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Recurrence of glioblastoma (GBM) mostly occurs in close vicinity to the resection cavity. Therefore, our group has previously designed an implant to locally apply repetitive photodynamic therapy to mitigate tumor recurrence. The penetration depths of different wavelengths in brain tissue were exhaustively studied before. However, the PDT-induced biological effects of 5-ALA-based PDT against GBM cells at different depths have not been evaluated yet. Therefore, a synthetic brain substitute material of 1-10 mm thickness and with optical properties comparable to the white or gray matter of pig brain was developed. Tumor cell viability was assessed in spheroids from six GBM cell lines using disks of varying thickness prepared from pig brain substitute material to mimic in vivo radiation attenuation. Using an artificial brain tissue optical model based on material science, we have established a relationship between the PDT-induced effect of our PDT implant and the distance of migrating GBM cells from the resection cavity wall. This model may be helpful to aid optimization of the irradiation doses and fractionation required to attain the maximal therapeutic effect by long-term PDT applications.

Wearable inertial measurement units (IMUs) provide a cost-effective approach to assessing human movement in clinical and everyday environments. However, developing the associated classification models for robust assessment of physiotherapeutic exercise and gait analysis requires large, diverse datasets that are costly and time-consuming to collect. We present a multimodal dataset of physiotherapeutic and gait-related exercises, including correct and clinically relevant variants, recorded from 19 healthy subjects using synchronized IMUs and optical marker-based motion capture (MoCap). It contains data from nine IMUs and 68 markers tracking full-body kinematics. Four markers per IMU allow direct comparison between IMU- and MoCap-derived orientations. We additionally provide processed IMU orientations aligned to common segment coordinate systems, subject-specific OpenSim models, inverse kinematics outputs, and visualization tools for IMU-derived orientations. The dataset is fully annotated with movement quality ratings and timestamped segmentations. It supports various machine learning tasks such as exercise evaluation, gait classification, temporal segmentation, and biomechanical parameter estimation. Code for postprocessing, alignment, inverse kinematics, and technical validation is provided to promote reproducibility.

This paper presents the basis for LoGlo PDT, a new treatment for glioblastoma. Glioblastoma is currently treated with maximal safe resection, temozolomide, and ionizing irradiation. Mortality in 2024 remains over 80% within several years from diagnosis. Oral 5-aminolevulinic acid (5-ALA) is an FDA/EMA approved drug that is selectively taken up by malignant cells, including by glioblastoma. In photodynamic treatment of glioblastoma, intense intraoperative light causes glioblastoma tissue that has taken up 5-ALA to generate cytotoxic reactive oxygen species. The requirement for intense light flux has restricted photodynamic treatment to a single one-hour intraoperative session. We analyze here published data showing that external light, illuminating the entire intact scalp, can attain low μW/cm2 flux several cm into intact brain that would be sufficient to mediate 5-ALA photodynamic treatment of glioblastoma if the light and 5-ALA are delivered continuously over 24 h. At the core of LoGlo PDT regimen is the dataset showing that, for a given fluence, as the duration of PDT light delivery goes down, light intensity (flux) delivered must go up to achieve the same glioblastoma cell cytotoxicity as would a weaker light (lower flux) delivered over a longer time. Thus, a repetitive, noninvasive PDT of glioblastoma using an external light source may be possible. We analyze 5-ALA cellular physiology to show that three non-oncology drugs, ciprofloxacin, deferiprone, and telmisartan, can be repurposed to increase light energy capture after 5-ALA, thereby increasing photodynamic treatment’s glioblastoma cell cytotoxicity. The LoGlo PDT approach uses both drug augmentation and prolonged ultra-low noninvasive transcranial light delivery for a repetitive, noninvasive 5-ALA photodynamic treatment of glioblastoma.

The CAALA (Complex Augmentation of ALA) regimen was developed with the goal of redressing some of the weaknesses of 5-aminolevulinic acid (5-ALA) use in glioblastoma treatment as it now stands. 5-ALA is approved for use prior to glioblastoma surgery to better demarcate tumor from brain tissue. 5-ALA is also used in intraoperative photodynamic treatment of glioblastoma by virtue of uptake of 5-ALA and its preferential conversion to protoporphyrin IX in glioblastoma cells. Protoporphyrin IX becomes cytotoxic after exposure to 410 nm or 635 nm light. CAALA uses four currently-marketed drugs—the antibiotic ciprofloxacin, the iron chelator deferiprone, the antimetabolite 5-FU, and the xanthine oxidase inhibitor febuxostat—that all have evidence of ability to both increase 5-ALA mediated intraoperative glioblastoma demarcation and photodynamic cytotoxicity of in situ glioblastoma cells. Data from testing the full CAALA on living minipigs xenotransplanted with human glioblastoma cells will determine safety and potential for benefit in advancing CAALA to a clinical trial.

The purpose of this study was to assess in vitro whether the biological effects of 5-aminolevulinic acid (5-ALA)-based photodynamic therapy are enhanced by inhibition of the anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL in different glioblastoma models. Pre-clinical testing of a microcontroller-based device emitting light of 405 nm wavelength in combination with exposure to 5-ALA (PDT) and the Bcl-2/Bcl-xL inhibitor ABT-263 (navitoclax) was performed in human established and primary cultured glioblastoma cells as well as glioma stem-like cells. We applied cell count analyses to assess cellular proliferation and Annexin V/PI staining to examine pro-apoptotic effects. Western blot analyses and specific knockdown experiments using siRNA were used to examine molecular mechanisms of action. Bcl-2/Bcl-xL inhibition synergistically enhanced apoptosis in combination with PDT. This effect was caspase-dependent. On the molecular level, PDT caused an increased Noxa/Mcl-1 ratio, which was even more pronounced when combined with ABT-263 in a Usp9X-independent manner. Our data showed that Bcl-2/Bcl-xL inhibition increases the response of glioblastoma cells toward photodynamic therapy. This effect can be partly attributed to cytotoxicity and is likely related to a pro-apoptotic shift because of an increased Noxa/Mcl-1 ratio. The results of this study warrant further investigation.

Wearable inertial measurement units (IMUs) provide a cost-effective approach to assessing human movement in clinical and everyday environments. However, developing the associated classification models for robust assessment of physiotherapeutic exercise and gait analysis requires large, diverse datasets that are costly and time-consuming to collect. We present a multimodal dataset of physiotherapeutic and gait-related exercises, including correct and clinically relevant variants, recorded from 19 healthy subjects using synchronized IMUs and optical marker-based motion capture (MoCap). It contains data from nine IMUs and 68 markers tracking full-body kinematics. Four markers per IMU allow direct comparison between IMU- and MoCap-derived orientations. We additionally provide processed IMU orientations aligned to common segment coordinate systems, subject-specific OpenSim models, inverse kinematics outputs, and visualization tools for IMU-derived orientations. The dataset is fully annotated with movement quality ratings and timestamped segmentations. It supports various machine learning tasks such as exercise evaluation, gait classification, temporal segmentation, and biomechanical parameter estimation. Code for postprocessing, alignment, inverse kinematics, and technical validation is provided to promote reproducibility.