An Accurate Deep Learning-Based System for Automatic Pill Identification: Model Development and Validation.

BACKGROUND: Medication errors account for a large proportion of all medical errors. In most homes, patients take a variety of medications for a long period. However, medication errors frequently occur because patients often throw away the containers of their medications. OBJECTIVE: We proposed a deep learning-based system for reducing medication errors by accurately identifying prescription pills. Given the pill images, our system located the pills in the respective pill databases in South Korea and the United States. METHODS: We organized the system into a pill recognition step and pill retrieval step, and we applied deep learning models to train not only images of the pill but also imprinted characters. In the pill recognition step, there are 3 modules that recognize the 3 features of pills and their imprints separately and correct the recognized imprint to fit the actual data. We adopted image classification and text detection models for the feature and imprint recognition modules, respectively. In the imprint correction module, we introduced a language model for the first time in the pill identification system and proposed a novel coordinate encoding technique for effective correction in the language model. We identified pills using similarity scores of pill characteristics with those in the database. RESULTS: We collected the open pill database from South Korea and the United States in May 2022. We used a total of 24,404 pill images in our experiments. The experimental results show that the predicted top-1 candidates achieve accuracy levels of 85.6% (South Korea) and 74.5% (United States) for the types of pills not trained on 2 different databases (South Korea and the United States). Furthermore, the predicted top-1 candidate accuracy of our system was 78% with consumer-granted images, which was achieved by training only 1 image per pill. The results demonstrate that our system could identify and retrieve new pills without additional model updates. Finally, we confirmed through an ablation study that the language model that we emphasized significantly improves the pill identification ability of the system. CONCLUSIONS: Our study proposes the possibility of reducing medical errors by showing that the introduction of artificial intelligence can identify numerous pills with high precision in real time. Our study suggests that the proposed system can reduce patients' misuse of medications and help medical staff focus on higher-level tasks by simplifying time-consuming lower-level tasks such as pill identification.

Sedation for magnetic resonance imaging in the prone position - A report of four cases.

BACKGROUND: Magnetic resonance imaging (MRI) is a useful tool, but it can be difficult to perform in those with claustrophobia as it requires being enclosed in a noisy cylindrical space. Being in the prone position is essential to spread breast tissue. However, sedation in a prone position is challenging because of the possibility of respiratory depression and the difficulty in manipulating the airway. CASE: Four patients with claustrophobia were sedated using dexmedetomidine, has minimal effect on respiration. Dexmedetomidine also enables the patient's cooperation in assuming the prone position while infusing loading time. But dexmedetomidine requires a longer time to reach moderate sedation, an intermittent bolus of midazolam was required for rapid induction of moderate sedation. All exams were conducted successfully without any complications. CONCLUSIONS: Administering dexmedetomidine and a midazolam bolus at the appropriate dose and timing will render MRI examinations in the prone position safe and satisfactory, without respiratory complications.

Patient blood management when blood is not an option: a report of two cases.

There are many patients who refuse to receive blood transfusions for religious or other reasons. Bloodless medicine and surgery are no longer new concept, but patients who refuse blood transfusion are still transferred to the bloodless center, regardless of patients' intention, for treatment. Here, we discuss the need for patient blood management when blood is not an option to treat them. Two patients of advanced age were transferred to our bloodless center due to refusal of transfusion. They are Jehovah's Witnesses and refused to receive blood transfusion despite life-threatening anemia and severe underlying diseases. Patient blood management protocols including iron supplementation, subcutaneous erythropoietin, folic acid and vitamin B were implemented to improve hematopoiesis, and supportive care was also performed to treat underlying diseases. Levels of Hemoglobin/Hematocrit and their symptom gradually improved about a week after treatment, and their condition had gradually stabilized. They were discharged safely. We treated patients of advanced age with severe underlying diseases and life-threatening anemia using patient blood management due to refusal of a blood transfusion. The patient blood management may be a useful alternative strategy, which meet the needs of patients who refuse blood transfusions as well as the need to reduce the use of blood products due to limited supply.

Effective contact resistance of zinc-tin oxide-based thin film transistors.

We investigated different source/drain (S/D) electrode materials in thin-film transistors (TFTs) based on amorphous zinc-tin oxide (ZTO) semiconductors. The transfer length, channel conductance, and effective contact resistance between the S/D electrodes and the a-ZTO channel layer were examined. Total ON resistance (R(T)), transfer length (L(T)) and effective contact resistance (R(c-eff)) were extracted by the well-known transmission-line method (TLM) using a series of TFTs with different channel lengths. When the width of ZTO channel layer was fixed as 50 µm, the lengths were varying from 10 to 50 µm. The channel layer and S/D electrode were defined by lift-off process and for the S/D electrodes, indium-tin oxide (ITO), Cu, and Mo were used. The resistivity and work function values of electrode materials were considered when selected as candidates for S/D electrodes of ZTO-TFTs. The results showed that the ZTO-TFTs with Mo S/D electrodes had the lowest effective contact resistance indicating that ZTO-TFTs with Mo electrodes have better electrical performance compared to others.

Comparison of the analytical and clinical performances of Abbott RealTime High Risk HPV, Hybrid Capture 2, and DNA Chip assays in gynecology patients.

The detection of high-risk (HR) HPV in cervical cancer screening is important for early diagnosis of cervical cancer or pre-cancerous lesions. We evaluated the analytical and clinical performances of 3 HR HPV assays in Gynecology patients. A total of 991 specimens were included in this study: 787 specimens for use with a Hybrid Capture 2 (HC2) and 204 specimens for a HPV DNA microarray (DNA Chip). All specimens were tested using an Abbott RealTime High Risk HPV assay (Real-time HR), PGMY PCR, and sequence analysis. Clinical sensitivities for severe abnormal cytology (severe than high-grade squamous intraepithelial lesion) were 81.8% for Real-time HR, 77.3% for HC2, and 66.7% for DNA Chip, and clinical sensitivities for severe abnormal histology (cervical intraepithelial neoplasia grade 2+) were 91.7% for HC2, 87.5% for Real-time HR, and 73.3% for DNA Chip. As compared to results of the sequence analysis, HC2, Real-time HR, and DNA Chip showed concordance rates of 94.3% (115/122), 90.0% (117/130), and 61.5% (16/26), respectively. The HC2 assay and Real-time HR assay showed comparable results to each other in both clinical and analytical performances, while the DNA Chip assay showed poor clinical and analytical performances. The Real-time HR assay can be a good alternative option for HR HPV testing with advantages of allowing full automation and simultaneous genotyping of HR types 16 and 18.

HER2 induces expression of leptin in human breast epithelial cells.

A close association between the obesity hormone leptin and breast cancer progression has been suggested. The present study investigated the molecular mechanism for enhanced leptin expression in breast cancer cells and its functional significance in breast cancer aggressiveness. We examined whether leptin expression level is affected by the oncoprotein human epidermal growth factor receptor2 (HER2), which is overexpressed in ∼30% of breast tumors. Here, we report, for the first time, that HER2 induces transcriptional activation of leptin in MCF10A human breast epithelial cells. We also showed that p38 mitogen-activated protein kinase signaling was involved in leptin expression induced by HER2. We showed a crucial role of leptin in the invasiveness of HER2-MCF10A cells using an siRNA molecule targeting leptin. Taken together, the results indicate a molecular link between HER2 and leptin, providing supporting evidence that leptin represents a target for breast cancer therapy. [BMB Reports 2012; 45(12): 719-723].

Wnt/ß-catenin signaling mediates the antitumor activity of magnolol in colorectal cancer cells.

Abnormal activation of the canonical Wnt/ß-catenin pathway and up-regulation of the ß-catenin/T-cell factor (TCF) response to transcriptional signaling play a critical role early in colorectal carcinogenesis. Therefore, Wnt/ß-catenin signaling is considered an attractive target for cancer chemotherapeutic or chemopreventive agents. Small molecules derived from the natural products were used in our cell-based reporter gene assay to identify potential inhibitors of Wnt/ß-catenin signaling. Magnolol, a neolignan from the cortex of Magnolia obovata, was identified as a promising candidate because it effectively inhibited ß-catenin/TCF reporter gene (TOPflash) activity. Magnolol also suppressed Wnt3a-induced ß-catenin translocation and subsequent target gene expression in human embryonic kidney 293 cells. To further investigate the precise mechanisms of action in the regulation of Wnt/ß-catenin signaling by magnolol, we performed Western blot analysis, real-time reverse transcriptase-polymerase chain reactions, and an electrophoretic mobility shift assay in human colon cancer cells with aberrantly activated Wnt/ß-catenin signaling. Magnolol inhibited the nuclear translocation of ß-catenin and significantly suppressed the binding of ß-catenin/TCF complexes onto their specific DNA-binding sites in the nucleus. These events led to the down-regulation of ß-catenin/TCF-targeted downstream genes such as c-myc, matrix metalloproteinase-7, and urokinase-type plasminogen activator in SW480 and HCT116 human colon cancer cells. In addition, magnolol inhibited the invasion and motility of tumor cells and exhibited antitumor activity in a xenograft nude mouse model bearing HCT116 cells. These findings suggest that the growth inhibition of magnolol against human colon cancer cells can be partly attributed to the regulation of the Wnt/ß-catenin signaling pathway.

Antimetastatic activity of pinosylvin, a natural stilbenoid, is associated with the suppression of matrix metalloproteinases.

Metastasis is a major cause of death in cancer patients. Our previous studies showed that pinosylvin, a naturally occurring trans-stilbenoid mainly found in Pinus species, exhibited a potential cancer chemopreventive activity and also inhibited the growth of various human cancer cell lines via the regulation of cell cycle progression. In this study, we further evaluated the potential antimetastatic activity of pinosylvin in in vitro and in vivo models. Pinosylvin suppressed the expression of matrix metalloproteinase (MMP)-2, MMP-9 and membrane type 1-MMP in cultured human fibrosarcoma HT1080 cells. We also found that pinosylvin inhibited the migration of HT1080 cells in colony dispersion and wound healing assay systems. In in vivo spontaneous pulmonary metastasis model employing intravenously injected CT26 mouse colon cancer cells in Balb/c mice, pinosylvin (10 mg/kg body weight, intraperitoneal administration) significantly inhibited the formation of tumor nodules and tumor weight in lung tissues. The analysis of tumor in lung tissues indicated that the antimetastatic effect of pinosylvin coincided with the down-regulation of MMP-9 and cyclooxygenase-2 expression, and phosphorylation of ERK1/2 and Akt. These data suggest that pinosylvin might be an effective inhibitor of tumor cell metastasis via modulation of MMPs.

Cytotoxic and antineoplastic activity of timosaponin A-III for human colon cancer cells.

The potential antitumor activity of timosaponin A-III (1), a steroidal saponin from the rhizomes of Anemarrhena asphodeloides, was investigated in human colorectal cancer HCT-15 cells both in cell culture and in an in vivo murine xenograft model. Compound 1 inhibited the proliferation of cancer cells with cell-cycle arrest and induction of apoptosis. Cell-cycle arrest in the G0/G1 and G2/M phase by 1 was correlated with the down-regulation of cyclin A, cyclin B1, cyclin-dependent kinase 2 (CDK2), CDK4, proliferating cell nuclear antigen, and c-Myc. The increase of the sub-G1 peak by 1 was also closely related to the induction of apoptosis, which was evidenced by the induction of DNA fragmentation, activation of caspases, induction of cleaved poly-(ADP ribose) polymerase, and suppression of Bcl-xL and Bcl-2 expression. In an in vivo xenograft model, treatment with 1 (2 or 5 mg/kg body weight, three times/week, ip administration) for four weeks significantly suppressed tumor growth in athymic nude mice bearing HCT-15 cells, without any overt toxicity. Cell-cycle arrest and induction of apoptosis might be plausible mechanisms of actions for the observed antineoplastic activity of 1.

Xanthorrhizol, a natural sesquiterpenoid, induces apoptosis and growth arrest in HCT116 human colon cancer cells.

Xanthorrhizol is a sesquiterpenoid from the rhizome of Curcuma xanthorrhiza. In our previous studies, xanthorrhizol suppressed cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expression, inhibited cancer cell growth, and exerted an anti-metastatic effect in an animal model. However, the exact mechanisms for its inhibitory effects against cancer cell growth have not yet been fully elucidated. In the present study, we investigated the growth inhibitory effect of xanthorrhizol on cancer cells. Xanthorrhizol dose-dependently exerted antiproliferative effects against HCT116 human colon cancer cells. Xanthorrhizol also arrested cell cycle progression in the G0/G1 and G2/M phase and induced the increase of sub-G1 peaks. Cell cycle arrest was highly correlated with the downregulation of cyclin A, cyclin B1, and cyclin D1; cyclin-dependent kinase 1 (CDK1), CDK2, and CDK4; proliferating cell nuclear antigen; and inductions of p21 and p27, cyclin-dependent kinase inhibitors. The apoptosis by xanthorrhizol was markedly evidenced by induction of DNA fragmentation, release of cytochrome c, activation of caspases, and cleavage of poly-(ADP-ribose) polymerase. In addition, xanthorrhizol increased the expression and promoter activity of pro-apoptotic non-steroidal anti-inflammatory drug-activated gene-1 (NAG-1). These findings provide one plausible mechanism for the growth inhibitory activity of xanthorrhizol against cancer cells.

Discovery of a new template for anticancer agents: 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl-cytosine (2'-F-4'-seleno-ara-C).

The first synthesis of 2'-deoxy-2'-fluoro-4'-selenoarabinofuranosyl pyrimidines as potent anticancer agents was accomplished using the DAST fluorination as a key step. It was first revealed that selenium atom participated in the DAST fluorination of 4'-selenonucleosides and that conformational bias induced by bulky selenium acted as a decisive factor in the DAST fluorination. Among compounds tested, 2'-F-4'-seleno-ara-C (4a) exhibited highly potent anticancer activity in all cancer cell lines tested and was more potent than ara-C (1).

Down-regulation of c-Src/EGFR-mediated signaling activation is involved in the honokiol-induced cell cycle arrest and apoptosis in MDA-MB-231 human breast cancer cells.

Honokiol is a naturally occurring neolignan abundant in Magnoliae Cortex and has showed anti-proliferative and pro-apoptotic effects in a wide range of human cancer cells. However, the molecular mechanisms on the anti-proliferative activity in cancer cells have been poorly elucidated. In this study, we evaluated the growth inhibitory activity of honokiol in cultured estrogen receptor (ER)-negative MDA-MB-231 human breast cancer cells. Honokiol exerted anti-proliferative activity with the cell cycle arrest at the G0/G1 phase and sequential induction of apoptotic cell death in a concentration-dependent manner. The honokiol-induced cell cycle arrest was well correlated with the suppressive expression of CDK4, cyclin D1, CDK2, cyclin E, c-Myc, and phosphorylated retinoblastoma protein (pRb) at Ser780. Apoptosis caused by honokiol was also concomitant with the cleavage of caspases (caspase-3, -8, and -9) and Bid along with the suppressive expression of Bcl-2, but it was independent on the expression of Bax and p53. In addition, honokiol-treated cells exhibited the cleavage of poly (ADP-ribose) polymerase (PARP) and DNA fragmentation. In the analysis of signal transduction pathway, honokiol down-regulated the expression and phosphorylation of c-Src, epidermal growth factor receptor (EGFR), and Akt, and consequently led to the inactivation of mTOR and its downstream signal molecules including 4E-binding protein (4E-BP) and p70 S6 kinase. These findings suggest that honokiol-mediated inhibitory activity of cancer cell growth might be related with the cell cycle arrest and induction of apoptosis via modulating signal transduction pathways.

Inhibition of cell proliferation through cell cycle arrest and apoptosis by thio-Cl-IB-MECA, a novel A3 adenosine receptor agonist, in human lung cancer cells.

Human A3 adenosine receptor (A3AR) agonists showed the anti-tumor activity in various in vitro and in vivo studies. The present study investigates the anti-proliferative effect of a novel adenosine analog 2-chloro-N6-(3-iodobenzyl)-4'-thioadenosine-5'-N-methyluronamide (thio-Cl-IB-MECA) in A549 human lung cancer cells. Thio-Cl-IB-MECA induced arrest of cell cycle progression in G0/G1 phase at lower concentrations (up to 20 microM) and apoptotic cell death at a higher concentration (80 microM), which were manifested by down-regulation of cyclin D1, c-myc, and CDK4, activation of caspase-3 and -9, and cleavage of poly(ADP-ribose) polymerase (PARP). The activation of Akt-mediated signaling was also inhibited by treatment with thio-Cl-IB-MECA. These data might suggest the potential therapeutic value of an adenosine analog in the treatment of human lung cancer.

Antiproliferative effects of dibenzocyclooctadiene lignans isolated from Schisandra chinensis in human cancer cells.

Dibenzocyclooctadiene lignans isolated from Schisandra chinensis showed antiproliferative effects in various human cancer cells. The methoxy groups at C-3, C-4, C-3', and C-4', the hydroxyl group at C-8', and the stereo-configuration of the biphenyl ring and the angeloyl group might have influence on these activities. Additional studies indicate that one of mechanism of action of an active compound schizantherin C in A549 human lung cancer cells was related to the inhibition of cell cycle progression in G0/G1 phase.

Prenylated flavonoids from the heartwood of Artocarpus communis with inhibitory activity on lipopolysaccharide-induced nitric oxide production.

A new prenylated chalcone, 3' ',3' '-dimethylpyrano[3',4']2,4,2'-trihydroxychalcone (1), was isolated from the heartwood of Artocarpus communis. Two flavonoid derivatives, (-)-cycloartocarpin (9) and (-)-cudraflavone A (10), were isolated as new isomers. In addition, eight known flavonoids, isobacachalcone (2), morachalcone A (3), gemichalcones B (4) and C (5), artocarpin (6), cudraflavone C (7), licoflavone C (8), and (2S)-euchrenone a(7) (11), were isolated and identified from this plant for the first time. Compounds 1-4, 6, and 11 exhibited potent inhibitory activity on nitric oxide production in RAW264.7 LPS-activated mouse macrophage cells with IC(50) values of 18.8, 6.4, 16.4, 9.3, 18.7, and 12.3 microM, respectively. The structure of compound 1 was elucidated by spectroscopic data analysis, including 1D and 2D NMR experiments.