The National Institutes of Health global score for chronic graft-versus-host disease was devised by experts but was not based on empirical data. We hypothesized that analysis of prospectively ...collected data would enable derivation of a more accurate model for estimating mortality risk. We analyzed 574 adult patients with chronic graft-versus-host disease enrolled in a multicenter, observational study, using multivariate time-varying analysis accounting for serial changes in severity of involvement of eight individual organ sites over time. In the training set, severity of skin, mouth, gastrointestinal tract, liver and lung involvement were independently associated with the risk of non-relapse mortality. Weighted mortality points were assigned to individual organs based on the hazard ratios and were summed. The population was divided into three risk groups based on the total mortality points. The three new risk groups were validated in an independent validation set, but did not show better discriminative performance than the National Institutes of Health global score. As compared to a moderate or mild global score, a severe global score was associated with increased risks of non-relapse and overall mortality across time but not with a decreased risk of recurrent malignancy. The National Institutes of Health global score predicts patients' mortality risk throughout the course of their chronic graft-versus-host disease. Further research is required in order to improve outcomes in patients with severe chronic graft-versus-host disease, since their risk of mortality remains elevated.
Microsomal prostaglandin E2 synthase-1 (mPGES-1), an inducible enzyme that converts prostaglandin H2 (PGH2) to prostaglandin E2 (PGE2), plays an important role in a variety of diseases. So far, the ...role of mPGES-1 in idiopathic pulmonary fibrosis (IPF) remained unknown. The current study aimed to investigate the role of mPGES-1 in pulmonary fibrosis induced by bleomycin in mice. We found that mPGES-1 deficient (mPGES-1-/-) mice exhibited more severe fibrotic lesions with a decrease in PGE2 content in lungs after bleomycin treatment when compared with wild type (mPGES-1+/+) mice. The mPGES-1 expression levels and PGE2 content were also decreased in bleomycin-treated mPGES-1+/+ mice compared to saline-treated mPGES-1+/+ mice. Moreover, in both mPGES-1-/- and mPGES-1+/+ mice, bleomycin treatment reduced the expression levels of E prostanoid receptor 2 (EP2) and EP4 receptor in lungs, whereas had little effect on EP1 and EP3. In cultured human lung fibroblast cells (MRC-5), siRNA-mediated knockdown of mPGES-1 augmented transforming growth factor-β1 (TGF-β1)-induced α-smooth muscle actin (α-SMA) protein expression, and the increase was reversed by treatment of PGE2, selective EP2 agonist and focal adhesion kinase (FAK) inhibitor. In conclusion, these findings revealed mPGES-1 exerts an essential effect against pulmonary fibrogenesis via EP2-mediated signaling transduction, and activation of mPGES-1-PGE2-EP2-FAK signaling pathway may represent a new therapeutic strategy for treatment of IPF patients.
Due to infectious and bleeding risks, adults with acute myeloid leukemia or high-risk myelodysplastic syndromes typically remain hospitalized after remission induction chemotherapy until blood count ...recovery. Here, we explored the medical and financial effects of discharge immediately after chemotherapy completion with close outpatient follow up. Within 12 months, 15 patients fulfilling both medical and logistical criteria were discharged early, whereas 5 patients meeting medical criteria only served as inpatient controls. No patient died. Patients discharged early spent a median of 8 days (range 3-36 days), or 54% of their study time, as outpatients. These patients required less time on intravenous antibiotics (6 vs. 16 days; P=0.11), received fewer red blood cell transfusions (0.25 vs. 0.48 units/day; P=0.08), and incurred lower median daily charges ($3,270 vs. $5,467; P=0.01) than controls. Thus, early discharge of selected patients appears, safe and may reduce cost and resource utilization. (ClinicalTrials.gov Identifier: NCT00844441).
Abstract Bronchiolitis obliterans syndrome (BOS) after allogeneic hematopoietic cell transplantation (HCT) is associated with high mortality. We hypothesized that inhaled fluticasone, azithromycin, ...and montelukast (FAM) with a brief steroid pulse could avert progression of new-onset BOS. We tested this in a phase II, single-arm, open-label, multicenter study ( NCT01307462 ). Thirty-six patients were enrolled within 6 months of BOS diagnosis. The primary endpoint was treatment failure, defined as 10% or greater forced expiratory volume in 1 second decline at 3 months. At 3 months, 6% (2 of 36, 95% confidence interval, 1% to 19%) had treatment failure (versus 40% in historical controls, P < .001). FAM was well tolerated. Steroid dose was reduced by 50% or more at 3 months in 48% of patients who could be evaluated (n = 27). Patient-reported outcomes at 3 months were statistically significantly improved for Short-Form 36 social functioning score and mental component score, Functional Assessment of Cancer Therapies emotional well-being, and Lee symptom scores in lung, skin, mouth, and the overall summary score compared to enrollment (n = 24). At 6 months, 36% had treatment failure (95% confidence interval, 21% to 54%, n = 13 of 36, with 6 documented failures, 7 missing pulmonary function tests). Overall survival was 97% (95% confidence interval, 84% to 100%) at 6 months. These data suggest that FAM was well tolerated and that treatment with FAM and steroid pulse may halt pulmonary decline in new-onset BOS in the majority of patients and permit reductions in systemic steroid exposure, which collectively may improve quality of life. However, additional treatments are needed for progressive BOS despite FAM.
To investigate the effects of cadmium chloride on cytoactive and immigration of mouse neural stem cell (mNSC).
MTT assay was used to detect cytoactive at 24 hours. The immigration of mNSC was ...determined by immunofluorescence staining.
Compared with control, CdCl2 treatment at 10.0 μmol/L for 24 h resulted in a decrease in cellular viability (70.08 ± 6.21)% (P < 0.05). Compared with control, Aa/Ab and Dm/Db display decreasing tendency in a dose-dependent manner (r(s Aa/Ab) = - 0.90, γ(s Dm/Db) = - 0.90, P < 0.05) after CdCl2 treatment at 0.1 - 10.0 μmol/L for 24 h.
Cadmium chloride treatment inhibits immigration of mNSC, and shows negative effect on cell viability. Meanwhile, the effect of cadmium chloride on immigration is more obvious than cell viability at the same concentration for same treatment time.
Abstract Several distinct graft-versus-host disease (GVHD)-related syndromes have been defined by the National Institutes of Health Consensus Conference. We enrolled a prospective cohort of 911 ...hematopoietic cell transplantation (HCT) recipients at 13 centers between March 2011 and May 2014 to evaluate 4 GVHD syndromes: late acute GVHD (aGVHD), chronic GVHD (cGVHD), bronchiolitis obliterans syndrome, and cutaneous sclerosis. The median age at HCT was 53.7 years. The majority of patients received a peripheral blood stem cell transplant (81%) following nonmyeloablative or reduced-intensity conditioning (55%). Pediatric age group and use of bone marrow and umbilical cord blood grafts were underrepresented in our cohort (≤11%). The cumulative incidence of late aGVHD (late onset and recurrent) was 10% at a median of 5.5 months post-HCT, that of cGVHD was 47% at a median of 7.4 months, that of bronchiolitis obliterans was 3% at a median of 12.2 months, and that of cutaneous sclerosis was 8% at a median onset of 14.0 months. Late aGVHD and bronchiolitis obliterans had particularly high nonrelapse mortality of 23% and 32%, respectively, by 2 years after diagnosis. The probability of late aGVHD- and cGVHD-free, relapse-free survival was 38% at 1 year post-HCT and 26% at 2 years post-HCT. This multicenter prospective study confirms the high rate of late aGVHD and cGVHD syndromes and supports the need for continuous close monitoring and development of more effective GVHD treatment strategies to improve HCT success.
In this study, the effect of different intensity electrostatic fields on the water holding capacity (WHC) of fresh meat during the early postmortem period in controlled freezing point storage (CFPS) ...were investigated. Significantly lower cooking loss were found in low voltage electrostatic field (LVEF) and high voltage electrostatic field (HVEF) compared to the control group (CK) (p < 0.05). The myofibril fragmentation index and microstructure results suggested that the sample under HVEF treatment remained relatively intact. It has been revealed that the changes in actomyosin properties under electrostatic field treatment groups were due to the combination and dissociation of actomyosin binding into myofilament concentration, which consequently affects the muscle WHC. The study further demonstrated that the electrostatic field, especially HVEF, might increase the WHC of fresh meat by affecting the distribution of water molecules and physiochemical properties of actomyosin during the early postmortem period.
Humans always identify persons through their characteristics, salient attributes, and these attributes’ locations on the body. Most person re-identification methods focus on global and local features ...corresponding to the former two discriminations, cropping person images into horizontal strips to obtain coarse locations of body parts. However, discriminative clues corresponding to location differences cannot be discovered, so persons with similar appearances are often confused because of their alike components. To address the above problem, we introduce pixel-wise relative positions for the invariance of their orientations in viewpoint changes. To cope with the scale change of relative position, we combine relative positions with self-attention modules that perform on multi-level features. Moreover, in the data augmentation stage, mirrored images are given new labels due to the conversion of the relative position along a horizontal orientation and change in visual chirality. Extensive experiments on four challenging benchmarks demonstrate that the proposed approach shows its superiority and effectiveness in discovering discriminating features.
To monitor rapeseed loss in real-time during the harvesting process, a rapeseed loss monitoring system based on the signal analysis of impacts, was developed. Firstly, to understand grain and MOG ...(material other than grain) collision signal characteristic, models for different threshed outputs components were established in the EDEM software, and the corresponding collision signal characteristic for different components were obtained, thereby laying the foundation for the design of a signal processing circuit. Secondly, using a P5-3B type piezoelectric ceramic as a sensitive element, a multi-block cleaning loss sensor and a signal processing circuit with amplification, filtering, rectification, comparison functions and early warning functions were developed. Finally, performance calibration tests with different grain flow rates, different rapeseed varieties and mixture were carried out in the laboratory. Calibration and field testing showed that the detection accuracy of the developed rapeseed loss monitoring sensor was high and the overall performance was acceptable.
•Rapeseed grain and MOG collision signal were obtained by discrete element method.•A signal processing circuit was designed according to the DEM simulation results.•Field experiment results indicates that the sensor monitored error was ≤10%.
•Four-point adjustable lifting chassis is designed to keep vehicle level when tilting.•Lifting mechanism under 3 adjustment conditions has been analyzed quantitatively.•It could be useful for solving ...problem of crawler agricultural vehicles levelling.
In agriculture, the body tilt of vehicles or platforms can be controlled by levelling technology to prevent rollover and improve efficiency when operated in rough terrain. Many researchers have carried out important study in this area based on mechanism development and optimization, but most of them are not effective to crawler vehicles. The objective of this research was to specifically develop a levelling mechanism for crawler combine harvester, since as a consequence, enhancing the operation performance and trafficability. This levelling method depends on a hydraulic four-point adjustable lifting chassis, which could adjust vehicle chassis by controlling hydraulic cylinders. Therefore, the mathematical models between chassis attitude (including ground clearance, the horizontal and longitudinal inclination angle) and each length of hydraulic cylinder were deduced. The principle of lifting mechanism of crawler vehicle chassis was analyzed by using virtual prototyping software ADAMS, as well as dynamic performance under three different attitude adjustment conditions. The maximum adjustment range of the ground clearance is 140 mm and the lateral inclination adjustment range is ±5.17°. Experiment showed that the designed levelling mechanism was feasible and with positive significance for crawler vehicles levelling.
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