Abstract
The interplay among magnetism, electronic nematicity, and superconductivity is the key issue in strongly correlated materials including iron-based, cuprate, and heavy-fermion ...superconductors. Magnetic fluctuations have been widely discussed as a pairing mechanism of unconventional superconductivity, but recent theory predicts that quantum fluctuations of nematic order may also promote high-temperature superconductivity. This has been studied in FeSe
1−
x
S
x
superconductors exhibiting nonmagnetic nematic and pressure-induced antiferromagnetic orders, but its abrupt suppression of superconductivity at the nematic end point leaves the nematic-fluctuation driven superconductivity unconfirmed. Here we report on systematic studies of high-pressure phase diagrams up to 8 GPa in high-quality single crystals of FeSe
1−
x
Te
x
. When Te composition
x
(Te) becomes larger than 0.1, the high-pressure magnetic order disappears, whereas the pressure-induced superconducting dome near the nematic end point is continuously found up to
x
(Te) ≈ 0.5. In contrast to FeSe
1−
x
S
x
, enhanced superconductivity in FeSe
1−
x
Te
x
does not correlate with magnetism but with the suppression of nematicity, highlighting the paramount role of nonmagnetic nematic fluctuations for high-temperature superconductivity in this system.
Regulatory T cells (Tregs), either natural or induced, suppress a variety of physiological and pathological immune responses. One of the key issues for understanding Treg function is to determine how ...they suppress other lymphocytes at the molecular level in vivo and in vitro. Here we propose that there may be a key suppressive mechanism that is shared by every forkhead box p3 (Foxp3)+ Treg in vivo and in vitro in mice and humans. When this central mechanism is abrogated, it causes a breach in self-tolerance and immune homeostasis. Other suppressive mechanisms may synergistically operate with this common mechanism depending on the environment and the type of an immune response. Further, Treg-mediated suppression is a multi-step process and impairment or augmentation of each step can alter the ultimate effectiveness of Treg-mediated suppression. These findings will help to design effective ways for controlling immune responses by targeting Treg suppressive functions.
The effect of graft-versus-host disease (GVHD) on transplant outcomes after unrelated cord blood transplantation (UCBT) has not been fully elucidated. We analyzed the impact of acute and chronic GVHD ...on outcomes in adult patients with acute leukemia or myelodysplastic syndrome who underwent their first UCBT (n=2558). The effect of GVHD on outcomes was analyzed after adjusting for other significant variables. The occurrence of GVHD was treated as a time-dependent covariate. The occurrence of grade 1-2 or 3-4 acute GVHD was significantly associated with a lower relapse rate. Grade 3-4 acute GVHD was associated with a higher risk of non-relapse and overall mortality than no acute GVHD, whereas grade 1-2 acute GVHD was associated with a lower risk of non-relapse and overall mortality than no acute GVHD. Limited or extensive chronic GVHD was significantly associated with a lower relapse rate. Limited chronic GVHD was associated with a lower overall and non-relapse mortality than no chronic GVHD. In conclusion, mild acute or chronic GVHD was associated not only with a low risk of relapse but also with a low risk of non-relapse mortality, and provides a survival benefit in UCBT.
Aims
This phase 3, 26‐week, open‐label, treat‐to‐target trial investigated the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) in insulin‐naïve Japanese adults with type 2 diabetes.
...Methods
Subjects were randomized to once‐daily injections of IDegAsp (n = 147) or insulin glargine (IGlar) (n = 149), both ±≤2 oral antidiabetic treatments. IDegAsp was given before the largest meal at the discretion of each subject (and maintained throughout the trial); IGlar was dosed according to label. Both insulins were titrated to a target prebreakfast self‐measured plasma glucose of 3.9 to <5.0 mmol/l.
Results
After 26 weeks, mean HbA1c was 7% with IDegAsp and 7.3% with IGlar; superiority of IDegAsp to IGlar was shown (estimated treatment difference, ETD; IDegAsp–IGlar: –0.28% points −0.46; –0.1095% CI, p < 0.01). At end‐of‐trial, mean fasting plasma glucose (FPG) was similar for IDegAsp and IGlar (5.7 vs. 5.6 mmol/l; ETD IDegAsp–IGlar: 0.15 mmol/l −0.29; 0.6095% CI, p = NS). IDegAsp was associated with numerically lower rates of overall confirmed (27%) and nocturnal confirmed hypoglycaemia (25%) versus IGlar (estimated rate ratio IDegAsp/IGlar: 0.73 0.50; 1.0895% CI, p = NS, and 0.75 0.34; 1.6495% CI, p = NS, respectively). Mean daily insulin doses were similar between groups at end‐of‐trial (both: 0.41 U/kg) as were the increases in body weight from baseline (both: 0.7 kg). Adverse event profiles were similar between groups.
Conclusions
IDegAsp provided superior long‐term glycaemic control compared to IGlar, with similar FPG and doses and numerically lower rates of overall and nocturnal hypoglycaemia (p = NS).
In order to examine GvHD prophylaxis in umbilical cord blood transplantation (UCBT) in more detail, we compared transplant outcomes after UCBT for acute leukemia among GvHD prophylaxes using registry ...data. We selected patients transplanted with a calcineurin inhibitor and methotrexate (MTX)/mycophenolate mofetil (MMF) combination. A total of 1516 first myeloablative UCBT between 2000 and 2012 (Cyclosporine A (CyA) plus MTX, 824, Tacrolimus (Tac) plus MTX, 554, Tac plus MMF, 138) were included. With adjusted analyses, Tac plus MMF showed a significantly higher risk for grade II-IV and III-IV acute GvHD than CyA or Tac plus MTX. Although NRM was similar, Tac plus MMF showed a significantly lower risk of relapse than CyA or Tac plus MTX. A significant difference was observed in the risk of overall mortality (OM) between the MTX-containing group and MMF-containing group. In patients with standard-risk disease, there was no significant difference in the risk of OM in any GvHD prophylaxis. However, in patients with advanced-risk disease, Tac plus MMF showed a significantly lower risk of OM. Therefore, MTX-containing prophylaxis is preferred in UCBT for standard-risk disease, whereas MMF-containing prophylaxis is preferred for advanced-risk disease. A prospective study to identify optimal GvHD prophylaxis for UCBT is warranted.
To assess the impact of minimal residual disease (MRD) and tyrosine kinase inhibitor (TKI) administration on allogeneic hematopoietic cell transplantation (allo-HCT) for Ph-positive ALL (Ph+ALL), we ...retrospectively analyzed data from a registry database for 432 adult Ph+ALL patients in first CR (CR1) who received pre-transplant TKI administration. Negative MRD (MRD(-)) at allo-HCT was achieved in 277 patients. OS in patients transplanted in MRD(-) was significantly better than that in patients transplanted in MRD(+) (MRD(-): 67% vs MRD(+): 55% at 4 years; P=0.001). MRD(-) at allo-HCT was a significant risk factor for survival along with age at allo-HCT in multivariate analyses. Incidence of relapse in patients transplanted in MRD(-) was significantly lower than that in patients transplanted in MRD(+) (MRD(-): 19% vs MRD(+): 29% at 4 years; P=0.006). In multivariate analyses, MRD(+) at allo-HCT was a significant risk factor for relapse. A post-transplant TKI was administered to 103 patients. In subanalyses regarding the effect of post-transplant TKI administration, post-transplant TKI administration was a significant risk factor for relapse in multivariate analyses (P<0.0001). MRD status at allo-HCT is one of the most important predictive factors for Ph+ALL patients transplanted in CR1.
Metal artifacts reduce the quality of CT images and increase the difficulty of interpretation. This study compared the ability of model-based iterative reconstruction and hybrid iterative ...reconstruction to improve CT image quality in patients with metallic dental artifacts when both techniques were combined with a metal artifact reduction algorithm.
This retrospective clinical study included 40 patients (men, 31; women, 9; mean age, 62.9 ± 12.3 years) with oral and oropharyngeal cancer who had metallic dental fillings or implants and underwent contrast-enhanced ultra-high-resolution CT of the neck. Axial CT images were reconstructed using hybrid iterative reconstruction and model-based iterative reconstruction, and the metal artifact reduction algorithm was applied to all images. Finally, hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithm data were obtained. In the quantitative analysis, SDs were measured in ROIs over the apex of the tongue (metal artifacts) and nuchal muscle (no metal artifacts) and were used to calculate the metal artifact indexes. In a qualitative analysis, 3 radiologists blinded to the patients' conditions assessed the image-quality scores of metal artifact reduction and structural depictions.
Hybrid iterative reconstruction + metal artifact reduction algorithms and model-based iterative reconstruction + metal artifact reduction algorithms yielded significantly different metal artifact indexes of 82.2 and 73.6, respectively (95% CI, 2.6-14.7;
< .01). The latter algorithms resulted in significant reduction in metal artifacts and significantly improved structural depictions(
< .01).
Model-based iterative reconstruction + metal artifact reduction algorithms significantly reduced the artifacts and improved the image quality of structural depictions on neck CT images.
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