Cadherin-6 is a novel mediator for the migration of mesenchymal stem cells to glioblastoma cells in response to stromal cell-derived factor-1.

Glioblastoma recruits various nontransformed cells from distant tissues. Although bone marrow-derived mesenchymal stem cells (MSCs) have been observed migrating to glioblastoma, the underlying mechanism driving MSC migration toward glioblastoma remains unclear. Tumor vascularity is critical in the context of recurrent glioblastoma and is closely linked to the expression of stromal cell-derived factor-1 (SDF-1). We demonstrated that cadherin-6 mediated MSC migration both toward SDF-1 and toward glioblastoma cells. Cadherin-6 knockdown resulted in the downregulation of MSCs capacity to migrate in response to SDF-1. Furthermore, MSCs with cadherin-6 knockdown exhibited impaired migration in response to conditioned media derived from glioblastoma cell lines (U87 and U373) expressing SDF-1, thus simulating the glioblastoma microenvironment. Moreover, MSCs enhanced the vasculogenic capacity of U87 cells without increasing the proliferation, cancer stem cell characteristics, or migration of U87. These results suggest that the current strategy of utilizing MSCs as carriers for antiglioblastoma drugs requires careful examination. Furthermore, cadherin-6 may represent a novel potential target for controlling the recruitment of MSCs toward glioblastoma.

Study of the soothing effects of troxerutin in alleviating skin sensitivity.

BACKGROUND: Transient receptor potential vanilloid 1 (TRPV1) is associated with skin sensitivity and mainly activated by capsaicin and heat. Interestingly, troxerutin can inhibit TRPV1 activation. However, its efficacy in reducing skin sensitivity remains undetermined. AIMS: We evaluated the efficacy of troxerutin in alleviating skin sensitivity using clinical tests and in vitro experiments. METHODS: For the in vitro experiment, HaCaT keratinocytes were pretreated with different concentrations of troxerutin, followed by incubation with 50 µM capsaicin for 1, 24, or 48 h. The gene and protein expressions of four inflammatory cytokines involved in skin irritation were determined. Among 35 Korean women with sensitive skin recruited for the clinical trial, 13 were involved in assessing the immediate soothing effects of 0.1% and 0.0095% troxerutin following capsaicin irritation, whereas 22 participated in evaluating the preventive soothing effect of 10% and 1% troxerutin over 4 weeks against capsaicin- and heat-induced irritation. We evaluated the soothing rate using skin redness, visual analog scale, and high temperature sensitive index as evaluation indices. RESULTS: Troxerutin inhibited the mRNA and protein expressions of cytokines in capsaicin-treated keratinocytes. In the clinical study, 0.1% and 0.0095% troxerutin promptly alleviated capsaicin-induced skin redness, whereas 10% troxerutin notably decreased both the visual analog scale and high temperature sensitive index for capsaicin- and heat-related irritation. However, 1% troxerutin was only effective in reducing the visual analog scale in response to capsaicin irritation. CONCLUSIONS: Troxerutin can inhibit TRPV1 activation in clinical and in vitro tests.

Automatic recognition of second language speech-in-noise.

Measuring how well human listeners recognize speech under varying environmental conditions (speech intelligibility) is a challenge for theoretical, technological, and clinical approaches to speech communication. The current gold standard-human transcription-is time- and resource-intensive. Recent advances in automatic speech recognition (ASR) systems raise the possibility of automating intelligibility measurement. This study tested 4 state-of-the-art ASR systems with second language speech-in-noise and found that one, whisper, performed at or above human listener accuracy. However, the content of whisper's responses diverged substantially from human responses, especially at lower signal-to-noise ratios, suggesting both opportunities and limitations for ASR--based speech intelligibility modeling.

Development of service standards and manpower calculation criteria for hospital clinical pharmacies in South Korea: a survey-based study.

BACKGROUND: After the revision of the Korean Pharmaceutical Affairs Act, the certification of specialized pharmacists is scheduled to be legally recognized in 2023. Considering that the specialized pharmacist certification was developed based on the working model of hospital clinical pharmacists, it is necessary to establish standards for clinical pharmacists in hospitals and to calculate appropriate manpower. Through this study, we aim to establish practical standards for clinical pharmacists and propose a method for calculating staffing levels based on an investigation of actual workloads. METHODS: This survey-based study consisted of two phases. In the first phase, a literature review was conducted to establish standards for clinical pharmacy services, and tasks in relevant literature were classified to identify clinical pharmacy service tasks that are applicable to the practice of Korean hospitals. Additionally, a preliminary survey was conducted to investigate the essential tasks. In the second phase of the investigation, a multicenter survey was conducted targeting pharmacists in facilities with more than 1,000 beds to explore their perceptions and actual workloads related to tasks. RESULTS: According to the standards for clinical pharmacists in Korea, clinical pharmacy services consist of a total of 23 tasks, of which 16 have been identified as essential tasks. Essential tasks accounted for 93% of the total tasks in clinical pharmacy services. The average full-time equivalent (FTE) through workload calculation was 2.5 ± 1.9 for each field, while the FTE allocated to actual practice was 2.1 ± 1.6. The distribution of each type of clinical pharmacy service was as follows: 77% for medication therapy management, 13% for medication education, 8% for multidisciplinary team activities, and 3% for medication use evaluation. CONCLUSION: This study identified essential tasks common to clinical pharmacy services across different healthcare institutions. However, the FTE of clinical pharmacists in actual practice was insufficient compared to the required amount. In order to establish and expand clinical pharmacy services in a hospital, it is necessary to ensure an adequate workforce for essential tasks.

Breast Tumor Cell-Stimulated Bone Marrow-Derived Mesenchymal Stem Cells Promote the Sprouting Capacity of Endothelial Cells by Promoting VEGF Expression, Mediated in Part through HIF-1α Increase.

Breast tumor cells recruit bone marrow-derived mesenchymal stem cells (BM-MSCs) and alter their cellular characteristics to establish a tumor microenvironment. BM-MSCs enhance tumor angiogenesis through various mechanisms. We investigated the mechanisms by which BM-MSCs promote angiogenesis in response to breast tumor. Conditioned media from MDA-MB-231 (MDA CM) and MCF7 (MCF7 CM) breast tumor cells were used to mimic breast tumor conditions. An in vitro spheroid sprouting assay using human umbilical vein endothelial cells (HUVECs) was conducted to assess the angiogenesis-stimulating potential of BM-MSCs in response to breast tumors. The ROS inhibitor N-acetylcysteine (NAC) and JAK inhibitor ruxolitinib attenuated increased HIF-1α in BM-MSCs in response to MDA CM and MCF7 CM. HIF-1α knockdown or HIF-1ß only partially downregulated VEGF expression and, therefore, the sprouting capacity of HUVECs in response to conditioned media from BM-MSCs treated with MDA CM or MCF7 CM. Inactivation of the VEGF receptor using sorafenib completely inhibited the HUVECs' sprouting. Our results suggest that increased HIF-1α expression under normoxia in BM-MSCs in response to breast tumor cells is mediated by ROS and JAK/Stat3, and that both HIF-1α-dependent and -independent mechanisms increase VEGF expression in BM-MSCs to promote the angiogenic sprouting capacity of endothelial cells in a VEGF-dependent manner.

Localizing category-related information in speech with multi-scale analyses.

Measurements of the physical outputs of speech-vocal tract geometry and acoustic energy-are high-dimensional, but linguistic theories posit a low-dimensional set of categories such as phonemes and phrase types. How can it be determined when and where in high-dimensional articulatory and acoustic signals there is information related to theoretical categories? For a variety of reasons, it is problematic to directly quantify mutual information between hypothesized categories and signals. To address this issue, a multi-scale analysis method is proposed for localizing category-related information in an ensemble of speech signals using machine learning algorithms. By analyzing how classification accuracy on unseen data varies as the temporal extent of training input is systematically restricted, inferences can be drawn regarding the temporal distribution of category-related information. The method can also be used to investigate redundancy between subsets of signal dimensions. Two types of theoretical categories are examined in this paper: phonemic/gestural categories and syntactic relative clause categories. Moreover, two different machine learning algorithms were examined: linear discriminant analysis and neural networks with long short-term memory units. Both algorithms detected category-related information earlier and later in signals than would be expected given standard theoretical assumptions about when linguistic categories should influence speech. The neural network algorithm was able to identify category-related information to a greater extent than the discriminant analyses.

Detectability of T-Measurable Diseases in Advanced Gastric Cancer on FDG PET-CT.

PURPOSE: Usefulness of FDG PET-CT in monitoring response in locally advanced gastric cancer has been reported. The purpose of this study was to evaluate the related factors to detect measurable diseases in advanced gastric cancer on FDG PET-CT. METHODS: We retrospectively reviewed 38 patients diagnosed as having advanced gastric cancer. We defined the measurable diseases when there was visualized tumor of which maximum standardized uptake value (SUVmax) was higher than 1.35*SUVmax of liver + 2*SD of liver SUV. We evaluated what kinds of factors from the clinicopathologic features were related to identifying measurable diseases. RESULTS: Of 38 patients with advanced gastric cancer, 18 (50 %) had measurable tumors on FDG PET-CT. Measurable tumors were significantly more frequent in well or moderately differentiated adenocarcinoma (70.5 % vs 35.3 %, p < 0.05), in the tumors located at antrum or angle (66.7 % vs 29.4 %, p < 0.05) and in the elderly group (age of 55 years old or more, 72.0 % vs 8.3 %, p < 0.001) than the others, respectively. By multivariate analysis, age at diagnosis was the only independent predictor for the measurable disease on FDG PET-CT. CONCLUSION: We found that age at diagnosis, as well as histologic types and location of tumors, were the affecting factors to detect measurable disease on FDG PET-CT in patients with advanced gastric cancer. Our study suggests that elderly patients of age of 55 years old or more can frequently have T-measurable disease on FDG PET-CT in advanced gastric cancer and FDG PET-CT will be helpful to monitor measurable disease.

Sentinel node identification using technetium-99m neomannosyl human serum albumin in esophageal cancer.

BACKGROUND: This study is a clinical trial designed to test the reliability and feasibility of sentinel node detection using a new mannose receptor radioactive binding agent in patients with esophageal squamous cell carcinoma. METHODS: Twenty-three patients (21 men, 2 women; mean age 61.0±8.60 years) who were candidates for esophagectomy with conventional lymph node dissection for thoracic esophageal cancer were enrolled. A total dose of 1 mCi of 99mTc-MSA [technetium-99m neomannosyl human serum albumin] in 0.2 mL was administered at 4 quadrants into the submucosal layer around the primary tumor under esophagoscopic guidance approximately 1 hour before surgery. Intraoperative sentinel node sampling was subsequently followed by esophagectomy. All harvested lymph nodes were cut into 2-mm slices and ultimately diagnosed using formalin-fixed and paraffin-embedded sections with hematoxylin and eosin staining. RESULTS: The number of dissected lymph nodes per patient was 30.5±9.18 (15-47). Among 23 patients, the sentinel lymph nodes could be identified in 21 patients (91.3%). The sentinel nodes could be identified in all 21 patients with cT1 or T2N0M0 (100%) disease; these patients were candidates for sentinel lymph node navigation surgery for the esophageal cancer. The mean number of sentinel nodes identified was 2.6±1.35 (range, 1-5) per patient. No false-negative sentinel lymph nodes were detected in any of the 8 patients with node-positive disease (0%). CONCLUSIONS: Intraoperative sentinel lymph node identification using 99mTc-MSA was feasible and reliable in patients with esophageal squamous cell carcinoma.

Vascular administration of adenoviral vector soaked in absorbable gelatin sponge particles (GSP) prolongs the transgene expression in hepatocytes.

Transcatheter hepatic arterial chemoembolization using emulsions composed of anticancer agents and gelatin sponges (GS) has been an efficient and safe palliative treatment for inoperable hepatocellular carcinoma (HCC). We employed catheter-mediated left hepatic arterial embolization (CHAE) to increase transduction efficiency of adenoviral vector in canine hepatocytes. The emulsion was prepared by mixing pieces of GSP and adenoviral vectors expressing recombinant beta-galactosidase (Ad.LacZ) or human hepatocyte growth factor (Ad.hHGF). After the left hepatic artery was catheterized under angiography, CHAE with Ad.LacZ or Ad.hHGF was performed. Livers were removed and stained for LacZ activity on day 7. The expression pattern of LacZ staining was either scarce or patchy around the central hilum of the hepatic artery, or was homogeneously distributed in whole lobes, depending on whether large or small pieces of GSP were used. Hematological and serum biochemical changes during CHAE exhibited only a few effects. The chronological measurement of serum HGF concentration showed that the duration of transgene expression was greater after CHAE with Ad.hHGF. A similar pattern of transgene expression was observed in a rat model after hepatic arterial embolization with differential doses of Ad.hHGF soaked in GSP. These results suggest that hepatic arterial embolization by transcatheter mediated infusion with a mixture of adenovirus-GSP could be used for human HCC.