Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an essential therapeutic approach for the management of acute myeloid leukemia (AML). Nevertheless, graft-versus-host disease (GVHD) ...remains a significant complication, significantly affecting the recipients' quality of life and overall survival. Antithymocyte globulin (ATG) has demonstrated promise in preventing GVHD during allo-HSCT. However, concerns persist regarding its potential impact on disease relapse. This retrospective single-center study aims to evaluate the prognostic implications of ATG based on cytogenetic risk stratification in AML patients undergoing transplantation from an HLA-matched sibling. A total of 124 AML patients who underwent allo-HSCT from an HLA-matched sibling in their first complete remission state between 2003 and 2022 were eligible for the study. Among them, fifty patients received rabbit ATG at a dose of 2.5mg/kg/day for days -2 to -1, while 74 patients did not receive ATG. All patients received cyclosporine and methotrexate in addition to their respective conditioning regimens (ATG or no ATG). The ATG group consisted of 38 patients classified as having a non-high cytogenetic risk, and 12 patients classified as having a high cytogenetic risk. Conversely, the non-ATG group included 68 patients with a non-high cytogenetic risk and 6 patients with a high cytogenetic risk. After a median follow-up of 48 months, there were no significant differences in median overall survival between the ATG and Non-ATG groups, regardless of cytogenetic risk status (non-high cytogenetic risk; 12.4 months vs. NA, p = 0.578; high cytogenetic risk; 13.2 months vs. 14.2 months, p = 0.729, Figure A-1,B-1). The ATG group in the non-high cytogenetic risk group demonstrated a significant decrease in the 1-year cumulative incidence (CI) of chronic GVHD compared to the non-ATG group (21.7% vs. 54.4%, p = 0.001, Figure A-2; and in those with moderate to severe cGVHD, it was 21.6% vs. 51.5%, p = 0.003, respectively). Additionally, the 1-year Chronic GVHD-free and relapse-free survival (cGRFS) was higher in the ATG group of the non-high cytogenetic risk group (45.8vs. 26.5%; p = 0.048, Figure A-3). Moreover, there were no significant differences in 1-year CI of relapse and 1-year non-relapse mortality (NRM) within the non-high cytogenetic risk group (ATG vs. non-ATG; 29.7% vs. 20.6%, p = 0.225; 8.4% vs. 4.4%, p = 0.635, Figure A-4,5). In the subgroup analysis of patients with high cytogenetic risk, although there was no statistical significance, the ATG group showed a trend towards decreased 1-year CI of chronic GVHD and higher cGRFS compared to the non-ATG group (10.4% vs. 40.0%, p = 0.342; 31.2% vs. 16.7%, p = 0.929, Figure B-2,3). However, the ATG group exhibited a significantly higher 1-year CI of relapse compared to the non-ATG group (60.0% vs. 16.7%, p = 0.019, Figure B-4). In conclusion, our study findings indicate that ATG was effective in preventing chronic GVHD and demonstrated higher cGRFS in AML patients undergoing matched sibling donor HSCT. However, AML patients with high cytogenetic risk should carefully consider the use of ATG due to the associated higher risk of relapse. Further investigations are warranted to validate these findings and determine the appropriate dosage of ATG for high cytogenetic risk AML patients.
Since cable members are the major structural components of cable bridges, they should be properly inspected for surface damage and inside defects such as corrosion and/or breakage of wires. This ...study introduces an efficient image-based damage detection system that can automatically identify damages to the cable surface through image processing techniques and pattern recognition. The damage detection algorithm combines image enhancement techniques with principal component analysis (PCA) algorithm. Images from three cameras attached to a cable climbing robot are wirelessly transmitted to a server computer located on a stationary cable support. To improve the overall quality of the images, this study utilizes an image enhancement method together with a noise removal technique. Next the input images are projected into PCA sub-space, the Mahalanobis square distance is used to determine the distances between the input images and sample patterns. The smallest distance is found to be a match for an input image. The proposed damage detection algorithm was verified through laboratory tests on three types of cables. Results of the tests showed that the proposed system could be used to detect damage to bridge cables.
Eclipta prostrata (EP) and its compounds are known to have several pharmacological effects including anti-inflammatory effects. In the present study, we demonstrated that EP improves the dextran ...sulfate sodium (DSS)-induced colitis symptoms such as body weight loss, colon length shortening and disease activity index. In DSS-induced colitis tissue, EP controls the protein expressions of cyclooxygenase-2 (COX-2) and hypoxia inducible factor-1Formula: see text (HIF-1Formula: see text). In addition, the release of prostaglandin E
and vascular endothelial growth factor-A were significantly reduced by EP administration. EP also inhibited COX-2 and HIF-1Formula: see text expressions in the tumor necrosis factor-Formula: see text stimulated HT-29 cells. These inhibitory effects of EP occurred by reducing the phosphorylation of IFormula: see textB and the translocation of the nuclear factor-Formula: see textB (NF-Formula: see textB). Additionally, we found through HPLC analysis that wedelolactone, which is an inhibitor of NF-Formula: see textB transcription, was contained in water extract of EP. These results indicate that EP can improve colitis symptoms through the modulation of immune function in intestinal epithelial cells and suggests that EP has the potential therapeutic effect to intestinal inflammation.
Background
The recurrence rate of posterior communicating artery (Pcom) aneurysms after endovascular treatment (EVT) is higher than that for aneurysms located in other sites. However, it is still ...unclear what mechanisms are responsible for the recanalization of cerebral aneurysms. In this investigation, we compared hemodynamic factors related with recanalization of Pcom aneurysms treated by endoluminal coiling using computational fluid dynamics (CFD) with high-resolution three-dimensional digital subtraction angiography images.
Methods
Twenty patients were enrolled. A double-sinogram acquisition was performed with and without contrast injection after coil embolization to get true blood vessel lumen by relatively complementing the first sinogram with the second. Adaptive Cartesian meshing was performed to produce vascular wall objects for CFD simulation. The boundary condition for inlet (ICA) was set for dynamic velocity according to the cardiac cycle (0.8 s). Hemodynamic parameters were recorded at two specific points (branching point of Pcom and residual sac). The peak pressure, peak WSS, and oscillatory shear index (OSI) were recorded and analyzed.
Results
The median age was 61.0 years, and 18 patients (90%) were female. During a median follow-up of 12 months, seven (35%) treated aneurysms showed recanalization. The median aneurysm volume was significantly higher, and aneurysm height and neck sizes were significantly longer in the recanalization group than those in the stable group. At the branching point of the Pcom, the peak pressure, peak WSS, or OSI did not significantly differ between the two groups. The only statistically significant hemodynamic parameter related with recanalization was the OSI at the aneurysm point. Multivariate logistic regression showed that with an increase of 0.01 OSI at the aneurysm point, the odds ratio for the aneurysm recanalization was 1.19.
Conclusions
A higher OSI is related with recanalization after coil embolization for a Pcom aneurysm.
The waiting time for deceased donor kidney transplants (DDKT) is increasing. We evaluated DDKT prognosis according to the pretransplant dialysis vintage. A total of 4117 first-time kidney transplant ...recipients were enrolled from a prospective nationwide cohort in Korea. DDKT recipients were divided into tertiles according to pretransplant dialysis duration. Graft failure, mortality, and composite were compared between DDKT and living donor kidney transplant (LDKT) recipients. Pretransplant dialysis vintage was longer annually in DDKT recipients. In the subdistribution of the hazard model for the competing risk, the first tertile did not show an increased risk of graft failure compared with LDKT recipients; however, the second and third tertile groups had an increased risk of graft failure compared to LDKT recipients (adjusted hazard ratio aHR 3.59; 95% confidence interval CI 1.69-7.63; P < 0.001; aHR 2.37; 95% CI 1.06-5.33; P = 0.037). All DDKT groups showed a significantly higher risk of patient death than LDKT, with the highest risk in the third tertile group (aHR 11.12; 95% CI 4.94-25.00; P < 0.001). A longer pretransplant dialysis period was associated with a higher risk of the composite of patient death and graft failure in DDKT recipients. DDKT after a short period of dialysis had non-inferior results on graft survival compared with LDKT.
Identifying patients with high bleeding risk (HBR) is important when making decisions for antiplatelet therapy strategy. This study evaluated the impact of ticagrelor monotherapy after 3-month dual ...antiplatelet therapy (DAPT) according to HBR in acute coronary syndrome (ACS) patients treated with drug eluting stents (DESs).
In this post-hoc analysis of the TICO trial, HBR was defined by 2 approaches: meeting Academic Research Consortium for HBR (ARC-HBR) criteria or Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent DAPT (PRECISE-DAPT) score ≥25. The primary outcome was a 3-12 months net adverse clinical event (composite of major bleeding and adverse cardiac and cerebrovascular events).
Of the 2,980 patients without adverse events during the first 3 months after DES implantation, 453 (15.2%) were HBR by ARC-HBR criteria and 504 (16.9%) were HBR by PRECISE-DAPT score. The primary outcome rate was higher in HBR versus non-HBR patients (by ARC-HBR criteria: hazard ratio HR, 2.87; 95% confidence interval CI, 1.76-4.69; p<0.001; by PRECISE-DAPT score: HR, 3.09; 95% CI, 1.92-4.98; p<0.001). Ticagrelor monotherapy after 3-month DAPT was associated with lower primary outcome rate than ticagrelor-based 12-month DAPT regardless of HBR by ARC-HBR criteria, with similar magnitudes of therapy effect for HBR and non-HBR patients (p-interaction=0.400). Results were consistent by PRECISE-DAPT score (p-interaction=0.178).
In ACS patients treated with DESs, ticagrelor monotherapy after 3-month DAPT was associated with lower rate of adverse clinical outcomes regardless of HBR, with similar magnitudes of therapy effect between HBR and non-HBR.
ClinicalTrials.gov Identifier: NCT02494895.
Linusorbs (LOs) are natural peptides found in flaxseed oil that exert various biological activities. Of LOs, LOB3 (1-9-NαC-linusorb B3) was reported to have antioxidative and anti-inflammatory ...activities; however, its anti-cancer activity has been poorly understood. Therefore, this study investigated the anti-cancer effect of LOB3 and its underlying mechanism in glioblastoma cells. LOB3 induced apoptosis and suppressed the proliferation of C6 cells by inhibiting the expression of anti-apoptotic genes, B cell lymphoma 2 (Bcl-2) and p53, as well as promoting the activation of pro-apoptotic caspases, caspase-3 and -9. LOB3 also retarded the migration of C6 cells, which was achieved by suppressing the formation of the actin cytoskeleton critical for the progression, invasion, and metastasis of cancer. Moreover, LOB3 inhibited the activation of the proto-oncogene, Src, and the downstream effector, signal transducer and activator of transcription 3 (STAT3), in C6 cells. Taken together, these results suggest that LOB3 plays an anti-cancer role by inducing apoptosis and inhibiting the migration of C6 cells through the regulation of apoptosis-related molecules, actin polymerization, and proto-oncogenes.
We designed a new 1-handed chest compression method, the "elbow-lock" chest compression (ELCC), for a single rescuer in pediatric cardiopulmonary resuscitation (CPR). Then, we compared the ...effectiveness between the ELCC and standard chest compression (SCC) method.
This prospective, randomized controlled, crossover simulation trial studied 34 emergency medical professionals, including physicians, nurses, and EMTs. We compare the quality of chest compression and fatigue point time between the ELCC and the SCC.
Participants who performed the ELCC method maintained a proper depth of compression compared with SCC method (50.0 ± 0.3 mm vs 40.5 ± 0.4 mm, P < 0.001). However, the 2 methods did not differ in terms of compression velocity since neither reached the standard velocity (96.7 ± 7.1/minutes vs 91.7 ± 7.0/minutes, P < 0.016). With respect to the overall score, ELCC was more effective than the SCC (91.6 ± 3.7% vs 85.3 ± 8.8%, P = 0.002). In addition, the fatigue point time was slower in the ELCC group than the SCC group (7.3 ± 0.3/minutes vs 6.1 ± 0.4/minutes, P < 0.001).
The single rescuer ELCC method is an effective alternative to the SCC method for pediatric CPR because the ELCC method can prevent elbow flexion.Trial registration: Our research is simulation manikin study. So we do not need to "trial registration".
Retinoids are lipophilic isoprenoids composed of a cyclic group and a linear chain with a hydrophilic end group. These compounds include retinol, retinal, retinoic acid, retinyl esters, and various ...derivatives of these structures. Retinoids are used as cosmetic agents and effective pharmaceuticals for skin diseases. Retinal, an immediate precursor of retinoids, is derived by β-carotene 15,15'-mono(di)oxygenase (BCM(D)O) from β-carotene, which is synthesized from the isoprenoid building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Retinoids are chemically unstable and biologically degraded via retinoic acid. Although extensive studies have been performed on the microbial production of carotenoids, retinoid production using microbial metabolic engineering has not been reported. Here, we report retinoid production using engineered Escherichia coli that express exogenous BCM(D)O and the mevalonate (MVA) pathway for the building blocks synthesis in combination with a two-phase culture system using a dodecane overlay.
Among the BCM(D)O tested in E. coli, the synthetic retinoid synthesis protein (SR), based on bacteriorhodopsin-related protein-like homolog (Blh) of the uncultured marine bacteria 66A03, showed the highest β-carotene cleavage activity with no residual intracellular β-carotene. By introducing the exogenous MVA pathway, 8.7 mg/L of retinal was produced, which is 4-fold higher production than that of augmenting the MEP pathway (dxs overexpression). There was a large gap between retinal production and β-carotene consumption using the exogenous MVA pathway; therefore, the retinal derivatives were analyzed. The derivatives, except for retinoic acid, that formed were identified, and the levels of retinal, retinol, and retinyl acetate were measured. Amounts as high as 95 mg/L retinoids were obtained from engineered E. coli DH5α harboring the synthetic SR gene and the exogenous MVA pathway in addition to dxs overexpression, which were cultured at 29°C for 72 hours with 2YT medium containing 2.0% (w/v) glycerol as the main carbon source. However, a significant level of intracellular degradation of the retinoids was also observed in the culture. To prevent degradation of the intracellular retinoids through in situ extraction from the cells, a two-phase culture system with dodecane was used. The highest level of retinoid production (136 mg/L) was obtained after 72 hours with 5 mL of dodecane overlaid on a 5 mL culture.
In this study, we successfully produced 136 mg/L retinoids, which were composed of 67 mg/L retinal, 54 mg/L retinol, and 15 mg/L retinyl acetate, using a two-phase culture system with dodecane, which produced 68-fold more retinoids than the initial level of production (2.2 mg/L). Our results demonstrate the potential use of E. coli as a promising microbial cell factory for retinoid production.
The power generated by the designed piezoelectric energy harvester replaces the standby power that is constantly used in sensors and driving circuits in commercial LED shoes; the harvester thus ...reduces battery consumption. LED shoes incorporating a piezoelectric energy harvester are designed for night workers who work near roads. The piezoelectric energy harvester, composed of a piezoelectric device (PZT ceramic), which is inserted under the insoles of shoes, converts mechanical energy generated by motion of user into electrical energy. The designed harvester has an area of 6 × 4 mm and height of 3 mm (pressed state); it weighs 14 g. Because of its small size and light weight, device is suitable for real workers’ shoes. This piezoelectric energy harvester produces 800 μW at a resistive matching point of 400 kΩ; it is used as a sensor to control an LED switching circuit, allowing the LEDs to blink based on user movements. By applying the piezoelectric energy harvester to LED shoes, battery usage time can be doubled compared to LED shoes that are turned on continuously.
•Designed piezoelectric energy harvester has an area of 6 × 4 mm and height of 3 mm.•Piezoelectric energy harvester produces 800 μW at a resistive matching point of 400 kΩ.•Harvester works as a sensor to drive an LED switching circuit in LED shoes.•The proposed LED shoes enhance the visibility of night workers in dark areas.•Battery usage time can be doubled compared to LED shoes.
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