Patients with resected stage III melanoma have a heterogeneous prognosis with an especially high risk of relapse for patients with stage IIIB, IIIC and IIID according to the 2018 classification in
, ...8
edition (AJCC-8). Ipilimumab was the first immune checkpoint inhibitor (ICI) to show prolonged overall survival (OS) but at the cost of high toxicity. Pembrolizumab and nivolumab are inhibitors of programmed cell death 1 (PD-1) and showed prolonged relapse-free survival (RFS) in patients with resected stage III melanoma at high risk of relapse compared to placebo and ipilimumab, respectively.
The aim of this article is to review the mechanisms of action, pharmacokinetics and safety data of pembrolizumab in resected stage III melanoma and to compare its safety profile to other immune checkpoint inhibitors for the same indication.
Pembrolizumab as adjuvant therapy of resected stage III melanoma showed an acceptable safety profile, which is comparable to that in advanced melanoma. However, it caused one death. There is uncertainty about its benefits in AJCC-8 stage IIIA melanoma patients. Additionally, caution is required since OS and long-term safety data are not available yet.
B-flavor tagging at Belle II Akopov, N.; Banerjee, Sw; Bauer, M. ...
The European physical journal. C, Particles and fields,
04/2022, Letnik:
82, Številka:
4
Journal Article
Recenzirano
Odprti dostop
We report on new flavor tagging algorithms developed to determine the quark-flavor content of bottom (
) mesons at Belle II. The algorithms provide essential inputs for measurements of quark-flavor ...mixing and charge-parity violation. We validate and evaluate the performance of the algorithms using hadronic
decays with flavor-specific final states reconstructed in a data set corresponding to an integrated luminosity of 62.8 fb
-
1
, collected at the
resonance with the Belle II detector at the SuperKEKB collider. We measure the total effective tagging efficiency to be
ε
eff
=
(
30.0
±
1.2
(
stat
)
±
0.4
(
syst
)
)
%
for a category-based algorithm and
ε
eff
=
(
28.8
±
1.2
(
stat
)
±
0.4
(
syst
)
)
%
for a deep-learning-based algorithm.
Stimulation of phosphatidylinositol 3'-kinase (PI3K) and protein kinase B (PKB) is implicated in the regulation of protein synthesis in various cells. One mechanism involves PI3K/PKB-dependent ...phosphorylation of 4E-BP1, which dissociates from eIF4E, allowing initiation of translation from the 7-methylGTP cap of mRNAs. We examined the effects of insulin and H(2)O(2) on this pathway in neonatal cardiac myocytes. Cardiac myocyte protein synthesis was increased by insulin, but was inhibited by H(2)O(2). PI3K inhibitors attenuated basal levels of protein synthesis and inhibited the insulin-induced increase in protein synthesis. Insulin or H(2)O(2) increased the phosphorylation (activation) of PKB through PI3K, but, whereas insulin induced a sustained response, the response to H(2)O(2) was transient. 4E-BP1 was phosphorylated in unstimulated cells, and 4E-BP1 phosphorylation was increased by insulin. H(2)O(2) stimulated dephosphorylation of 4E-BP1 by increasing protein phosphatase (PP1/PP2A) activity. This increased the association of 4E-BP1 with eIF4E, consistent with H(2)O(2) inhibition of protein synthesis. The effects of H(2)O(2) were sufficient to override the stimulation of protein synthesis and 4E-BP1 phosphorylation induced by insulin. These results indicate that PI3K and PKB are important regulators of protein synthesis in cardiac myocytes, but other factors, including phosphatase activity, modulate the overall response.
Synthesizing two key texts from Frédéric Pham's groundbreaking research in algebraic geometry, this essential introduction to the singularities of integrals focuses on topological and geometrical ...aspects before moving on to explain the analytical approach.
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