bluuebunny/crossref_metadata_2025 huggingface dataset:
GENDER BASED ANALYSIS OF SOCIAL AND ECONOMIC CONDITIONS OF CHILD LABOURERS LIVING IN KARACHI
Authors: Aslam Shah Nasreen , Iqbal Rashid , Ul Haque Aamir
Published: May 2020

This study aims to draw a gender based analysis of social and economic conditions of child labourers living in Karachi. Globally the issue of child labour is growing constantly and children are engaged in all sorts of hazardous forms of work, like adults, which deprives them from education, healthy life, child hood activities and balanced diet. In Pakistan the child labour is very common in all economic sectors, but it is mainly found in the informal sector and the household sector. Purposive and convenience sampling techniques of non-probability sampling are used to collect data through structured questionnaire from 900 respondents from eighteen (18) administrative districts of Karachi, which is based upon primarily quantitative and narrowly focused qualitative research methods. The findings of the study reveal that mostly children between the ages of 12 to 14 years are commonly inducted in different economic sectors. This clear violation of child rights makes them vulnerable to health and safety threats and putting them forcefully in hazardous occupations to earn bread and butter for their family by compromising their education.
NON-VERBAL REASONING IN FIGURATIVE TREATMENT A CORRELATION BETWEEN THE PROCESSES OF RESEARCH AND DRAWING: A CASE STUDY OF SADEQUAIN
Authors: Khan Umaira Hussain
Published: May 2020

This paper draws a correlation between processes of research and drawing by analyzing the formation of emotional content and stylistic representation in art. The paper suggests that research process fundamentally involves a systematic development of understanding on a particular issue through a process of rational inquiry. The research outcome or an intellectual understanding is therefore nothing more than a thoroughly investigated form of a hypothesis/ premise/ theory/ idea that has undergone a careful process of scrutiny, comparison and evaluation. On similar grounds, drawing process also involves a systematic development of form in which adjustments are made with the help of nonverbal reasoning till the final form is evolved. The development of form in drawing becomes a systematic rational process but operates at a subconscious plane; reason is substituted by aesthetic sensibility. It is suggested that aesthetic sensibility is a judgment that the human mind tailors through the use of non-verbal criteria of evaluating the beautiful and ugly. The paper develops a theoretical model in the light of above and then applies it to analyze various drawing conventions used by Sadequain in figurative treatment.
AROUSAL SAFETY LEADING TO PURCHASE INTENTION; THE ROLE OF MODERATING AND MEDIATING VARIABLES IN STRUCTURAL MODEL
Authors: Hameed Irfan , Zainab Bibi , Shamim Syed Jazib
Published: May 2020

The effect of arousal safety has been analyzed on purchase intention, then attitude towards the advertisement and attitude towards the brand have been incorporated as intervening variables between the relationships. The interaction effect of self-monitoring and message arguments have also been taken in to consideration for better understanding of the consumer’s response. The data has been gathered from 206 respondents by using purposive sampling method. The research instrument was comprised of summated rating/additive scale (likert scale) and semantic differential scaling. Confirmatory Factor Analysis has been applied after the application of preliminary tests on the data. Structure Equation Modeling and moderation and mediation analysis have also been applied to test the hypotheses. Arousal safety in the advertisements shape consumers response and it proved to be a fully mediated model. Self-monitoring also probes the relationship. Message arguments haven’t had any affect as moderator, hence can be used as a focal predictor. The study is a starting point for future research to provide a coherent methodology for capturing the necessary data, processing the underlying information and evaluating the effects of arousal safety in advertisements. The study extends the field of advertising in the direction of arousal safety (Humor) effects. In comparison to previous research, empirical evidence on the arousal safety in television advertising and purchase intention in relation with moderating and mediating variables is provided.
THE ROAD TO CHAGHI: A HISTORICAL PERSPECTIVE ON PAKISTAN’S NUCLEAR PROGRAM
Authors: Ali Muhammad , Qadri Suwaibah , Jabeen Rizwana
Published: May 2020

Nuclearization of South Asia always remains the most imperative concern for the international community particularly when In May 1998, India and Pakistan tested their nuclear devices which plunged South Asia into a relentless nuclear arms race. Since then, the nuclearization of South Asia has been a reality but the region is as insecure as it was before. Historically, Pakistan’s nuclear program has been a subject of contention with the Western world. Pakistan has worked hard and successfully to build diverse nuclear capabilities. It will preserve these capabilities for the predictable future as a necessary deterrent against perceived existential threats from India. The objective of this study is to provide historical background of the initiatives undertaken by Pakistan towards the development of its nuclear program and highlight the major challenges and hurdles that stood in the way of achieving this goal. Paper conclude that under the present turbulent regional and international environment, Pakistan should carefully weigh its options to become an internationally acceptable normal nuclear state without compromising its genuine security concerns. It is hoped that the finding of this qualitative work would not only facilitate scholars and experts of international relations, but also be a massive contribution for the students in this field.
ISLAMIC MICROFINANCE; DEMAND AND CHALLENGES: A CASE STUDY OF DISTRICT GHOTKI, SINDH
Authors: Ahmed Syed Ghazanfar , Ismile Muhammad
Published: May 2020

Pakistan is a developing country and it has been showed remarkable development in many areas since its foundation in 1947. However, still some issues have not been handled properly, like poverty, corruption, load shedding, water crises etc. Apart from other issues, poverty is a big issue of the country and it can be observed more or less in every province. In this paper, we have analyzed the ground situation of district Ghotki, through surveys, which is considered last district of Sindh. We tried to find the problems of poor people of district Ghotki, observed their general life style, discussed their issues and inquired about government’s role to provide the people with basic necessities of life. In this paper, mainly qualitative method is adopted to reach to best conclusion. However, partially quantitative style could also be observed, especially where concepts of Microfinance are discussed. We realized that around 40% people of the district need microfinance services and they are ready to welcome Islamic Microfinance banks, because people don’t want to opt interest based conventional microfinance services, and secondly, conventional microfinance banks don’t have capacity to cover vast area of the district.
UNDERSTANDING PORTRAYED MENTAL DISABILITY AND SOCIAL DISTRESS IN YOUNG ADULT LITERATURE AND ITS IMPACT: A THEMATIC ANALYSIS
Authors: Inayat Awaisha , Ali Saima , Khawaja Ghazal
Published: May 2020

Young adult literature has been studied to understand how authors represent characters who denotes their version of experiencing mental disability or social distress. Thus the following thematic analysis of young adult novels points a question, that whether portrayal of mental disability/social distress is empowering or not. Certainly, mental disabilities seem to be different in novels: in their attempts to represent mental disability/social distress as a real experience, they’re sometimes also attached to popular conceptions of protagonist’s love-affair. Hence, to focus on novels representing mental disability/social distress; themes are hypothesized to explore the identity of the protagonist, society’s influence on protagonist and whether novel romanticize or represents realistic portrayal of disability/distress. Six novels have been selected-One memory of Flora Banks, Everything-Everything, All the Bright Places, 13 Reasons Why, When we Collided and Will Grayson, Will Grayson. These novels calls attention towards how society aggravates disability and shun those who don’t meet certain expectations to be mentally healthy. Literature is a powerful social force and conversation starter about disability/distress awareness to address and deal with challenges. Thus it’s important to recognize that it plays a key role in the empowerment and appreciation for disability which has been the center of this analysis.
THE NEXUS BETWEEN INVESTMENT AND INTEREST RATE: NEW DIMENSIONS FOR PAKISTAN
Authors: Mujahid Nooreen , Noman Muhammad , Nargis
Published: May 2020

The nexus between investment and interest rate is always considered essential to analyze the economic activity as these variables are important economic indicators in defining macroeconomic activity. However, the unchanged condition of investment in Pakistan has raised the cost of investment and crates uncertainty in investors. The paper investigates the link between rate of interest and investment to incorporate a new dimension of call money rate that may enhance the investment opportunities in Pakistan, employing time series analysis for the time span of 1973 - 2015. The ARDL Bound Testing Approach and ECM are employed to capture both the long and short-run dynamics of the variables in the model. The results of the study indicate that the call money rate has significant effect on investment and thus on economic growth. Therefore, the preparation and implementation of financial policies may increase the investmentfriendly rate of interest to stimulate economic growth in Pakistan.
THE RELATIONSHIP BETWEEN FOREIGN DIRECT INVESTMENT AND ECONOMIC GROWTH OF PAKISTAN
Authors: Zaheer Rummana , Kiramat Shahana
Published: May 2020

Although it is very common to argue that the foreign direct investment is beneficial for the economic development of a nation. This exploration investigates the connection amongst FDI and economic development in case of Pakistan. In this study secondary data from 1985 to 2016 is taken to examine the relationship. The investigation included GDP as explained and exports and FDI as explanatory variables. To check data either it is stationary or not the study used Augmented Dickey Fuller test in our study. After making data stationary we have used OLS method to investigate the nature of relationship between the variables. Our results show that there is direct link amongst explained and explanatory variable. The findings also show that there is significant relationship between FDI and economic growth. After analyzing the calculations we came to know that foreign direct investment is a significant element for the economic development because it has positive impact and have significant relation with growth of an economy. Since FDI is an impressive element in economic development so, government should take steps to attract the foreign investors and make policies to encourage the trade liberalization to gain more from the foreign investment.
ASEAN(‘S) WAY OF CONFLICT MANAGEMENT: ACTIVE AND EFFECTIVE ROLE
Authors: Soomro Naureen Nazar , Behan Ronaque Ali , Siddiqui Sohni
Published: May 2020

ASEAN is widely praised for its establishing regional cooperation among countries of Southeast Asia and attracting countries from rest of the world too because of its core objective of bringing peace and stability in the region. Promotion of regional trade and investment followed by unprecedented economic growth is the major credit of ASEAN which is widely appreciated. Nevertheless, despite 50 years of its age, it hasn’t been fully successful in managing internal conflicts among its member states and conflicts with external states. Its ineffectiveness to manage conflicts have raised concerns over the relevance of ASEAN in 21st century where Asian continent is said to be playground for major powers because of shifting of epicenter of International Politics from America and Europe to Asia. ASEAN’s role is limited by its charter of Non-interference into the internal affairs of its member states. This article looks into the basic weaknesses in ASEAN as an organization thus providing recommendation to overcome its shortcomings and improve its performance. The article concludes that ASEAN, because of increasing demands of amendments in conflict management techniques due to changes in the nature of conflict, needs to transform from its modest goals and principles to deal with conflict to new trends of conflict management, perhaps from soft mediation to hard mediation in near future.
LIVES IN DARK: A STUDY OF COMMERCIAL CHILD SEX WORKERS IN KARACHI
Authors: Bilgrami Aliyah Ali
Published: May 2020

Child prostitution is defined as a youngster is given cash or products by the culprit party previously or later than sexual relation, in any age children are liable to prostitution. The powerless and frequently misled youngster, there might be few or no elective alternatives. Unfortunately, children may regularly persuade themselves that they have settled on a free decision, instead of recognizing that their own lives are not in their control. Rising destitution is driving a developing figure of family unit to offer kids, along with girl child specifically get involved in sex work. The research study is basically qualitative. Recent situation analyses and reports shows acceleration in different security issues of children for example camel race, and the sexual commercial exploitation of children and juvenile justice. These incorporate physical and mental handicap children, from ethnic minorities and minimized populaces, children live and chipping away at the road, in strife with the law, kid outcasts, isolated kids without their families, kids in spots of contention and catastrophic events, marginalized sexual minority, kids living in ghettos and the offspring of sex workers. Children who have a place with a few of these gatherings are much more helpless. The sampling method is simple random because to find such children. A semi structured interview schedule was prepared before interviews.
IMPACT OF ADVERTISING: END USER PERSPECTIVE
Authors: MasKhanam Masroor , Ali Akbar
Published: May 2020

The purpose of this study is to investigate the end user perspective of advertising in Pakistan. This involves exploring and examining the consumer feedback about advertising from multiple dimensions. In this regard, survey was done for the current developments in literature so far, in order to discover a general pattern of consumer attitude that has been developing over time. This leads us to the realization that the advertising has been radically changing since its beginning with the change in literature. Advertisers communicate with consumers through advertising, public relations, direct marketing, interactive/Internet marketing, sales promotion etc. organizations must use all available communication tools to communicate consumer and to create awareness about the need of consumer. Advertising is used to create awareness for products and services. Advertisers should know the needs of consumers, target audience, their culture, likes and dislikes. Advertising create feelings and satisfaction in consumer’s mind. Many food and beverage brands use advertising for the promotion of their products. Advergames have an advertisement for a product, service, or company and have become popular. Cultural frame work plays important role in advertising and consumer behavior. Music plays an imported role in advertising; it has recently attracted interest in marketing and consumer psychology. Music is key elements of the culture; it plays an important role in consumers’ perceptions, moods, and in the theme of the advertisements.
PEACE EDUCATION AND PEACE-BUILDING IN MAINSTREAM EDUCATION SYSTEM
Authors: Zarif Tayyaba , Urooj Safia , Munir Rizwana
Published: May 2020

Globally human societies are battling with diverse challenges from socio-cultural apprehension to the wave of religious extremism & conflicts consequently it is a quite high time for human societies and its stakeholders to come up with the possible applied framework with solutions to face these challenges. The one specific solution is to aware of the new generation by educating them to adopt a positive attitude to resolve the issues of conflicts. Keeping the above view there is a need for introducing peace education and Peace-building in the mainstream education system at all levels. The primary objective of the current study was to explore the perception of senior University teachers as internal stakeholders of education system regarding the need for Peace Education & Peacebuilding in the mainstream education system at higher education level specifically. The selected population was public sector Universities of District Shaheed Benazirabad while the sample was thirty percent randomly selected senior teachers of three departments. The data was collected with the help of a questionnaire which was structured on the fivepoint Likert scale. The data were analyzed accordingly. The study revealed the different aspects of peace education and Peace-building. The findings recommended that high importance should be given to peace education in the mainstream education system.
JOB SATISFACTION: INVESTIGATING THE ROLE OF EXPERIENCE AND MOTIVATION OF UNIVERSITY ACADEMICIANS IN PAKISTAN
Authors: Hanafi Munazza Rahim , Iraqi Khalid
Published: May 2020

The key resource for the achievement of institutional objectives and enhancement of high quality education are teachers. Well motivated and satisfied teachers cultivate the successful education system in the country. Thus, the present study attempts to observe the impact of motivation and experience on job satisfaction of teachers through the perspective of Herzberg’s ideology of employee motivation and job satisfaction by conducting the comparative study of both public and private sector universities in Karachi. The sample was purposively drawn from 300 teachers and the data was analyzed by using partial least squares - Structural Equation Modeling (SEM). Additionally, significant differences were found in the job satisfaction and motivation level among private and public university teachers. The presented findings embrace the implications for higher education institutions and HR practitioners.
UNDERSTANDING RESILIENCE AND AGGRESSION IN MIDDLE ADULTHOOD
Authors: Naseem Sabahat , Munaf Seema
Published: May 2020

The ability to be resilient in the face of adversity requires the absence of unhealthy coping behaviors, one of which is aggression. Middle adulthood is the developmental stage of various midlife stressors. Limited data is available with regards to this age group especially in Pakistan. The present study was conducted to determine the relationship between resilience and aggression in middle adulthood. For this purpose, 200 participants (100 men; 100 women) with Mage = 42.67 years & SD = 6.04, from different work places and residential areas of Karachi, Pakistan participated in the study. The Brief Resilience Scale was used to measure resilience whereas aggression was measured using the Short Form of the Buss-Perry Aggression Questionnaire. Pearson product-moment correlation and regression analysis, conducted using the SPSS, indicated the presence of a significant negative correlation between resilience and aggression. This study would help in understanding how resilience and aggression plays a role during middle adulthood. It would further be beneficial for mental health professionals to identify, devise, and implement better ways of enhancing resilience and helping people to deal with adversities in a healthy manner.
IMPACT OF EXCESSIVE USE OF FACEBOOK ON THE YOUTH OF KARACHI
Authors: Sultana Yasmeen , Ghaffar Sadaf , Saman Samia
Published: May 2020

This research study has done to identify and investigate the major factors behind the excessive usage of Facebook by the youth of Karachi and what kind of impacts they have to face on various aspects of their lives due to this much consumption of Facebook. In this research paper, the researcher has applied both types of methodology, Qualitative as well as Quantitative. The researcher has selected Karachi (The city of Pakistan) as the universe of the study. The data has collected in the manner of survey forms filled by students of different universities and colleges of Karachi; aged from 18 to 30 and the sample size is 50 in which half of the population includes males and half females and 10 interviews are also conducted from teachers and parents of Facebook users. This research study raises major points related to the extreme usage of Facebook which includes the mental and physical conditions of adolescents, children’s progress in their academic lives, impacts on relationships and disturbance in routine works. The data has collected in a fair way. The results revealed that Facebook repercussion only happens when an individual is using it in an excessive amount. The researcher suggests that using Facebook could be beneficial only if people learns to use it in manageable levels and if they are able to create a balance between the virtual world and real world.
GENESIS OF COALITION POLITICS IN INDIA: A REVIEW OF EARLY TO PRESENT
Authors: Singh Rajkumar , Prakash Chandra Singh
Published: May 2020

In the election of 17th Lok Sabha  held in mid-2019, the Indian political parties  tried hard to be a tie-up with each other against the present Modi-led NDA dispensation. In independent India, first, such attempt was made early in 1974 and started a new process of consolidation of opposition forces by the merger. In line, the Bharatiya Lok Dal (BLD) was formed by the merger of seven political parties and in this process, the constituent units lost their identity in the BLD. At the time although Congress (O) and the Jana Sangh were ready to cooperate but refused to lose their existence. Their experiences of emergency proved a blessing for them and they came together and formed an alliance called Janata Party, to challenge the Congress leadership of the time. Likewise, as of today in 2018-19 the Bharatiya Janata Party is the country’s largest political party in terms of representation in the national parliament and state assemblies and all political parties of present-day India with Indian National Congress as forerunner with the help of regional party try a futile attempt first to challenge and then to defeat the BJP in various elections. Although with a great difference in the situation the motto of opposition parties has been one and only to give weighty protest to turn the events in their favour. This ups and downs of Indian politics may prove a path-breaking for other developing countries where political parties are struggling hard to gain power but did not succeed on account of causes best known to them.
FOSTERING STANDARDIZATION AND QUALITY IN HIGHER EDUCATION- A STUDENTS’ PERSPECTIVE
Authors: Masroor Nida , Asim Muhammad
Published: May 2020

Universities are specialized units aimed to deliver quality education and shaping future leadership to provide competent professionals to the industry. The establishment of ORIC in universities and significant increase in academia-industry linkage activities is strategic move towards achievement of the mentioned objectives. Bridging up the gap between academia and industry by adopting such strategies defines the successful role of HEIs. In view of increasing number of universities and continuous outflow of graduates it seems imperative to analyze and capitalize their potential towards the growth of economy. However, the unemployment ratio and limited growth in SME (Small & Medium sized Entities) sector reflect the insignificant absorption of graduates in corporate sector. The study aims to determine the factors that serve as barriers in achieving goals of HEIs by understanding the problems faced by university students in general and business graduates in particular on the basis of data gathered from 100 students from different universities present in Karachi. It shall also assists the policy makers in devising policy as per market demands, level of quality attained by universities, their involvement with corporate sector and in turn need of the industry to keep both parties at par in the fluctuating and contemporary era.
FLOUTING OF GRICEANS MAXIMS IN COMEDY DRAMAS
Authors: Zeb Faiza
Published: May 2020

The only way to be successful now days in every field of life is the effective use of verbal expression. Language serves as a toolkit to inform, reveal, explore, expose, explain, manipulate, exaggerate, intensify, mitigate and what not. It has every hidden potential to serve its users. Significance of this toolkit of language can also be a bravura feature in gaining comic and/or tragic effects in media. The language of the media violates its few communicative principles which can be termed as Gricean cooperative principle, to serve the specific interests via playing upon the common use of language.  The present study explores the intricacies involved in any communication to achieve comic effects. For this purpose, Gricean maxims have been investigated thoroughly with the help of Pakistani comedy show “Bulbulay” which is a famous TV series all over the country. The TV series is considered to be popular among the masses due to its different and unique language that is achieved by flouting the maxims in Gricean’s terminology. The study explains the inimitable ways of achieving comic effects in series and also suggests further work on other areas regarding the unusual use of language to achieve desired results.
A double-blind, placebo-controlled clinical trial to assess the effects of a combined nutraceutical on endothelial function in patients with mild-to-moderate hypercholesterolaemia
Authors: Pecchioli Valerio , Cicero Arrigo F.G. , Lomartire Nazareno , Gemmiti Maria , Colangeli Antonello , Germanò Rosanna , Corsi Maria , Germanò Giuseppe
Published: May 2020

Introduction

There is growing interest in lipid-lowering nutraceuticals; however, there are a relative scarcity of data on combined compounds. This study was aimed to assess the efficacy and tolerability of a combined nutraceutical (CARDIOL® Forte – CF) containing polyunsaturated fatty acids, hydroxytyrosol, Coenzyme Q10, folic acid, B12 and E vitamins, piperine, and red yeast rice in patients with mild-to-moderate hypercholesterolaemia.

Material and methods

In this single-centre, double-blinded, placebo-controlled study enrolled subjects who were randomised to receive the tested combined nutraceutical for 16 weeks (CF group) or placebo (control group), in association with a low-fat diet. After 8 weeks of treatment, all patients underwent a 15-day washout period; then, a further 8 weeks of treatment was planned.

Results

Of 80 enrolled subjects, 37 completed the study in the CF group and 38 in the control group. After 8 weeks of treatment, low-density lipoprotein cholesterol levels were reduced by 17% in the CF group and by 6.4% in the control group, compared to baseline (p = 0.0001); these changes were improved at the end of study. Total cholesterol and triglyceride levels significantly decreased during treatment; high-density lipoprotein cholesterol did not change. In the CF group, flow-mediated dilation increased by 18.8% after 8 weeks and by 39.3% at the end of treatment. No adverse events or musculoskeletal disorders were reported in either group.

Conclusions

The tested combined nutraceutical, in association with a controlled diet, can reduce cholesterol levels and improve endothelial function, thus reducing the cardiovascular risk in patients with mild-to-moderate hypercholesterolaemia.
Interferon-γ release assays for tuberculous meningitis diagnosis: a meta-analysis
Authors: Lan You , Chen Wei , Yan Qun , Liu Wenen
Published: May 2020

Introduction

Tuberculous meningitis (TBM) is still a great challenge to global public health. As conventional diagnostic methods for TBM are unsatisfactory, interferon-γ release assays (IGRAs) have been introduced for TBM diagnosis tentatively. However, the role of IGRAs for diagnosing TBM remains unclear. Thus, we systematically evaluated the diagnostic performance of cerebrospinal fluid (CSF) and peripheral blood (PB) IGRAs in TBM to fill this blank.

Material and methods

Relevant studies were systematically searched in both foreign and Chinese databases up to March 2018. Studies in which TBM diagnosis was based on microbiological or clinical criteria were included. The quality of the included studies was assessed through the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Main outcome measures, including sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR), were pooled statistically using random effects models. The potential heterogeneity was explored by threshold effect analysis, subgroup analyses and meta-regression. Funnel plots and Egger’s test were used to test the potential publication bias. Statistical analyses were performed using Stata and Meta-DiSc software.

Results

Twenty-six out of 656 publications were eligible for meta-analysis, including 1892 participants in total. The pooled estimates of PB IGRAs for TBM diagnosis are as follows: sensitivity: 0.81 (95% CI: 0.78–0.84); specificity: 0.76 (95% CI: 0.73–0.78); PLR: 4.23 (95% CI: 2.95–6.07); NLR: 0.24 (95% CI: 0.19–0.32) and DOR: 21.06 (11.91-37.24). The corresponding estimates for CSF IGRAs were obtained: sensitivity: 0.81 (95% CI: 0.76–0.85); specificity: 0.89 (95% CI: 0.86–0.92); PLR: 7.87 (95% CI: 4.98–12.46); NLR: 0.19 (95% CI: 0.13–0.29); and DOR: 47.74 (25.02–91.12).

Conclusions

The diagnostic performance of IGRAs is suboptimal. In terms of cost, turn-around time and accessibility, these assays are unsuitable for use as biomarkers for TBM diagnosis.
The most frequent Polish ATM mutations are not susceptibility factors for tobacco-related cancers
Authors: Podralska Marta , Dzikiewicz-Krawczyk Agnieszka , Mosor Maria , Żurawek Magdalena , Iżykowska Katarzyna , Słomski Ryszard , Rydzanicz Małgorzata , Gabryel Piotr , Dyszkiewicz Wojciech , Ziółkowska-Suchanek Iwona
Published: May 2020

Introduction

The inactivation of both alleles of the ATM gene leads to ataxia-telangiectasia syndrome, whereas carriers of monoallelic mutations in the ATM gene are associated with increased risk of different types of cancer. Three substitutions in the ATM gene (c.6095G>A, c.7630-2A>C, c.5932G>T) are the most common mutations causing ataxia-telangiectasia among Polish patients. The aim of this study was to determine whether these ATM mutations are associated with increased risk of tobacco-related cancers.

Material and methods

783 Polish patients with tobacco-related cancers were included in the study (468 with lung cancer, 153 with a single laryngeal cancer, 86 with multiple primary tumors localized in the larynx and 76 multiple primary tumors localized in the head or neck). The control group consisted of 464 healthy subjects from the Polish population. Three ATM mutations – c.5932G>T, c.6095G>A, c.7630-2A>C – were tested among selected patients. Molecular analyses were performed using high resolution melting analysis and restriction fragment length polymorphism.

Results

In the present study, we detected only one mutation, c.7630-2A>C, and no carriers of c.5932G>T, c.6095G>A mutations in the ATM gene among Polish patients with tobacco-related cancers. A patient with c.7630-2A>C mutation was diagnosed with lung adenocarcinoma, the most common type of lung cancer. One carrier of c.6095G>A mutation was found in the control group.

Conclusions

The results indicate that the studied ATM variants do not seem to be associated with tobacco-related cancers in Poland.
Electrical stimulation therapy for chronic constipation: a systematic review and meta-analysis
Authors: Chen Min , Qiu Xiao-Ping , Yang Sheng-Lan , Ye Xu-Jun , Luo Jun , Wu Ying , Yang Gui-Fang
Published: May 2020

Introduction

Treatment of chronic constipation often is challenging, and non-traditional treatment methods, including nonpharmacological methods, may be attempted. Electrical stimulation therapy (EST) has been tried in many small and uncontrolled series. Although most results have been encouraging, validity of the method has not been established.

Material and methods

Five articles, concerning 338 patients (average age: 40.8–63.6 years) with constipation, were included in the study. Electroacupuncture or transcutaneous interferential electrical stimulation was the modality used. The causes of the constipation were stroke, slow transit, functional, opioid use, or unknown etiology. The primary and secondary outcomes were response rate and degree of constipation, respectively. Adverse events were also assessed.

Results

The results of the meta-analysis yielded a significant improvement in treatment response for EST compared with control treatment (medications or sham control), with the odds ratio 4.263 (95% CI: 1.456–12.484, p = 0.008). A significant reduction in degree of constipation also was found, with the pooled estimate of standardized difference in mean change 1.039 (95% CI: 0.315–1.763, p = 0.005). The average percentage of adverse events associated with EST was < 5%.

Conclusions

The EST with electroacupuncture or transcutaneous interferential electrical stimulation for the treatment of constipation due to various causes is effective and reasonably safe. However, further detailed studies using these methods are needed.
CBP-mediated acetylation of NF-κB p65 contributes to the proliferation of human nasopharyngeal carcinoma cells
Authors: Han Yaqian , Liu Feng , Xi Xuping , Wang Hui , Liao Qianjin , He Qian , Hu Xiaobo , Wu Xiangwei
Published: May 2020

Introduction

Reportedly, activation of the NF-B signaling pathway is related to the proliferation of nasopharyngeal carcinoma (NPC) cells; however, the underlying mechanism by which NF-B is activated in NPC cells is yet to be addressed. In our present studies, CREB-binding protein (CBP)-mediated acetylation of the NF-B p65 subunit and its effect on activation of NF-B p65 as well as its role in the proliferation of NPC cells were explored.

Material and methods

Human NPC cell lines CNE1 and C666-1 were cultured in vitro. The acetylation (Lys310) and phosphorylation (Ser536) levels of NF-B p65 in NPC cell lines were detected by Western blot. Then, the mRNA levels of CBP, p300, PCAF and GCN5 in NPC cell lines were determined by real-time PCR. Subsequently, the interaction of p65 with CBP in NPC cell lines was detected by a co-immunoprecipitation experiment. Furthermore, an NF-B p65 mutant (at Lys310), NF-B inhibitor and CBP shRNA were used to study the effect of CBP-mediated acetylation of NF-B p65 on the proliferation of NPC cell lines by CCK-8 assay.

Results

NF-B p65 was markedly acetylated at the site of Lys310 in NPC cells. Moreover, the mutation of NF-B p65 at the acetylation site markedly reduced proliferation of human NPC cells. Further investigation revealed that CBP was up-regulated and physically associated with NF-B p65 at the protein level in NPC cells. CBP-mediated NF-B p65 acetylation enhanced its phosphorylation and further contributed to the proliferation of NPC cells.

Conclusions

This study indicated that CBP-mediated NF-B p65 acetylation promotes the proliferation of NPC cells.
MicroRNA-143 functions as a tumor suppressor
in neuroblastoma by targeting bone morphogenetic protein-7
Authors: Li Ying , Gao Jie , Wang Qiwei , Ma Xiaojian
Published: May 2020

Introduction

Neuroblastoma (NB) is one of the most common types of extracranial malignant solid tumor in infants and children. MicroRNA-143 (miR-143) was reported to be dysregulated in several human cancers. However, the function and mechanism of miR-143 in NB are still unclear. The purpose of this study was to explore the biological functions of miR-143 in NB progression.

Material and methods

The expression of miR-143 in 32 NB tissue samples and 4 NB cell lines was detected by quantitative real-time PCR. Then, bioinformatics analysis combined with luciferase reporter assay were used to identify the target gene of miR-143 in SK-N-SH cells. Cell proliferation, migration and invasion assay were performed to investigate the roles of miR-143 in NB progression.

Results

Our study revealed that miR-143 was significantly downregulated in NB tissues as well as cell lines. Bone morphogenetic protein-7 (BMP7) was a direct target of miR-143 in NB cells and inversely associated with the expression of miR-143 in NB tissues. Overexpression of miR-143 inhibited NB cell proliferation, migration and invasion through targeting BMP7.

Conclusions

Our data for the first time demonstrated that miR-143 functions as a tumor suppressor in NB by directly targeting BMP7, and also suggest miR-143 as a potential thera­peutic target for NB patients in the future.
Microstructural changes in postoperative cervical cords with cervical spondylotic myelopathy evaluated by neurite orientation dispersion and density imaging: a preliminary study
Authors: Jiang Wen , Han Xiao , Li Guangqi , Li Donghang , Wang Jinchao , Guo Hua , Cheng Xiaoguang
Published: May 2020

Introduction

Neurite orientation dispersion and density imaging (NODDI) is a new diffusion magnetic resonance imaging technique that can provide specific microstructural evaluation including nervous tissue density, free water fraction, and neurite orientation dispersion. In this study, we explored the microstructural changes in reduced area (RA) and T2 high signal intensity (T2-HSI) postoperative cervical cords with cervical spondylotic myelopathy (CSM) by NODDI.

Material and methods

A prospective study. CSM patients with surgery planned were recruited in Beijing Jishuitan Hospital from September 2016 to March 2017 (excluding other cervical spondylosis and spinal diseases and postoperative stenosis) and underwent postoperative NODDI scans and modified Japanese Orthopaedic Association (mJOA) scoring. The patients were divided into RA and T2-HSI, normal area (NA) and T2-HSI, and NA and non-T2HSI groups. The differences in NODDI metrics and mJOA score between different groups were assessed respectively.

Results

Nervous tissue density in cervical cords with postoperative constant RA was decreased (RA-T2HSI (0.510, 0.330–0.670) vs. NA-T2HSI (0.585, 0.380–0.870) (p = 0.019), RA-T2HSI vs. NA-nT2HSI (0.620, 0.460–0.770) (p = 0.003)), and a certain degree of free water increase and nervous tissue density decline was observed in postoperative cervical cords with T2-HSI, even if not all of the outcomes were very significant. Moreover, the postoperative mJOA score in combined RA and T2-HSI was lower than that in single T2-HSI.

Conclusions

The microstructural changes in postoperative RA and T2-HSI cervical cords could be evaluated by NODDI metrics and RA and T2-HSI were useful as brief evaluations for postoperative CSM cervical cords.
Fucoxanthin protects neonatal rat cardiomyocytes and attenuates high glucose-mediated oxidative stress via the AMPK pathway
Authors: Li Fengyue , Lei Chunxia
Published: May 2020

Introduction

Diabetic cardiomyopathy (DC) is associated with impaired diastolic function. Hyperglycemia-mediated oxidative stress and apoptosis are the major factors responsible for DC. Also NADPH oxidase is the main source of ROS in cardiac cells or cardiomyocytes. Here we evaluated the effect of fucoxanthin (FXN) on high glucose cultured neonatal rat cardiomyocytes.

Material and methods

For the study, Iry neonatal rat cardiomyocytes were cultured in a high glucose environment (30 mM/l) in the presence and absence of FXN. Apoptosis, cell viability, activity of NADPH oxidase and expression level of its subunits, levels of MDA and activity of endogenous antioxidant enzymes were studied. We also confirmed the involved pathway by studying the expression of AMPK, GSK-3 and Akt in the cardiomyocytes.

Results

The high glucose environment increased the production of ROS, and FXN decreased the oxidative burden by inhibiting ROS in cultured neonatal rat cardiomyocytes. FXN inhibited the activity of NADPH oxidase and Rac1 also increased the expression of its subunits. Treatment of FXN reversed the MDA, CAT, GSHpx, SOD activity and GSH contents. FXN down-regulated the levels of Bax and up-regulated the levels of Bcl-2 (anti-apoptotic protein); treatment protected the cardiomyocytes from injury. Also, FXN increased the levels of pAMPK in cardiac cells treated with high glucose. The pharmacological inhibitor of AMPK abolished the activities of FXN in high glucose induced cardiomyocytes.

Conclusions

FXN exerted protective action on cardiac cells subjected to high glucose-mediated apoptosis by suppressing NADPH oxidase-mediated production of ROS and maintaining the antioxidant defense in the tissues. The attenuating activity of FXN was propagated via the AMPK cascade.
Prognostic value of TIMM50 expression in colorectal cancer
Authors: Sun Bo , Wang Jun , Zhu Yan-Feng , Li Zhen-Yang , Xiang Jian-Bin , Chen Zong-You , He Zhi-Gang , Gu Xiao-Dong
Published: May 2020

Introduction

Translocase of the inner mitochondrial membrane 50 (TIMM50) is universally considered to play a key role in several malignancies. However, its role in predicting colorectal cancer (CRC) patient prognosis remains unclear.

Material and methods

A total of 192 CRC patients (123 men and 69 women) who underwent radical resection participated in this study. The patients were followed up every three months after surgery for five years. TIMM50 expression in tumour tissues was measured by quantitative real-time PCR, Western blotting and immunohistochemistry. TIMM50 expression was studied to assess correlations with clinicopathological factors and survival time.

Results

TIMM50 expression increased significantly in CRC tumour tissues. Moreover, high TIMM50 expression was related to pathologic stage (p = 0.043), N stage (p = 0.048) and distant metastasis (p = 0.015), but TIMM50 expression was not related to other clinical factors. A Kaplan-Meier survival analysis indicated that patients with low TIMM50 expression had a longer overall survival than those with high TIMM50 expression (p = 0.002). Furthermore, distant metastasis and high TIMM50 expression were confirmed as independent prognostic factors for the overall survival of CRC patients in a multivariate analysis (p = 0.003).

Conclusions

TIMM50 may be a key factor for monitoring CRC and a new prog¬nosis indicator for CRC patients.
Assessment of inflammatory markers, disease severity and comorbidities in very elderly patients with acute respiratory diseases
Authors: Hazar Armagan , Gundogus Baran
Published: May 2020

Introduction

The study aimed to evaluate the potential role of inflammatory markers (neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), platelet to mean platelet volume (PLT/MPV), C-reactive protein (CRP), CRP/albumin) and demographic, clinical and laboratory parameters in predicting mortality in elderly patients.

Material and methods

A total of 1971 very elderly (age ≥ 80 years) patients hospitalized due to acute respiratory diseases were included in this retrospective cohort study. Data on patients’ demographics, reasons for admission, comorbidities, inflammatory markers on admission, hospitalization unit, length of hospital stay and survivorship status were recorded. A receiver operating characteristics (ROC) curve was plotted to determine performance of inflammatory marker levels for mortality risk. Logistic regression analysis for hospital mortality was used.

Results

A total of 1971 patients were admitted, in-ward (n = 1470), intensive care unit (ICU, n = 352), or palliative care unit (PCU, n = 149), and mortality rates were 12.7% (n = 250), 4.5% (n = 66), 34.9% (n = 123), 40.9% (n = 61) respectively. ROC analysis for area under curve (AUC) revealed significant cut-off levels for hospital mortality NLR  7.75 (AUC = 0.79), CRP  44 (AUC = 0.82); CRP/albumin  13.5 (AUC = 0.84) each p < 0.001. For ICU mortality, the cut-off values and AUC were significant respectively for NLR  7.75 (AUC = 0.82), CRP  60 (AUC = 0.82), APACHE II  24 (AUC = 0.76), CRP/albumin  26 (AUC = 0.78), PLT/MPV < 26.2 (AUC = 0.31) (each p < 0.001). Binary logistic regression revealed that age above 90, PCU and ICU admission, acute and chronic renal failure and NLR  7.75 were significant mortality predictors (odds ratio, 95% CI, p-value: 2.57, 1.05–6.31, 0.039; 77.18, 18.98–313.81, < 0.001; 20.75, 1.96–98.73, < 0.001; 18.99, 1.31–275.31, 0.031; 3.35, 1.06–10.54, 0.039; 7.83, 3.34–18.38, 0.001).

Conclusions

Very elderly patients with respiratory diseases who are admitted to the ICU or PCU with acute and chronic renal failure requiring ICU admission and with NLR values above 7.75 on admission have very high risk for mortality.
Encapsulation of granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor in liposomes prepared by thin film hydration and their transfer to mesenchymal stem cells and cord blood hematopoietic stem cells
Authors: Lewicki Sławomir , Leśniak Monika , Sobolewska-Ruta Agnieszka , Lewicka Aneta , Grodzik Marta , Machaj Eugeniusz , Saracyn Marek , Kubiak Jacek , Pojda Zygmunt
Published: May 2020

Introduction

Cytokines are important immune modulator factors controlling homeostasis of the body and are involved in tissue regeneration after wound healing. The encapsulation of cytokines in liposomes has many advantages potentially useful for their transfer to the cells. Liposomes protect cytokines from neutralization, improving their pharmacokinetics or biologic activity in vivo. They are targeted to specific cell types and may delay the release of cytokines, allowing their sustained paracrine delivery. Their physicochemical characteristics such as size, shape, charge, and stability are important parameters improving bio-distribution and prolonged pharmacokinetics of encapsulated cytokines.

Material and methods

We developed an efficient protocol for the encapsulation of two types of cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF), in liposomes that can be stored long term in the active state.

Results

This method allows for the encapsulation of 12–13% of the total amount of cytokines and 50% of encapsulated cytokines are entrapped in liposomes of more than ≤ 600 nm in diameter. We show that in the studied cell lines the liposome-encapsulated cytokines do not affect cell morphology, proliferation or mortality.

Conclusions

The G-CSF or GM-CSF can be delivered to the cells in working concentrations through the encapsulation in the liposomes. Before the clinical application, the efficiency of these liposomes should be confirmed by an in vivo study.