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Background and Objectives: Preoperative echocardiography is widely performed in patients undergoing major surgeries to evaluate cardiac functions and detect structural abnormalities. However, studies on the clinical usefulness of preoperative echocardiography in patients undergoing cerebral aneurysm clipping are limited. Therefore, this study aimed to investigate the correlation between preoperative echocardiographic parameters and the incidence of postoperative complications in patients undergoing clipping of unruptured intracranial aneurysms. Materials and Methods: Electronic medical records of patients who underwent clipping of an unruptured intracranial aneurysm from September 2018 to April 2020 were retrospectively reviewed. Data on baseline characteristics, laboratory variables, echocardiographic parameters, postoperative complications, and hospital stays were obtained. Univariable and multivariable logistic regression analyses were performed to identify independent variables related to the occurrence of postoperative complications and prolonged hospital stay (≥8 d). Results: Among 531 patients included in the final analysis, 27 (5.1%) had postoperative complications. In multivariable logistic regression, the total amount of crystalloids infused (1.002 (1.001–1.003), p = 0.001) and E/e' ratio (1.17 (1.01–1.35), p = 0.031) were significant independent factors associated with the occurrence of a postoperative complication. Additionally, the maximal diameter of a cerebral aneurysm (1.13 (1.02–1.25), p = 0.024), total amount of crystalloids infused (1.001 (1.000–1.002), p = 0.031), E/A ratio (0.22 (0.05–0.95), p = 0.042), and E/e' ratio (1.16 (1.04–1.31), p = 0.011) were independent factors related to prolonged hospitalization. Conclusions: Echocardiographic parameters related to diastolic function might be associated with postoperative complications in patients undergoing clipping of unruptured intracranial aneurysms. [ABSTRACT FROM AUTHOR]

The longitudinal effect of B12 insufficiency on sarcopenia has not yet been investigated in older adults. We aimed to study the impact of B12 levels on alterations in muscle mass, function and strength over two years. Non-sarcopenic older adults (n = 926) aged 70–84 were included. Using the Korean Frailty and Aging Cohort Study, this two-year longitudinal study used data across South Korea. The tools used for assessing muscle criteria were based on the Asian Working Group for Sarcopenia guidelines. Participants were divided into the insufficiency (initial serum B12 concentration < 350 pg/mL) and sufficiency groups (≥350 pg/mL). Logistic regression analyses were performed to evaluate the effect of initial B12 concentration on sarcopenia parameters over a two-year period. In women, multivariate analysis showed that the B12 insufficiency group had a significantly higher incidence of low SPPB scores (odds ratio [OR] = 3.28, 95% confidence interval [CI] = 1.59–6.76) and sarcopenia (OR = 3.72, 95% CI = 1.10–12.62). However, the B12 insufficiency group did not have a greater incidence of sarcopenia or other parameters in men. Our findings suggest B12 insufficiency negatively impacts physical performance and increases the incidence of sarcopenia only in women. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic cancer tissue is resistant to anticancer drugs because of its complex microenvironment. Cancer-associated fibroblasts (CAFs) are an important source of extracellular matrix components, which alter the physical and chemical properties of pancreatic tissue, thus impairing effective intratumoral drug delivery and resulting in resistance to conventional chemotherapy. In this study, we developed a novel CAF-integrated pancreatic cancer organoid (CIPCO) model that can mimic the tumor microenvironment and confirmed that the gene expression and pathological characteristics of CIPCO are similar to those of human cancer tissue. The organoid model could serve as a preclinical model for developing individualized therapies. Pancreatic cancer is a devastating disease and is highly resistant to anticancer drugs because of its complex microenvironment. Cancer-associated fibroblasts (CAFs) are an important source of extracellular matrix (ECM) components, which alter the physical and chemical properties of pancreatic tissue, thus impairing effective intratumoral drug delivery and resulting in resistance to conventional chemotherapy. The objective of this study was to develop a new cancer organoid model, including a fibrous tumor microenvironment (TME) using CAFs. The CAF-integrated pancreatic cancer organoid (CIPCO) model developed in this study histologically mimicked human pancreatic cancer and included ECM production by CAFs. The cancer cell–CAF interaction in the CIPCO promoted epithelial–mesenchymal transition of cancer cells, which was reversed by CAF inhibition using all-trans retinoic acid. Deposition of newly synthesized collagen I in the CIPCO disturbed the delivery of gemcitabine to cancer cells, and treatment with collagenase increased the cytotoxic effect of gemcitabine. This model may lead to the development of next-generation cancer organoid models recapitulating the fibrous TME. [ABSTRACT FROM AUTHOR]

The accurate estimation of acute ischemic stroke (AIS) using diffusion-weighted imaging (DWI) is crucial for assessing patients and guiding treatment options. This study aimed to propose a method that estimates AIS volume in DWI objectively, quickly, and accurately. We used a dataset of DWI with AIS, including 2159 participants (1179 for internal validation and 980 for external validation) with various types of AIS. We constructed algorithms using 3D segmentation (direct estimation) and 2D segmentation (indirect estimation) and compared their performances with those annotated by neurologists. The proposed pretrained indirect model demonstrated higher segmentation performance than the direct model, with a sensitivity, specificity, F1-score, and Jaccard index of 75.0%, 77.9%, 76.0, and 62.1%, respectively, for internal validation, and 72.8%, 84.3%, 77.2, and 63.8%, respectively, for external validation. Volume estimation was more reliable for the indirect model, with 93.3% volume similarity (VS), 0.797 mean absolute error (MAE) for internal validation, VS of 89.2% and a MAE of 2.5% for external validation. These results suggest that the indirect model using 2D segmentation developed in this study can provide an accurate estimation of volume from DWI of AIS and may serve as a supporting tool to help physicians make crucial clinical decisions. [ABSTRACT FROM AUTHOR]

Simple Summary: Cyclin-dependent kinase (CDK) 4/6 inhibitors, in combination with endocrine therapies, are now the standard of care for patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. Despite the effectiveness of CDK4/6 inhibitors, acquired resistance occurs in almost all cases. We developed and used a palbociclib-resistant preclinical model and studied the overcoming strategies, using FDA-approved chemotherapy in combination with a CDK4/6 inhibitor. We demonstrated that sequential abemaciclib treatment following eribulin-enhanced anti-tumor activity in vitro and in vivo on the CDK4/6 inhibitor-resistant cells by more effectively inhibiting the G2/M cell cycle phase. The sequential combination of abemaciclib following eribulin could be an effective treatment strategy in overcoming resistance to CDK4/6 inhibitors in HR-positive breast cancer. Breast cancer remains a leading cancer burden among women worldwide. Acquired resistance of cyclin-dependent kinase (CDK) 4/6 inhibitors occurs in almost all hormone receptor (HR)-positive subtype cases, comprising 70% of breast cancers, although CDK4/6 inhibitors combined with endocrine therapy are highly effective. CDK4/6 inhibitors are not expected to cooperate with cytotoxic chemotherapy based on the basic cytotoxic chemotherapy mode of action that inhibits rapidly proliferating cells. The palbociclib-resistant preclinical model developed in the current study investigated whether the combination of abemaciclib, CDK4/6 inhibitor with eribulin, an antimitotic chemotherapy could be a strategy to overcome palbociclib-resistant HR-positive breast cancer. The current study demonstrated that sequential abemaciclib treatment following eribulin synergistically suppressed CDK4/6 inhibitor-resistant cells by inhibiting the G2/M cell cycle phase more effectively. The current study showed the significant association of the pole-like kinase 1 (PLK1) level and palbociclib resistance. Moreover, the cumulative PLK1 inhibition in the G2/M phase by each eribulin or abemaciclib proved to be a mechanism of the synergistic effect. The synergistic antitumor effect was also supported by in vivo study. The sequential combination of abemaciclib following eribulin merits further clinical trials to overcome resistance to CDK4/6 inhibitors in HR-positive breast cancer. [ABSTRACT FROM AUTHOR]

Recently, cyclin-dependent kinase (CDK) 4/6 inhibitors have been widely used to treat advanced hormone receptor-positive breast cancer. Despite promising clinical outcomes, almost all patients eventually acquire resistance to CDK4/6 inhibitors. Here, we screened genes associated with palbociclib resistance through genomics and transcriptomics in preclinical breast cancer models. Palbociclib-resistant cells were generated by exposing hormone receptor-positive breast cancer cell lines to palbociclib. Whole-exome sequencing (WES) and a mRNA microarray were performed to compare the genomic and transcriptomic landscape between both palbociclib-sensitive and resistant cells. Microarray analysis revealed 651 differentially expressed genes (DEGs), while WES revealed 107 clinically significant mutated genes. Furthermore, pathway analysis of both DEGs and mutated genes revealed immune pathway deregulation in palbociclib-resistant cells. Notably, DEG annotation revealed activation of type I interferon pathway, activation of immune checkpoint inhibitory pathway, and suppression of immune checkpoint stimulatory pathway in palbociclib-resistant cells. Moreover, mutations in NCOR1, MUC4, and MUC16 genes found in palbociclib-resistant cells were annotated to be related to the immune pathway. In conclusion, our genomics and transcriptomics analysis using preclinical model, revealed that deregulated immune pathway is an additional mechanism of CDK4/6 inhibitor resistance besides the activation of cyclin E-CDK2 pathway and loss of RB, etc. Further studies are warranted to evaluate whether immune pathways may be a therapeutic target to overcome CDK4/6 inhibitor resistance. [ABSTRACT FROM AUTHOR]

It has recently been reported that identifying the depression severity of a person requires involvement of mental health professionals who use traditional methods like interviews and self-reports, which results in spending time and money. In this work we made solid contributions on short-term depression detection using every-day mobile devices. To improve the accuracy of depression detection, we extracted five factors influencing depression (symptom clusters) from the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders), namely, physical activity, mood, social activity, sleep, and food intake and extracted features related to each symptom cluster from mobile devices' sensors. We conducted an experiment, where we recruited 20 participants from four different depression groups based on PHQ-9 (the Patient Health Questionnaire-9, the 9-item depression module from the full PHQ), which are normal, mildly depressed, moderately depressed, and severely depressed and built a machine learning model for automatic classification of depression category in a short period of time. To achieve the aim of short-term depression classification, we developed Short-Term Depression Detector (STDD), a framework that consisted of a smartphone and a wearable device that constantly reported the metrics (sensor data and self-reports) to perform depression group classification. The result of this pilot study revealed high correlations between participants' Ecological Momentary Assessment (EMA) self-reports and passive sensing (sensor data) in physical activity, mood, and sleep levels; STDD demonstrated the feasibility of group classification with an accuracy of 96.00% (standard deviation (SD) = 2.76). [ABSTRACT FROM AUTHOR]

The Oncotype DX® recurrence score (RS) predictor has been clinically utilized to appropriately select adjuvant chemotherapy for patients with estrogen receptor (ER)-positive early breast cancer. However, the selection of chemotherapy for patients with intermediate RSs remains controversial. We assessed the prognostic value of a 70-gene signature (70GS) among patients with ER-positive breast cancer and intermediate RSs. In addition, we sought to identify genes associated with poor 70GS scores based on gene expression profiling (GEP). GEP was performed using gene expression data from 186 patients with ER-positive breast cancer. The RS and 70GS score were calculated on the basis of GEP. Among 186 patients, 82 ER-positive patients with intermediate RSs were identified. These patients were stratified by 70GS, overall survival (OS) significantly differed according to 70GS (p=0.013). In a supervised hierarchical analysis according to 70GS, the expression of several representative genes for cell proliferation was significantly higher in the poor 70GS cluster than in the good 70GS cluster. Furthermore, among these patients, FOXM1, AURKA, AURKB, and BIRC5 displayed prognostic significance for OS. In conclusion, 70GS can help to discriminate survival differences among ER-positive patients with intermediate RSs. FOXM1, AURKA, AURKB, and BIRC5, are associated with poor 70GS scores.