We investigated the differential spatial covariance pattern of blood oxygen level-dependent (BOLD) responses to single-task and multitask functional magnetic resonance imaging (fMRI) between patients ...with psychophysiological insomnia (PI) and healthy controls (HCs), and evaluated features generated by principal component analysis (PCA) for discrimination of PI from HC, compared to features generated from BOLD responses to single-task fMRI using machine learning methods. In 19 patients with PI and 21 HCs, the mean beta value for each region of interest (ROIbval) was calculated with three contrast images (i.e., sleep-related picture, sleep-related sound, and Stroop stimuli). We performed discrimination analysis and compared with features generated from BOLD responses to single-task fMRI. We applied support vector machine analysis with a least absolute shrinkage and selection operator to evaluate five performance metrics: accuracy, recall, precision, specificity, and F2. Principal component features showed the best classification performance in all aspects of metrics compared to BOLD response to single-task fMRI. Bilateral inferior frontal gyrus (orbital), right calcarine cortex, right lingual gyrus, left inferior occipital gyrus, and left inferior temporal gyrus were identified as the most salient areas by feature selection. Our approach showed better performance in discriminating patients with PI from HCs, compared to single-task fMRI.
We conducted a phase III randomized clinical trial to compare two myeloablative conditioning regimens for allogeneic hematopoietic cell transplantation (HCT) in patients with leukemia and ...myelodysplastic syndrome.
After randomization, 64 patients received busulfan (3.2 mg/kg per day × 4 days) plus cyclophosphamide (60 mg/kg per day × 2 days; BuCy), and 62 patients received busulfan (same dose and schedule) plus fludarabine (30 mg/m(2) per day × 5 days; BuFlu).
The median age was 41 years (range, 17 to 59 years). Five patients in the BuFlu arm experienced graft failure (primary, n = 1; secondary, n = 4). At 4 weeks after HCT, the median percentage of recipient hematopoietic chimerism was significantly greater in the BuFlu arm (0% v 5.5%; P < .001), and complete donor chimerism was greater in the BuCy arm (97.2% v 44.4%; P < .001). Severe (grade 3 or higher) infection and gastrointestinal adverse events were significantly more common in the BuCy arm, but the frequencies of hepatic adverse events were similar in the two arms. Nonrelapse mortality was similar in the two arms, but the BuCy arm had better overall survival (OS), relapse-free survival (RFS), and event-free survival (EFS; OS at 2 years, 67.4% v 41.4%, P = .014; RFS, 74.7% v 54.9%, P = .027; EFS, 60.7% v 36.0%, P = .014).
Our results indicate that the BuFlu regimen is not a suitable replacement for the BuCy regimen in young adults who are eligible for myeloablative conditioning therapy for allogeneic HCT.
Bisphenol A (BPA) exposure during the perinatal and postnatal periods increases the susceptibility to disease over the life cycle. However, information on the BPA delivered to fetuses or infants via ...the placenta and breastfeeding is limited. We determined the BPA exposure levels in various bodily fluids and tissues of pregnant women and described fetus and infant exposures to BPA based on associations and BPA ratios in mother–neonate paired samples. Maternal serum, urine, placenta, breast milk, cord serum, and neonatal urine samples were collected from 318 mother–neonate pairs at six university hospitals in Korea. BPA levels were detected using liquid chromatography tandem mass spectrometry. The ratios of the BPA levels in the other sample types to the levels in maternal serum were calculated. BPA was detected in 79.5–100% of the maternal and fetal samples. The median BPA concentration in the samples decreased in the order of neonatal urine (4.75ng/mL), maternal urine (2.86ng/mL), cord serum (1.71ng/mL), maternal serum (1.56ng/mL), breast milk (0.74ng/mL), and the placenta (0.53ng/g). We estimated the ratios of BPA levels in the other sample types to those in maternal serum. The median (95th percentile) cord serum-to-maternal serum ratio was 1.12 (15.2) for 160 mother–fetal pairs, in which BPA was detected in both samples. The placenta-, maternal urine-, neonatal urine-, and breast milk-to-maternal serum ratios were 0.28 (5.31), 1.79 (29.9), 1.98 (28.2), and 0.51 (10.5), respectively. In addition, the median (95th percentile) cord serum-to-placenta ratio was 4.03 (45.8), and the neonatal urine-to-cord serum ratio was 1.95 (25.6). The 95th percentile values were 14–20-fold greater than the medians. Urine contained the highest BPA concentrations, followed by serum, breast milk, and the placenta. The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
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•Not enough data on tissue distribution of BPA in mother‑neonate (or fetus) pair•The order of BPA concentrations in examined tissue or bio-samples are urine in mother and neonates>cord serum>maternal serum>breast milk>placenta.•BPA in cord serum, significantly associated with in maternal serum and urine but not in others.•The variations of BPA ratio show individual differences in the amounts of BPA delivered from mother to fetus.
Purpose We compared two induction regimens, idarubicin (12 mg/m
/d for 3 days) versus high-dose daunorubicin (90 mg/m
/d for 3 days), in young adults with newly diagnosed acute myeloid leukemia ...(AML). Patients and Methods A total of 299 patients (149 randomly assigned to cytarabine plus idarubicin AI and 150 assigned to cytarabine plus high-dose daunorubicin AD) were analyzed. All patients received cytarabine (200 mg/m
/d for 7 days). Results Complete remission (CR) was induced in 232 patients (77.6%), with no difference in CR rates between the AI and AD arms (80.5% v 74.7%, respectively; P = .224). At a median follow-up time of 34.9 months, survival and relapse rates did not differ between the AI and AD arms (4-year overall survival, 51.1% v 54.7%, respectively; P = .756; cumulative incidence of relapse, 35.2% v 25.1%, respectively; P = .194; event-free survival, 45.5% v 50.8%, respectively; P = .772). Toxicity profiles were also similar in the two arms. Interestingly, overall and event-free survival times of patients with FLT3 internal tandem duplication (ITD) mutation were significantly different (AI v AD: median overall survival, 15.5 months v not reached, respectively; P = .030; event-free survival, 11.9 months v not reached, respectively; P = .028). Conclusion This phase III trial comparing idarubicin with high-dose daunorubicin did not find significant differences in CR rates, relapse, and survival. Significant interaction between the treatment arm and the FLT3-ITD mutation was found, and high-dose daunorubicin was more effective than idarubicin in patients with FLT3-ITD mutation.
This study aimed to investigate the correlation between melatonin and the reproductive mechanism of farmed female red‐spotted groupers, Epinephelus akaara. Through the reproductive cycle experiment, ...the sexual maturity period was determined to be from June to July, following which the spawning season occurred in August. In addition, kiss1, kiss2, and GPR54 mRNA expression levels peaked in January, whereas that of sbGnRH mRNA remained at high levels from January to May and decreased during the sexual maturity and spawning seasons. During the day–night cycle, a nocturnal rhythm of AANAT2 mRNA expression was observed in the brain, and AANAT2 mRNA expression showed a seasonal pattern with increased expression during summer compared with that in winter. A correlation between melatonin and reproduction‐related genes could not be observed via melatonin administration, and sexual maturity was observed to be more induced under long photoperiod conditions compared with short photoperiod conditions. These results indicate that the reproductive mechanism of the farmed female red‐spotted grouper is related to changes in photoperiod and melatonin, and further research is needed to clarify the reproductive mechanism. Our findings provide basic information for identifying the reproductive mechanisms of farmed E. akaara.
Omega-3 fatty acid (
-3 FA) intake is known to have a preventive effect on depressive symptoms in a general population. This study assessed the effects of
-3 FA intake on depressive symptoms and ...brain function in middle-aged women. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II) and Center for Epidemiologic Studies-Depression scale (CES-D) assessment questionnaires, and
-3 FA intakes were assessed using semiquantitative food frequency questionnaire. We found that
-3 FA intakes were negatively associated with depressive symptoms in middle-aged women. Psychiatrists diagnosed the presence of depressive disorders using the 5th edition of the Mental Disorder Diagnosis and Statistics Manual (DSM-5). Resting-state functional magnetic resonance imaging (rs-fMRI) was performed to investigate the association between
-3 FA intake and brain functional connectivity. Functional connectivity of the right middle frontal cortex (default mode network) and the right middle temporal pole (frontoparietal network) was positively associated with depressive symptom scores and negatively associated with
-3 FA intakes. In conclusion, high
-3 FA intake decreases the risk of depressive symptoms and modifies the brain functional connectivity in middle-aged women.
In this article, we present a novel stationary electromagnetic actuation system (EMS) and a redundant magnetic field control approach that can enhance the magnetic actuation ability for a capsule ...endoscope. The EMS configured with multiple electromagnets has an intrinsic redundant problem when computing input current to each coil from inverse formulation. Here, we propose a redundant electromagnetic field control scheme of utilizing this redundancy to increase magnetic force and reduce the peak input current that deteriorates the performance. It is based on the optimization of magnetic field encountering input current and null-space equations of a pseudoinverse matrix. We validated the proposed methods in simulation and experiments through the prototyped EMS designed by considering actual human size and a magnetic capsule endoscope. The results show significant improvements in the magnetic field and lower input current compared to the conventional method as well as extended operating time through reduced heating effects. Especially, the in vitro in a gastric phantom and in vivo experiments in a live pig could prove the practical applicability of the developed method for a magnetic capsule endoscope toward upper stomach diagnosis in the clinical environment.
Abstract Transplantation of mesenchymal stem cells (MSCs) has been shown to enhance the recovery of brain functions following ischemic injury. Although immune modulation has been suggested to be one ...of the mechanisms, the molecular mechanisms underlying improved recovery has not been clearly identified. Here, we report that MSCs secrete transforming growth factor-beta (TGF-β) to suppress immune propagation in the ischemic rat brain. Ischemic stroke caused global death of resident cells in the infarcted area, elevated the monocyte chemoattractant protein-1 (MCP-1) level, and evoked massive infiltration of circulating CD68 + immune cells through the impaired blood–brain barrier. Transplantation of MSCs at day 3 post-ischemia blocked the subsequent upregulation of MCP-1 in the ischemic area and the infiltration of additional CD68 + immune cells. MSC-conditioned media decreased the migration and MCP-1 production of freshly isolated immune cells in vitro, and this effect was blocked by an inhibitor of TGF-β signaling or an anti-TGF-β neutralizing antibody. Finally, transplantation of TGF-β1-silenced MSCs failed to attenuate the infiltration of CD68 + cells into the ischemic brain, and was associated with only minor improvements in motor function. These results indicate that TGF-β is key to the ability of MSCs to beneficially attenuate immune reactions in the ischemic brain. Our findings offer insight into the interactions between allogeneic MSCs and the host immune system, reinforcing the prospective clinical value of using MSCs in the treatment of neurological disorders involving inflammation-mediated secondary damage.
As a preliminary investigation into the effects of environmental factors on gonadal development using adaptive physiological characteristics, we examined the involvement of photoperiod and water ...temperature in the ovarian development of the red‐spotted grouper, Epinephelus akaara. During October 2014 (non‐breeding season), the photoperiod and water temperature were adjusted to 12L:12D and 18°C respectively. Every 3 weeks, daylight was increased as follows a 13L:11D and 14L:10D in the photo‐thermal treatment group, and the control group was maintained under natural conditions. After 9 weeks, water temperature was increased to 23°C in the photo‐thermal treatment group. In photo‐thermal treatment group, GSI increased significantly after 9 weeks (1.36 ± 0.19) and 12 weeks (3.31 ± 0.20) compared with the control group. At 12 weeks after photo‐thermal treatment, all fishes matured into ovaries containing late vitellogenic oocytes. The expression of FSHβ and LHβ mRNAs also increased significantly. However, in the control group, the ovarian development was maintained at an immature stage. Based on these results, we demonstrate that exposure to long photoperiod and high water temperature can induce the sexual maturation of immature red‐spotted grouper during the non‐breeding season.
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