Variable three-term conjugate gradient method for training artificial neural networks.

Artificial neural networks (ANNs) have been widely adopted as general computational tools both in computer science as well as many other engineering fields. Stochastic gradient descent (SGD) and adaptive methods such as Adam are popular as robust optimization algorithms used to train the ANNs. However, the effectiveness of these algorithms is limited because they calculate a search direction based on a first-order gradient. Although higher-order gradient methods such as Newton's method have been proposed, they require the Hessian matrix to be semi-definite, and its inversion incurs a high computational cost. Therefore, in this paper, we propose a variable three-term conjugate gradient (VTTCG) method that approximates the Hessian matrix to enhance search direction and uses a variable step size to achieve improved convergence stability. To evaluate the performance of the VTTCG method, we train different ANNs on benchmark image classification and generation datasets. We also conduct a similar experiment in which a grasp generation and selection convolutional neural network (GGS-CNN) is trained to perform intelligent robotic grasping. After considering a simulated environment, we also test the GGS-CNN with a physical grasping robot. The experimental results show that the performance of the VTTCG method is superior to that of four conventional methods, including SGD, Adam, AMSGrad, and AdaBelief.

Correction to: Genetic and genomic basis of the mismatch repair system involved in Lynch syndrome.

In the original publication, part d of Figure 2 was mistakenly not included.

Genetic and genomic basis of the mismatch repair system involved in Lynch syndrome.

Lynch syndrome is a cancer-predisposing syndrome inherited in an autosomal-dominant manner, wherein colon cancer and endometrial cancer develop frequently in the family, it results from a loss-of-function mutation in one of four different genes (MLH1, MSH2, MSH6, and PMS2) encoding mismatch repair proteins. Being located immediately upstream of the MSH2 gene, EPCAM abnormalities can affect MSH2 and cause Lynch syndrome. Mismatch repair proteins are involved in repairing of incorrect pairing (point mutations and deletion/insertion of simple repetitive sequences, so-called microsatellites) that can arise during DNA replication. MSH2 forms heterodimers with MSH6 or MSH3 (MutSα, MutSß, respectively) and is involved in mismatch-pair recognition and initiation of repair. MLH1 forms a complex with PMS2, and functions as an endonuclease. If the mismatch repair system is thoroughly working, genome integrity is maintained completely. Lynch syndrome is a state of mismatch repair deficiency due to a monoallelic abnormality of any mismatch repair genes. The phenotype indicating the mismatch repair deficiency can be frequently shown as a microsatellite instability in tumors. Children with germline biallelic mismatch repair gene abnormalities were reported to develop conditions such as gastrointestinal polyposis, colorectal cancer, brain cancer, leukemia, etc., and so on, demonstrating the need to respond with new concepts in genetic counseling. In promoting cancer genome medicine in a new era, such as by utilizing immune checkpoints, it is important to understand the genetic and genomic molecular background, including the status of mismatch repair deficiency.

Cascade regulation of PPARγ(2) and C/EBPα signaling pathways by celastrol impairs adipocyte differentiation and stimulates lipolysis in 3T3-L1 adipocytes.

OBJECTIVE: Celastrol, a triterpene from the root bark of the Chinese medicinal plant Tripterygium wilfordii, has been shown to exhibit anti-oxidant, anti-inflammatory, anti-cancer and insecticidal activities. Also, it has been demonstrated that celastrol has obesity-controlling effects in diet-induced obesity mice. However, direct evidence that celastrol contributes to the development of adipocyte differentiation and lipolysis has not been fully elucidated. Moreover, no previous studies have evaluated whether celastrol may regulate adipogenic transcriptional markers in adipocytes. MATERIALS/METHODS: In order to address the questions above, we extended previous observations and investigated in vitro celastrol signaling study whether celastrol may regulate differentiation, lipolysis and key adipogenic transcriptional pathways in 3T3-L1 adipocytes. RESULTS: Treatment of celastrol not only inhibited adipocyte differentiation (lipid accumulation, glyceraldehyde-3-phosphate dehydrogenase activity and triglyceride content) but also increased lipolysis (glycerol release and free fatty acid release) in 3T3-L1 adipocytes. In addition, all celastrol-regulated functional activities were controlled by PPARγ(2) and C/EBPα signaling pathways in duration of celastrol's treatment in 3T3-L1 adipocytes. CONCLUSION: Our initial data from in vitro celastrol signaling studies suggest novel insights into the role of PPARγ(2) and C/EBPα as probable mediators of the action of celastrol in regulating adipocyte differentiation and lipolysis in 3T3-L1 adipocytes.

Association between Muscle Loss and Urinary Incontinence in Elderly Korean Women.

BACKGROUND: Incontinence and muscle loss are important senior health issues. Nevertheless, there are no available domestic or international studies on the association between urinary incontinence and muscle loss. The aim of this study was to investigate the association between muscle loss and urinary incontinence in elderly Korean woman. METHODS: Korean women (1,313) ≥65 years of age whose complete body composition data were collected using dual X-ray absorptiometry were analyzed from the Fourth Korean National Health and Nutritional Examination Surveys. Class I and II losses of the appendicular, truncal, and total muscle mass were defined using adjustments for weight and height. Each participant's incontinence status was collected using constructed questionnaires. Multiple logistic regression was performed to examine the association between muscle loss and incontinence. RESULTS: On the basis of physician-diagnosed incontinence, weight- and height-adjusted muscle loss showed no association with urinary incontinence (weight-adjusted muscle loss: class I adjusted odds ratio [aOR], 0.77; 95% confidence interval [CI], 0.34 to 1.73; class II aOR, 1.37; 95% CI, 0.59 to 3.18; height-adjusted muscle loss: class I aOR, 0.51; 95% CI, 0.18 to 1.51; class II aOR, 1.86; 95% CI, 0.22 to 15.79). Similar results were observed for truncal muscle and total muscle mass as well as self-reported urinary incontinence. CONCLUSION: Our study found no association between urinary incontinence and appendicular, truncal, and total muscle loss in elderly Korean women.

Fabrication of electroless nickel plated aluminum freeform mirror for an infrared off-axis telescope.

Freeform mirrors can be readily fabricated by a single point diamond turning (SPDT) machine. However, this machining process often leaves mid-frequency errors (MFEs) that generate undesirable diffraction effects and stray light. In this work, we propose a novel thin electroless nickel plating procedure to remove MFE on freeform surfaces. The proposed procedure has a distinct advantage over a typical thick plating method in that the machining process can be endlessly repeated until the designed mirror surface is obtained. This is of great importance because the sophisticated surface of a freeform mirror cannot be optimized by a typical SPDT machining process, which can be repeated only several times before the limited thickness of the nickel plating is consumed. We will also describe the baking process of a plated mirror to improve the hardness of the mirror surface, which is crucial for minimizing the degradation of that mirror surface that occurs during the polishing process. During the whole proposed process, the changes in surface figures and textures are monitored and cross checked by two different types of measurements, as well as by an interference pattern test. The experimental results indicate that the proposed thin electroless nickel plating procedure is very simple but powerful for removing MFEs on freeform mirror surfaces.

Preoperative predictable factors for the occurrence of adjacent segment degeneration requiring second operation after spinal fusion at isolated L4-L5 level.

STUDY DESIGN: Retrospective study. OBJECTIVE: The purpose of this study was to clarify (1) the overall prevalence of radiologic and clinical adjacent segment disease (ASD), (2) the prevalence of radiologic ASD at cranial versus caudal adjacent segments, and (3) preoperative risk factors and preoperative radiologic features associated with radiologic disc degeneration of the cranial and caudal adjacent segments. METHODS: A total of 154 patients who underwent posterior lumbar interbody fusion and screw-rod fixation at the L4-L5 level were retrospectively evaluated more than 2 years after surgery. We analyzed demographic factors and radiographic features. Special focus was preoperative radiographic features of patients who required additional surgery. These patients were studied to detect risk factors for clinical deterioration. RESULTS: Of 154 patients, 103 (66.8%) showed radiologic degeneration at an adjacent segment after surgery-92 (59.7%) at the cranial adjacent segment and 61 (39.6%) at the caudal adjacent segment-and 10 patients (6.4%) required second operation because of radicular pain as well as severe back pain or spinal instability with back pain and neurologic deficits. Age, body mass index (BMI), and preexisting stenosis at the cranial adjacent segment were identified as important risk factors for clinical ASD requiring second operation. CONCLUSION: Age, BMI, and preexisting stenosis at the cranial adjacent segment were the most important risk factors for clinical ASD requiring a second operation. Careful consideration is warranted when these risk factors are present.

Recognition of and interventions for Mibyeong (subhealth) in South Korea: a national web-based survey of Korean medicine practitioners.

BACKGROUND: Medically unexplained symptoms (MUSs) are common in primary care. At present, there are no proven, comprehensive treatments available in primary care for patients with MUSs. However, MUS has parallels with "subhealth" or Mibyeong from traditional East-Asian medicine, and thus, Mibyeong interventions could be effective in treating MUS. Unfortunately, studies on Mibyeong and its intervention methods are relatively rare. METHODS: We administered a web-based survey to 17,279 Korean medicine (KM) practitioners registered with the Association of Korean Medicine. The response rate was 4.9% (n = 849). Based on the responses received, we assessed how much they agreed with concepts related to Mibyeong on a 7-point scale from "do not agree" to "strongly agree." Respondents were also asked to indicate how frequently they encountered various subtypes and patterns of Mibyeong, and how frequently they use listed intervention methods. RESULTS: Data from 818 respondents were analyzed after excluding those with no clinical experience. On average, respondents were male general practitioners aged between 30 years and 49 years, working or living in metropolitan areas such as Seoul, Incheon, and Gyeonggi-do. Responses did not differ by demographics. Respondents generally thought that Mibyeong referred to subjective or borderline findings without certain disease, and that Mibyeong has various subtypes and patterns. Subtypes included fatigue, pain, and digestion problems; patterns were either deficiencies (e.g., qi, blood, and yin deficiency) or stagnations (e.g., liver qi depression and qi stagnation). Decoction was the most frequently used type of intervention for Mibyeong of all items listed, followed by acupuncture and moxibustion. Patient education was also recommended, suggesting healthy eating, promoting healthy environment, and exercise. CONCLUSION: We were able to provide preliminary results on KM practitioners' recognition of and interventions for Mibyeong, but further research is needed to develop a detailed definition of Mibyeong and its myriad subtypes and patterns, and evaluations of the efficacy of Mibyeong interventions.

Recurrence Rate after Herniotomy only versus Discectomy in Lumbar Disc Herniation.

OBJECTIVE: Lumbar disc herniation (LDH) recurrence necessitating reoperation can pose problems following spinal surgery, with an overall reported incidence of approximately (3-13%). The purpose of this study is to identify the rate of recurrent disc herniation, to discuss the radiologic indications for herniotomy and to analyze clinical outcomes compared with conventional discectomy. METHODS: This study is a retrospective case control study. The authors retrospectively reviewed 114 patients who underwent herniotomy & conventional discectomy by a single surgeon for single-level LDH between June 2009 and May 2012. Herniotomy group was 57 patients and conventional discectomy group was 57 patients that were selected from 631 patients using stratified randomization. Evaluation for LDH recurrence included detailed medical chart and radiologic review and telephone interview. Postoperative VAS and the Korean version of ODI were examined one week after surgery. Clinical outcome was investigated according to Odom's criteria from three months to three years. RESULTS: Of the 114 patients for whom the authors were able to definitively assess symptomatic recurrence status, four patients (7%) experienced LDH recurrence following single-level herniotomy and three patients (5.2%) conventional discectomy. There were no differences in the VAS and Korean version of ODI between herniotomy group and conventional discectomy group. The herniotomy group had better results than the conventional discectomy group in clinical outcome from three months to three years, but the difference was not significant. CONCLUSION: There were no significant differences in clinical outcome between herniotomy and conventional discectomy. Recurrence rates following herniotomy for LDH compare favorably with those in patients who have undergone conventional discectomy, lending further support for its effectiveness in treating herniotomy.

Is the Cross-sectional Area after Unilateral Open Door Laminoplasty Wider than that after Midline Splitting Laminoplasty ? : Mathematical Approach.

OBJECTIVE: The aim of this study was to compare geometrically cross-sectional areas of two different laminoplasty techniques in same opening size. Some investigators have studied the expanded areas of the two different techniques using imaging study. Although it is unclear that postoperative spinal canal is correlated with the surgical outcome we just focused on mathematical and geometrical correlation of the expandable area with surgical opening size in different laminoplasty techniques. METHODS: To predict the expandable area by a midline splitting technique and a unilateral open door technique, we placed an imaginary isosceles triangle in the spinal canal and drew graphs for the equation of the expandable areas in same opening size using the Pythagorean theorem and mathematical program. To substitute the constant figures of mathematical formula we estimated the normal cervical spine CT scans of 50 Korean adults. RESULTS: We subtracted the imaginary triangle from the spinal canal and were left with the remaining area of the spinal canal that was not changed before and after surgery. In same opening size the expandable area by the midline splitting technique was same but slightly wider than the unilateral open door technique, irrespective of the triangular shape. For a normal isosceles triangle the results were the same. CONCLUSION: Using mathematical proof, the expandable area after the midline splitting technique was same but slightly larger than that after the unilateral open door technique, irrespective of the size of the lamina opening.

Alterations of the base excision repair gene MUTYH in sporadic colorectal cancer.

The base excision repair gene MUTYH encodes glycosylase which removes adenine residues mispaired with 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHG). Biallelic germline mutations of the MUTYH gene are known to cause multiple colorectal adenomas including polyposis and cancer, mostly due to G:C➝T:A transversions in proto-oncogenes or tumor suppressor genes. The risk of colorectal cancer (CRC) in monoallelic mutation carriers of MUTYH is estimated to be higher in comparison with non-carriers. To investigate the possible role in sporadic CRC, we examined alterations of the MUTYH gene including somatic mutations and allelic loss in 101 cases of sporadic CRC, together with the KRAS mutation in some cases. MUTYH mutations in cancer DNA were detected in 3 cases, while mutations were also found in DNA samples from normal tissues, indicating that all were germline mutations. Allelic loss at the MUTYH locus was found in 10 of 51 (20.0%) CRC cases and KRAS mutations were found in 33 of the 101 (32.7%) samples. There was no significant difference in the rate of G:C➝T:A transversion in KRAS between cases with allelic loss (1 of 10, 10.0%) and without allelic loss (9 of 41, 22.0%). Investigation of quantitative allelic imbalance at SNP rs3219489 of MUTYH showed that CRC cases with C allele dominance (minor type corresponding to His) were more frequently detected with G:C➝T:A transversions than in those with G allele dominance (major type corresponding to Gln). In conclusion, somatic alterations of MUTYH in sporadic CRC were rare, similar to other DNA repair genes. However, it is possible that unknown mutations of regions not analyzed in this study and epigenetic changes of the promoter region of MUTYH may contribute to the disease.

Chronic pure radiculopathy in patient with organizing epidural hematoma around C8 nerve root.

Spontaneously occurring spinal epidural hematomas are uncommon clinical findings, and the chronic form is the rarest and its most frequent location is the lumbar spine. Pure radicular involvement is far less frequent than myelopathy. We report a case of progressive radiculopathy in a 52-year-old man with spontaneously occurring cervical epidural hematoma (SCEH). The patient had left hand weakness and numbness for 4 months. MRI scan showed small space-occupying lesion around left 8th cervical nerve root. After surgery we confirmed chronic organizing epidural hematoma. To the best of our knowledge, this is the second reported case in the worldwide literature of pure radiculopathy in a patient with chronic SCEH.

The clinical and radiological outcomes of minimally invasive transforaminal lumbar interbody single level fusion.

STUDY DESIGN: This is a retrospective study that was done according to clinical and radiological evaluation. PURPOSE: We analyzed the clinical and radiological outcomes of minimally invasive transforaminal lumbar interbody single level fusion. OVERVIEW OF LITERATURE: Minimally invasive transforaminal lumbar interbody fusion is effective surgical method for treating degenerative lumbar disease. METHODS: The study was conducted on 56 patients who were available for longer than 2 years (range, 24 to 45 months) follow-up after undergoing minimally invasive transforminal lumbar interbody single level fusion. Clinical evaluation was performed by the analysis of the visual analogue scale (VAS) score and the Oswestry Disability Index (ODI) and the Kirkaldy-Willis score. For the radiological evaluation, the disc space height, the segmental lumbar lordotic angle and the whole lumbar lordotic angle were analyzed. At the final follow-up after operation, the fusion rate was analyzed according to Bridwell's anterior fusion grade. RESULTS: For the evaluation of clinical outcomes, the VAS score was reduced from an average of 6.7 prior to surgery to an average of 1.8 at the final follow-up. The ODI was decreased from an average of 36.5 prior to surgery to an average of 12.8 at the final follow-up. In regard to the clinical outcomes evaluated by the Kirkaldy-Willis score, better than good results were obtained in 52 cases (92.9%). For the radiological evaluation, the disc space height (p = 0.002), and the whole lumbar lordotic angle (p = 0.001) were increased at the final follow-up. At the final follow-up, regarding the interbody fusion, radiological union was obtained in 54 cases (95.4%). CONCLUSIONS: We think that if surgeons become familiar with the surgical techniques, this is a useful method for minimally invasive spinal surgery.

Trends of the New Outpatients in a University-based Family Practice.

BACKGROUND: Analysis of outpatient visits to primary care offers essential data for residency training by understanding 'reasons for encounter (RFE).' This study was designed to recognize the effect of population aging on demographic characteristics and RFEs. METHODS: We included all patients who had visited family practice clinic in Kyung Hee University Hospital in Seoul during each first 5 working days of September, October, and November in 2001 and 2008. New patients included those who hadn't visited within the last 6 months or more. Information on each patient's age, sex, and reason for encounter was obtained from the electronic medical record. The RFEs were compared using International Classification of Primary Care (ICPC)-2-E. RESULTS: Mean age of overall outpatients was 50.5 and 52.4 years in 2001 and 2008 respectively. The number of new outpatient visits increased from 215 (21.3%) to 326 (29.7%) between 2001 and 2008 (P < 0.001) along with the number of patients aged 65 or more from 7.4% to 12.0% (P = 0.08). Mean age of established patients was 52.5 and 56.9 years (P < 0.001), and the patients aged 65 or more was 14.1% and 35.8% (P < 0.001) in 2001 and 2008 respectively. Analysis by ICPC-2-E revealed a decrease in chapter A in 2008 (P = 0.03) and an increase in chapter F, L, and X (P = 0.01, 0.003, <0.001). Component 1 had increased (P = 0.01), and component 2 had decreased (P = 0.04) in proportion. CONCLUSION: Changes in population composition have brought a shift of the distribution of age in outpatients, more significantly in follow-up patients. Comparison by ICPC-2-E showed changes in RFEs of new patients between 2001 and 2008.

Abnormal posterior insertion of the lateral rectus muscle.

Ectopic insertion of the lateral rectus muscle is a rare congenital abnormality. The authors present the case of an exotropic patient with an abnormal posterior insertion of the lateral rectus muscle.

Progressive atlanto-axial subluxation in Behcet's disease.

Behcet's disease is a chronic inflammatory condition involving several organs, such as the skin, mucous membranes, eyes, joints, intestines, lungs and central nervous system. It rarely affects the spinal column. We describe a case of progressive atlanto-axial subluxation in a 44-year-old woman with Behcet's disease. The patient started complaining of posterior neck pain 10 years after the diagnosis of her Behcet's disease. Initial radiographs showed no abnormal finding, but follow-up radiographs 6 month later demonstrated atlanto-axial subluxation. To the best of our knowledge, this is the second reported case in the worldwide literature of an atlanto-axial instability in a patient with Behcet's disease.

Extraction of P300 using constrained independent component analysis.

A brain computer interface (BCI) uses electrophysiological activities of the brain such as natural rhythms and evoked potentials to communicate with some external devices. P300 is a positive evoked potential (EP), elicited approximately 300 ms after an attended external stimulus. A P300-based BCI uses this evoked potential as a means of communication with the external devices. Until now this P300-based BCI has been rather slow, as it is difficult to detect a P300 response without averaging over a number of trials. Previously, independent component analysis (ICA) has been used in the extraction of P300. However, the drawback of ICA is that it extracts not only P300 but also non-P300 related components requiring a proper selection of P300 ICs by the system. In this study we propose an algorithm based on constrained independent component analysis (cICA) for P300 extraction which can extract only the relevant component by incorporating a priori information. A reference signal is generated as this a priori information of P300 and cICA is applied to extract the P300 related component. Then the extracted P300 IC is segmented, averaged, and classified into target and non-target events by means of a linear classifier. The method is fast, reliable, computationally inexpensive as compared to ICA and achieves an accuracy of 98.3% in the detection of P300.

Finite element simulation of ultrasound propagation in bone for quantitative ultrasound toward the diagnosis of osteoporosis.

Osteoporosis is a serious bone disease which leads to the increased risk of bone fractures. For prevention and therapy, early detection of osteoporosis is critical. In general, for diagnosis of osteoporosis, dual-energy X-ray absoptiometry (DXA) or densitometry is most commonly used. However DXA exhibits some disadvantages such as ionizing radiation, relatively expensive cost, and limited information on mineralization and geometry of the bone. As an alternative method of DXA, quantitative ultrasound (QUS) is being investigated. In contrast to DXA, QUS is non-ionizing and relatively inexpensive. It can also provide some bone-related parameters (e.g., quantitative measurements including speed of sound and frequency-dependent attenuation). However the estimation of these parameters is difficult and few analytical solutions exist due to the complex behavior of ultrasound propagation in bone. As an alternative to the analytical methods, in most attempts, finite difference time domain (FDTD) method is used for simulation of ultrasound propagation in bone with a limited capability of modeling complex geometries of the bone. Finite element method (FEM) is a better solution since it can handle the complex geometry, but has been rarely applied due to its computational complexity. In this work, we propose an approach of FEM-based simulation of ultrasound propagation in bone. To validate our approach, we have tested simulated and real bone models from micro-CT using the index of speed-of-sound. Our results achieve an average of 97.54% in the computational accuracy.

Analysis of skin humidity variation between sasang types.

The purpose of this study was to examine the relationship between variations in skin humidity (SH) induced by perspiration across Sasang types and to identify novel and effective Sasang classification factors. We also analyzed the responses of each Sasang type to sweating-related QSCC II items. The results revealed a significant difference in SH across gender and significant differences in SH before and after perspiration between Tae-Eum and So-Eum men. In addition, Tae-Eum women showed significant differences in SH compared with women classified as another Sasang type. Furthermore, evaluation of the items related to sweating in the QSCC II and their relationship to each constitution revealed a significant difference between Tae-Eum and other Sasang types. Overall, the results of this study indicate that there is a distinct SH difference following perspiration between Tae-Eum and other Sasang types. Such findings may aid in Sasang typology diagnostic testing with the support of further sophisticated clinical studies.

High-level secretory expression of human procarboxypeptidase B by Fed-Batch cultivation of Pichia pastoris and its partial characterization.

The procpb gene encoding human procarboxypeptidase B (proCPB, GeneBank access code AJ224866) was cloned and its Pichia expression plasmid, pPIC9alpha/hproCPB (9.2 kb), was constructed, in which procpb was under the control of the AOX1 promoter and connected to the downstream of the mating factor alpha-1 (MFalpha1) signal sequence. The plasmid was linearized by digestion with SacI, and integrated into the genome of P. pastoris strain GS115. By culturing of Pichia transformant on methanol medium, the human proCPB was successfully expressed and secreted into the culture supernatant. Moreover, Western blot analysis of the extracellular proteins showed proCPB bands clearly at a molecular mass of 45 kDa, confirming the expression of proCPB with its right size. The CPB activity reached about 3.5 U/ml and 12.7 U/ml in the flask and fermentor batch cultures of Pichia transformant, respectively. No CPB enzyme activity was found in the intracellular fraction. When the fedbatch cultivation was performed with methanol and glycerol mixture as a feeding medium, the extracellular CPB activity was increased to 42.0 U/ml, which corresponds to a 3.3-fold higher level of CPB activity than that of batch culture. The Km and kcat values of recombinant human CPB enzyme for hippuryl-L-Arg as a substrate were estimated to be 0.16mM and 11.93 sec-1, respectively.