Factors Influencing the Effectiveness of Adopting Electronic Medical Record-Based Reporting Systems for Notifiable Disease Surveillance: A Quantitative Analysis.

The coronavirus disease 2019 (COVID-19) pandemic has led to greater attention being given to infectious disease surveillance systems and their notification functionalities. Although numerous studies have explored the benefits of integrating functionalities with electronic medical record (EMR) systems, empirical studies on the topic are rare. The current study assessed which factors influence the effectiveness of EMR-based reporting systems (EMR-RSs) for notifiable disease surveillance. This study interviewed staff from hospitals with a coverage that represented 51.39% of the notifiable disease reporting volume in Taiwan. Exact logistic regression was employed to determine which factors influenced the effectiveness of Taiwan's EMR-RS. The results revealed that the influential factors included hospitals' early participation in the EMR-RS project, frequent consultation with the information technology (IT) provider of the Taiwan Centers for Disease Control (TWCDC), and retrieval of data from at least one internal database. They also revealed that using an EMR-RS resulted in more timely, accurate, and convenient reporting in hospitals. In addition, developing by an internal IT unit instead of outsourcing EMR-RS development led to more accurate and convenient reporting. Automatically loading the required data enhanced the convenience, and designing input fields that may be unavailable in current databases to enable physicians to add data to legacy databases also boosted effectiveness of the reporting system.

Mutant Isocitrate Dehydrogenase 1 Expression Enhances Response of Gliomas to the Histone Deacetylase Inhibitor Belinostat.

Histone deacetylase inhibitors (HDACis) are drugs that target the epigenetic state of cells by modifying the compaction of chromatin through effects on histone acetylation. Gliomas often harbor a mutation of isocitrate dehydrogenase (IDH) 1 or 2 that leads to changes in their epigenetic state presenting a hypermethylator phenotype. We postulated that glioma cells with IDH mutation, due to the presence of epigenetic changes, will show increased sensitivity to HDACis. This hypothesis was tested by expressing mutant IDH1 with a point alteration-converting arginine 132 to histidine-within glioma cell lines that contain wild-type IDH1. Glioma cells engineered to express mutant IDH1 produced D-2-hydroxyglutarate as expected. When assessed for response to the pan-HDACi drug belinostat, mutant IDH1-expressing glioma cells were subjected to more potent inhibition of growth than the corresponding control cells. Increased sensitivity to belinostat correlated with the increased induction of apoptosis. Finally, a phase I trial assessing the addition of belinostat to standard-of-care therapy for newly diagnosed glioblastoma patients included one patient with a mutant IDH1 tumor. This mutant IDH1 tumor appeared to display greater sensitivity to the addition of belinostat than the other cases with wild-type IDH tumors based on both standard magnetic resonance imaging (MRI) and advanced spectroscopic MRI criteria. These data together suggest that IDH mutation status within gliomas may serve as a biomarker of response to HDACis.

Disordered Vector Models: From Higher Spins to Incipient Strings.

We present a one-parameter family of large N disordered models, with and without supersymmetry, in three spacetime dimensions. They interpolate from the critical large N vector model dual to a classical higher spin theory toward a theory with a classical string dual. We analyze the spectrum and operator product expansion data of the theories. While the supersymmetric model is always well-behaved the nonsupersymmetric model is unitary only over a small parameter range. We offer some speculations on the origin of strings from the higher spins.

Two-Dimensional Bis(dithiolene)iron(II) Self-Powered UV Photodetectors with Ultrahigh Air Stability.

Organometallic two-dimensional (2D) nanosheets with tailorable components have recently fascinated the optoelectronic communities due to their solution-processable nature. However, the poor stability of organic molecules may hinder their practical application in photovoltaic devices. Instead of conventional organometallic 2D nanosheets with low weatherability, an air-stable π-conjugated 2D bis(dithiolene)iron(II) (FeBHT) coordination nanosheet (CONASH) is synthesized via bottom-up liquid/liquid interfacial polymerization using benzenehexathiol (BHT) and iron(II) ammonium sulfate [Fe(NH4)2(SO4)2] as precursors. The uncoordinated thiol groups in FeBHT are easily oxidized, but the Fe(NH4)2(SO4)2 dissociation rate is slow, which facilitates the protection of sulfur groups by iron(II) ions. The density functional theory calculates that the resultant FeBHT network gains the oxygen-repelling function for oxidation suppression. In air, the FeBHT CONASH exhibits self-powered photoresponses with short response times (<40 ms) and a spectral responsivity of 6.57 mA W-1, a specific detectivity of 3.13 × 1011 Jones and an external quantum efficiency of 2.23% under 365 nm illumination. Interestingly, the FeBHT self-powered photodetector reveals extremely high long-term air stability, maintaining over 94% of its initial photocurrent after aging for 60 days without encapsulation. These results open the prospect of using organometallic 2D materials in commercialized optoelectronic fields.

Solution-processed organometallic quasi-two-dimensional nanosheets as a hole buffer layer for organic light-emitting devices.

Two-dimensional (2D) vdW materials have been integrated into optoelectronic devices to achieve exceptional functionality. However, the integration of large-area 2D thin films into organic light-emitting devices (OLEDs) remains challenging because of the finite number of inorganic 2D materials and the high-temperature requirements of their deposition process. The construction of 2D organometallic materials holds immense potential because of their solution synthesis and unlimited structural and functional diversity. Here, we report a facile route using an oil-water interfacial coordination reaction between organic ligands and divalent metal ions to synthesize crystalline quasi-2D organometallic bis(dithiolato)nickel (NiDT) nanosheets with a centimeter scale and a tunable thickness. The NiDT nanosheets can be directly integrated into OLEDs for use as a hole buffer layer and a fluorescent mounting medium without the aid of a transfer process. Moreover, OLEDs with NiDT nanosheets show not only comparable efficiency to conventional OLEDs but also prolonged device lifetime by nearly 2 times. These results open up a new dimension to use quasi-2D organometallic nanosheets as functional layers in large-area organic devices.

Cyclooxygenase-2 Induction by Amino Acid Deprivation Requires p38 Mitogen-Activated Protein Kinase in Human Glioma Cells.

Glioblastomas (GBMs) are malignant brain tumors that can outstrip nutrient supplies due to rapid growth. Cyclooxygenase-2 (COX-2) has been linked to GBMs and may contribute to their aggressive phenotypes. Amino acid starvation results in COX-2 mRNA and protein induction in multiple human glioma cell lines in a process requiring p38 mitogen-activated protein kinase (p38-MAPK) and the Sp1 transcription factor. Increased vascular endothelial growth factor expression results from starvation-dependent COX-2 induction. These data suggest that COX-2 induction with amino acid deprivation may be a part of the adaptation of glioma cells to these conditions, and potentially alter cellular response to anti-neoplastic therapy.

Toward Automatic Reporting of Infectious Diseases.

Accurate, complete, and timely disease surveillance data are vital for disease control. We report a national scale effort to automatically extract information from electronic medical records as well as electronic laboratory systems. The extracted information is then transferred to the centers of disease control after a proper confirmation process. The coverage rates of the automated reporting systems are over 50%. Not only is the workload of surveillance greatly reduced, but also reporting is completed in near real-time. From our experiences, a system sustainable strategy, well-defined working plan, and multifaceted team coordination work effectively. Knowledge management reduces the cost to maintain the system. Training courses with hands-on practice and reference documents are useful for LOINC adoption.

The incidence of Japanese encephalitis in Taiwan--a population-based study.

BACKGROUND: A mass Japanese encephalitis (JE) vaccination program targeting children was launched in Taiwan in 1968, and the number of pediatric JE cases substantially decreased thereafter. The aim of this study was to elucidate the long-term trend of JE incidence, and to investigate the age-specific seroprevalence of JE-neutralizing antibodies. METHODOLOGY/PRINCIPAL FINDINGS: A total of 2,948 laboratory-confirmed JE cases that occurred between 1966 and 2012 were analyzed using a mandatory notification system managed by the Centers for Disease Control, Taiwan. A total of 6,594 randomly-sampled serum specimens obtained in a nationwide population-based survey in 2002 were analyzed to estimate the seroprevalence of JE-neutralizing antibodies in the general population. The average annual JE incidence rate of the group aged 30 years and older was 0.167 cases per 100,000 people between 2001 and 2012, which was higher than the 0.052 cases per 100,000 people among those aged under 30 years. These seroepidemiological findings indicate that the cohort born between 1963 and 1975, who generally received two or three doses of the vaccine and were administered the last booster dose more than 20 years ago, exhibited the lowest positive rate of JE-neutralizing antibodies (54%). The highest and second highest antibody rates were observed, respectively, in the oldest unvaccinated cohort (86%) and in the youngest cohort born between 1981 and 1986, who received four doses 10-15 years ago (74%). CONCLUSION/SIGNIFICANCE: Over the past decade, the main age group of the confirmed JE cases in Taiwan shifted from young children to adults over 30 years of age. People who were born between 1963 and 1975 exhibited the lowest seroprevalence of JE-neutralizing antibodies. Thus, the key issue for JE control in Taiwan is to reduce adult JE cases through a cost-effective analysis of various immunization strategies.

Immunohistochemical demonstration of isocitrate dehydrogenase 1 (IDH1) mutation in a small subset of prostatic carcinomas.

Recent advances in genomic sequencing have resulted in the discovery of the somatic mutations of cytoplasmic isocitrate dehydrogenase 1 (IDH1) in human solid tumors such as gliomas. The most common IDH1 mutation affects codon 132 and results in the conversion of amino acid residue arginine (R) to histidine (H). This IDH1 mutation is associated with a genetic and clinical characteristic group of gliomas in terms of grade and prognosis. We investigated whether immunohistochemistry (IHC) using a monoclonal antibody against the IDH1 mutant protein could be used in routine surgical pathology for identification of the mutation in solid human tumors. A total of 549 solid human tumors were examined in tissue microarrays, including prostate, thyroid, renal cell, ovarian, endometrial, breast, colorectal, non-small cell lung carcinoma, melanomas, and gliomas. IHC detected the IDH1 mutation in 72% (13/18) anaplastic astrocytomas and 30% (3/10) astrocytomas; however, it failed to detect the mutation in 258 thyroid, 11 renal cell, 10 ovarian, 18 endometrial, 20 breast, 25 colorectal, 22 non-small cell lung carcinoma, 25 melanomas, and 8 thyroid follicular adenomas. In contrast, expression of the IDH1 mutation was noted in 3 of 118 (2.5%) prostate carcinomas. Western blotting and polymerase chain reaction-based sequencing confirmed the mutation in 2 prostate carcinomas. This study indicates that IHC is a reliable method for the pathologic identification of the IDH1 mutation in solid human cancers such as prostate carcinomas.

Computer-aided system for health economic evaluation.

BACKGROUND: Health policy makers are usually stranded by the complicated infrastructure and intensive computation related to economic evaluation. OBJECTIVES: It is therefore valuable to develop a computer-aided tool to help health personnel to perform economic evaluation with ease. METHOD: The infrastructure for economic evaluation was first designed. Markov process with micro-simulation was applied to model the disease natural history or lifetime sequale to project the effectiveness by comparing all possible decisions. All the essential elements of economic evaluation together with sensitivity analysis are encoded in this computer-aided software written with SAS Screen Control Language in user-defined menu style. ILLUSTRATION: Screening versus no screening for colorectal cancer was used as an example. CONCLUSION: The computer-aided model for economic evaluation was developed in this study. It is anticipated that the flexibility and user-defined menu style facilitate the wide application of economic evaluation to health care intervention program.

Estimation and prediction system for multi-state disease process: application to analysis of organized screening regime.

RATIONALE, AIMS AND OBJECTIVES: The disease progression of cancer and non-malignant chronic disease often involve a multi-state transition. However, estimation of parameters and prediction regarding the multi-state disease process are complex. This study aimed to develop an estimation and prediction system with a computer-assisted software using SAS/SCL as a platform to predict the risk of any outcome arising from the underlying multi-state process with or without the incorporation of individual characteristics. METHOD: The computer-aided system is first constructed following the theoretical framework of stochastic process. The functions provided in this software include model specification, formulation of likelihood function, parameter estimation, model validation and model prediction. An example of breast cancer screening for a high-risk group in Taiwan was used to demonstrate the usefulness of this software. RESULTS: The natural history of breast cancer of a three-state disease process has been demonstrated. Two suspected risk factors, late age at first full-term pregnancy and obesity, were considered by the form of the proportional hazard model. Formulation of intensity matrix, likelihood function, assignment of initial values, and parameter constraint and estimation were successfully demonstrated in model specification. Model validation suggested a good fit of the constructed model. The application of model prediction enables one to project the effectiveness of organized screening by different inter-screening intervals from a policy level or from an individual basis. CONCLUSIONS: A computer-aided estimation and prediction system for multi-state disease process was developed and demonstrated. This system can be applied to data with the property of multi-state transitions in association with events or disease.

Computer-aided disease prediction system: development of application software with SAS component language.

AIMS: The intricacy of predictive models associated with prognosis and risk classification of disease often discourages medical personnel who are interested in this field. The aim of this study was therefore to develop a computer-aided disease prediction model underpinning a step-by-step statistics-guided approach including five components: (1) data management; (2) exploratory analysis; (3) type of predictive model; (4) model verification; (5) interactive mode of disease prediction using SAS 8.02 Windows 2000 as a platform. METHODS: The application of this system was illustrated by using data from the Swedish Two-County Trial on breast cancer screening. The effects of tumour size, node status, and histological grade on breast cancer death using logistic regression model or survival models were predicted. A total of 20 questions were designed to exemplify the usefulness of each component. We also evaluated the system using a controlled randomized trial. Times to finish the above 20 questions were used as endpoint to evaluate the performance of the current system. User satisfaction with the current system such as easy to use, the efficiency of risk prediction, and the reduction of barrier to predictive model was also evaluated. RESULTS: The intervention group not only performed more efficiently than the control group but also satisfied with this application software. CONCLUSIONS: The MD-DP-SOS system characterized by menu-driven style, comprehensiveness, accuracy and adequacy assessment, and interactive mode of disease prediction is helpful for medical personnel who are involved in disease prediction.

Mutant epidermal growth factor receptor displays increased signaling through the phosphatidylinositol-3 kinase/AKT pathway and promotes radioresistance in cells of astrocytic origin.

Amplification and mutation of the epidermal growth factor receptor (EGFR) are common features of malignant gliomas. The most frequent mutation seen in these tumors involves deletion of exon 2-7 resulting in a constitutively active form of the receptor (EGFRvIII, or deltaEGFR). Since EGFRvIII is found primarily in gliomas and has not been reported in sarcomas, we compared the effects of this altered receptor in immortalized primary astrocytes and fibroblasts. While EGFRvIII displayed ligand-independent autophosphorylation in both cell types, downstream signaling differed. While EGFRvIII increased the proliferative capacity of both astrocytes and fibroblasts consistent with activation of ERK in these cells, EGFRvIII activated AKT only in the immortalized astrocytes. EGFRvIII expression in astrocytes also led to increased radioresistance in that cell type. Furthermore, specific inhibition of phosphotidylinositol-3 kinase (PI-3K) with LY294002 reverted the radioresistant phenotype in the immortalized astrocytes. Thus, selective activation of PI-3K/AKT in astrocytes expressing EGFRvIII appears to be responsible for the observed increase in radioresistance. EGFRvIII's differential ability to activate the PI-3K downstream signal may explain why this mutant receptor is such a prominent lesion in malignant gliomas but less often seen in other tumor types, even those where EGFR signaling has a prominent role.

Resistance to small molecule inhibitors of epidermal growth factor receptor in malignant gliomas.

Epidermal growth factor (EGF) receptor (EGFR) is commonly amplified and/or mutated in high-grade gliomas. Abnormal signaling from this receptor tyrosine kinase is believed to contribute to the malignant phenotypes seen in these tumors. Highly specific small molecule inhibitors of this receptor tyrosine kinase have been developed and may potentially improve the treatment of these highly aggressive brain tumors. A glioma cell line overexpressing EGFR was developed to mimic the situation of a malignant glioma with amplified EGFR, and this line was used to characterize the response to specific EGFR inhibitors. Treatment of our in vitro glioma model with the EGFR kinase inhibitors ZD1839 (Iressa) or PD153035, synthetic anilinoquinazolines with high specificity for EGFR, resulted in significant suppression of EGFR autophosphorylation even with very low levels of drug. However, significantly higher levels of drug were required to fully inhibit signaling through the phosphatidylinositol 3'-kinase/AKT and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) pathways. Interestingly, not all downstream signaling pathways displayed this resistance to inhibition. EGF-dependent activation of signal transducers and activators of transcription-3 occurred at low doses of EGFR inhibitors. The uncoupling of EGFR autophosphorylation and signaling through AKT and ERK was not dependent on EGFR overexpression. In addition, although this response was seen in other glioma and the SK-BR3 breast cancer cell lines, it was not universally present. The SQ20B head and neck squamous carcinoma cell line demonstrated loss of EGF-dependent AKT and ERK activation even at low doses of inhibitor. Despite significant loss of EGF-dependent autophosphorylation, the inability of low levels of EGFR inhibitor to suppress some downstream signaling pathways in our model glioma cell line permitted continued EGF-responsive decreases in the expression of the cyclin-dependent kinase inhibitor p27KIP and EGF-dependent proliferation/cell cycle progression. Although the mechanism responsible for the differential sensitivity of the various signal transduction pathways to EGFR inhibitors remains unclear, signaling through erbB2 does not appear to be involved. The ability of certain tumor cells to maintain signaling through AKT and ERK under EGFR inhibition may represent a potential mechanism of resistance by which a tumor cell may escape the antiproliferative activity of this new class of drugs.