Control of cell-matrix adhesion has become an important issue in the regulation of stem cell function. In this study, a maltose-binding protein (MBP)-linked basic fibroblast growth factor ...(FGF2)-immobilised polystyrene surface (PS-MBP-FGF2) was applied as an artificial matrix to regulate integrin-mediated signalling. We sought to characterise human mesenchymal-stem cell (hMSC) behaviour in response to two different mechanisms of cell adhesion; (i) FGF2-heparan sulphate proteoglycan (HSPG)-mediated adhesion vs. (ii) fibronectin (FN)-integrin-mediated adhesion. Heparin inhibited hMSC adhesion to PS-MBP-FGF2 but not to FN-coated surface. The phosphorylation of focal adhesion kinase, cytoskeletal re-organisation, and cell proliferation were restricted in hMSCs adhering to PS-MBP-FGF2 compared to FN-coated surface. Expression of MSC markers, such as CD105, CD90 and CD166, decreased in hMSCs expanded on PS-MBP-FGF2 compared to expression in cells expanded on FN-coated surface. hMSCs that were expanded on FN-coated surface differentiated into osteogenic and adipogenic cells more readily than those that were expanded on PS-MBP-FGF2. Furthermore, we characterised the N-linked glycan structures of hMSCs depending on the cell adhesion mechanism using mass spectrometry (MS)-based quantitative techniques. MS analysis revealed that 2,3-sialylated glycans, a potential marker of stem cell function, were more abundant on hMSCs expanded on FN-coated surface than on those expanded on PS-MBP-FGF2. Thus, the differentiation potential of hMSCs is controlled by the type of adhesion substrate that might provide an idea for the design of biomaterials to control stem cell fate. Elucidation of the glycan structure on the cell membrane may help characterise hMSC function.
We investigated the prognostic relevance of IKZF1 deletions in 118 adult Ph-positive ALL patients who had minimal residual disease (MRD) data under a uniform treatment of allo-SCT following ...first-line imatinib-based chemotherapy. IKZF1 deletions were identified in 93 patients (78.8%). IKZF1-deleted patients had a lower proportion of early-stable molecular responders compared with wild-type patients (28.0 vs 56.0%, P=0.028). After a median follow-up of 72 months, IKZF1-deleted patients had a trend for higher cumulative incidence of relapse (CIR) (38.0 vs 13.3%, P=0.052), particularly in a subgroup of early-stable molecular responders (n=40; 21.4 vs 0%, P=0.088), but comparable disease-free survival to wild-type patients. Patients with biallelic-null deletions showed higher CIR (74.6 vs 13.3%, P=0.003) and lower disease-free survival (20.0 vs 67.5%, P=0.022) than wild-type patients. In multivariate analysis, MRD kinetics were closely related to outcomes, while neither IKZF1 deletions nor their functional subtypes retained an independent statistical power. Within the limitation of sample size, however, considering both the negative impact of IKZF1 deletions on MRD kinetics and a trend for relationship between IKZF1 deletions and relapse in early-stable molecular responders, IKZF1 deletions may have a potentially additive effect on unfavorable prognosis in a specific MRD-based subgroup of adult Ph-positive ALL transplants.
The range of recently discovered phenomena in complex oxide heterostructures, made possible owing to advances in fabrication techniques, promise new functionalities and device concepts. One issue ...that has received attention is the bistable electrical modulation of conductivity in ferroelectric tunnel junctions (FTJs) in response to a ferroelectric polarization of the tunnelling barrier, a phenomenon known as the tunnelling electroresistance (TER) effect. Ferroelectric tunnel junctions with ferromagnetic electrodes allow ferroelectric control of the tunnelling spin polarization through the magnetoelectric coupling at the ferromagnet/ferroelectric interface. Here we demonstrate a significant enhancement of TER due to a ferroelectrically induced phase transition at a magnetic complex oxide interface. Ferroelectric tunnel junctions consisting of BaTiO3 tunnelling barriers and La(0.7)Sr(0.3)MnO3 electrodes exhibit a TER enhanced by up to ~10,000% by a nanometre-thick La(0.5)Ca(0.5)MnO3 interlayer inserted at one of the interfaces. The observed phenomenon originates from the metal-to-insulator phase transition in La(0.5)Ca(0.5)MnO3, driven by the modulation of carrier density through ferroelectric polarization switching. Electrical, ferroelectric and magnetoresistive measurements combined with first-principles calculations provide evidence for a magnetoelectric origin of the enhanced TER, and indicate the presence of defect-mediated conduction in the FTJs. The effect is robust and may serve as a viable route for electronic and spintronic applications.
A performance of forced arterial suction thrombectomy was not reported for the treatment of acute basilar artery occlusion. This study compared revascularization performance between intra-arterial ...fibrinolytic treatment and forced arterial suction thrombectomy with a Penumbra reperfusion catheter in patients with acute basilar artery occlusion.
Fifty-seven patients with acute basilar artery occlusion were treated with intra-arterial fibrinolysis (n = 25) or forced arterial suction thrombectomy (n = 32). Baseline characteristics, successful revascularization rate, and clinical outcomes were compared between the groups.
Baseline characteristics, the frequency of patients receiving intravenous recombinant tissue plasminogen activator, and mean time interval between symptom onset and femoral puncture did not differ between groups. The forced arterial suction thrombectomy group had a shorter procedure duration (75.5 minutes versus 113.3 minutes, P = .016) and higher successful revascularization rate (88% versus 60%, P = .017) than the fibrinolysis group. Fair outcome, indicated by a modified Rankin Scale 0-3, at 3 months was achieved in 34% of patients undergoing forced arterial suction thrombectomy and 8% of patients undergoing fibrinolysis (P = .019), and the mortality rate was significantly higher in the fibrinolysis group (25% versus 68%, P = .001). Multiple logistic regression analysis identified the forced arterial suction thrombectomy method as an independent predictor of fair outcome with adjustment for age, sex, initial NIHSS score, and the use of intravenous recombinant tissue plasminogen activator (odds ratio, 7.768; 95% CI, 1.246-48.416; P = .028).
In acute basilar artery occlusion, forced arterial suction thrombectomy demonstrated a higher revascularization rate and improved clinical outcome compared with traditional intra-arterial fibrinolysis. Further clinical trials with the newer Penumbra catheter are warranted.
The precipitation and crystallization of amorphous calcium carbonate (ACC) from metastable calcium carbonate solutions in the concentration range 2–10 mM have been investigated in situ in solution in ...the absence of additives, and in the presence of Mg2+ and poly(acrylic acid). We demonstrate that measurement of the intensity of transmitted light provides an effective method for monitoring the early stages of precipitation of calcium carbonate in solution, where the nature of the scattering particles was confirmed with transmission electron microscopy. The recorded changes in light transmission with time and concentration can be related to the precipitation and aggregation of ACC, its subsequent crystallization to calcite (or vaterite), and the gravitational sedimentation of the growing crystals. Addition of Mg2+ or poly(acrylic acid) is shown to retard the process, delaying the precipitation of ACC and increasing the lifetime of this phase. These results show that measurement of turbidity provides an effective route for monitoring the complex precipitation and crystallization behavior of aqueous CaCO3 and suggests that this method has widespread applicability for studying solution precipitation and crystallization.
There is a growing interest in the role of timing of daily behaviors in improving health. However, little is known about the optimal timing of physical activity to maximize health benefits. We ...perform a cohort study of 92,139 UK Biobank participants with valid accelerometer data and all-cause and cause-specific mortality outcomes, comprising over 7 years of median follow-up (638,825 person-years). Moderate-to-vigorous intensity physical activity (MVPA) at any time of day is associated with lower risks for all-cause, cardiovascular disease, and cancer mortality. In addition, compared with morning group (>50% of daily MVPA during 05:00-11:00), midday-afternoon (11:00-17:00) and mixed MVPA timing groups, but not evening group (17:00-24:00), have lower risks of all-cause and cardiovascular disease mortality. These protective associations are more pronounced among the elderly, males, less physically active participants, or those with preexisting cardiovascular diseases. Here, we show that MVPA timing may have the potential to improve public health.
Background In patients with bleeding peptic ulcers in whom endoscopic hemostasis fails, surgery usually follows. Transarterial embolization (TAE) has been proposed as an alternative. Objective To ...compare the outcomes of TAE and salvage surgery for patients with peptic ulcers in whom endoscopic hemostasis failed. Design Retrospective study. Setting A university hospital. Patients Patients with peptic ulcer bleeding in whom endoscopic hemostasis failed. Interventions TAE and surgery as salvage of peptic ulcer bleeding. Main Outcomes Measurements All-cause mortality, rebleeding, reintervention, and complication rate. Results Thirty-two patients underwent TAE and 56 underwent surgery. In those who underwent TAE, the bleeding vessels were gastroduodenal artery (25 patients), left gastric artery (4 patients), right gastric artery (2 patients), and splenic artery (1 patient). Active extravasation was seen in 15 patients (46.9%). Embolization was attempted in 26 patients, and angiographic coiling was successful in 23 patients (88.5%). Bleeding recurred in 11 patients (34.4%) in the TAE group and in 7 patients (12.5%) in the surgery group ( P = .01). More complications were observed in patients who underwent surgery (40.6% vs 67.9%, P = .01). There was no difference in 30-day mortality (25% vs 30.4%, P = .77), mean length of hospital stay (17.3 vs 21.6 days, P = .09), and need for transfusion (15.6 vs 14.2 units, P = .60) between the TAE and surgery groups. Limitations Retrospective study. Conclusions In patients with ulcer bleeding after failed endoscopic hemostasis, TAE reduces the need for surgery without increasing the overall mortality and is associated with fewer complications.
Metal halide perovskite solar cells (PSCs) have undergone rapid progress. However, unstable performance caused by sensitivity to environmental moisture and high temperature is a major impediment to ...commercialization of PSCs. In the present work, a low-temperature, glass–glass encapsulation technique using high performance polyisobutylene (PIB) as the moisture barrier is investigated on planar glass/FTO/TiO2/FAPbI3/PTAA/gold perovskite solar cells. PIB was applied as either an edge seal or blanket layer. Electrical connections to the encapsulated PSCs were provided by either the FTO or Au layers. Results of a “calcium test” demonstrated that a PIB edge-seal effectively prevents moisture ingress. A shelf life test was performed and the PIB-sealed PSC was stable for at least 200 days. Damp heat and thermal cycling tests, in compliance with IEC61215:2016, were used to evaluate different encapsulation methods. Current–voltage measurements were performed regularly under simulated AM1.5G sunlight to monitor changes in PCE. The best results we have achieved to date maintained the initial efficiency after 540 h of damp heat testing and 200 thermal cycles. To the best of the authors’ knowledge, these are among the best damp heat and thermal cycle test results for perovskite solar cells published to date. Given the modest performance of the cells (8% averaged from forward and reverse scans) especially with the more challenging FAPbI3 perovskite material tested in this work, it is envisaged that better stability results can be further achieved when higher performance perovskite solar cells are encapsulated using the PIB packaging techniques developed in this work. We propose that heat rather than moisture was the main cause of our PSC degradation. Furthermore, we propose that preventing the escape of volatile decomposition products from the perovskite solar cell materials is the key for stability. PIB encapsulation is a very promising packaging solution for perovskite solar cells, given its demonstrated effectiveness, ease of application, low application temperature, and low cost.
It remains controversial whether metastasectomy is still feasible in patients with pulmonary recurrence from colorectal cancer, after initial metastasectomy. The aim of this study was to evaluate ...outcomes of repeated metastasectomy in these patients.
From 1995 to 2007, 202 patients had received a pulmonary metastasectomy from colorectal cancer at our institution. Over a median follow-up of 28.9 months, 48 patients received second metastasectomy (29 wedge resections, 5 segmentectomies, 13 lobectomies, and 1 completion pneumonectomy). The median disease-free interval was 9.6 months. Among these 48 patients, 28 showed pulmonary recurrence again and of those, 10 patients received third metastasectomy (two wedge resections, two segmentectomies, four lobectomies, and two completion pneumonectomies).
There was no postoperative mortality. Of the 48 patients who underwent second metastasectomy, overall and disease-free 5-year survivals were 79% and 49%, respectively, after second operation. Of the 10 patients who received third metastasectomy, overall survival was 78% at 5 years after last operation.
Repeated resection after initial metastasectomy can be carried out safely and provides long-term survival in patients with recurrent pulmonary metastasis from colorectal cancer. Our findings indicate that close follow-up for the early detection of recurrence and parenchyma-saving resection can improve the results after repeated resection.
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