Quantifying the parameter dependent basin of the unsafe regime of asymmetric Lévy-noise-induced critical transitions

In real systems, the unpredictable jump changes of the random environment can induce the critical transitions (CTs) between two non-adjacent states, which are more catastrophic. Taking an asymmetric Lévy-noise-induced tri-stable model with desirable, sub-desirable, and undesirable states as a prototype class of real systems, a prediction of the noise-induced CTs from the desirable state directly to the undesirable one is carried out. We first calculate the region that the current state of the given model is absorbed into the undesirable state based on the escape probability, which is named as the absorbed region. Then, a new concept of the parameter dependent basin of the unsafe regime (PDBUR) under the asymmetric Lévy noise is introduced. It is an efficient tool for approximately quantifying the ranges of the parameters, where the noise-induced CTs from the desirable state directly to the undesirable one may occur. More importantly, it may provide theoretical guidance for us to adopt some measures to avert a noise-induced catastrophic CT. © 2021, The Author(s)

Radiotherapy dosimetry and radiotherapy related complications of immediate implant-based reconstruction after breast cancer surgery

BackgroundsThe impact of immediate implant-based breast reconstruction (IBBR) on the delivery of radiotherapy plans remains controversial. This study aimed to compare the differences in radiotherapy dosimetry, complications of radiotherapy, and quality of life in patients who underwent modified radical mastectomy combined with or without IBBR.MethodsWe retrospectively collected 104 patients with breast cancer who underwent intensity-modulated radiation therapy after modified radical mastectomy with IBBR (n =46) or not (n =58) from January 2017 to December 2021. The dosimetric differences in radiotherapy of planning target volume (PTV) and organs at risk and the differences in complications of radiotherapy between the two groups were compared. We also applied the functional assessment of cancer therapy-breast cancer (FACT-B) score to compare the difference in quality of life. The chi-square test and independent samples t-test were used to analyze the above data.ResultsIBBR group was associated with higher PTV volumes, PTV D98, V95, and lower PTV Dmean, D2 compared with the non-reconstruction group (P<0.05). IBBR group also had lower radiotherapy dosimetric parameters in the ipsilateral lung and the heart of left breast cancer patients. The differences in the rates of radiation pneumonia (RP) and radiation dermatitis (RD) between the two groups were not statistically significant (P > 0.05). Moreover, FACT-B scores at 6 months after radiotherapy in patients with IBBR were higher than those without reconstruction (P < 0.05).ConclusionPatients with IBBR achieved better radiation dosimetry distribution and higher quality of life without more complications of radiotherapy

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Impact of direct-acting antivirals on de novo occurrence of hepatocellular carcinoma in hepatitis C virus patients

Hepatitis C Virus (HCV) infection constitutes a significant burden to world health, leading to liver cirrhosis and hepatocellular carcinoma (HCC). In the past decades, pegylated interferon combined with ribavirin has been used extensively for HCV treatment, and interferon (IFN) is thought to have antitumor property. Direct-acting antivirals (DAAs) have fundamentally changed HCV therapy, due to their high efficacy and tolerability. However, recent studies have reported relatively high rates of HCC occurrence, and recurrence, following successful HCV treatment using DAAs. These studies were grossly underpowered due to their retrospective design, lack of untreated or IFN controls, small sample size, and limited patient follow-up time. From then, many retrospective and prospective cohort studies with larger size and longer follow-up duration after DAAs therapy have been published. These studies showed that treatment with DAAs can reduce the risk of HCC compared to no treatment, didn’t increase the risk of HCC compared to IFN-based therapy after adjusting for the potential confounders of these two groups, and DAAs-induced sustained virological response decreased the risk of HCC compared to DAAs treatment failure. In conclusion, DAAs treatment doesn’t appear to increase the development of HCC, even in cirrhotic patients. However, cirrhotic patients should be monitored for the development of HCC during and after DAAs treatment

Suppression of noise-induced critical transitions: a linear augmentation method

In stochastic complex systems, some sudden critical transitions (CTs) from one desirable state to another contrasting one can take place because of noise, which may even lead to catastrophic consequences. To keep a certain system in one desirable state of performance, methods that suppress these catastrophic CTs in the presence of noise need to be developed. In this paper, the ability of an external linear augmentation method to suppress Gaussian white noise-induced CTs away from a desirable state is investigated from a new perspective. This control is designed in such a way that, as a noise-induced CT is impending, the desirable state of performance in a stochastic complex system can be stabilized using a specific type of coupling with a linear dynamical system. Then, the contrasting state is annihilated with increasing coupling strength. Taking a bi-stable system with one CT (from the desirable state to the undesirable one) and a tri-stable system with two CTs (from the desirable state to the sub-desirable one and from the sub-desirable state to the undesirable one) as the prototype class of real complex systems, the potential of our technique is demonstrated

Additional suture augmentation to anterior cruciate ligament reconstruction with hamstring autografts bring no benefits to clinical results, graft maturation and graft-bone interface healing

Abstract Background From the perspective of graft protection and early rehabilitation during the maturation and remodeling phases of graft healing, suture augmentation (SA) for anterior cruciate ligament reconstruction (ACLR) has attracted more and more attention. Study Design Retrospective study. Purpose To determine whether the additional SA affects clinical results, graft maturation and graft-bone interface healing during two years follow-up after ACLR. Methods 20 ACLRs with additional SA (ACLR-SA group) and 20 ACLRs without additional SA (ACLR group) were performed between January 2020 and December 2021 by the same surgeon and were retrospectively analyzed. Pre- and postoperative International Knee Documentation Committee (IKDC) scores, Lysholm scores, graft failure and reoperation were evaluated. The signal/noise quotient (SNQ) of autografts and the signal intensity of graft-bone interface were analyzed. All 40 patients in ACLR-SA group and ACLR group completed 2-years follow-up. Results There was no patient in the two cohorts experienced graft failure and reoperation. The postoperative IKDC and Lysholm scores have been significantly improved compared with preoperative scored in both ACLR-SA group and ACLR group, however, there was no significant difference between two groups. The SNQ of proximal graft of ACLR-SA group (14.78 ± 8.62 vs. 8.1 ± 5.5, p = 0.041) was significantly greater while the grades of graft-bone interface healing of posterior tibial was significantly lower than that of ACLR group at 1-year postoperatively (p = 0.03), respectively. There were no significant differences between the two groups of the SNQ of proximal, distal medial graft segments, and the graft-bone interface healing grades of anterior femoral, posterior femoral, anterior tibial and posterior tibial at other time points (p>0.05). Conclusions The additional SA in ACLR had no effect on IKDC scores, Lysholm scores, graft maturation and graft-bone interface healing at 2-year postoperatively. Our research does not support the routine use of SA in ACLR

Ginsenoside Rk3 Inhibits the Extramedullary Infiltration of Acute Monocytic Leukemia Cell via miR-3677-5p/CXCL12 Axis

Background. Acute monocytic leukemia belongs to type M5 of acute myeloid leukemia (AML) classified by FAB, which appears a high incidence of extramedullary infiltration (EMI) and poor prognosis. In this study, we observed the inhibitory effect of ginsenoside Rk3 on the EMI of monocytic leukemia cells and initially explored its related mechanism of targeting the miR-3677-5p/CXCL12 axis. Methods. The MTT assay and colony formation assay were used to detect the inhibitory effect of Rk3 on proliferation. Both cellular migration and invasion were observed by the Transwell assay. The expression levels of miR-3677-5p, CXCL12, and CXCR4 were detected by RT-qPCR and Western blot, as well as overexpression of miR-3677-5p by transfected with lentivirus and detection of a dual luciferase reporter gene. The expression of MMP2 and TIMP2 was detected by immunofluorescence. Results. Rk3 effectively inhibits the proliferation, migration, and invasion associated with EMI of leukemia. The leukemia cells of M5 patients with EMI showed low expression of miR-3677-5p but high expression of the mRNA of CXCL12 and CXCR4. Overexpression of miR-3677-5p or intervention of CXCL12 effectively inhibited the proliferation, migration, and invasion of SHI-1 cells. The luciferase assay showed that CXCL12 was the downstream target gene of miR-3677-5p. After overexpression of miR-3677-5p or intervention of CXCL12 in combination with Rk3, the inhibitory effect on the proliferation, migration, and invasion of SHI-1 cells was more obvious. Importantly, Rk3 significantly regulated the expression levels of miR-3677-5p, CXCL12, CXCR4, and EMI-related functional proteins including MMP2 and TIMP2. Overexpression of miR-3677-5p or intervention of CXCL12 also regulated the expression of MMP2 and TIMP2. Conclusions. The leukemia cells of M5 patients with EMI appeared to have low expression of miR-3677-5p and high expression of the mRNA of CXCL12 and CXCR4, which may be used as indicators of EMI and poor prognosis. Rk3 is effective in inhibiting the EMI of SHI-1 cells by targeting the miR-3677-5p/CXCL12 axis

Homoharringtonine Combined with the Heat Shock Protein 90 Inhibitor IPI504 in the Treatment of FLT3-ITD Acute Myeloid Leukemia

As a heterogeneous group of clonal disorders, acute myeloid leukemia with internal tandem duplication of fms-like tyrosine kinase 3 (FLT3-ITD) mutation usually shows an inferior prognosis. In the present study, we found that homoharringtonine (HHT), a protein translation inhibitor of plant alkaloid in China, exhibited potent cytotoxic effect against FLT3-ITD (+) cell lines and primary leukemia cells, and a remarkable synergistic anti-leukemia action was demonstrated in vitro and in vivo in xenograft mouse models when co-treated with the heat shock protein 90 inhibitor IPI504. Mechanistically, HHT combined with IPI504 synergistically inhibited the growth of leukemia cells by inducing apoptosis and G1 phase arrest. This synergistic action resulted in a prominent reduction of total and phosphorylated FLT3 (p-FLT3) as well as inhibition of its downstream signaling molecules such as STAT5, AKT, ERK and 4E-BP1. Furthermore, co-treatment of HHT and IPI504 led to a synergistic or additive effect on 55.56%(10/18) of acute myeloid leukemia cases tested, including three relapsed/refractory patients. In conclusion, our findings indicate that the combination of HHT and HSP90 inhibitor provides an alternative way for the treatment of FLT3-ITD positive acute myeloid leukemia, especially for relapsed/refractory AML