The kinetics of NKG2C
adaptive natural killer (ANK) cells and NKG2A
inhibitory NK (iNK) cells with respect to the incidence of SARS-CoV-2 infection were studied for 6 months in a cohort of healthcare ...workers following the administration of the heat-killed
(Mw group) in comparison to a control group. In both groups, corona virus disease 2019 (COVID-19) correlated with lower NKG2C
ANK cells at baseline. There was a significant upregulation of NKG2C expression and IFN-γ release in the Mw group (p=0.0009), particularly in those with a lower baseline NKG2C expression, along with the downregulation of iNK cells (p<0.0001). This translated to a significant reduction in the incidence and severity of COVID-19 in the Mw group (incidence risk ratio-0.15, p=0.0004). RNA-seq analysis at 6 months showed an upregulation of the ANK pathway genes and an enhanced ANK-mediated antibody-dependent cellular cytotoxicity (ADCC) signature. Thus, Mw was observed to have a salutary impact on the ANK cell profile and a long-term upregulation of ANK-ADCC pathways, which could have provided protection against COVID-19 in a non-immune high-risk population.
Objective
SARS‐CoV‐2 infection results in severe lung disease in up to 50% of hospitalised patients. The aetiopathogenesis in a subset of such patients, who continue to have progressive pulmonary ...disease following virus clearance, remains unexplored.
Methods
We investigated the role of NKG2C+/NKG2A− adaptive natural killer (ANK) cells, KLRC2 genotype and cytomegalovirus (CMV) reactivation in 22 such patients.
Results
The median duration of virus positivity was 23 days, and the median duration of hospitalisation was 48 days. The overall survival at 60 days in this group was 50%. Older age and comorbidities impacted survival negatively. CMV viraemia was documented in 11 patients, with a survival of 25% vs 80% in those without viraemia with viral load correlating with mortality. Both NK and T cells were markedly depressed in all patients at day 15. However, only persistently low ANK cells at 30 days along with an inversely high NKG2C−/NKG2A+ inhibitory NK cells significantly correlated with high CMV viraemia and mortality, irrespective of KLRC2 genotype. However, day 30 ANK cells were significantly lower in the KLRC2 deletion group. The release of IFN‐γ and perforin was severely compromised in all patients at day +15, with significant improvement in the survivors at day +30, but not in those with adverse outcome.
Conclusion
Patients with progressive lung disease even after negative SARS‐CoV‐2 status, with persistently reduced and functionally compromised ANK cells, are more likely to have CMV reactivation and an adverse outcome, independent of KLRC2 genotype.
In a cohort of patients with severe COVID‐19 lung disease who continued to have severe illness even after clearance of virus, lack of recovery of NKG2C+ adaptive NK cells correlated with cytomegalovirus viral load and increased mortality.
Mycobacterium-
(Mw) was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers (HCW) ...who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw + ChAdOx1 group) were monitored for symptomatic COVID-19 during a major outbreak with the delta variant of SARS-CoV-2 (April-June 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in the Mw + ChAdOx1 group, only two had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46,
= 0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw + ChAdOx1 group, along with downregulation of the TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.
Mycobacterium-w (Mw) was shown to boost adaptive natural killer (ANK) cells and protect against COVID-19 during the first wave of the pandemic. As a follow-up of the trial, 50 healthcare workers ...(HCW) who had received Mw in September 2020 and subsequently received at least one dose of ChAdOx1 nCoV-19 vaccine (Mw + ChAdOx1 group) were monitored for symptomatic COVID-19 during a major outbreak with the delta variant of SARS-CoV-2 (April–June 2021), along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Despite 48% having received just a single dose of the vaccine in the Mw + ChAdOx1 group, only two had mild COVID-19, compared to 36 infections in the ChAdOx1 group (HR-0.46, p = 0.009). Transcriptomic studies revealed an enhanced adaptive NK cell-dependent ADCC in the Mw + ChAdOx1 group, along with downregulation of the TLR2-MYD88 pathway and concomitant attenuation of downstream inflammatory pathways. This might have resulted in robust protection during the pandemic with the delta variant.
Allogenic hematopoietic cell transplantation (HCT) is the best curative approach for patients with severe aplastic anemia (SAA). The outcomes of HCT from haploidentical family donors (HFDs) have ...improved, making it a feasible option for patients lacking an HLA-identical donor. However, data on HFD-HCT for younger patients with SAA is sparse. In this multicenter retrospective study, we evaluated the outcomes of 79 patients undergoing HFD-HCT for SAA. All the patients were heavily pretransfused, the median time to HCT was >12 months, and 67% had failed previous therapies. Conditioning was based on fludarabine (Flu)-cyclophosphamide (Cy)-antithymocyte globulin (ATG)/total body irradiation (TBI) with or without thiotepa/melphalan (TT/Mel). Post-transplantation Cy (PTCy) and calcineurin inhibitors (CNIs)/sirolimus were used as graft-versus-host disease (GVHD) prophylaxis with or without abatacept. The rate of primary graft failure (PGF) was 16.43% overall, lower in patients conditioned with TT/Mel. The incidences of acute and chronic GVHD were 26.4% and 18.9%, respectively. At a median follow-up of 48 months, the overall survival (OS) and event-free survival (EFS) were 61.6% and 58.1%, respectively. Both OS and EFS were better in the TT/Mel recipients and with abatacept as GVHD prophylaxis. On multivariate analysis, the use of abatacept was found to favorably impact the outcome variables, including GVHD and EFS. Our study suggests that PTCy-based HFD-HCT is a reasonable option for young patients with high-risk SAA, in whom optimization of conditioning and GVHD prophylaxis might further improve outcomes.
The information aggregation operator plays a key rule in the group decision making problems. The aim of this paper is to investigate the information aggregation operators method under the picture ...fuzzy environment with the help of Einstein norms operations. The picture fuzzy set is an extended version of the intuitionistic fuzzy set, which not only considers the degree of acceptance or rejection but also takes into the account of neutral degree during the analysis. Under these environments, some basic aggregation operators namely picture fuzzy Einstein weighted and Einstein ordered weighted operators are proposed in this paper. Some properties of these aggregation operators are discussed in detail. Further, a group decision making problem is illustrated and validated through a numerical example. A comparative analysis of the proposed and existing studies is performed to show the validity of the proposed operators.
Improvement of agricultural water use efficiency is of major concern with drought problems being one of the most important factors limiting grain production worldwide. Effective management of water ...for crop production in water-scarce areas requires efficient approaches. Increasing crop water use efficiency and drought tolerance by genetic improvement and physiological regulation may be a means to achieve efficient and effective use of water. A limited water supply inhibits the photosynthesis of plants, causes changes of chlorophyll contents and components and damage to photosynthetic apparatus. It also inhibits photochemical activities and decreases the activities of enzymes in plants. Water stress is one of the important factors inhibiting the growth and photosynthetic abilities of plants through disturbing the balance between the production of reactive oxygen species and the antioxidant defence, causing accumulation of reactive oxygen species which induce oxidative stress to proteins, membrane lipids and other cellular components. A number of approaches are being used to enhance water use efficiency and to minimize the detrimental effect of water stress in crop plants. Proper plant nutrition is a good strategy to enhance water use efficiency and productivity in crop plants. Plant nutrients play a very important role in enhancing water use efficiency under limited water supply. In this paper we discuss the possible effective techniques to improve water use efficiency and some macronutrients (nitrogen, phosphorus, potassium, calcium and magnesium), micronutrients (zinc, boron, iron, manganese, molybdenum and chloride), and silicon (a beneficial nutrient) in detail to show how these nutrients play their role in enhancing water use efficiency in crop plant.
The Pythagorean fuzzy set (PFS) is one of the most important concepts to accommodate more uncertainties than the intuitionistic fuzzy sets, fuzzy sets and hence its applications are more extensive. ...The well-known sine trigonometric function ensures the periodicity and symmetry of the origin in nature and thus satisfies the expectations of decision-makers over the parameters of the multi-time process. Keeping the features of sine function and the importance of the PFS, introduce the novel sine trigonometric operational laws (STOLs) under Pythagorean Fuzzy Settings. In addition, novel sine-trigonometric Pythagorean fuzzy aggregation operators are established based on these STOLs. The core of the study is the decision-making algorithm for addressing multi-attribute decision-making problems based on the proposed aggregation operators with unknown weight information of the given criteria. Finally, an illustrative example on internet finance soft power evaluation is provided to verify the effectiveness. Sensitivity and comparative analyses are also implemented to assess the stability and validity of our method.
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