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Local differential privacy algorithms combined with deep generative models can enhance secure medical image sharing among researchers in the public domain without central administrators; however, these images were limited to the generation of low-resolution images, which are very insufficient for diagnosis by medical doctors. To enhance the performance of deep generative models so that they can generate high-resolution medical images, we propose a large-scale diffusion model that can, for the first time, unconditionally generate high-resolution ( 256 × 256 × 256 ) volumetric medical images (head magnetic resonance images). This diffusion model has 19 billion parameters, but to make it easy to train it, we temporally divided the model into 200 submodels, each of which has 95 million parameters. Moreover, on the basis of this new diffusion model, we propose another formulation of image anonymization with which the processed images can satisfy provable Gaussian local differential privacy and with which we can generate images semantically different from the original image but belonging to the same class. We believe that the formulation of this new diffusion model and the implementation of local differential privacy algorithms combined with the diffusion models can contribute to the secure sharing of practical images upstream of data processing. [ABSTRACT FROM AUTHOR]

This study aimed to explore the relationship between thyroid-stimulating hormone (TSH) elevation and the baseline computed tomography (CT) density and volume of the thyroid. We examined 86 cases with new-onset hypothyroidism (TSH > 4.5 IU/mL) and 1071 controls from a medical check-up database over 5 years. A deep learning-based thyroid segmentation method was used to assess CT density and volume. Statistical tests and logistic regression were employed to determine differences and odds ratios. Initially, the case group showed a higher CT density (89.8 vs. 81.7 Hounsfield units (HUs)) and smaller volume (13.0 vs. 15.3 mL) than those in the control group. For every +10 HU in CT density and −3 mL in volume, the odds of developing hypothyroidism increased by 1.40 and 1.35, respectively. Over the course of the study, the case group showed a notable CT density reduction (median: −8.9 HU), whereas the control group had a minor decrease (−2.9 HU). Thyroid volume remained relatively stable for both groups. Higher CT density and smaller thyroid volume at baseline are correlated with future TSH elevation. Over time, there was a substantial and minor decrease in CT density in the case and control groups, respectively. Thyroid volumes remained consistent in both cohorts. [ABSTRACT FROM AUTHOR]

Simple Summary: In order to develop a biomarker predicting the efficacy of chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT) for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with each therapy. The frequencies of PD-1+ or TIM-3+CD4+ T cells were significantly higher in patients with cStage IV. PD-1+CD4+ and TIM-3+CD8+ T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4+ and CD8+ central memory T cells (TCM) were significantly decreased during NT in the progressive disease group. Taken together, the alteration in frequency of TCM during NT may be a biomarker to predict its therapeutic response in ESCC patients. In order to develop a biomarker predicting the efficacy of treatments for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT). Fifty-five ESCC patients were enrolled in this study, and peripheral blood samples were collected before and after CT or CRT and during NT. Frequencies of memory, differentiated, and exhausted T cells were evaluated using flow cytometry among cStages, treatment strategies, pathological responses of CT/CRT, and during NT. The frequencies of PD-1+ or TIM-3+CD4+ T cells were significantly higher in patients with cStage IV. PD-1+CD4+ and TIM-3+CD8+ T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4+ and CD8+ CD45RA−CD27+CD127+ central memory T cells (TCM) were significantly decreased during the course of NT in the progressive disease group. Taken together, the alteration in frequency of CD45RA−CD27+CD127+ TCM during NT may be a biomarker to predict its therapeutic response in ESCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Although the tumor cell-intrinsic cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment in colorectal cancer (CRC), its impact on the infiltration of immune cells and clinical outcomes in patients with mismatch repair proficient/microsatellite stable (pMMR/MSS) CRC has not been thoroughly investigated. In this study, we examine the expression pattern of cGAS-STING in tumor cells and its effect on the infiltrations of CD8+ and CD4+ T cells, as well as clinical outcomes including survival and recurrence in patients with pMMR/MSS CRC. Our current findings may offer novel insights and therapeutic strategies for patients with pMMR/MSS CRC. The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway plays a crucial role in activating immune cells in the tumor microenvironment, thereby contributing to a more favorable response to immune checkpoint inhibitors (ICI) in colorectal cancer (CRC). However, the impact of the expression of cGAS-STING in tumor cells on the infiltration of CD8+ T cells and clinical outcomes in mismatch repair proficient/microsatellite stable (pMMR/MSS) CRC remains largely unknown. Our findings reveal that 56.8% of all pMMR CRC cases were cGAS-negative/STING-negative expressions (cGAS−/STING−) in tumor cells, whereas only 9.9% of all pMMR CRC showed cGAS-positive/STING-positive expression (cGAS+/STING+) in tumor cells. The frequency of cGAS+/STING+ cases was reduced in the advanced stages of pMMR/MSS CRC, and histone methylation might be involved in the down-regulation of STING expression in tumor cells. Since the expression level of cGAS-STING in tumor cells has been associated with the infiltration of CD8+ and/or CD4+ T cells and the frequency of recurrence in pMMR/MSS CRC, decreased expression of cGAS-STING in tumor cells might lead to poor immune cell infiltration and worse prognosis in most pMMR/MSS CRC patients. Our current findings provide a novel insight for the treatment of patients with pMMR/MSS CRC. [ABSTRACT FROM AUTHOR]

In order to develop a biomarker predicting the efficacy of treatments for patients with esophageal squamous cell carcinoma (ESCC), we evaluated the subpopulation of T cells in ESCC patients treated with chemotherapy (CT), chemoradiotherapy (CRT), and nivolumab therapy (NT). Fifty-five ESCC patients were enrolled in this study, and peripheral blood samples were collected before and after CT or CRT and during NT. Frequencies of memory, differentiated, and exhausted T cells were evaluated using flow cytometry among cStages, treatment strategies, pathological responses of CT/CRT, and during NT. The frequencies of PD-1 + or TIM-3 + CD4 + T cells were significantly higher in patients with cStage IV. PD-1 + CD4 + and TIM-3 + CD8 + T-cell populations were significantly higher in patients treated with CRT but were not associated with treatment response. The frequencies of both CD4 + and CD8 + CD45RA - CD27 + CD127 + central memory T cells (T CM ) were significantly decreased during the course of NT in the progressive disease group. Taken together, the alteration in frequency of CD45RA - CD27 + CD127 + T CM during NT may be a biomarker to predict its therapeutic response in ESCC patients.