Senescence compromises the essential role that the endothelium plays in maintaining vascular homeostasis, so promoting endothelial dysfunction and the development of age-related vascular diseases. Their biological and clinical significance calls for strategies for identifying and therapeutically targeting senescent endothelial cells. While senescence and endothelial dysfunction have been studied extensively, distinguishing what is distinctly endothelial senescence remains a barrier to overcome for an effective approach to addressing it. Here, we review the mechanisms underlying endothelial senescence and the evidence for its clinical importance. Furthermore, we discuss the current state and the limitations in the approaches for the detection and therapeutic intervention of target cells, suggesting potential directions for future research.

Abstract Introduction Addition of ovarian function suppression to conventional endocrine therapy alone in premenopausal women provides a survival benefit with moderate to high risk hormone-receptor positive breast cancer, especially who received chemotherapy Prediction of menstruation recovery after chemotherapy is important for deciding subsequent endocrine treatment and addressing fertility issues. Methods In the adding OFS after chemotherapy trial (ASTRRA), patients who resumed ovarian function up to 2 years after chemotherapy were randomized to receive either 5 years of tamoxifen or adding 2 years of OFS with tamoxifen. With these 1383 patients, we developed a model that predicts when patients recover menstruation within 3 years after chemotherapy using several variables including age, BMI, chemotherapy regimen and duration, serum E2 and FSH level. Results A total of 1017 patients data were used to develop prediction model and 366 patients data were used for external validation. In development group, 546 (53.6%) patients resumed menstruation during follow up period of 5 years. In multivariable analysis, younger age and AC based regimen without taxane were strong predictive factor for menstruation recovery. However predictive value of chemotherapy regimen was not constant over time. Therefore, we conducted another model with patients (n= 624) who did not recover menstruation within one year. In this patient group, predictive factors for menstruation recovery was age and serum E2 level at 6 months after chemotherapy. We also conducted a simplified scoring system to estimate change of recovery by using risk factors mentioned above. Conclusion Younger age is an important persisting factor predicting menstrual recovery after chemotherapy. Although chemotherapy regimen predicts shor-term menstrual recovery, over time, patient factors have more predictive influence on recovery. Recovery of serum E2 level would be important to predict subsequent menstruation recovery. Citation Format: Young Joo Lee, Woo C Noh, Seok J Nam, Byeong-Woo Park, Eun S Lee, Seock A Im, Yong S Jung, Jung H Yoon, Sung S Kang, Kyong H Park, Soo-Jung Lee, Min H Lee, Joon Jeong, Sung Y Kim, Hyun-Ah Kim, Se-Hwan Han, Wonshik Han, Min H Hur, Seonok Kim, Sei-hyun Ahn, Hee J Kim. Prediction of menstruation recovery timing in premenopausal breast cancer patients taking tamoxifen after chemotherapy: An ASTRRA substudy [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-10-07.

The problem of single-image rain streak removal goes beyond simple noise suppression, requiring the simultaneous preservation of fine structural details and overall visual quality. In this study, we propose a novel image restoration network that effectively constrains the restoration process by introducing a Corner Loss, which prevents the loss of object boundaries and detailed texture information during restoration. Furthermore, we propose a Residual Convolutional Block Attention Module (R-CBAM) Block into the encoder and decoder to dynamically adjust the importance of features in both spatial and channel dimensions, enabling the network to focus more effectively on regions heavily affected by rain streaks. Quantitative evaluations conducted on the Rain100L and Rain100H datasets demonstrate that the proposed method significantly outperforms previous approaches, achieving a PSNR of 33.29 dB on Rain100L and 26.16 dB on Rain100H.

Use of LB and provider LB use rate are associated with improved patient clinical, service utilization, and expenditure outcomes.

Toll-like receptor 5 (TLR5) plays a critical role beyond its traditional function in innate immunity, significantly impacting metabolic regulation and liver health. Previously, we reported that TLR5 activation extends the healthspan and lifespan of aging mice. This study demonstrates that TLR5 deficiency leads to pronounced metabolic abnormalities with age, primarily affecting liver metabolic functions rather than intestinal inflammation. Comprehensive RNA sequencing analysis revealed that TLR5 deficiency induces gene expression changes in liver tissue similar to those caused by the methionine-choline deficient (MCD) diet, particularly affecting lipid metabolism and circadian rhythm-related genes. TLR5 knockout (TLR5 KO) mice displayed an increased propensity for liver fibrosis and lipid accumulation under the MCD diet, exacerbating liver pathology. Both hepatocytes and hepatic stellate cells in TLR5 KO mice were functionally impacted, leading to metabolic dysfunction and fibrosis. These findings suggest that TLR5 could be a significant target for addressing metabolic diseases that arise and worsen with aging. Furthermore, understanding the mechanisms by which TLR5 activation extends healthspan could provide valuable insights into therapeutic strategies for enhancing longevity and managing age-related metabolic disorders.

Senescent cells drive age-related tissue dysfunction via the induction of a chronic senescence-associated secretory phenotype (SASP). The cyclin-dependent kinase inhibitors p21^Cip1 and p16^Ink4a have long served as markers of cellular senescence. However, their individual roles remain incompletely elucidated, particularly in vivo. Thus, we conducted a comprehensive examination of multiple single-cell RNA sequencing datasets spanning both murine and human tissues during aging. Our analysis revealed that p21^Cip1 and p16^Ink4a transcripts demonstrate significant heterogeneity across distinct cell types and tissues, frequently exhibiting a lack of co-expression. Moreover, we identified tissue-specific variations in SASP profiles linked to p21^Cip1 or p16^Ink4a expression. Using RNA velocity and pseudotime analyses, we discovered that p21+ and p16+ cells follow independent trajectory dynamics, with no evidence of direct transitions between these two states. Despite this heterogeneity, we identified a limited set of shared "core" SASP factors that may drive common senescence-related functions. Our study underscores the substantial diversity of cellular senescence and the SASP, emphasizing that these phenomena are inherently cell- and tissue-dependent.

Radiation treatment plays a mainstream role in the management of head and neck squamous cell carcinomas (HNSCCs). Adverse effects from radiation therapy include osteoradionecrosis of the jaw, and rarely, pathologic fracture. Immune checkpoint inhibitors (ICI) such as pembrolizumab are of growing relevance to the management of metastatic and recurrent HNSCCs. Adverse impacts on bone secondary to medications such as pembrolizumab and nivolumab have been sporadically documented in the literature. The objective of this manuscript is to raise awareness of possible increase in risk for adverse jaw outcomes in patients with HNSCCs exposed to both radiation treatment to the jaws and ICI therapy. This manuscript documents adverse jaw outcomes including osteonecrosis and pathologic fracture of the mandible in two patients receiving pembrolizumab for management of HNSCC who had received prior radiation treatment. A potential link between immunotherapy and adverse jaw outcomes is consistent with the growing understanding of osteoimmunology, investigating the closely interrelated processes in bone remodeling and immune system function, in health and disease. It is important to ascertain if pembrolizumab poses an incremental risk for such outcomes, beyond the risk from prior radiation, for patients managed with radiation treatment and ICI therapy for HNSCC. The general dental practitioner may encounter such patients either in the context of facilitating dental clearance prior to initiation of chemotherapy, or rarely, with poorly explained jaw symptoms and must be alert to the possibility of occurrence of such adverse jaw events to facilitate timely diagnosis and optimal patient management.

Senescence compromises the essential role that the endothelium plays in maintaining vascular homeostasis, so promoting endothelial dysfunction and the development of age-related vascular diseases. Their biological and clinical significance calls for strategies for identifying and therapeutically targeting senescent endothelial cells. While senescence and endothelial dysfunction have been studied extensively, distinguishing what is distinctly endothelial senescence remains a barrier to overcome for an effective approach to addressing it. Here, we review the mechanisms underlying endothelial senescence and the evidence for its clinical importance. Furthermore, we discuss the current state and the limitations in the approaches for the detection and therapeutic intervention of target cells, suggesting potential directions for future research.