Protein arginine N-methyltransferase 5 in colorectal carcinoma:Insights into mechanisms of pathogenesis and therapeutic strategies

Protein arginine N-methyltransferase 5 (PRMT5) enzyme is one of the eight canonical PRMTs, classified as a type II PRMT, induces arginine monomethylation and symmetric dimethylation. PRMT5 is known to be overexpressed in multiple cancer types, including colorectal cancer (CRC), where its overexpression is associated with poor survival. Recent studies have shown that upregulation of PRMT5 induces tumor growth and metastasis in CRC. Moreover, various novel PRMT5 inhibitors tested on CRC cell lines showed promising anticancer effects. Also, it was suggested that PRMT5 could be a valid biomarker for CRC diagnosis and prognosis. Hence, a deeper understanding of PRMT5-mediated CRC carcinogenesis could provide new avenues towards developing a targeted therapy. In this study, we started with in silico analysis correlating PRMT5 expression in CRC patients as a prelude to further our investigation of its role in CRC. We then carried out a comprehensive review of the scientific literature that dealt with the role(s) of PRMT5 in CRC pathogenesis, diagnosis, and prognosis. Also, we have summarized key findings from in vitro research using various therapeutic agents and strategies directly targeting PRMT5 or disrupting its function. In conclusion, PRMT5 seems to play a significant role in the pathogenesis of CRC; therefore, its prognostic and therapeutic potential merits further investigation.</p

Collaboration with Families of Children with Disabilities in Qatar: A Parent's Perspective

The purpose of this study was to explore the perspectives of parents of children with disabilities in regard of the components of true collaboration practices in different educational institutions. As well as to solicit their understanding of the important components of collaboration that might improve services. A model based on the work of Blue-Banning, Summers, Frankland, Nelson and Beegle (2004) was adopted having six original domains including communication, knowledge, respect, trust, equality, commitment, a seventh domain of advocacy was added. A sample of 163 parents of families with disabilities was interviewed and a survey was collected accordingly, validity and reliability of the tool were checked in addition to an exploratory factor analysis, which confirmed the previous model. Results showed a great need for collaboration between families and school personnel especially teachers, all components are important and need to be addressed; still communication and equality were the major components of collaboration that needs to be addressed to achieve proper collaboration. Further analysis showed some differences according to other variables, like educational institute type, further implications are discussed

The Relationship Between Dark and Light Dimensions of Personality with Life Satisfaction Mediated by Value Orientations

Different studies have examined the relationship between dark and light personality dimensions and life satisfaction. Using the structural equation method, this correlational descriptive study aimed to determine the relationship between dark and light dimensions of personality with life satisfaction as mediated by value orientations. To this end, 400 people who referred to health centers in Tabriz, Iran were selected through convenience sampling method. To collect data, Life Satisfaction Questionnaire, Dark Triad Personality Questionnaire, Light Triad Personality Questionnaire, and the Value System Questionnaire were used. Then the data were analyzed using the structural equation method. While the dark dimensions had a negative effect on life satisfaction, the light dimensions had a positive effect. There was a negative relationship between dark dimensions and life satisfaction as mediated by value orientations. Meanwhile, there was a positive relationship between light dimensions and life satisfaction as mediated by value orientations. Therefore, the dark and light dimensions of personality and the way of value orientation are related to the level of life satisfaction. Accordingly, researchers can examine the effectiveness of these variables on life satisfaction through developing psychotherapy interventions influencing the variables of dark and light dimensions of personality and value orientation.  Introduction*Various personality variables affect the level of life satisfaction. The dark dimensions, including antisocial, narcissism, and Machiavellianism, have a direct role in people's attitudes towards life (Paulhus ­­­&Williams, 2002). Various studies have shown the negative relationship between dark personality traits and life satisfaction (Marashi et al., 2017; Sharifinia & Harun Rashidi, 2020). The light dimensions, including three dimensions of humanity, faith in humanity, and Kantianism (Kaufman et al., 2019) along with the way of value orientation have a positive relationship with life satisfaction (Sadeghi et al., 2018). While people with light personality traits use developed defense mechanisms (Wood et al., 2010) leading to life satisfaction, people with dark personality traits choose anti-moral values ‌‌in life (Oboyle et al., 2012) which result in dissatisfaction with life. Considering the essential role of personality traits and the type of value orientation in the level of life satisfaction, this study aimed to investigate the relationship between the dark and light dimensions of personality with life satisfaction mediated by value orientation. MethodThis descriptive correlational research used structural equation method. Using the available sampling method, a total of 400 individuals referring to the health centers in Tabriz, Iran were selected. The following four questionnaires were completed by participants.Life Satisfaction Questionnaire: This five-item scale was developed by Diener et al. (1985). A higher score indicates more satisfaction with life. Diener et al. obtained the reliability of this scale with Cronbach's alpha method (0.86). In the present study, Cronbach's alpha obtained for this scale was 0.78. Dark Triads Personality Questionnaire: This 12-item scale was designed by Johnson and Webster (2010) and includes three subscales: Machiavellianism, antisociality, and narcissism. Johnson and Webster reported the test-retest reliability coefficient of this questionnaire as 0.89 for the entire scale. In the present study, Cronbach's alphas obtained for Machiavellian, antisocial, and narcissistic subscales were 0.79, 0.69, and 0.73, respectively. Light Triads Personality Questionnaire: This scale was designed by Kaufman et al. (2019) and consists of three subscales: Kantianism, humanity, and faith in humanity. The internal reliability coefficient for this scale was estimated as 0.84 in the original study (Kaufman et al., 2019). In our study, Cronbach's alphas obtained for the variables of Kantianism, humanity, and faith in humanity were 0.69, 0.72, and 0.68, respectively. The Value System Questionnaire: This scale was developed by Schwartz (2006) and consists of 57 questions and ten scales of the value system. The Cronbach's alphas reported by Schwartz for the subscales of benevolence, traditionalism, conformity, security, power, arousal, hedonism, success, spontaneity, and cosmopolitanism were 0.61, 0.37, 0.48, 0.64, 0.50, 0.69, 0.79, 0.52, 0.53, 0.57, respectively. In the present study, the alpha obtained for each of the subscales was estimated to be more than 0.67. ResultsWhile the dark dimensions had a negative effect on life satisfaction, the light dimensions had a positive effect. There was a significant relationship between the dark and light dimensions with life satisfaction as mediated by value orientations. Table 1 shows the Pearson’s correlation matrix for the studied variables.  Table 1. Pearson’s Correlation Matrix for The Relationships between Research Variables4321Variables   11- Dark dimensions    1-0/61**2- Light dimensions   10/56**-0/58**3- Value orientation10/62**0/69**-0/64**4- Life satisfactionP<.01 According to Table 1, there was a significant negative relationship between the dark dimensions with light dimensions, value orientation, and life satisfaction. There was a significant positive relationship between the light dimensions with value orientations and life satisfaction. Also, there was a significant positive relationship between value orientations and life satisfaction.   .83                                                                                                                                .68                        .58               Figure 1. Structural Model of Dark and Light Dimensions Mediated by Value Orientation on Life Satisfaction To investigate the indirect relationship between the dark and light dimensions with life satisfaction as mediated by value orientations, the bootstrap method was used (Table 2).  Table 2. Bootstrap Results for Indirect Model RelationshipspUpper limitLower limitStandardized estimatorVariables 0/006 -0/027 - 0/200 -0/097The relationship between dark dimensions with life satisfaction mediated by value orientations0/0040/1940/0220/092The relationship between light dimensions with life satisfaction mediated by value orientations       P<0.05 The bootstrapping test results showed that dark dimensions had a negative indirect effect on life satisfaction mediated by value orientations (= -0.097); Also, light personality dimensions had a positive indirect effect on life satisfaction mediated by value orientations (= 0.092).ConclusionThis study investigated the relationship between the dark and light dimensions with life satisfaction through the mediating role of value orientation. According to the results, while the dark dimensions had a negative effect on life satisfaction, the light dimensions had a positive effect on it.  According to psychological theories, life satisfaction is widely influenced by a person's developmental background such as personality traits. Dark personality traits show the tendency to experience more unpleasant emotional states such as anger, sadness, despair, and other negative emotions. These people perceive life stressful and are dissatisfied with their social support, which can explain lower levels of life satisfaction. People with clear personality traits have extensive verbal and communication skills, which facilitates relationships with others, provides them with more social support, and increases life satisfaction.In our study, there was a relationship between the dark and light dimensions of personality with life satisfaction mediated by value orientations. People who have light personality dimensions experience more life satisfaction through choosing positive defense mechanisms, realistic views, and moral value orientations in life. People with dark personality dimensions adopt an anti-moral value orientation, which ultimately causes dissatisfaction with life. Accordingly, psychologists and counselors should pay more attention to the role of personality variables and value orientations in the beginning and continuation of psychological interventions in primary prevention programs and interventional and clinical work.Ethical ConsiderationCompliance with Ethical Guidelines: This research has the code of ethics IR.IAU.TABRIZ.REC.1400089 from the ethics committee of the research vice-chancellor of Islamic Azad University, Tabriz Branch.Authors’ Contributions: All authors contributed to the study. The first author written the first draft of the manuscript. The second author edited the manuscript. The third author advised result sections. The fourth author written the methods sections.Conflict of Interest: The authors declare no conflict of interest for this study.Funding: This study was conducted with no financial support.Acknowledgment: The authors thank all participants in the study.     *. Corresponding autho

Pediatric Traumatic Brain Injury in the Middle East and North Africa Region: A Systematic Review and Meta-Analysis to Assess Characteristics, Mechanisms, and Risk Factors

Pediatric traumatic brain injury (pTBI) represents a major cause of child injuries in the Middle East and North Africa (MENA) region. This review aims to assess pTBIs in the MENA region and reports their clinical severity and outcomes. A search was conducted using major electronic databases, including Medline/Ovid, PubMed, EMBASE, Web of Science, and SCOPUS. Abstracts were screened independently and in duplicate to detect original research. The objective and study findings for each article were recorded, along with the mechanism of pTBI, patient age and sex, injury assessment tool(s) used, and outcome. A total of 1345 articles were retrieved, of which 152 met the criteria for full-text review, and 32 were included in this review. Males predominantly suffered from pTBIs (78%). Motor vehicle accidents, followed by child abuse, were the leading causes of pTBI. Overall, 0.39% of cases were mild, 0.58% moderate, 16.25% severe, and 82.27% unclassified. The mortality rate was 13.11%. Most studies used the computed tomography scan, Glasgow Coma Scale, Abbreviated Injury Scale, and Injury Severity Score as investigation methods. This review reports on the alarming rate of child-abuse-related pTBI and offers further understanding of pTBI-associated risk factors and insight into the development of strategies to reduce their occurrence, as well as policies to promote child well-being

Attitudes towards gender roles and prevalence of intimate partner violence perpetrated against pregnant and postnatal women: Differences between women immigrants from conflict-affected countries and women born in Australia

BACKGROUND: The aim was to compare, for the first time in a large systematic study, women born in conflict-affected countries who immigrated to Australia with women born in Australia for attitudes towards gender roles and men\u27s use of IPV and the actual prevalence of IPV. The study also examined if any associations remained across the two timepoints of pregnancy and postpartum. METHODS: Women were interviewed during their first visit to one of three Australian public hospital antenatal clinics and re-interviewed at home six months after giving birth. A total of 1111 women completed both interviews, 583 were born in conflict-affected countries and 528 born in Australia. Associations between attitudes towards gender roles and men\u27s use of IPV, socio-demographic characteristics and reported actual experiences of IPV were examined using bivariate and multiple logistic regression analyses. RESULTS: Attitudes toward inequitable gender roles including those that condone men\u27s use of IPV, and prevalence of IPV, were significantly higher (p \u3c 0.001) among women born in conflict-affected countries compared to Australia-born women. Women born in conflict-affected countries with the strongest held attitudes towards gender roles and men\u27s use of IPV had an adjusted odds ratio (aOR) of 3.18 for IPV at baseline (95% CI 1.85-5.47) and an aOR of 1.83 for IPV at follow-up (95% CI 1.11-3.01). Women born in Australia with the strongest held attitudes towards gender roles and IPV had an aOR of 7.12 for IPV at baseline (95% CI 2.12-23.92) and an aOR of 10.59 for IPV at follow-up (95% CI 2.21-50.75). CONCLUSIONS: Our results underscore the need for IPV prevention strategies sensitively targeted to communities from conflict-affected countries, and for awareness among clinicians of gender role attitudes that may condone men\u27s use of IPV, and the associated risk of IPV. The study supports the need for culturally informed national strategies to promote gender equality and to challenge practices and attitudes that condone men\u27s violence in spousal relationships

Transcriptomic Alterations in Lung Adenocarcinoma Unveil New Mechanisms Targeted by the TBX2 Subfamily of Tumor Suppressor Genes

T-box (TBX) transcription factors are evolutionary conserved genes and master transcriptional regulators. In mammals, TBX2 subfamily (TBX2, TBX3, TBX4, and TBX5) genes are expressed in the developing lung bud and tracheae. Our group previously showed that the expression of TBX2 subfamily was significantly high in human normal lungs, but markedly suppressed in lung adenocarcinoma (LUAD). To further elucidate their role in LUAD pathogenesis, we first confirmed abundant expression of protein products of the four members by immunostaining in adult human normal lung tissues. We also found overall suppressed expression of these genes and their corresponding proteins in a panel of human LUAD cell lines. Transient over-expression of each of the genes in human (NCI-H1299), and mouse (MDA-F471) derived lung cancer cells was found to significantly inhibit growth and proliferation as well as induce apoptosis. Genome-wide transcriptomic analyses on NCI-H1299 cells, overexpressing TBX2 gene subfamily, unraveled novel regulatory pathways. These included, among others, inhibition of cell cycle progression but more importantly activation of the histone demethylase pathway. When using a pattern-matching algorithm, we showed that TBX's overexpression mimic molecular signatures from azacitidine treated NCI-H1299 cells which in turn are inversely correlated to expression profiles of both human and murine lung tumors relative to matched normal lung. In conclusion, we showed that the TBX2 subfamily genes play a critical tumor suppressor role in lung cancer pathogenesis through regulating its methylating pattern, making them putative candidates for epigenetic therapy in LUAD

The Association between Intimate Partner Violence, Depression and Influenza-like Illness Experienced by Pregnant Women in Australia

Intimate Partner Violence (IPV) is a major public health issue, including during pregnancy where it poses a serious risk to the woman’s health. Influenza-Like Illness (ILI) also causes significant morbidity for women during pregnancy. It may be possible that ILI in pregnancy is associated with IPV, and that depression and trauma history play a role in the connection. 524 Australia-born women and 578 refugee-background women participated in the study. Baseline participants were randomly recruited and interviewed from antenatal clinics between January 2015 and March 2016, and they were reinterviewed six months post-partum. Bivariate and path analysis were used to assess links between IPV, depression and ILI. One in 10 women (10%; 111 out of 1102) reported ILI during their pregnancy period and this rate was significantly (p &lt; 0.001) higher for women born in conflict-affected countries (13%; 76 out of 578) as compared to Australian-born women (7%; 35 out of 524). In both groups, Time 1 traumatic events, IPV and depression symptoms were significantly associated with ILI at Time 2. A significant association between IPV at Time 1 and ILI at Time 2 was fully mediated by depression symptoms at Time 1 (Beta = 0.36 p &lt; 0.001). A significant direct path was shown from depression symptoms to ILI (Beta = 0.26, p &lt; 0.001). Regardless of migration history, pregnant women who have experienced IPV and depression are more likely to report influenza-like symptoms in pregnancy. This may suggest that trauma and depression negatively affect immunity, although it could also indicate a connection between depressive symptoms and physical experiences of ILI.</jats:p

Measurement of prompt open-charm production cross sections in proton-proton collisions at root s=13 TeV

The production cross sections for prompt open-charm mesons in proton-proton collisions at a center-of-mass energy of 13TeV are reported. The measurement is performed using a data sample collected by the CMS experiment corresponding to an integrated luminosity of 29 nb(-1). The differential production cross sections of the D*(+/-), D-+/-, and D-0 ((D) over bar (0)) mesons are presented in ranges of transverse momentum and pseudorapidity 4 < p(T) < 100 GeV and vertical bar eta vertical bar < 2.1, respectively. The results are compared to several theoretical calculations and to previous measurements.Peer reviewe

Search for new particles in events with energetic jets and large missing transverse momentum in proton-proton collisions at root s=13 TeV

A search is presented for new particles produced at the LHC in proton-proton collisions at root s = 13 TeV, using events with energetic jets and large missing transverse momentum. The analysis is based on a data sample corresponding to an integrated luminosity of 101 fb(-1), collected in 2017-2018 with the CMS detector. Machine learning techniques are used to define separate categories for events with narrow jets from initial-state radiation and events with large-radius jets consistent with a hadronic decay of a W or Z boson. A statistical combination is made with an earlier search based on a data sample of 36 fb(-1), collected in 2016. No significant excess of events is observed with respect to the standard model background expectation determined from control samples in data. The results are interpreted in terms of limits on the branching fraction of an invisible decay of the Higgs boson, as well as constraints on simplified models of dark matter, on first-generation scalar leptoquarks decaying to quarks and neutrinos, and on models with large extra dimensions. Several of the new limits, specifically for spin-1 dark matter mediators, pseudoscalar mediators, colored mediators, and leptoquarks, are the most restrictive to date.Peer reviewe

Search for Physics beyond the Standard Model in Events with Overlapping Photons and Jets

Results are reported from a search for new particles that decay into a photon and two gluons, in events with jets. Novel jet substructure techniques are developed that allow photons to be identified in an environment densely populated with hadrons. The analyzed proton-proton collision data were collected by the CMS experiment at the LHC, in 2016 at root s = 13 TeV, and correspond to an integrated luminosity of 35.9 fb(-1). The spectra of total transverse hadronic energy of candidate events are examined for deviations from the standard model predictions. No statistically significant excess is observed over the expected background. The first cross section limits on new physics processes resulting in such events are set. The results are interpreted as upper limits on the rate of gluino pair production, utilizing a simplified stealth supersymmetry model. The excluded gluino masses extend up to 1.7 TeV, for a neutralino mass of 200 GeV and exceed previous mass constraints set by analyses targeting events with isolated photons.Peer reviewe