Robust Model Selection for Classification of Microarrays

Recently, microarray-based cancer diagnosis systems have been increasingly investigated. However, cost reduction and reliability assurance of such diagnosis systems are still remaing problems in real clinical scenes. To reduce the cost, we need a supervised classifier involving the smallest number of genes, as long as the classifier is sufficiently reliable. To achieve a reliable classifier, we should assess candidate classifiers and select the best one. In the selection process of the best classifier, however, the assessment criterion must involve large variance because of limited number of samples and non-negligible observation noise. Therefore, even if a classifier with a very small number of genes exhibited the smallest leave-one-out cross-validation (LOO) error rate, it would not necessarily be reliable because classifiers based on a small number of genes tend to show large variance. We propose a robust model selection criterion, the min-max criterion, based on a resampling bootstrap simulation to assess the variance of estimation of classification error rates. We applied our assessment framework to four published real gene expression datasets and one synthetic dataset. We found that a state-of-the-art procedure, weighted voting classifiers with LOO criterion, had a non-negligible risk of selecting extremely poor classifiers and, on the other hand, that the new min-max criterion could eliminate that risk. These finding suggests that our criterion presents a safer procedure to design a practical cancer diagnosis system

Predicting the Route of Delivery in Women with Low-Lying Placenta Using Transvaginal Ultrasonography: Significance of Placental Migration and Marginal Sinus

Background/Aims: To examine the significance of placental migration and the presence of a placental marginal sinus to predict the eventual route of delivery in low-lying placenta. Methods: 49 women with a low-lying placenta after 30 weeks' gestation were studied. The distance between the internal os and leading edge of the placenta was measured weekly using transvaginal ultrasonography until 37 weeks' gestation. The relationship between the rate of placental migration, the presence of a placental marginal sinus and the eventual mode of delivery was investigated. Results: Although the cesarean section rate was 56.3% (9/16) in the 'slow' migration (0-2.0 mm/week) group, no patient (0/33) in the 'fast' (>2.0 mm/week) migration group underwent a cesarean section (p<0.01). The cesarean section rate was 71.4% (5/7) in patients with a placental marginal sinus, significantly greater than the rate of 9.5% (4/42) in patients without a marginal sinus (p<0.01). Conclusion:A decreased rate of placental migration until 37 weeks' gestation and the presence of a placental marginal sinus were associated with subsequent cesarean delivery because of antepartum vaginal bleeding. These parameters may be useful for predicting the route of delivery in women with a low-lying placenta.ArticleGYNECOLOGIC AND OBSTETRIC INVESTIGATION. 73(3):217-222 (2012)journal articl

hCG values and gestational sac size as indicators of successful systemic methotrexate treatment in cesarean scar pregnancy

Objective: To retrospectively investigate cesarean scar pregnancy (CSP) patients who received systemic methotrexate (MTX) and to clarify the criteria for administering systemic MTX to CSP patients. Materials and methods: Fifteen CSP patients who were initially treated with systemic MTX (50 mg/m2/ week) were included. Nine patients, who needed a uterine artery embolization (UAE) or a laparotomy, including a transabdominal hysterectomy (TAH), were defined as the unsuccessful MTX group. Six patients who did not require UAE or a laparotomy were defined as the successful MTX group. Furthermore, the hCG cut-off value and the GS cut-off size at the time of CSP diagnosis, which differentiated successful and unsuccessful patients, were defined. MTX success rates were investigated by combining the hCG and gestational sac (GS) size cut-off values. Results: The hCG cut-off value was 17757.0 mIU/mL, and the GS cut-off size was 10.4 mm. In patients with hCG values less than 17757.0 mIU/mL, the MTX success rate was 75.0%. Fewer patients needed UAE or a laparotomy compared to patients with hCG values higher than 17757.0 mIU/mL (P = 0.007). In patients with a GS size less than 10.4 mm, the MTX success rate was 80.0%. Fewer patients among them needed UAE or a laparotomy compared to those among patients with a GS size greater than 10.4 mm (P = 0.089). In patients with hCG values and GS sizes lower than the cut-off values, the MTX success rate was 80.0%. Fewer patients among them needed UAE or a laparotomy compared to those among patients with hCG values and/or GS sizes higher than the cut-off values, respectively (P = 0.010). Conclusion: Patients with hCG values less than 17757.0 mIU/mL and GS sizes less than 10.4 mm may have a greater chance of successful systemic MTX treatment when it is used as the first line of treatment for CSP

Region-Specific Responses of Adductor Longus Muscle to Gravitational Load-Dependent Activity in Wistar Hannover Rats

Response of adductor longus (AL) muscle to gravitational unloading and reloading was studied. Male Wistar Hannover rats (5-wk old) were hindlimb-unloaded for 16 days with or without 16-day ambulation recovery. The electromyogram (EMG) activity in AL decreased after acute unloading, but that in the rostral region was even elevated during continuous unloading. The EMG levels in the caudal region gradually increased up to 6th day, but decreased again. Approximately 97% of fibers in the caudal region were pure type I at the beginning of experiment. Mean percentage of type I fibers in the rostral region was 61% and that of type I+II and II fiber was 14 and 25%, respectively. The percent type I fibers decreased and de novo appearance of type I+II was noted after unloading. But the fiber phenotype in caudal, not rostral and middle, region was normalized after 16-day ambulation. Pronounced atrophy after unloading and re-growth following ambulation was noted in type I fibers of the caudal region. Sarcomere length in the caudal region was passively shortened during unloading, but that in the rostral region was unchanged or even stretched slightly. Growth-associated increase of myonuclear number seen in the caudal region of control rats was inhibited by unloading. Number of mitotic active satellite cells decreased after unloading only in the caudal region. It was indicated that the responses of fiber properties in AL to unloading and reloading were closely related to the region-specific neural and mechanical activities, being the caudal region more responsive

Modulation of Emotion by Cognitive Activity

While emotions themselves are beneficial for our survival, they are also the targets to be regulated appropriately to adapt to social environments. Previous studies have demonstrated that cognitive strategies such as cognitive reappraisal and expressive suppression can effectively enhance and attenuate emotions. Such cognitive strategies of emotion regulation are based on cortical modulation of sub-cortical emotion-related brain regions. Though in the prior studies emotion regulation was conducted in parallel with or after the emotion elicitation, a series of our studies showed that prior cognitive activities can automatically and unintentionally attenuate subsequent emotional responses. In this article, after reviewing the previous findings about emotion regulation, we introduce our empirical findings showing that cognitive activities where the neural system of emotion regulation would be recruited can unintentionally and automatically dampen psychological and physiological emotional responses. Finally, we propose possible neural mechanisms underlying modulation of emotion by cognitive activity

EG-VEGF Induces Invasion of a Human Trophoblast Cell Line via PROKR2

Extravillous trophoblast (EVT) invasion is important for embryo implantation, placental development, and successful remodeling of the uterine spiral artery. Endocrine gland derived-vascular endothelial growth factor (EG-VEGF) and matrix metalloproteinases (MMPs) are implicated in EVT invasion; however, the high con-centrations found in pregnancy pathologies have not been investigated in non-tumor trophoblasts. The roles of EG-VEGF, prokineticin receptors (PROKR1/2), MMP-2, and MMP-9 in EVT invasion during spiral artery remodeling were evaluated using human EVT from HTR-8/SVneo cell lines. The expression of MMP-2, MMP-9, and mitogen-activated protein kinase (MAPK), and Akt pathways in HTR-8/SVneo cells treated with recom-binant EG-VEGF alongside anti-PROKR1 and/or anti-PROKR2 antibodies was evaluated using quantitative reverse transcription-PCR and western blotting. Wound-healing and cell invasion assays were performed to assess the migration and invasion of these treated cells. Interestingly, 20 nM EG-VEGF activated ERK1/2 sig-naling and upregulated MMP-2 and MMP-9. This effect was suppressed by anti-PROKR2 antibody via ERK1/2 downregulation. Anti-PROKR2 antibody inhibited the migration and invasion of EG-VEGF-stimulated HTR-8/SVneo cells. Elevated concentrations of EG-VEGF enhance EVT invasion in a human trophoblast cell line by upregulating MMP-2 and MMP-9 via PROKR2. These new insights into the regulation of epithelial cell invasion may help in developing therapeutic interventions for placental-related diseases during pregnancy

Fetal Goitrous Hypothyroidism due to Maternal Thyroid Stimulation-Blocking Antibody: A Case Report

Most fetal goitrous hypothyroidisms are reportedly caused by the maternal use of an antithyroid drug or fetal dyshormonogenesis. However, fetal goitrous hypothyroidism due to the transplacental passage of maternal thyroid stimulation-blocking antibody (TSBAb) is extremely rare. A woman at 28 weeks of gestation was found to have a fetal goiter by ultrasonography. Because the maternal serum showed hypothyroidism with an elevated titer of TSBAb, levothyroxine sodium was administered. The patient delivered a male infant, 3,412 g, with a goiter at term. Umbilical blood revealed primary hypothyroidism with increased TSBAb, and the infant was given levothyroxine sodium. After a month, neonatal thyroid function and TSBAb levels became normal. Attention should be paid to possible fetal hypothyroidism when a fetal goiter is observed to avoid impaired mental development of the neonate.ArticleFETAL DIAGNOSIS AND THERAPY. 28(4):220-224 (2010)journal articl