicator of cell membrane integrity. FINDINGS: Results showed that high concentrations (100 mg/L) of all pesticides significantly reduced cell viability and vitality. Notably, glyphosate and tebuconazole exhibited significant toxicity even at lower concentrations, respectively 0.1 mg/L and 10 mg/L. Combination treatments (Top 3 and Top 8 pesticide mixtures) retained the cytotoxic effects observed for individual compounds, showing additive (non-synergistic) effects. CONCLUSIONS: Overall, these findings indicate that certain pesticides-based herbicides can exert cytotoxic effects on intestinal cells even at relatively low concentrations and highlight the importance of using the component-based approach in mixture risk assessment for humans. This study was performed as part of the EU SPRINT (Sustainable Plant Protection Transition: A Global Health Approach) project.