Aims
Nurses are at the forefront of public health emergencies facing psychological pressures ensuing from the loss of patients and potential risk of infection while treating the infected. This study ...examines whether inclusive leadership has a causal relationship with psychological distress and to assess the mediation effect of psychological safety on this relationship in the long run. The hypotheses are developed and interpreted with the help of theoretical underpinnings from job demands resources theory and the theory of shattered assumptions.
Design
Three‐wave longitudinal study.
Methods
Questionnaire was used to carry out three waves of data collection from 405 nurses employed at five hospitals in Wuhan during the COVID‐19 outbreak between the months of January–April 2020. Partial least square structural equation modelling (PLS‐SEM) was used to analyze data while controlling for age, gender, education, experience, and working hours.
Results
Results supported the hypothesized relationships where inclusive leadership indicated significant inverse causal relationship with psychological distress and a positive causal relationship with psychological safety. Mediation effect of psychological safety was found significant, while the model explained 73.9% variance in psychological distress.
Conclusion
Inclusive leadership, through its positive and supportive characteristics, can pave way for such mechanisms that improve the psychological safety of employees in the long run and curbs psychological distress.
Impact
This is the first longitudinal study to examine the relationship between inclusive leadership and psychological distress in health care and also examines the mediating mechanism of psychology safety. There is scarcity of empirical research on factors that determine and affect behavioural mechanism of healthcare workers during traumatic events and crisis. Clinical leaders and healthcare policy makers must invest in and promote inclusive and supportive environment characterized with open and accessible leaders at workplace to improve psychological safety; it helps reduce levels of psychological distress.
摘要
目的
护士处于公共卫生紧急情况的最前沿,面临着因患者流失以及在治疗被感染者时潜在的感染风险而产生的心理压力。该研究审查了包容性领导是否对心理困扰具有因果关系,并从长远角度评估心理安全对因果关系的调解作用。该假设的发展和理解与工作需求资源理论和分离假设理论有关。
设计
三波纵向研究。
方法
从2020年1月到4月,新冠疫情爆发期间,募集了武汉五家医院的405名护士,采用问卷调查的形式进行三波数据采集。采用偏最小二乘法结构方程模型(PLS‐SEM),分析数据,同时控制年龄、性别、学历、经验和工作时间。
结果
结果支持该假设关系,其中心理困扰和包容型领导呈反因果关系,而和心理安全呈正因果关系。心理安全的中间效果尤为重要,而该模型表明心理困扰的变化率为73.9%。
结论
由于具有积极和支撑性特点,包容型领导可对长期改善员工心理安全并抑制心理困扰的机制发挥作用。
影响
这是第一项纵向研究,旨在探讨医疗保健中包容性领导与心理困扰之间的关系,并探讨心理安全的中间机制。在创伤和危机期间,确定和影响医护人员行为机制的因素的实证研究较匮乏。临床领导者和医疗保健政策制定者必须投资并促进具有包容性和支持性的环境,其特点是工作场所应具有开放性和可及性的领导者,以改善心理安全;其有助于改善心理困扰。
Amino acids are known regulators of cellular signaling and physiology, but how they are sensed intracellularly is not fully understood. Herein, we report that each aminoacyl-tRNA synthetase (ARS) ...senses its cognate amino acid sufficiency through catalyzing the formation of lysine aminoacylation (K-AA) on its specific substrate proteins. At physiologic levels, amino acids promote ARSs bound to their substrates and form K-AAs on the ɛ-amine of lysines in their substrates by producing reactive aminoacyl adenylates. The K-AA marks can be removed by deacetylases, such as SIRT1 and SIRT3, employing the same mechanism as that involved in deacetylation. These dynamically regulated K-AAs transduce signals of their respective amino acids. Reversible leucylation on ras-related GTP-binding protein A/B regulates activity of the mammalian target of rapamycin complex 1. Glutaminylation on apoptosis signal-regulating kinase 1 suppresses apoptosis. We discovered non-canonical functions of ARSs and revealed systematic and functional amino acid sensing and signal transduction networks.
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•Amino acids modify ɛ-amines of lysines•Each tRNA synthetase is the aminoacyl transferase of its cognate amino acid•Aminoacylations can be reversed by deacetylases•Aminoacylations transmit amino acid signals to regulate cellular functions
He et al. reveal that tRNA synthetases sense sufficiency of amino acids and act as aminoacyl transferases to modify ɛ-amines of lysines in proteins, with leucylation of RagA/B regulating mTORC1 activity and glutaminylation of ASK1 inhibiting apoptosis. Lysine aminoacylation marks are removed by SIRT1 and SIRT3.
Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid‐gestational age—the sensitivity of which varies among centers and practitioners. ...An objective method for early diagnosis is needed. Here, we conducted a case–control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.
Synopsis
Mass spectrometry‐based proteomics for plasma proteome profiling were performed on early gestational pregnant women with or without congenital heart disease (CHD) offspring. In‐depth analysis revealed a potential pathogenic mechanism and identified a set of biomarkers in early gestational plasma predicting fetal CHD.
A total of 104 early gestational pregnant women with CHD offspring and 103 controls with healthy offspring were included.
A total of 264 proteins were found significantly upregulated and 358 proteins downregulated in the plasma of early gestational pregnant women with CHD offspring.
Dyslipidemia and CD4+ might be involved in the occurrence of CHD.
Nine CHD‐related biomarkers had been identified.
Mass spectrometry‐based proteomics for plasma proteome profiling was performed on early gestational pregnant women with or without congenital heart disease (CHD) offspring. In‐depth analysis revealed a potential pathogenic mechanism and identified a set of biomarkers in early gestational plasma predicting fetal CHD.
Dysregulated maternal nutrition, such as vitamin deficiencies and excessive levels of glucose and fatty acids, increases the risk for congenital heart disease (CHD) in the offspring. However, the ...association between maternal amino‐acid levels and CHD is unclear. Here, it is shown that increased leucine levels in maternal plasma during the first trimester are associated with elevated CHD risk in the offspring. High levels of maternal leucine increase embryonic lysine‐leucylation (K‐Leu), which is catalyzed by leucyl‐tRNA synthetase (LARS). LARS preferentially binds to and catalyzes K‐Leu modification of lysine 339 within T‐box transcription factor TBX5, whereas SIRT3 removes K‐Leu from TBX5. Reversible leucylation retains TBX5 in the cytoplasm and inhibits its transcriptional activity. Increasing embryonic K‐Leu levels in high‐leucine‐diet fed or Sirt3 knockout mice causes CHD in the offspring. Targeting K‐Leu using the leucine analogue leucinol can inhibit LARS activity, reverse TBX5 K‐Leu modification, and decrease the occurrence of CHD in high‐leucine‐diet fed mice. This study reveals that increased maternal leucine levels increases CHD risk in the offspring through inhibition of embryonic TBX5 signaling, indicating that leucylation exerts teratogenic effects during heart development and may be an intervening target of CHD.
Increased gestational leucine levels are significantly associated with risk for congenital heart disease (CHD) in offspring. Increased embryonic lysine‐leucylation (K‐Leu), generated via maternal high‐leucine‐chow feeding, or Sirt3 knockout, causes CHD in the offspring of mice, through elevating embryonic K‐Leu of TBX5 and inhibiting TBX5 activity. Targeting K‐Leu via leucinol reverses K‐Leu modifications and lowers the occurrence of CHD in mice.
Signal transducer and activator 5a (STAT5A) is a classical transcription factor that plays pivotal roles in various biological processes, including tumor initiation and progression. A fraction of ...STAT5A is localized in the mitochondria, but the biological functions of mitochondrial STAT5A remain obscure. Here, we show that STAT5A interacts with pyruvate dehydrogenase complex (PDC), a mitochondrial gatekeeper enzyme connecting two key metabolic pathways, glycolysis and the tricarboxylic acid cycle. Mitochondrial STAT5A disrupts PDC integrity, thereby inhibiting PDC activity and remodeling cellular glycolysis and oxidative phosphorylation. Mitochondrial translocation of STAT5A is increased under hypoxic conditions. This strengthens the Warburg effect in cancer cells and promotes in vitro cell growth under hypoxia and in vivo tumor growth. Our findings indicate distinct pro-oncogenic roles of STAT5A in energy metabolism, which is different from its classical function as a transcription factor.
Low-dose CT (LDCT) is currently used in lung cancer screening of high-risk populations for early lung cancer diagnosis. However, 96% of individuals with detected nodules are false positives.
In order ...to develop an efficient early lung cancer predictor from clinical, demographic and LDCT features, we studied a total of 218 subjects with lung cancer or benign nodules. Probabilistic graphical models (PGMs) were used to integrate demographics, clinical data and LDCT features from 92 subjects (training cohort) from the Pittsburgh Lung Screening Study cohort.
Learnt PGMs identified three variables directly (causally) linked to malignant nodules and the largest benign nodule and used them to build the Lung Cancer Causal Model (LCCM), which was validated in a separate cohort of 126 subjects. Nodule and vessel numbers and years since the subject quit smoking were sufficient to discriminate malignant from benign nodules. Comparison with existing predictors in the training and validation cohorts showed that (1) incorporating LDCT scan features greatly enhances predictive accuracy; and (2) LCCM improves cancer detection over existing methods, including the Brock parsimonious model (p
0.001). Notably, the number of surrounding vessels, a feature not previously used in predictive models, significantly improves predictive efficiency. Based on the validation cohort results, LCCM is able to identify 30% of the benign nodules without risk of misclassifying cancer nodules.
LCCM shows promise as a lung cancer predictor as it is significantly improved over existing models. Validated in a larger, prospective study, it may help reduce unnecessary follow-up visits and procedures.
Schizophrenia is linked with abnormal brain neurodevelopment, on which IGF-2 (insulin-like growth factor-2) has a great impact. The purpose of this study was to assess the levels of serum IGF-2 and ...its binding proteins IGFBP-3 and IGFBP-7 in schizophrenia patients and the associations of these proteins with schizophrenia psychopathology and cognitive deficits.
Thirty-two schizophrenia patients and 30 healthy controls were recruited. The PANSS and a neurocognitive test battery were used to assess schizophrenic symptomatology and cognition, respectively. Serum IGF-2, IGFBP-3 and IGFBP-7 levels were determined using ELISA.
The schizophrenia patients had a much lower content of serum IGF-2, IGFBP-3 and IGFBP-7 than controls. For the patients, IGF-2 levels were negatively correlated with the PANSS negative scores and positively associated with working memory, attention, and executive function. The correlations between IGF-2 and the PANSS negative scores, working memory or executive function were still significant after controlling for age, sex, education level, BMI, illness history and age of onset. No significant associations of IGFBP-3 or IGFBP-7 with the PANSS scores and cognitive function were observed in the patients.
Our study demonstrates that serum IGF-2 was significantly correlated with negative and cognitive symptoms in patients with schizophrenia, suggesting that altered IGF-2 signaling may be implicated in the psychopathology and cognitive deficits in schizophrenia.
Cholangiocarcinoma (CCA) is a highly heterogeneous cancer with limited understanding and few effective therapeutic approaches. We aimed at providing a proteogenomic CCA characterization to inform ...biological processes and treatment vulnerabilities.
Integrative genomic analysis with functional validation uncovered biological perturbations downstream of driver events including DPCR1 , RBM47 mutations, SH3BGRL2 copy number alterations, and FGFR2 fusions in CCA. Proteomic clustering identified three subtypes with distinct clinical outcomes, molecular features, and potential therapeutics. Phosphoproteomics characterized targetable kinases in CCA, suggesting strategies for effective treatment with CDK and MAPK inhibitors. Patients with CCA with HBV infection showed increased antigen processing and presentation (APC) and T cell infiltration, conferring a favorable prognosis compared with those without HBV infection. The characterization of extrahepatic CCA recommended the feasible application of vascular endothelial-derived growth factor inhibitors. Multiomics profiling presented distinctive molecular characteristics of the large bile duct and the small bile duct of intrahepatic CCA. The immune landscape further revealed diverse tumor immune microenvironments, suggesting immune subtypes C1 and C5 might benefit from immune checkpoint therapy. TCN1 was identified as a potential CCA prognostic biomarker, promoting cell growth by enhancing vitamin B12 metabolism.
We characterized the proteogenomic landscape of 217 CCAs with 197 paired normal adjacent tissues and identified their subtypes and potential therapeutic targets. The multiomics analyses with other databases and some functional validations have indicated strategies regarding the clinical, biological, and therapeutic approaches to the management of CCA.
Background and Purpose
The aim of this study is to identify the early predictors for delayed cerebral ischemia (DCI) and develop a risk stratification score by focusing on the early change after ...aneurysmal subarachnoid hemorrhage (aSAH).
Methods
The study retrospectively reviewed aSAH patients between 2014 and 2015. Risk factors within 72 hours after aSAH were included into univariable and multivariable logistic regression analysis to screen the independent predictors for DCI and to design a risk stratification score.
Results
We analyzed 702 aSAH patients; four predictors were retained from the final multivariable analysis: World Federation of Neurosurgical Societies scale (WFNS; OR = 4.057, P < .001), modified Fisher Scale (mFS; OR = 2.623, P < .001), Subarachnoid Hemorrhage Early Brain Edema Score (SEBES; OR = 1.539, P = .036), and intraventricular hemorrhage (IVH; OR = 1.932, P = .002). According to the regression coefficient, we created a risk stratification score ranging from 0 to 7 (WFNS = 3, mFS = 2, SEBES = 1, and IVH = 1). The new score showed a significantly higher area under curve (0.785) compared with other scores (P < .001).
Conclusion
The early DCI score provides a practical method at the early 72 hours after aSAH to predict DCI.
Abstract
We did 194 epochs of simultaneous 2.25/8.60 GHz observations of XTE J1810−197 in 926 days shortly following its reactivation in 2018 with Shanghai Tian Ma Radio Telescope (TMRT). Although ...its integrated profiles changed with both time and frequency during this period, they could be classified into 12 types according to phase areas of active radiation components. After MJD 59015, XTE J1810−197 turned from the normal emission state into the spiky emission state that was manifesting as a series of bright narrow sub-pulse bursts at both 2.25 and 8.60 GHz. Due to its variable integrated profiles and unsteady rotations, we got the spin frequency
ν
and spin-frequency derivatives
ν
̇
with the piecewise fitting method. In addition, its long-term declining trend of
ν
was also obtained as
ν
̇
=
−
3.2
(
1
)
×
10
−
13
s
−2
with the linear fitting method based on our observations spanning a comparatively longer period. We found its flux densities went through three stages: sharp decrease, stabilization, and day-to-day fluctuations in our dual-frequency observations. Although the flux density showed different stages, XTE J1810−197 showed a relatively flat spectrum (
α
> –1) in most observations. Assuming an ideal dipole magnetic field as some previous research works, we obtained the emission heights of XTE J1810−197 were about 7.5(9) × 10
4
km and 2.38(7) × 10
4
km at 2.25 and 8.60 GHz, respectively. We also found that its emission heights would decrease rapidly with the degree of magnetic field twisting.
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