The Oncolytic Adenovirus Delta-24-RGD in Combination With ONC201 Induces a Potent Antitumor Response in Pediatric High-Grade and Diffuse Midline Glioma Models

BACKGROUND: Pediatric high-grade gliomas (pHGGs), including diffuse midline gliomas (DMGs), are aggressive pediatric tumors with one of the poorest prognoses. Delta-24-RGD and ONC201 have shown promising efficacy as single agents for these tumors. However, the combination of both agents has not been evaluated. METHODS: The production of functional viruses was assessed by immunoblotting and replication assays. The antitumor effect was evaluated in a panel of human and murine pHGG and DMG cell lines. RNAseq, the seahorse stress test, mitochondrial DNA content, and γH2A.X immunofluorescence were used to perform mechanistic studies. Mouse models of both diseases were used to assess the efficacy of the combination in vivo. The tumor immune microenvironment was evaluated using flow cytometry, RNAseq, and multiplexed immunofluorescence staining. RESULTS: The Delta-24-RGD/ONC201 combination did not affect the virus replication capability in human pHGG and DMG models in vitro. Cytotoxicity analysis showed that the combination treatment was either synergistic or additive. Mechanistically, the combination treatment increased nuclear DNA damage and maintained the metabolic perturbation and mitochondrial damage caused by each agent alone. Delta-24-RGD/ONC201 cotreatment extended the overall survival of mice implanted with human and murine pHGG and DMG cells, independent of H3 mutation status and location. Finally, combination treatment in murine DMG models revealed a reshaping of the tumor microenvironment to a proinflammatory phenotype. CONCLUSIONS: The Delta-24-RGD/ONC201 combination improved the efficacy compared to each agent alone in in vitro and in vivo models by potentiating nuclear DNA damage and in turn improving the antitumor (immune) response to each agent alone

Omics-based profiles and biomarkers of respiratory infections: are we there yet?

Descriptive omics-based clinical research provides valuable early steps in understanding host immune responses to respiratory pathogens in our global efforts to mitigate the impacts of severe respiratory infections with rapidly evolving technologies https://bit.ly/4bjJsv

The Use of Apparent Diffusion Coefficient Values for Differentiating Bevacizumab-Related Cytotoxicity from Tumor Recurrence and Radiation Necrosis in Glioblastoma

OBJECTIVES: Glioblastomas (GBM) are the most common primary invasive neoplasms of the brain. Distinguishing between lesion recurrence and different types of treatment related changes in patients with GBM remains challenging using conventional MRI imaging techniques. Therefore, accurate and precise differentiation between true progression or pseudoresponse is crucial in deciding on the appropriate course of treatment. This retrospective study investigated the potential of apparent diffusion coefficient (ADC) map values derived from diffusion-weighted imaging (DWI) as a noninvasive method to increase diagnostic accuracy in treatment response. METHODS: A cohort of 21 glioblastoma patients (mean age: 59.2 ± 11.8, 12 Male, 9 Female) that underwent treatment with bevacizumab were selected. The ADC values were calculated from the DWI images obtained from a standardized brain protocol across 1.5-T and 3-T MRI scanners. Ratios were calculated for rADC values. Lesions were classified as bevacizumab-induced cytotoxicity based on characteristic imaging features (well-defined regions of restricted diffusion with persistent diffusion restriction over the course of weeks without tissue volume loss and absence of contrast enhancement). The rADC value was compared to these values in radiation necrosis and recurrent lesions, which were concluded in our prior study. The nonparametric Wilcoxon signed rank test with RESULTS: The mean ± SD age of the selected patients was 59.2 ± 11.8. ADC values and corresponding mean rADC values for bevacizumab-induced cytotoxicity were 248.1 ± 67.2 and 0.39 ± 0.10, respectively. These results were compared to the ADC values and corresponding mean rADC values of tumor progression and radiation necrosis. Significant differences between rADC values were observed in all three groups ( CONCLUSION: The study demonstrates the potential of ADC values as noninvasive imaging biomarkers for differentiating recurrent glioblastoma from radiation necrosis and bevacizumab-induced cytotoxicity

Learning From Data in Dentistry: Summary of the Third Annual OpenWide Conference

The overarching goal of the third scientific oral health symposium was to introduce the concept of a learning health system to the dental community and to identify and discuss cutting-edge research and strategies using data for improving the quality of dental care and patient safety. Conference participants included clinically active dentists, dental researchers, quality improvement experts, informaticians, insurers, EHR vendors/developers, and members of dental professional organizations and dental service organizations. This report summarizes the main outputs of the third annual OpenWide conference held in Houston, Texas, on October 12, 2022, as an affiliated meeting of the American Dental Association (ADA) 2022 annual conference

A Pilot Acceptability Evaluation of Mommind: A Digital Health Intervention for Peripartum Depression Prevention and Management Focused on Health Disparities

Health disparities cause significant strain on the wellbeing of individuals and society. In this study, we focus on the health disparities present in the condition of Peripartum Depression (PPD), a significant public health issue. While PPD can be managed through therapy and medication, many women do not receive adequate PPD treatment due to issues of social stigma and limited access to healthcare resources. Digital health technologies can offer practical tools for PPD management. However, current solutions do not integrate behavior theory and are rarely responsive to the transient information needs stemming from women\u27s unique sociodemographic, clinical and psychosocial profiles. We describe a pilot acceptability evaluation of MomMind, a health-disparities focused digital health intervention for the prevention and management of PPD. A crucial MomMind advantage is its basis on behavior change theory and patient engagement as enabled by the Digilego digital health framework. Following an internal usability evaluation, MomMind was evaluated by patients through cross-sectional acceptability surveys, pre-and-post PPD health literacy surveys, and interviews. Survey respondents included n = 30 peripartum women, of whom n = 16 (53.3%) were Hispanic and n = 17 (56.7%) of low-income. Survey results show that 96.6% of participants (n = 29) approved and welcomed MomMind, and 90% (n = 27) found MomMind to be an appealing intervention. Additionally, significant improvements (p\u3c = 0.05) were observed in participants\u27 PPD health literacy, specifically their ability to recognize PPD symptoms and knowledge of how to seek PPD information. Interview main themes include MomMind\u27s straightforward design and influence of others (family members, providers) on use of technology. Results suggest that enhancement of a digital health framework with health literacy theory can support production of digital health solutions acceptable to vulnerable populations. This study incorporates existing theories from different disciplines into a unified approach for mitigating health disparities, and produced a novel solution for promotion of health in a vulnerable population

SAFER: Sub-Hypergraph Attention-Based Neural Network for Predicting Effective Responses to Dose Combinations

BACKGROUND: The potential benefits of drug combination synergy in cancer medicine are significant, yet the risks must be carefully managed due to the possibility of increased toxicity. Although artificial intelligence applications have demonstrated notable success in predicting drug combination synergy, several key challenges persist: (1) Existing models often predict average synergy values across a restricted range of testing dosages, neglecting crucial dose amounts and the mechanisms of action of the drugs involved. (2) Many graph-based models rely on static protein-protein interactions, failing to adapt to dynamic and higher-order relationships. These limitations constrain the applicability of current methods. RESULTS: We introduce SAFER, a Sub-hypergraph Attention-based graph model, addressing these issues by incorporating complex relationships among biological knowledge networks and considering dosing effects on subject-specific networks. SAFER outperformed previous models on the benchmark and the independent test set. The analysis of subgraph attention weight for the lung cancer cell line highlighted JAK-STAT signaling pathway, PRDM12, ZNF781, and CDC5L that have been implicated in lung fibrosis. CONCLUSIONS: SAFER presents an interpretable framework designed to identify drug-responsive signals. Tailored for comprehending dose effects on subject-specific molecular contexts, our model uniquely captures dose-level drug combination responses. This capability unlocks previously inaccessible avenues of investigation compared to earlier models. Furthermore, the SAFER framework can be leveraged by future inquiries to investigate molecular networks that uniquely characterize individual patients and can be applied to prioritize personalized effective treatment based on safe dose combinations

Isotherms, Kinetics and Thermodynamic Mechanism of Methylene Blue Dye Adsorption on Synthesized Activated Carbon

The treatment of methylene blue (MB) dye wastewater through the adsorption process has been a subject of extensive research. However, a comprehensive understanding of the thermodynamic aspects of dye solution adsorption is lacking. Previous studies have primarily focused on enhancing the adsorption capacity of methylene blue dye. This study aimed to develop an environmentally friendly and cost-effective method for treating methylene blue dye wastewater and to gain insights into the thermodynamics and kinetics of the adsorption process for optimization. An adsorbent with selective methylene blue dye adsorption capabilities was synthesized using rice straw as the precursor. Experimental studies were conducted to investigate the adsorption isotherms and models under various process conditions, aiming to bridge gaps in previous research and enhance the understanding of adsorption mechanisms. Several adsorption isotherm models, including Langmuir, Temkin, Freundlich, and Langmuir-Freundlich, were applied to theoretically describe the adsorption mechanism. Equilibrium thermodynamic results demonstrated that the calculated equilibrium adsorption capacity (qe) aligned well with the experimentally obtained data. These findings of the study provide valuable insights into the thermodynamics and kinetics of methylene blue dye adsorption, with potential applications beyond this specific dye type. The utilization of rice straw as an adsorbent material presents a novel and cost-effective approach for MB dye removal from wastewater

#ColorOurCollections Page 14

McGoverrn Historical Center joins other libraries, archives, and cultural heritage institutions sharing coloring pages created from our historical materials the first time. This annual celeberatiion is hosted by The New York Academy of Medicine. Images selected for this coloring book come from The Heart Bulletin. The McGovern Historical Center is home to the Medical Arts Publishing Foundation\u27s archives, including an extensive collection of original artwork created for its publications.https://digitalcommons.library.tmc.edu/colorourcollections/1013/thumbnail.jp

#ColorOurCollections Page 4

McGoverrn Historical Center joins other libraries, archives, and cultural heritage institutions sharing coloring pages created from our historical materials the first time. This annual celeberatiion is hosted by The New York Academy of Medicine. Images selected for this coloring book come from The Heart Bulletin. The McGovern Historical Center is home to the Medical Arts Publishing Foundation\u27s archives, including an extensive collection of original artwork created for its publications.https://digitalcommons.library.tmc.edu/colorourcollections/1003/thumbnail.jp

#ColorOurCollections Page 7

McGoverrn Historical Center joins other libraries, archives, and cultural heritage institutions sharing coloring pages created from our historical materials the first time. This annual celeberatiion is hosted by The New York Academy of Medicine. Images selected for this coloring book come from The Heart Bulletin. The McGovern Historical Center is home to the Medical Arts Publishing Foundation\u27s archives, including an extensive collection of original artwork created for its publications.https://digitalcommons.library.tmc.edu/colorourcollections/1006/thumbnail.jp