Barriers and Facilitators of Obtaining Social Determinants of Health of Patients With Cancer Through the Electronic Health Record Using Natural Language Processing Technology: Qualitative Feasibility Study With Stakeholder Interviews.

BACKGROUND: Social determinants of health (SDoH), such as geographic neighborhoods, access to health care, education, and social structure, are important factors affecting people's health and health outcomes. The SDoH of patients are scarcely documented in a discrete format in electronic health records (EHRs) but are often available in free-text clinical narratives such as physician notes. Innovative methods like natural language processing (NLP) are being developed to identify and extract SDoH from EHRs, but it is imperative that the input of key stakeholders is included as NLP systems are designed. OBJECTIVE: This study aims to understand the feasibility, challenges, and benefits of developing an NLP system to uncover SDoH from clinical narratives by conducting interviews with key stakeholders: (1) oncologists, (2) data analysts, (3) citizen scientists, and (4) patient navigators. METHODS: Individuals who frequently work with SDoH data were invited to participate in semistructured interviews. All interviews were recorded and subsequently transcribed. After coding transcripts and developing a codebook, the constant comparative method was used to generate themes. RESULTS: A total of 16 participants were interviewed (5 data analysts, 4 patient navigators, 4 physicians, and 3 citizen scientists). Three main themes emerged, accompanied by subthemes. The first theme, importance and approaches to obtaining SDoH, describes how every participant (n=16, 100%) regarded SDoH as important. In particular, proximity to the hospital and income levels were frequently relied upon. Communication about SDoH typically occurs during the initial conversation with the oncologist, but more personal information is often acquired by patient navigators. The second theme, SDoH exists in numerous forms, exemplified how SDoH arises during informal communication and can be difficult to enter into the EHR. The final theme, incorporating SDoH into health services research, addresses how more informed SDoH can be collected. One strategy is to empower patients so they are aware about the importance of SDoH, as well as employing NLP techniques to make narrative data available in a discrete format, which can provide oncologists with actionable data summaries. CONCLUSIONS: Extracting SDoH from EHRs was considered valuable and necessary, but obstacles such as narrative data format can make the process difficult. NLP can be a potential solution, but as the technology is developed, it is important to consider how key stakeholders document SDoH, apply the NLP systems, and use the extracted SDoH in health outcome studies.

Anti-EGFR antibody conjugated thiol chitosan-layered gold nanoshells for dual-modal imaging-guided cancer combination therapy.

Developing a novel multifunctional theranostic agent for cancer combination therapy has attracted tremendous attention in recent years. In this report, we designed and developed a new multifunctional nanocarrier based on anti-epidermal growth factor receptor antibody-conjugated and paclitaxel loaded-thiol chitosan-layered gold nanoshells (anti-EGFR-PTX-TCS-GNSs) as a theranostic agent for the first time used for fluorescence/photoacoustic dual-modal imaging-guided chemophotothermal synergistic therapy. The resulting anti-EGFR-PTX-TCS-GNSs showed excellent biosafety, biocompatibility, broad near-infrared (NIR) absorbance, photostability, fast and laser irradiation-controllable drug release, and higher targeting efficiency for efficient chemophotothermal combination therapy of cancer under the guidance of photoacoustic imaging (PAI). The combination therapy was investigated in vitro and in vivo, displaying a powerful anticancer efficiency. More importantly, an in vivo experiment of anti-EGFR-PTX-TCS-GNSs with laser irradiation showed heavy damage to the tumor tissue, killing the tumor cells almost completely. Anti-EGFR-PTX-TCS-GNSs also showed a powerful capacity to visualize tumors, and therefore it is considered a new PAI contrast agent for subsequent therapy. Histological analysis and TUNEL assay further showed much more apoptotic cells, confirming the value of anti-EGFR-PTX-TCS-GNSs. Our results provide a new concept and a promising strategy to develop a novel multifunctional nanotheranostic agent for future clinical applications in diagnosis and therapy.

Chitosan/fucoidan multilayer coating of gold nanorods as highly efficient near-infrared photothermal agents for cancer therapy.

Photothermal therapy (PTT) using chitosan/fucoidan multilayer coating of gold nanorods (CS/F-GNRs) has emerged as an alternative strategy for cancer therapy. In this study, biocompatible CS/F-GNRs were synthesized as a new generation of photothermal therapeutic agents for in vivo cancer treatments owing to their good biocompatibility, photostability, and strong absorption in the near-infrared (NIR) region. The CS/F-GNRs showed a good size distribution (51.87 ± 3.03 nm), and the temperature variation of the CS/F-GNRs increased by 54.4 °C after laser irradiation (1.0 W/cm2) for 5 min. The in vitro photothermal efficiency of CS/F-GNRs indicated that significantly more cancer cells were killed under laser irradiation at 1.0 W/cm2 for 5 min. On the 20th day of treatment, the MDA-MB-231 tumor cells in mice treated with CS/F-GNRs under laser irradiation had almost completely disappeared. Therefore, the biocompatible CS/F-GNRs have shown great promise as safe and highly efficient near-infrared photothermal agents for future cancer therapy.

Multimodal tumor-homing chitosan oligosaccharide-coated biocompatible palladium nanoparticles for photo-based imaging and therapy.

Palladium, a near-infrared plasmonic material has been recognized for its use in photothermal therapy as an alternative to gold nanomaterials. However, its potential application has not been explored well in biomedical applications. In the present study, palladium nanoparticles were synthesized and the surface of the particles was successfully modified with chitosan oligosaccharide (COS), which improved the biocompatibility of the particles. More importantly, the particles were functionalized with RGD peptide, which improves particle accumulation in MDA-MB-231 breast cancer cells and results in enhanced photothermal therapeutic effects under an 808-nm laser. The RGD peptide-linked, COS-coated palladium nanoparticles (Pd@COS-RGD) have good biocompatibility, water dispersity, and colloidal and physiological stability. They destroy the tumor effectively under 808-nm laser illumination at 2 W cm-2 power density. Further, Pd@COS-RGD gives good amplitude of photoacoustic signals, which facilitates the imaging of tumor tissues using a non-invasive photoacoustic tomography system. Finally, the fabricated Pd@COS-RGD acts as an ideal nanotheranostic agent for enhanced imaging and therapy of tumors using a non-invasive near-infrared laser.

Biocompatible Chitosan Oligosaccharide Modified Gold Nanorods as Highly Effective Photothermal Agents for Ablation of Breast Cancer Cells.

Photothermal therapy (PTT) using biocompatible nanomaterials have recently attracted much attention as a novel candidate technique for cancer therapy. In this work we report the performance of newly synthesized multidentate chitosan oligosaccharide modified gold nanorods (AuNRs-LA-COS) as novel agents for PTT of cancer cells due to their excellent biocompatibility, photothermal stability, and high absorption in the near-infrared (NIR) region. The AuNRs-LA-COS exhibit a strong NIR absorption peak at 838 nm with a mean length of 26 ± 3.1 nm and diameter of 6.8 ± 1.7 nm, respectively. The temperature of AuNRs-LA-COS rapidly reached 52.6 °C for 5 min of NIR laser irradiation at 2 W/cm². The AuNRs-LA-COS had very low cytotoxicity and exhibited high efficiency for the ablation of breast cancer cells in vitro. The tumor-bearing mice were completely ablated without tumor recurrence after photothermal treatment with AuNRs-LA-COS (25 µg/mL) under laser irradiation. In summary, this study demonstrated that AuNRs-LA-COS with laser irradiation as novel agents pave an alternative way for breast cancer therapy and hold great promise for clinical trials in the near future.

Prussian blue decorated mesoporous silica hybrid nanocarriers for photoacoustic imaging-guided synergistic chemo-photothermal combination therapy.

The fabrication of nanotherapeutic systems capable of stimuli-responsive drug delivery and photoacoustic imaging (PAI)-guided photothermal therapy (PTT) is considered significant for chemo-photothermal therapy applications in cancer therapy. In the present study, the Prussian blue nanoflake (PBNF) decorated mesoporous silica hybrid nanoparticle (PB@MSH-EDA NPs) is reported for PAI-guided chemo-photothermal therapy applications. The amine group enriched mesoporous silica channels can be used to encapsulate an anticancer drug for chemotherapy, and the surface decorated PBNFs can convert a near-infrared (NIR) laser (808 nm) into heat for photothermal therapy and can also be used for PAI applications. The PB@MSH-EDA NPs show pH-responsive drug release efficiency under acidic pH (pH 5.0 and 4.0) conditions. Furthermore, the PB@MSH-EDA NPs system shows strong NIR laser absorption and photothermal conversion efficiency under 808 nm laser irradiation. The in vitro experimental result shows that the PB@MSH-EDA NPs are biocompatible and could be efficiently taken up by MDA-MB-231 cells. In addition, the in vivo results demonstrate that the tumor-bearing mice fully recovered after injecting the drug (Dox)-loaded PB@MSH-EDA/Dox NPs and being further irradiated with the 808 nm laser. We believe that the PB@MSH-EDA NPs system could be utilized as an efficient PAI-guided chemo-photothermal therapy agent for the detection and treatment of tumors in an emerging cancer therapy application.

Organization of calbindin D28K-immunoreactive neurons in the dog superior colliculus.

We localized calbindin D28K-immunoreactive (IR) neurons in the superior colliculus (SC) of the dog and studied the distribution and effect of enucleation on the distribution of this protein. We also compared this labeling to that of GABA. Calbindin D28K was localized with antibody immunocytochemistry. Calbindin D28K-IR neurons formed three laminar tiers in the SC, one within the lower superficial gray layer (SGL), the second within the upper intermediate gray layers (IGL), and the third within the deep gray layer (DGL). The third tier was not very distinctive when compared with the other two tiers. Calbindin D28K-IR neurons in the SC varied dramatically in morphology and size, and included round/oval, vertical fusiform, stellate, pyriform, and horizontal neurons. Neurons with varicose dendrite were also labeled in the IGL. Enucleation appeared to have no effect on the distribution of calbindin D28K-IR neurons in the contralateral SC. Two-color immunofluorescence revealed that a small percentage (11.20%) of calbindin D28K-IR neurons co-localized with GABA. The current results demonstrate that the patterned distribution of calbindin D28K-IR neurons in the intermediate and deep SC is comparable with other animals, but that the distribution of this protein in the superficial SC is strikingly different from that in previously studied animals. The results also suggest that retinal projection may not control the activity of the expression of calbindin D28K in the dog SC. These results will not only provide valuable knowledge of the basic neurochemical architecture of the dog visual system, but also provide clues for the understanding of the similarities and differences among species.