scholarly journals TET2 mutations as a part of DNA dioxygenase deficiency in myelodysplastic syndromes

2021 ◽  
Author(s):  
Carmelo Gurnari ◽  
Simona Pagliuca ◽  
Yihong Guan ◽  
Vera Adema ◽  
Courtney E Hershberger ◽  
...  
Keyword(s):  
Myelodysplastic Syndromes ◽  
Prognostic Significance ◽  
Age Groups ◽  
Feedback Mechanism ◽  
Dna Demethylation ◽  
Compensatory Mechanisms ◽  
Poor Outcomes ◽  
Relationship Of ◽  
The Impact

Decrease in DNA dioxygease activity generated by TET2 gene family is crucial in myelodysplastic syndromes (MDS). The general down-regulation of 5-hydroxymethylcytosine (5-hmC) argues for a role of DNA demethylation in MDS beyond TET2 mutations, which albeit frequent, do not convey any prognostic significance. We investigated TETs expression to identify factors which can modulate the impact of mutations and thus 5-hmC levels on clinical phenotypes and prognosis of MDS patients. DNA/RNA-sequencing and 5-hmC data were collected from 1,665 patients with MDS and 91 controls. Irrespective of mutations, a significant fraction of MDS patients exhibited lower TET2 expression, while 5-hmC levels were not uniformly decreased. In searching for factors explaining compensatory mechanisms, we discovered that TET3 was up-regulated in MDS and inversely correlated with TET2 expression in wild-type cases. While TET2 was reduced across all age-groups, TET3 levels were increased in a likely feedback mechanism induced by TET2 dysfunction. This inverse relationship of TET2 and TET3 expression also corresponded to the expression of L-2-hydroxyglutarate dehydrogenase, involved in agonist/antagonist substrate metabolism. Importantly, elevated TET3 levels influenced the clinical phenotype of TET2-deficiency whereby the lack of compensation by TET3 (low TET3 expression) was associated with poor outcomes of TET2 mutant carriers.

The Health of Refugees

2019 ◽  
Keyword(s):  
Age Groups ◽  
Refugee Health ◽  
Mass Movements ◽  
Ethical Challenges ◽  
Displaced Populations ◽  
Political Landscape ◽  
The Media ◽  
Multidisciplinary Perspective ◽  
The Impact

There have been significant changes in the numbers, patterns, and circumstances of refugees and in the political landscape to support humanitarianism since the publication of the first edition of this collection. Like the first edition, this volume provides a multidisciplinary perspective on refugee health, tracing the health repercussions on individuals and populations from the drivers of forced mass movements of populations from situations of conflict and other disasters through to the process of resettlement in countries other than their countries of origin. Drawing on the expertise of academics, practitioners, and UN frontline experts, the collection covers three main aspects of refugee health: the concepts, definitions, and context from a human rights, humanitarianism, and social determinants of health perspective; the intersection of vulnerabilities across age groups and settings; and the ethical challenges for practitioners and researchers working with forcibly displaced populations seeking to resettle. The collection concludes with an analysis of the role of the media in shaping our perceptions of refugees and the impact on policy and access to care.

scholarly journals Impact of Authoritative and Laissez-Faire Leadership on Thriving at Work: The Moderating Role of Conscientiousness

2021 ◽  
Vol 11 (3) ◽  
pp. 667-685
Author(s):  
Zulfiqar Ahmed Iqbal ◽  
Ghulam Abid ◽  
Muhammad Arshad ◽  
Fouzia Ashfaq ◽  
Muhammad Ahsan Athar ◽  
...  
Keyword(s):  
Leadership Style ◽  
Positive Impact ◽  
Work Relationship ◽  
Laissez Faire ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship ◽  
Moderating Role ◽  
Thriving At Work

This study empirically investigates the less discussed catalytic effect of personality in the relationship of leadership style and employee thriving at work. The growth and sustainability of the organization is linked with the association of leadership style and employee thriving at the worplace. The objectives of this study are to explore the impact of authoritative and laissez-faire leadership styles and the moderating role of the personality trait of conscientiousness on thriving in the workplace. A sample of 312 participants was taken from a leading school system with its branches in Lahore and Islamabad, Pakistan. The participants either worked as managers, teachers in headquarters, or school campuses, respectively. The regression results of the study show that authoritative leadership and conscientiousness have a significantly positive impact on thriving at work. Furthermore, conscientiousness moderates the relationship between laissez-faire style of leadership and thriving at work relationship. The findings of this study have theoretical implications for authoritative and laissez-faire leadership, employee conscientiousness, and managerial applications for the practitioners.

The impact of Traditional Chinese Medicine on mitophagy in disease models

2021 ◽  
Vol 27 ◽  
Author(s):  
Li-Ping Yu ◽  
Ting-Ting Shi ◽  
Yan-Qin Li ◽  
Jian-Kang Mu ◽  
Ya-Qin Yang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Human Diseases ◽  
Regulatory Mechanisms ◽  
Disease Models ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

: Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

scholarly journals Impact of non-menthol flavours in e-cigarettes on perceptions and use: an updated systematic review

BMJ Open ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. e031598 ◽  
Author(s):  
Clare Meernik ◽  
Hannah M Baker ◽  
Sarah D Kowitt ◽  
Leah M Ranney ◽  
Adam O Goldstein
Keyword(s):  
Systematic Review ◽  
Risk Perceptions ◽  
Longitudinal Research ◽  
Age Groups ◽  
Experimental Studies ◽  
Final Analysis ◽  
Eligibility Criteria ◽  
Product Appeal ◽  
The Impact

ObjectivesGiven the exponential increase in the use of e-cigarettes among younger age groups and in the growth in research on e-cigarette flavours, we conducted a systematic review examining the impact of non-menthol flavoured e-cigarettes on e-cigarette perceptions and use among youth and adults.DesignPubMed, Embase, PyscINFO and CINAHL were systematically searched for studies published and indexed through March 2018.Eligibility criteriaQuantitative observational and experimental studies that assessed the effect of non-menthol flavours in e-cigarettes on perceptions and use behaviours were included. Specific outcome measures assessed are appeal, reasons for use, risk perceptions, susceptibility, intention to try, initiation, preference, current use, quit intentions and cessation.Data extraction and synthesisThree authors independently extracted data related to the impact of flavours in tobacco products. Data from a previous review were then combined with those from the updated review for final analysis. Results were then grouped and analysed by outcome measure.ResultsThe review included 51 articles for synthesis, including 17 published up to 2016 and an additional 34 published between 2016 and 2018. Results indicate that non-menthol flavours in e-cigarettes decrease harm perceptions (five studies) and increase willingness to try and initiation of e-cigarettes (six studies). Among adults, e-cigarette flavours increase product appeal (seven studies) and are a primary reason many adults use the product (five studies). The role of flavoured e-cigarettes on smoking cessation remains unclear (six studies).ConclusionThis review provides summary data on the role of non-menthol flavours in e-cigarette perceptions and use. Consistent evidence shows that flavours attract both youth and adults to use e-cigarettes. Given the clear findings that such flavours increase product appeal, willingness to try and initiation among youth, banning non-menthol flavours in e-cigarettes may reduce youth e-cigarette use. Longitudinal research is needed to examine any role flavours may play in quit behaviours among adults.

Probing the impact of transformational leadership on job embeddedness: the moderating role of job characteristics

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Usman Khalid ◽  
Rabia Mushtaq ◽  
Abdul Zahid Khan ◽  
Faisal Mahmood
Keyword(s):  
Transformational Leadership ◽  
Job Characteristics ◽  
Job Embeddedness ◽  
Transformational Leaders ◽  
Content Type ◽  
Work Settings ◽  
Leadership Research ◽  
Relationship Of ◽  
The Impact

Purpose This paper aims to evaluate how transformational leadership can increase job embeddedness in their employees that persuade them to stay in their organization and how this relationship is contingent upon the job characteristics. Design/methodology/approach Sample of 328 useable responses was available for analysis. Questionnaires were distributed to the employees who are working in different Pakistani organizations. Regression analysis was used to test for hypotheses. Findings The findings support that there is a significant impact of transformational leadership for shaping job embeddedness, and the results endorsed the role of job characteristics as a moderator in describing the relationship of transformational leadership and job embeddedness. Transformational leaders would motivate employees to work together in productive manners in challenging work settings. Originality/value This paper makes three key contributions to the literature on job design. First, this inquiry shows that a strong link does exist between transformational leadership in creating organizational job embeddedness. Second, it highlights how job characteristics of highly challenging work settings may shape employees’ job embeddedness. Third, this paper offers a novel perspective in leadership research by incorporating high challenging work setting (i.e. job characteristics) as moderator. Managers may get new insight by opting for transformational leaders' attributes and concentrating on high challenging work settings for creating embeddedness in employees to prolong their stay with the job and firm.

scholarly journals Risk factors for respiratory Aspergillus fumigatus in German Cystic Fibrosis patients and impact on lung function

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Uta Düesberg ◽  
Julia Wosniok ◽  
Lutz Naehrlich ◽  
Patience Eschenhagen ◽  
Carsten Schwarz
Keyword(s):  
Risk Factors ◽  
Cystic Fibrosis ◽  
Lung Function ◽  
Aspergillus Fumigatus ◽  
Age Groups ◽  
Antibiotic Use ◽  
Lower Lung ◽  
Lung Infections ◽  
The Impact

Abstract Airway inflammation and chronic lung infections in cystic fibrosis (CF) patients are mostly caused by bacteria, e.g. Pseudomonas aeruginosa (PA). The role of fungi in the CF lung is still not well elucidated, but evidence for a harmful and complex role is getting stronger. The most common filamentous fungus in CF is Aspergillus fumigatus (AF). Age and continuous antibiotic treatment have been discussed as risk factors for AF colonisation but did not differentiate between transient and persistent AF colonisation. Also, the impact of co-colonisation of PA and AF on lung function is still under investigation. Data from patients with CF registered in the German Cystic Fibrosis Registry database in 2016 and 2017 were retrospectively analysed, involving descriptive and multivariate analysis to assess risk factors for transient or persistent AF colonisation. Age represented an independent risk factor for persistent AF colonisation. Prevalence was low in children less than ten years, highest in the middle age and getting lower in higher age (≥ 50 years). Continuous antibiotic lung treatment was significantly associated with AF prevalence in all age groups. CF patients with chronic PA infection had a lower lung function (FEV1%predicted), which was not influenced by an additional AF colonisation. AF colonisation without chronic PA infection, however, was significantly associated with a lower function, too. Older age up to 49 years and continuous antibiotic use were found to be the main risk factors for AF permanent colonisation. AF might be associated with decrease of lung function if not disguised by chronic PA infection.

scholarly journals The Impact of Project Manager Soft Competences on Project Sustainability

2020 ◽  
Vol 12 (16) ◽  
pp. 6537
Author(s):  
Jian Xue ◽  
Zeeshan Rasool ◽  
Aqsa Gillani ◽  
Ahmad Imran Khan
Keyword(s):  
Structural Equation ◽  
Positive Impact ◽  
Project Managers ◽  
Project Manager ◽  
Equation Modeling ◽  
Project Sustainability ◽  
Relationship Of ◽  
The Impact ◽  
The Given

The current study suggests a different and innovative view by testing a unique combination of variables, which are unproven in a single model for the purpose of increasing the ratio of sustainable projects. The project manager can use the model to look their projects and can compose necessary changes for better outcomes. The study objects to postulate the competence breach of project managers with regard to sustainability, and to deliver direction that how to fulfill the research gap. The given work is centered on the result of project supervisor soft capabilities on project sustainability mediated by innovation. To achieve this aim, deductive approach was adopted. The sample size of the study was 242 respondents, and data were collected from software houses. The collected data were then analyzed by doing the structural equation modeling in PLS-SEM in order to examine the relationships. The outcomes demonstrate positive impact of project manager soft competences on project sustainability and mediating impact of innovation among the relationship of project manager soft competences and project sustainability. Innovation is directly linked to project sustainable development, and was accepted, which aligns with the previous studies. This research reflects the role of project manager soft competences on innovation and project sustainability. The study is unique in its scope and implications as the focus is upon empirical investigation of the project manager soft competences and project sustainability in the context of Pakistan.

The Role of Unabsorbed Slack in Internal and Collaborative Innovation Processes — A Resource-Based Framework

2016 ◽  
Vol 13 (03) ◽  
pp. 1640007 ◽  
Author(s):  
Ulrich Lichtenthaler
Keyword(s):  
Critical Role ◽  
Slack Resources ◽  
Fine Grained ◽  
Collaborative Innovation ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship ◽  
Unabsorbed Slack ◽  
Innovation Processes

Extant research has highlighted the critical role of unabsorbed slack resources in internal innovation processes. In recent years, many firms have continued to open up their innovation processes to actively collaborate with external partners. In light of a limited understanding of the determinants of collaborative innovation, we provide new theoretical arguments about the relationship of unabsorbed slack resources with internal and collaborative innovation processes. Specifically, we draw on resource-based and competence-based logic and develop a conceptual framework for intraorganizational and interorganizational innovation with propositions for the impact of unabsorbed slack resources on internal and external knowledge acquisition and commercialization processes. The arguments underscore the critical role of excess resources in collaborative innovation, and they highlight the need for a fine-grained examination of the impact of unabsorbed slack resources in innovation processes. The arguments are particularly important in light of a renewed interest in essential enablers and barriers to collaborative innovation processes.

Impact of the type of first-cancer therapy in therapy-related myelodysplastic syndromes outcomes.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18555-e18555
Author(s):  
Ana Alfonso Pierola ◽  
Guillermo Montalban-Bravo ◽  
Koichi Takahashi ◽  
Elias Jabbour ◽  
Tapan M. Kadia ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Myelodysplastic Syndromes ◽  
Alkylating Agents ◽  
Complex Karyotype ◽  
Topoisomerase Inhibitors ◽  
Previous Therapy ◽  
Hematological Cancers ◽  
Background Therapy ◽  
Poor Outcomes ◽  
The Impact

e18555 Background: Therapy-related myelodysplastic syndromes (t-MDS) are known to have poor outcomes. The impact of the therapy received for the first cancer remains unknown. Methods: 228 t-MDS diagnosed between July 2001 and December 2015 were retrospectively reviewed. Results: Median age at diagnosis of t-MDS was 66 years (range 13-87). Previous malignancies: 54% hematological cancers and 47% solid tumors. 14% had multiple cancers before the t-MDS. Previous therapy received: 119 (52%) chemotherapy (CT), 17 (8%) radiotherapy (RT), or 92 (40%) both (Table). Median time to develop t-MDS was 73 months (range 5-355). According to IPSS, 13 patients (6%) had low-risk, 65 (29%) intermediate-1 risk, 119 (53%) intermediate-2 risk and 29 (13%) high-risk. 124 patients (58%) had complex karyotype. The most frequent cytogenetic abnormalities detected were: -7/7q (n=99; 46%), -5/5q (n=77; 36%), and +8 (n=13; 6%). TP53was observed in 51% (n=21/41). Median OS was 12 months (CI95% = 10-14). Univariate and multivariate analysis revealed that CT vs RT (p=0.028; HR [CI95%] = 1.988 [1.08-3.67]), and higher IPSS risk (low: p=0.027; intermediate-1: p=0.285 HR [CI95%] = 1.48 [0.72-3.01]; intermediate-2: p=0.055, HR [CI95%] = 1.95 [0.99-3.88]; high: p=0.015 HR [CI95%] = 2.59 [1.21-5.55]), had a poor impact in OS. No statistical differences between OS and type of CT received, molecular or cytogenetic alterations were observed. However, complex karyotype (71% vs 51%, p=0.007) and -7/7 abnormalities (61% vs 36%; p=0.001) were more frequent in patients who had received platinum; -7/7q- abnormalities were also associated to alkylating agents (50% vs 27%, p=0.012), antibiotics (74% vs 42%; p=0.003) and topoisomerase inhibitors (60% vs 37%; p=0.002). Conclusions: t-MDS is associated with poor outcomes. Receiving CT vs RT and higher IPSS risk had a poor impact in OS. The type of CT may be associated with specific cytogenetic alterations. [Table: see text]

Impact of genomic alterations (GAs) on outcomes and their distribution by age groups in metastatic colorectal cancer (mCRC) patients (pts).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 560-560 ◽  
Author(s):  
Ibrahim Halil Sahin ◽  
Wanqi H Chen ◽  
Zhengjia Chen ◽  
Mehmet Akce ◽  
Olatunji B. Alese ◽  
...  
Keyword(s):  
Survival Data ◽  
Cox Model ◽  
Prognostic Significance ◽  
Age Groups ◽  
Survival Outcomes ◽  
Age Group ◽  
Term Survival ◽  
Exact Test ◽  
Initial Stage ◽  
The Impact

560 Background: Although clinical outcomes has substantially improved over the last decade, long term survival in mCRC remains rare. Molecular profiling (MP) of CRC is routinely conducted to identify potential therapeutic targets. The aim of this project is to evaluate the impact of uncommon GAs on outcomes and characterize their distribution by age. Methods: Pts were eligible if they had mCRC (synchronous or metachronous) and underwent MP between 01/2013 and 05/2018. GAs were obtained from Foundation Medicine reports. Clinical data were collected by trained personnel by detailed chart review. Multivariable survival analyses (MA) with Cox model were conducted for survival outcomes and Fisher’s exact test was used to assess the differences among age groups (< 45, 45-60, > 60). The study was reviewed by Institutional IRB ( IRB00097021 ). Results: 161 patients with mCRC had MP, and 159 of those patients had survival data. The most commonly detected GAs were APC (133/161, 82.6%) TP53 (128/161, 79.5%). In univariate analyses mutations in BRCA 1/2, RB1, SOX9, CDK8, FLT3, and IRS2 amplification were associated with worse survival outcomes. In MA, including initial stage of disease, GAs in BRCA1/2, RB1, FLT3, SOX9, and IRS2 remained statistically significant (Table). When we performed MA by age groups, mutations SOX9 in age group < 45 and BRCA1/2 in age group 45-60 were significant predictors of worse outcomes. We also compared the frequency of mutations among age groups and FAM123B was significantly more common in age group 45-60 (P = 0.038). Conclusions: Our data suggests that GAs in BRCA1/2, RB1, FLT3, SOX9, and IRS2 may predict worse outcomes in mCRC. Therapeutic approaches targeting these pathways should be investigated. Differences in distribution and prognostic significance of mutations were observed based on age. [Table: see text]

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