Augmented decision-making for acral lentiginous melanoma detection using deep convolutional neural networks.

BACKGROUND: Several studies have achieved high-level performance of melanoma detection using convolutional neural networks (CNNs). However, few have described the extent to which the implementation of CNNs improves the diagnostic performance of the physicians. OBJECTIVE: This study is aimed at developing a CNN for detecting acral lentiginous melanoma (ALM) and investigating whether its implementation can improve the initial decision for ALM detection made by the physicians. METHODS: A CNN was trained using 1072 dermoscopic images of acral benign nevi, ALM and intermediate tumours. To investigate whether the implementation of CNN can improve the initial decision for ALM detection, 60 physicians completed a three-stage survey. In Stage I, they were asked for their decisions solely on the basis of dermoscopic images provided to them. In Stage II, they were also provided with clinical information. In Stage III, they were provided with the additional diagnosis and probability predicted by the CNN. RESULTS: The accuracy of ALM detection in the participants was 74.7% (95% confidence interval [CI], 72.6-76.8%) in Stage I and 79.0% (95% CI, 76.7-81.2%) in Stage II. In Stage III, it was 86.9% (95% CI, 85.3-88.4%), which exceeds the accuracy delivered in Stage I by 12.2%p (95% CI, 10.1-14.3%p) and Stage II by 7.9%p (95% CI, 6.0-9.9%p). Moreover, the concordance between the participants considerably increased (Fleiss-κ of 0.436 [95% CI, 0.437-0.573] in Stage I, 0.506 [95% CI, 0.621-0.749] in Stage II and 0.684 [95% CI, 0.621-0.749] in Stage III). CONCLUSIONS: Augmented decision-making improved the performance of and concordance between the clinical decisions of a diverse group of experts. This study demonstrates the potential use of CNNs as an adjoining, decision-supporting system for physicians' decisions.

Combined analysis of the MspI and XbaI polymorphisms in intron 22 of the factor VIII gene for detection of hemophilia A in a Korean population.

To determine the usefulness of MspI/int22h-1 (intron 22 homologous region-1) polymorphism of the factor VIII gene for molecular genetic diagnosis of hemophilia A in the Korean population, MspI/intron 22 and XbaI/intron 22 polymorphisms were analyzed in 101 unrelated Korean families with severe hemophilia A. The expected heterozygosity rates of MspI/int22h-1 and XbaI/int22h-1 polymorphisms were 49.5 and 43.6%, respectively; these polymorphisms were not in complete linkage disequilibrium. Combined analysis using both polymorphisms provided an informative rate of 66.3%. These results suggest that PCR analysis of the MspI/int22h-1 polymorphism of the factor VIII gene would be useful for carrier detection and prenatal diagnosis of hemophilia A in the Korean population.

Initiation of bacteriophage PRD1 DNA replication on single-stranded templates.

In vitro studies have demonstrated that single-stranded DNA molecules containing the 3' terminal nucleotides of the PRD1 DNA replication origin can support initiation by a protein-primed mechanism. We have determined the minimal requirements for priming by analyzing the template activity of various deletion derivatives. Our results showed that the 3'-terminal 15 nucleotides of the replication origin are sufficient for priming. The finding that the requirements for recognition of replication origin are different from those for priming suggests that there are two distinct steps during initiation of PRD1 DNA replication: first, recognition of the replication origin on double-stranded DNA and second, the priming event on single-stranded DNA. In addition our results showed that additional bases at the 3' end of templates did not affect priming activity, suggesting that the priming site is searched for from inside the template.

Sequence requirements for protein-primed DNA replication of bacteriophage PRD1.

In vitro studies have demonstrated that linear duplex, protein-free DNA molecules containing an inverted terminal repeat (ITR) sequence of the PRD1 genome at one end can undergo replication by a protein-primed mechanism. No DNA replication was observed when the ITR sequence was deleted or was not exposed at the terminus of the template DNA. We have determined the minimal origin of replication by analyzing the template activity of various deletion derivatives. Our results showed that the terminal 20 base-pairs of ITR are required for efficient in vitro DNA replication. We have found that, within the minimal replication origin region, there are complementary sequences. A site-specific mutagenesis analysis showed that most of the point mutations in the complementary sequences markedly reduced the template activity. The analyses of the results obtained with synthetic oligonucleotides have revealed that the specificity of the replication origin is strand specific and even on a single-stranded template a particular DNA sequence including a 3'-terminal C residue is required for the initiation of PRD1 DNA replication in vitro.

A radioimmunoassay method for detection of DNA based on chemical immobilization of anti-DNA antibody.

High selectivity provided by biomolecules such as antibodies and enzymes has been exploited during the last two decades for development of biosensors. Of particular importance are efficient immobilization methods for biomolecules in order to preserve their biological activities. In this study, we have evaluated immobilization strategies for an anti-DNA antibody on a self-assembled monolayer of omega-functionalized thiols. The antibody was immobilized via peptide bond formation between the primary amines in the antibody and the carboxyl groups on the self-assembled monolayer. The peptide bond coupling was achieved by activating COOH groups on the surface through N-Hydroxysuccimide (NHS)-ester formation, followed by acylation of NH2 group in the antibody. DNA binding activity of the immobilized antibody was examined by counting beta emission from 35S-labeled DNA.

Cloning, sequencing and expression in Escherichia coli of a thermophilic lipase from Bacillus thermoleovorans ID-1.

A thermophilic lipase of Bacillus thermoleovorans ID-1 was cloned and sequenced. The lipase gene codes 416 amino acid residues and contains the conserved pentapeptide Ala-X-Ser-X-Gly as other Bacillus lipase genes. The optimum temperature of the lipase is 75 degrees C, which is higher than other known Bacillus lipases. For expression in Escherichia coli, the lipase gene was subcloned in pET-22b(+) vector with a strong T7 promoter. Lipase activity was approximately 1.4-fold greater than under the native promoter.

Characterization of glk, a gene coding for glucose kinase of Corynebacterium glutamicum.

The glk gene from Corynebacterium glutamicum was isolated by complementation using Escherichia coli ZSC113 (ptsG ptsM glk). We sequenced a total of 3072 bp containing the 969-bp open reading frame encoding glucose kinase (Glk). The glk gene has a deduced molecular mass of 34.2 kDa and contains a typical ATP binding site. Comparison with protein sequences revealed homologies to Glk from Streptomyces coelicolor (43%) and Bacillus megaterium (35%). The glk gene in C. glutamicum was inactivated on the chromosome via single crossover homologous recombination and the resulting glk mutant was characterized. Interestingly, the C. glutamicum glk mutant showed poor growth on rich medium such as LB medium or brain heart infusion medium in the presence or absence of glucose, fructose, maltose or sucrose as the sole carbon source. Growth yield was reduced significantly when maltose was used as the sole carbon source using minimal medium. The growth defect of glk mutant on rich medium was complemented by a plasmid-encoded glk gene. A chromosomal glk-lacZ fusion was constructed and used to monitor glk expression, and it was found that glk was expressed constitutively under all tested conditions with different carbon sources.

Genomic structure of ornithine carbamoyltransferase gene from Canavalia lineata.

The nucleotide sequences of the complete ornithine carbamoyltransferase (OCT) gene containing 3,964 bp 3' region and 1,701 bp promoter region were determined from Canavalia lineata leaves. The exons range in size from 131 bp to 390 bp, while the introns range in size from 102 bp to the relatively large size of 1,465 bp; all the splicing junctions followed the conserved GT/AG rule. The transcription initiation site is located 12 bp upstream of the ATG translation initiation site and 69 bp downstream of TATA-box. The regulatory elements located in the 1,701 bp 5' upstream region are GT-1, GATA motif, I-box, SBF-1, Nit2 etc. The structure of the OCT gene from C. lineata was compared with Arabidopsis thaliana, in which two genes consist of 5 exons and 4 introns. The nucleotide sequence of exons and deduced amino acid sequence exhibits 70% and 69% homology, respectively. The deduced amino acid sequences show identical conserved "HPXQ" box, carbamoyl phosphate and ornithine binding sites. The introns of C. lineata OCT gene are larger than those of A. thaliana, except for intron 3. Genomic DNA blot analysis showed that a single ornithine-dependent OCT gene exists in the C. lineata genome.

Three-dimensional geometric modeling of the cochlea using helico-spiral approximation.

In this paper, the three-dimensional geometry of the human cochlea is modeled by the helico-spiral seashell model. The 3-D helico-spiral model, the generalized representation of the Archimedian spiral model, provides a framework for measuring cochlear features based on consistent estimation of model parameters. Nonlinear least square minimization based algorithms are developed for the identification of rotation, center and intrinsic parameters of the helico-spiral representation. Two algorithms are designed for the rotation axis aligned to the modiolar axis: one is more susceptible in the presence of noise, while the other allows applicability to two-dimensional data sets. The estimated center and intrinsic parameters allow the calculation of length, height and angular positions needed for frequency mapping of multichannel cochlear implant electrodes. Model performance is evaluated with numerically synthesized curves with different levels of added random noise, histologic data and real human cochlear spiral computed tomography data.

The effects of mild hypothermia on thiopental-induced electroencephalogram burst suppression.

Thiopental intravenous injections before temporary clipping and mild hypothermia have protective effects in the setting of cerebral ischemia, and are used clinically in some centers. However, it is not known whether mild hypothermia affects thiopental-induced electroencephalogram (EEG) burst suppression. In this study, the authors compared the onset and duration of EEG suppression by thiopental in normothermic (n=10) and mildly hypothermic (n=10) patients undergoing cerebral aneurysm surgery. Spectral analysis was used to compare the prethiopentonal continuous EEG patterns in normothermic and mild hypothermic patients. The patients' body temperatures were controlled by a circulating water mattress and intravenous fluids (normothermia = 36.4+/-0.1 degrees C, mild hypothermia = 33.3+/-0.1 degrees C). Immediately before temporary clipping, thiopental sodium (5 mg/kg) was administered intravenously. Onset time (the amount of time from thiopental injection to the first complete EEG suppression), duration of suppression (the amount of time from the first complete EEG suppression to recovery on continuous EEG from burst suppression), and maximum duration of isoelectric EEG (the longest time interval between two bursts during burst suppression) were measured. Onset time was shortened (25.8+/-1.4 versus 43.5+/-5.6 seconds), and duration of suppression (531.0+/-56.6 versus 165.0+/-16.9 seconds) and the maximum duration of isoelectric EEG (47.7+/-5.8 versus 22.8+/-2.0 seconds) were prolonged in the patients with mild hypothermia. In two normothermic patients, the standard dose of thiopental did not produce burst suppression, but only a mild decrease in spectral edge frequency. The authors concluded that the effects of mild hypothermia on thiopental-induced EEG suppression are not simply additive, but synergistic.

Design of an emergency teleradiology system based on progressive transmission.

In clinical surgery, there are frequent needs for communication between the house staff and the attending physician in an emergency situation. To overcome the limitation of voice communication through the telephone line, we have designed an 'emergency teleradiology system' which can be used for emergency surgical and medical decision making. This system can transmit the high quality images of CT, MRI, and other X-ray data using a PC attached to a modem through the conventional telephone line. It is based on the progressive transmission system which enables the successive update of a received image. The iterative residual coding/decoding algorithm efficiently compresses the image to maximally utilize the low bandwidth PSTN channels. This system also satisfies design requirements such as low-cost, ease of operation, fast transmission, and interactive image communication including voice. Test results using several CT, MR, and X-ray images evaluate the compression performance, image quality, transmission time and computational time of the coding and decoding processes, thus demonstrate the usefulness of this system in an emergency situation.

Development of a computerized EEG imaging system with a personal computer.

The authors developed a computerized electroencephalography imaging system with an IBM PC AT. The EEG signals amplified with a 16 channel EEG machine were digitized at 51.2 Hz (512 samples per epoch). The shifted DC potential and 60Hz artificats were removed by a high pass filter and 60Hz notch filter. A window function consisting of a 10% cosine taper was obtained by weighting the points at either end of the epoch by a cosine bell. A fast Fourier transform was applied to every epoch and the power spectrum estimates were computed in 0.39 Hz steps. The activity estimates for the delta, theta, alpha and beta bands were computed by summimg adjacent values. The outline of the top-down maps was formed from a series of sagittal cuts, then 32 electrodes were placed on the map. A file was created which contained a table of weighting parameters for calculating the interpolated values for every point within the outline. Each weight was in inverse linear proportion to the distance of the pixel to the nearest four electrodes. The map was finally generated with computation of the spectral EEG in each pixel according to the weighting parameter. The functioning of this system was tested with a functional generator and a human subject.

Design of a medical image processing software for clinical-PACS.

Software modules for interactive display, manipulation and retrieval of medical images have been designed for a Picture Archiving and Communications System (PACS). The target of these modules is not for a high-end diagnostic workstation for radiologists, but for a PC-based low cost clinical workstation for a referring physician. This software is constructed based on a concept of an object-oriented language which is designed to be modular and expandable. It consists of several functional modules: (a) a communication module for image retrieval, (b) a standard module for the interpretation of the DICOM images, (c) a user interface module for the non-computer oriented clinicians and (d) a tool module for viewing and manipulating images as well as editing the annotation.

Three-dimensional modeling and visualization of the cochlea on the Internet.

Three-dimensional (3-D) modeling and visualization of the cochlea using the World Wide Web (WWW) is an effective way of sharing anatomic information for cochlear implantation over the Internet, particularly for morphometry-based research and resident training in otolaryngology and neuroradiology. In this paper, 3-D modeling, visualization, and animation techniques are integrated in an interactive and platform-independent manner and implemented over the WWW. Cohen's template shape with mean cross-sectional areas of the human cochlea is extended into a 3-D geometrical model. Also, spiral computer tomography data of a patient's cochlea is digitally segmented and geometrically represented. The cochlear electrode array is synthesized according to its specification. Then, cochlear implantation is animated with both idealized and real cochlear models. Insertion length, angular position, and characteristic frequency of individual electrodes are estimated online during the virtual insertion. The optimization of the processing parameters is done to demonstrate the feasibility of this technology for clinical applications.

Design of a PC-based multimedia telemedicine system for brain function teleconsultation.

During time-critical brain surgery, the detection of developing cerebral ischemia is particularly important because early therapeutic intervention may reduce the mortality of the patient. The purpose of this system is to provide an efficient means of remote teleconsultation for the early detection of ischemia, particularly when subspecialists are unavailable. The hardware and software design architecture for the multimedia brain function teleconsultation system including the dedicated brain function monitoring system is described. In order to comprehensively support remote teleconsultation, multi-media resources needed for ischemia interpretation were included: EEG signals, CSA, CD-CSA, radiological images, surgical microscope video images and video conferencing. PC-based system integration with standard interfaces and the operability over the Ethernet meet the cost-effectiveness while the modular software was customized with a diverse range of data manipulations and control functions necessary for shared workspace and standard interfaces.

Yuk-Hap-Tang induces apoptosis by intervening mn-SOD in human cervical carcinoma HeLa cells.

Yuk-Hap-Tang (YHT) induces cell death in human cervical carcinoma HeLa cells. Caspase-3, -6 and -9 were markedly activated in HeLa cells treated with YHT. The preferred substrate for caspase-3 cysteine protease, PARP, was cleaved to its 85-kDa cleavage product. YHT increased the amount of the anti-apoptotic protein, Bcl-2, and the pro-apoptotic protein, Bax. Although p53 has been reported to accumulate in cancer cells in response to anticancer agents, the p53 expression level was not changed in HeLa cells treated with YHT. Manganese (Mn)-TBAP, a mitochondria-specific SOD mimetic agent and NAC/GSH (N-acetyl cysteine/ reduced glutathione) reduced the YHT-induced cytotoxicity and decreased the number of the YHT-induced apoptotic cells. Furthermore, YHT reduced the expression of Mn-SOD protein and its activity in HeLa cells. The data demonstrate that YHT induces the apoptosis of human cervical carcinoma HeLa cells by intervening Mn-SOD.

Development of a medical record and radiographic image transmission system using a high-speed communication network.

A medical record and radiographic image transmission system has been developed using a high-speed communication network. The databases are designed to store and transmit the data acquired from the scanner. To maximally utilize the communication bandwidth, the medical records and radiographic images are compressed using the G3 facsimile and JPEG coding standard method, respectively. TCP/IP, OOP and Windows-based system software enable a modular design, future expandability, open system interconnectivity, and diverse image manipulation functions.

Implementation of a low-cost PACS/CR for clinical use in Yonsei Cardiovascular Center.

The PACS/CR for clinical use in Yonsei Cardiovascular Center has been designed and implemented. Our system is open architecture to comply with emerging standards such as DICOM. database SQL, TCP/IP and to reduce operational and maintenance costs, PC-based low cost workstations running Microsoft Windows, database as Microsoft SQL based on Client/Server, Long-term storage using CD-ROM Jukebox are developed. Also, auto routing and image pre-fetching are implemented.

Characteristics of the pulse wave in patients with chronic gastritis and the healthy in Korean medicine.

Chronic gastritis is a disease that occurs in one in every 10 persons in Korea. Endoscopic examination is needed to diagnose chronic gastritis in western medicine, but it causes patients pain, long period of examinations and financial burden. In KM (Korean Medicine), on the other hand, it can be known whether stomach is abnormal or not through a pulse diagnosis. The 'Guan' position of the right wrist is related to a stomach in KM. Thus, the pulse wave of the right-hand "Guan" of patients with chronic gastritis and the healthy were measured. Then, the diagnostic parameter and features to distinguish between the patients with chronic gastritis and the healthy were discovered. Through P-H curve, consequently, it can be concluded that the pulse waves of patients with chronic gastritis appear as a floating pulse, whereas the pulse waves of the healthy appear as a normal pulse.