Search results for: crow search

Authors: Fasil Wagnew, Kefyalew Addis Alene, Setegn Eshetie, Tom Wingfield, Matthew Kelly, Darren Gray

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Introduction: Undernutrition is a major and under-appreciated risk factor for TB, which is estimated to be responsible for 1.9 million TB cases per year globally. The effectiveness of micronutrient supplementation on TB treatment outcomes and its prognostic markers such as sputum conversion and serum zinc, retinol, and hemoglobin levels has been poorly understood. This systematic review and meta-analysis aimed to determine the association between zinc and vitamin A supplementation and TB treatment outcomes and its prognostic markers. Methods: A systematic literature search for randomized controlled trials (RCTs) was performed in PubMed, Embase, and Scopus databases. Meta-analysis with a random effect model was performed to estimate risk ratio (RR) and mean difference (MD), with a 95% confidence interval (CI), for dichotomous and continuous outcomes, respectively. Results: Our search identified 2,195 records. Of these, nine RCTs consisting of 1,375 participants were included in the final analyses. Among adults with pulmonary TB, zinc (RR: 0.94, 95%CI: 0.86, 1.03), vitamin A (RR: 0.90, 95%CI: 0.80, 1.01), and combined zinc and vitamin A (RR: 0.98, 95%CI: 0.89, 1.08) supplementation were not significantly associated with TB treatment success. Combined zinc and vitamin A supplementation was significantly associated with increased sputum smear conversion at 2 months (RR: 1.16, 95%CI: 1.03, 1.32), serum zinc levels at 2 months (MD of 0.86umol/l, 95% CI: 0.14, 1.57), serum retinol levels at 2 months (MD: 0.06umol/l, 95 % CI: 0.04, 0.08) and 6 months (MD: 0.12umol/l, 95 % CI: 0.10, 0.14), and serum hemoglobin level at 6 months (MD: 0.29 ug/dl, 95% CI: 0.08 to 0.51), among adults with TB. Conclusions: Providing zinc and vitamin A supplementation to adults with pulmonary TB during treatment may increase early sputum smear conversion, serum zinc, retinol, and hemoglobin levels. However, the use of zinc, vitamin A, or both were not associated with TB treatment success.

Keywords: zinc and vitamin A supplementation, tuberculosis, treatment outcomes, meta-analysis, RCT

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Authors: Kathrina Aseanne Acapulco-Gomez, Shayne Julieane Morales, Tzar Francis Verame

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Mean platelet volume (MPV) is the most accurate measure of the size of platelets and is routinely measured by most automated hematological analyzers. Several studies have shown associations between MPV and cardiovascular risks and outcomes. Although its measurement may provide useful data, MPV remains to be a diagnostic tool that is yet to be included in routine clinical decision making. The aim of this systematic review and meta-analysis is to determine summary estimates of the diagnostic accuracy of mean platelet volume for the diagnosis of myocardial infarction among adult patients with angina and/or its equivalents in terms of sensitivity, specificity, diagnostic odds ratio, and likelihood ratios, and to determine the difference of the mean MPV values between those with MI and those in the non-MI controls. The primary search was done through search in electronic databases PubMed, Cochrane Review CENTRAL, HERDIN (Health Research and Development Information Network), Google Scholar, Philippine Journal of Pathology, and Philippine College of Physicians Philippine Journal of Internal Medicine. The reference list of original reports was also searched. Cross-sectional, cohort, and case-control articles studying the diagnostic performance of mean platelet volume in the diagnosis of acute myocardial infarction in adult patients were included in the study. Studies were included if: (1) CBC was taken upon presentation to the ER or upon admission (within 24 hours of symptom onset); (2) myocardial infarction was diagnosed with serum markers, ECG, or according to accepted guidelines by the Cardiology societies (American Heart Association (AHA), American College of Cardiology (ACC), European Society of Cardiology (ESC); and, (3) if outcomes were measured as significant difference AND/OR sensitivity and specificity. The authors independently screened for inclusion of all the identified potential studies as a result of the search. Eligible studies were appraised using well-defined criteria. Any disagreement between the reviewers was resolved through discussion and consensus. The overall mean MPV value of those with MI (9.702 fl; 95% CI 9.07 – 10.33) was higher than in those of the non-MI control group (8.85 fl; 95% CI 8.23 – 9.46). Interpretation of the calculated t-value of 2.0827 showed that there was a significant difference in the mean MPV values of those with MI and those of the non-MI controls. The summary sensitivity (Se) and specificity (Sp) for MPV were 0.66 (95% CI; 0.59 - 0.73) and 0.60 (95% CI; 0.43 – 0.75), respectively. The pooled diagnostic odds ratio (DOR) was 2.92 (95% CI; 1.90 – 4.50). The positive likelihood ratio of MPV in the diagnosis of myocardial infarction was 1.65 (95% CI; 1.20 – 22.27), and the negative likelihood ratio was 0.56 (95% CI; 0.50 – 0.64). The intended role for MPV in the diagnostic pathway of myocardial infarction would perhaps be best as a triage tool. With a DOR of 2.92, MPV values can discriminate between those who have MI and those without. For a patient with angina presenting with elevated MPV values, it is 1.65 times more likely that he has MI. Thus, it is implied that the decision to treat a patient with angina or its equivalents as a case of MI could be supported by an elevated MPV value.

Keywords: mean platelet volume, MPV, myocardial infarction, angina, chest pain

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Authors: Assil Ghariri

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This article studies the process of rewriting the self through memory in Kazuo Ishiguro’s novel, the Unconsoled (1995). It deals with the journey that the protagonist Mr. Ryder takes through the unconscious, in search for his real self, in which trauma stands as an obstacle. The article uses Carl Jung’s theory of archetypes. Trauma, in this article, is discussed as one of the true obstacles of the unconscious that prevent people from realizing the truth about their selves.

Keywords: Carl Jung, Kazuo Ishiguro, memory, trauma

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Authors: K. O'Malley

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Background: The emergence and rapid evolution of large language models (LLMs) (i.e., models of generative artificial intelligence, or AI) has been unprecedented. ChatGPT is one of the most widely used LLM platforms. Using natural language processing technology, it generates customized responses to user prompts, enabling it to mimic human conversation. Responses are generated using predictive modeling of vast internet text and data swathes and are further refined and reinforced through user feedback. The popularity of LLMs is increasing, with a growing number of students utilizing these platforms for study and revision purposes. Notwithstanding its many novel applications, LLM technology is inherently susceptible to bias and error. This poses a significant challenge in the educational setting, where academic integrity may be undermined. This study aims to evaluate the performance of the latest iteration of ChatGPT (ChatGPT4.0) in standardized state medical licensing examinations. Methods: A considered search strategy was used to interrogate the PubMed electronic database. The keywords ‘ChatGPT’ AND ‘medical education’ OR ‘medical school’ OR ‘medical licensing exam’ were used to identify relevant literature. The search included all peer-reviewed literature published in the past five years. The search was limited to publications in the English language only. Eligibility was ascertained based on the study title and abstract and confirmed by consulting the full-text document. Data was extracted into a Microsoft Excel document for analysis. Results: The search yielded 345 publications that were screened. 225 original articles were identified, of which 11 met the pre-determined criteria for inclusion in a narrative synthesis. These studies included performance assessments in national medical licensing examinations from the United States, United Kingdom, Saudi Arabia, Poland, Taiwan, Japan and Germany. ChatGPT 4.0 achieved scores ranging from 67.1 to 88.6 percent. The mean score across all studies was 82.49 percent (SD= 5.95). In all studies, ChatGPT exceeded the threshold for a passing grade in the corresponding exam. Conclusion: The capabilities of ChatGPT in standardized academic assessment in medicine are robust. While this technology can potentially revolutionize higher education, it also presents several challenges with which educators have not had to contend before. The overall strong performance of ChatGPT, as outlined above, may lend itself to unfair use (such as the plagiarism of deliverable coursework) and pose unforeseen ethical challenges (arising from algorithmic bias). Conversely, it highlights potential pitfalls if users assume LLM-generated content to be entirely accurate. In the aforementioned studies, ChatGPT exhibits a margin of error between 11.4 and 32.9 percent, which resonates strongly with concerns regarding the quality and veracity of LLM-generated content. It is imperative to highlight these limitations, particularly to students in the early stages of their education who are less likely to possess the requisite insight or knowledge to recognize errors, inaccuracies or false information. Educators must inform themselves of these emerging challenges to effectively address them and mitigate potential disruption in academic fora.

Keywords: artificial intelligence, ChatGPT, generative ai, large language models, licensing exam, medical education, medicine, university

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Authors: Tess Hartland, Moitree Banerjee, Sue Churchill, Antonina Pereira, Ian Tyndall, Ruth Lowry

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Background: Sexual health services and policies for middle-aged and older adults are underdeveloped, while global sexually transmitted infections in this age group are on the rise. The Interreg cross-Europe Sexual Health In Over 45s (SHIFT) project aims to increase participation in sexual health services and improve sexual health and wellbeing in people aged over 45, with an additional focus on disadvantaged groups. Methods: A two-pronged mixed-methodology is being used to develop a model for good service provision in sexual health for over 45s. (1) Following PRISMA-ScR guidelines, a scoping review is being conducted, using the databases PsychINFO, Web of Science, ERIC and PubMed. A key search strategy using terms around sexual health, good practice, over 45s and disadvantaged groups. The initial search for literature yielded 7914 results. (2) Surveys (n=1000) based on the Theory of Planned Behaviour are being administered across the UK, Belgium and Netherlands to explore current sexual health knowledge, awareness and attitudes. Expected results: It is expected that sexual health needs and potential gaps in service provision will be identified in order to inform good practice for sexual health services for the target population. Results of the scoping review are being analysed, while focus group and survey data is being gathered. Preliminary analysis of the survey data highlights barriers to access such as limited risk awareness and stigma. All data analysis will be completed by the time of the conference. Discussion: Findings will inform the development of a model to improve sexual health and wellbeing for among over 45s, a population which is often missed in sexual health policy improvement.

Keywords: adult health, disease prevention, health promotion, over 45s, sexual health

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Authors: Sajjad Izadpanah, Seyed Hadi Ghaderi, Morteza Sayah Irani, Mahdi Gerdooei

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In this research work, a sophisticated yield criterion known as BBC2003, capable of describing planar anisotropic behaviors of aluminum alloy sheets, was integrated into the commercial finite element code ABAQUS/Standard via a user subroutine. The complete formulation of the implementation process using a fully implicit integration scheme, i.e., the classic backward Euler method, is presented, and relevant aspects of the yield criterion are introduced. In order to solve nonlinear differential and algebraic equations, the line-search algorithm was adopted in the user-defined material subroutine (UMAT) to expand the convergence domain of the iterative Newton-Raphson method. The developed subroutine was used to simulate a challenging computational problem with complex stress states, i.e., deep drawing of an anisotropic aluminum alloy AA3105. The accuracy and stability of the developed subroutine were confirmed by comparing the numerically predicted earing and thickness variation profiles with the experimental results, which showed an excellent agreement between numerical and experimental earing and thickness profiles. The integration of the BBC2003 yield criterion into ABAQUS/Standard represents a significant contribution to the field of computational mechanics and provides a useful tool for analyzing the mechanical behavior of anisotropic materials subjected to complex loading conditions.

Keywords: BBC2003 yield function, plastic anisotropy, fully implicit integration scheme, line search algorithm, explicit and implicit integration schemes

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Authors: Mathieu Hemono, Sophie Puig-Malet, Patrick Zylberman, Avner Bar-Hen, Rainer Sauerborn, Stefanie Schütte, Niamh Herlihi, Antoine Flahault et Anneliese Depoux

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Since the IPCC released its first report in 1990, an increasing number of peer-reviewed publications have reported the health risks associated with climate change. Although there is a large body of evidence supporting the association between climate change and poor health outcomes, the media is inconsistent in the attention it pays to the subject matter. This study aims to analyze the modalities and rhetoric in the media concerning the impact of climate change on health in order to better understand its role in information dissemination. A review was conducted of articles published between 1990 and 2015 in the francophone newspapers Le Monde and Jeune Afrique. A detailed search strategy including specific climate and health terminology was used to search the newspapers’ online databases. 1202 articles were identified as having referenced the terms climate change and health. Inclusion and exclusion criteria were applied to narrow the search to articles referencing the effects of climate change on human health and 160 articles were included in the final analysis. Data was extracted and categorized to create a structured database allowing for further investigation and analysis. The review indicated that although 66% of the selected newspaper articles reference scientific evidence of the impact of climate change on human health, the focus on the topic is limited major political events or is circumstances relating to public health crises. Main findings also include that among the many direct and indirect health outcomes, infectious diseases are the main health outcome highlighted in association with climate change. Lastly, the articles suggest that while developed countries have caused most of the greenhouse effect, the global south is more immediately affected. Overall, the reviewed articles reinforce the need for international cooperation in finding a solution to mitigate the effects of climate change on health. The manner in which scientific results are communicated and disseminated, impact individual and collective perceptions of the topic in the public sphere and affect political will to shape policy. The results of this analysis will underline the modalities of the rhetoric of transparency and provide the basis for a perception study of media discourses. This study is part of an interdisciplinary project called 4CHealth that confronts results of the research done on scientific, political and press literature to better understand how the knowledge on climate changes and health circulates within those different fields and whether and how it is translated to real world change.

Keywords: climate change, health, health impacts, communication, media, rhetoric, awareness, Global South, Africa

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Authors: Darshana Lal, Sonu Rana

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Learning Resource Centers (LRC) are acquiring different kinds of documents like books, journals, thesis, dissertations, standard, databases etc. in print and e-form. This article deals with the different types of sources available in LRC. It also discusses the concept of the web, as a tool, as a multimedia system and the different interfaces available on the web. The reasons for establishing LRC are highlighted along with the assignments of LRC. Different features of LRC‘S like self-learning and group learning are described. It also implements a group of activities like reading, learning, educational etc. The use of LRC by students and faculties are given and concluded with the benefits.

Keywords: internet, search engine, resource centre, opac, self-learning, group learning

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Authors: R. R. Billones, N. Lukkahatai, L. N. Saligan

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Mindfulness based interventions (MBIs) have been used in medically unexplained symptoms (MUS). This systematic review describes the literature investigating the general effect of MBIs on MUS and identifies the effects of specific MBIs on specific MUS conditions. The preferred reporting items for systematic reviews and meta-analysis guidelines (PRISMA) and the modified Oxford quality scoring system (JADAD) were applied to the review, yielding an initial 1,556 articles. The search engines included PubMed, ScienceDirect, Web of Science, Scopus, EMBASE, and PsychINFO using the search terms: mindfulness, or mediations, or mindful or MBCT or MBSR and medically unexplained symptoms or MUS or fibromyalgia or FMS. A total of 24 articles were included in the final systematic review. MBIs showed large effects on socialization skills for chronic fatigue syndrome (d=0.65), anger in fibromyalgia (d=0.61), improvement of somatic symptoms (d=1.6) and sleep (d=1.12) for painful conditions, physical health for chronic back pain (d=0.51), and disease intensity for irritable bowel disease/syndrome (d=1.13). A manualized MBI that applies the four fundamental elements present in all types of interventions were critical to efficacy. These elements were psycho-education sessions specific to better understand the medical symptoms, the practice of awareness, the non-judgmental observance of the experience at the moment, and the compassion to ones’ self. The effectiveness of different mindfulness interventions necessitates giving attention to improve the gaps that were identified related to home-based practice monitoring, competency training of mindfulness teachers, and sound psychometric properties to measure the mindfulness practice.

Keywords: mindfulness-based interventions, medically unexplained symptoms, mindfulness-based cognitive therapy, mindfulness-based stress reduction, fibromyalgia, irritable bowel syndrome

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Authors: Rabih Joseph Nabhan

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This case study explores the impact of two major computer software programs Learn to Speak English and Learn English Spelling and Pronunciation, and some Internet search engines such as Google on mending the decoding and spelling deficiency of Simon X, a dyslexic student. The improvement in decoding and spelling may result in better reading comprehension and composition writing. Some computer programs and Internet materials can help regain the missing awareness and consequently restore his self-confidence and self-esteem. In addition, this study provides a systematic plan comprising a set of activities (four computer programs and Internet materials) which address the problem from the lowest to the highest levels of phoneme and phonological awareness. Four methods of data collection (accounts, observations, published tests, and interviews) create the triangulation to validly and reliably collect data before the plan, during the plan, and after the plan. The data collected are analyzed quantitatively and qualitatively. Sometimes the analysis is either quantitative or qualitative, and some other times a combination of both. Tables and figures are utilized to provide a clear and uncomplicated illustration of some data. The improvement in the decoding, spelling, reading comprehension, and composition writing skills that occurred is proved through the use of authentic materials performed by the student under study. Such materials are a comparison between two sample passages written by the learner before and after the plan, a genuine computer chat conversation, and the scores of the academic year that followed the execution of the plan. Based on these results, the researcher recommends further studies on other Lebanese dyslexic learners using the computer to mend their language problem in order to design and make a most reliable software program that can address this disability more efficiently and successfully.

Keywords: analysis, awareness, dyslexic, software

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Authors: Petronella Lunda, Catharina Susanna Minnie, Welma Lubbe

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Background This review aimed to provide healthcare professionals with a scientific summary of the best available research evidence on factors influencing respectful perinatal care. The review question was ‘What were the perceptions of midwives and doctors on factors that influence respectful perinatal care?’ Methods A detailed search was done on electronic databases: EBSCOhost: Medline, OAlster, Scopus, SciELO, Science Direct, PubMed, Psych INFO, and SocINDEX. The databases were searched for available literature using a predetermined search strategy. Reference lists of included studies were analysed to identify studies missing from databases. The phenomenon of interest was factors influencing maternity care practices according to midwives and doctors. Pre-determined inclusion and exclusion criteria were used during the selection of potential studies. In total, 13 studies were included in the data analysis and synthesis. Three themes were identified and a total of nine sub-themes. Results Studies conducted in various settings were included in the study. Multiple factors influencing respectful perinatal care were identified. During data synthesis, three themes emerged: healthcare institution, healthcare professionals, and women-related factors. Alongside the themes were sub-themes human resources, medical supplies, norms and practices, physical infrastructure, healthcare professional competencies and attributes, women’s knowledge, and preferences. The three factors influence the provision of respectful perinatal care; addressing them might improve the provision of the care. Conclusion Addressing factors that influence respectful perinatal care is vital towards the prevention of compromised patient care during the perinatal period as these factors have the potential to accelerate or hinder provision of respectful care.

Keywords: doctors, maternity care, midwives, obstetrician, perceptions, perinatal care, respectful care

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Authors: Abir Derouiche, Abdesslem Layeb

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Association Rule Mining (ARM) is one of the most popular data mining tasks and it is widely used in various areas. The search for association rules is an NP-complete problem that is why metaheuristics have been widely used to solve it. The present paper presents the ARM as an optimization problem and surveys the proposed approaches in the literature based on metaheuristics.

Keywords: Optimization, Metaheuristics, Data Mining, Association rules Mining

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Authors: Carlos Alberto Ríos Reyes, Andrés Felipe Mejía Durán, Oscar Mauricio Castellanos Alarcón

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There is no doubt of great importance to make it known that planet Earth is an entity in constant change and transformation; processes such as construction and destruction are part of the evolution of the territory. Geoeducation workshops represent a significant contribution to the search for educational projects focused on teaching relevant geoscience topics to make natural threats known in schools through recreational and didactic activities. This initiative represents an educational alternative that must be developed with the participation of primary and secondary schools, universities, and local communities. The methodology is based on several phases, which include: diagnosis to know the best teaching method for basic concepts and establish a starting point for the topics to be taught, as well as to identify areas and concepts that need to be reinforced and/or deepened; design of activities that involve all students regardless of their ability or level; use of accessible materials and experimentation to support clear and concise explanations for all students; adaptation of the teaching-learning process to individual needs; sensitization about natural threats; and evaluation and feedback. It is expected to offer a series of activities and materials as a significant contribution to the search for educational projects focused on teaching relevant geoscientific topics such as natural threats associated with earthquakes, volcanic eruptions, floods, landslides, etc. The major findings of this study are the pedagogical strategies that primary and secondary school teachers can appropriate to face the challenge of transferring geological knowledge and to advise decision-makers and citizens on the importance of geosciences for daily life. We conclude that the knowledge of the natural threats to our planet is very important to contribute to mitigating their risk.

Keywords: workshops, geoeducation, curriculum, geosciences, natural threats

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Authors: Betül Sönmez, Aytolan Yıldırım

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Objective: This systematic review aims to methodically analyze studies regarding mobbing behavior prevalence, individuals performing this behavior and the effects of mobbing on Turkish nurses. Background: Worldwide reports on mobbing cases have increased in the past years, a similar trend also observable in Turkey. It has been demonstrated that among healthcare workers, mobbing is significantly widespread in nurses. The number of studies carried out in this regard has also increased. Method: The main criteria for choosing articles in this systematic review were nurses located in Turkey, regardless of any specific date. In November 2014, a search using the keywords 'mobbing, bullying, psychological terror/violence, emotional violence, nurses, healthcare workers, Turkey' in PubMed, Science Direct, Ebscohost, National Thesis Centre database and Google search engine led to 71 studies in this field. 33 studies were not met the inclusion criteria specified for this study. Results: The findings were obtained using the results of 38 studies carried out in the past 13 years in Turkey, a large sample consisting of 8,877 nurses. Analysis of the incidences of mobbing behavior revealed a broad spectrum, ranging from none-slight experiences to 100% experiences. The most frequently observed mobbing behaviors include attacking personality, blocking communication and attacking professional and social reputation. Victims mostly experienced mobbing from their managers, the most common consequence of these actions being psychological effects. Conclusions: The results of studies with various scales indicate exposure of nurses to similar mobbing behavior. The high frequency of exposure of nurses to mobbing behavior in such a large sample highlights the importance of considering this issue in terms of individual and institutional consequences that adversely affect the performance of nurses.

Keywords: mobbing, bullying, workplace violence, nurses, Turkey

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Authors: Atsebaha Gebrekidan Kahsay, Tsehaye Asmelash, Enquebaher Kassaye

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Background: Salmonella remains a global public health problem with a significant burden in sub-Saharan African countries. Human restricted cause of typhoid and paratyphoid fever are S. Typhi and S. Paratyphi, whereas S. Enteritidis and S. Typhimurium is the causative agent of invasive nontyphoidal diseases among humans and animals are their reservoir. The antibiotic resistance of Salmonella is another public health threat around the globe. To come up with full information about human and animal salmonellosis, we made a systematic review of the prevalence, serotypes, and antibiotic resistance of Salmonella in Ethiopia. Methods: This systematic review used Google Scholar and PubMed search engines to search articles from Ethiopia that were published in English in peer-reviewed international journals from 2010 to 2022. We used keywords to identify the intended research articles and used a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to ensure the inclusion and exclusion criteria. Frequencies and percentages were analyzed using Microsoft Excel. Results: Two hundred seven published articles were searched, and 43 were selected for a systematic review, human (28) and animals (15). The prevalence of Salmonella in humans and animals was 434 (5.2%) and 641(10.1%), respectively. Fourteen serotypes were identified from animals, and S. Typhimurium was among the top five. Among the ciprofloxacin-resistant isolates in human studies, 16.7% was the highest, whereas, for ceftriaxone, 100% resistance was reported. Conclusions: The prevalence of Salmonella among diarrheic patients and food handlers (5.2%) was lower than the prevalence in food animals (10.1%). We did not find serotypes of Salmonella in human studies, although fourteen serotypes were included in food-animal studies, and S. Typhimurium was among the top five. Salmonella species from some human studies revealed a non-susceptibility to ceftriaxone. We recommend further study about invasive nontyphoidal Salmonella and predisposing factors among humans and animals in Ethiopia.

Keywords: antibiotic resistance, prevalence, systematic review, serotypes, Salmonella, Ethiopia

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Authors: Mao Zhaofang, Xu Yida, Fang Kan, Fu Enyuan, Zhao Zhao

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Nowadays, last-mile distribution plays an increasingly important role in the whole industrial chain delivery link and accounts for a large proportion of the whole distribution process cost. Promoting the upgrading of logistics networks and improving the layout of final distribution points has become one of the trends in the development of modern logistics. Due to the discrete and heterogeneous needs and spatial distribution of customer demand, which will lead to a higher delivery failure rate and lower vehicle utilization, last-mile delivery has become a time-consuming and uncertain process. As a result, courier companies have introduced a range of innovative parcel storage facilities, including pick-up points and lockers. The introduction of pick-up points and lockers has not only improved the users’ experience but has also helped logistics and courier companies achieve large-scale economy. Against the backdrop of the COVID-19 of the previous period, contactless delivery has become a new hotspot, which has also created new opportunities for the development of collection services. Therefore, a key issue for logistics companies is how to design/redesign their last-mile distribution network systems to create integrated logistics and distribution networks that consider pick-up points and lockers. This paper focuses on the introduction of self-pickup facilities in new logistics and distribution scenarios and the heterogeneous demands of customers. In this paper, we consider two types of demand, including ordinary products and refrigerated products, as well as corresponding transportation vehicles. We consider the constraints associated with self-pickup points and lockers and then address the location-routing problem with self-pickup facilities and heterogeneous demands (LRP-PFHD). To solve this challenging problem, we propose a mixed integer linear programming (MILP) model that aims to minimize the total cost, which includes the facility opening cost, the variable transport cost, and the fixed transport cost. Due to the NP-hardness of the problem, we propose a hybrid adaptive large-neighbourhood search algorithm to solve LRP-PFHD. We evaluate the effectiveness and efficiency of the proposed algorithm by using instances generated based on benchmark instances. The results demonstrate that the hybrid adaptive large neighbourhood search algorithm is more efficient than MILP solvers such as Gurobi for LRP-PFHD, especially for large-scale instances. In addition, we made a comprehensive analysis of some important parameters (e.g., facility opening cost and transportation cost) to explore their impacts on the results and suggested helpful managerial insights for courier companies.

Keywords: city logistics, last-mile delivery, location-routing, adaptive large neighborhood search

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Authors: Kanupriya Rawat, Aleksandra Błachnio, Paweł Izdebski

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Achievement motivation, which drives a person to strive for success, is an important construct in sports psychology. This systematic review aims to analyze the methods of measuring achievement motivation used in previous studies published over the past four decades and to find out which method of measuring achievement motivation is the most prevalent and the most effective by thoroughly examining measures of achievement motivation used in each study and by evaluating most highly cited achievement motivation measures in sport. In order to understand this latent construct, thorough measurement is necessary, hence a critical evaluation of measurement tools is required. The literature search was conducted in the following databases: EBSCO, MEDLINE, APA PsychARTICLES, Academic Search Ultimate, Open Dissertations, ERIC, Science direct, Web of Science, as well as Wiley Online Library. A total of 26 articles met the inclusion criteria and were selected. From this review, it was found that the Achievement Goal Questionnaire- Sport (AGQ-Sport) and the Task and Ego Orientation in Sport Questionnaire (TEOSQ) were used in most of the research, however, the average weighted impact factor of the Achievement Goal Questionnaire- Sport (AGQ-Sport) is the second highest and most relevant in terms of research articles related to the sport psychology discipline. Task and Ego Orientation in Sport Questionnaire (TEOSQ) is highly popular in cross-cultural adaptation but has the second last average IF among other scales due to the less impact factor of most of the publishing journals. All measures of achievement motivation have Cronbach’s alpha value of more than .70, which is acceptable. The advantages and limitations of each measurement tool are discussed, and the distinction between using implicit and explicit measures of achievement motivation is explained. Overall, both implicit and explicit measures of achievement motivation have different conceptualizations of achievement motivation and are applicable at either the contextual or situational level. The conceptualization and degree of applicability are perhaps the most crucial factors for researchers choosing a questionnaire, even though they differ in their development, reliability, and use.

Keywords: achievement motivation, task and ego orientation, sports psychology, measures of achievement motivation

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Authors: Abdorrasoul Malekpour, Mohammad Ghorbani Mojtaba Mortazavi, Mohammadreza Fattahi, Mohammad Hassan Meshkibaf, Ali Fakhrzad, Saeid Salehi, Saeideh Zahedi, Amir Ahmadimoghaddam, Parviz Farzadnia Dr., Mohammadreza Hajyani Asl Bs

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Hepatitis B as an infectious disease has eight main genotypes (A–H). The aim of this study is to Bioinformatically identify Rare Codon Clusters (RCC) in proteins structure of HBV. For detection of protein family accession numbers (Pfam) of HBV proteins; used of uni-prot database and Pfam search tool were used. Obtained Pfam IDs were analyzed in Sherlocc program and RCCs in HBV proteins were detected. In further, the structures of TrEMBL entries proteins studied in PDB database and 3D structures of the HBV proteins and locations of RCCs were visualized and studied using Swiss PDB Viewer software. Pfam search tool have found nine significant hits and 0 insignificant hits in 3 frames. Results of Pfams studied in the Sherlocc program show this program not identified RCCs in the external core antigen (PF08290) and truncated HBeAg protein (PF08290). By contrast the RCCs become identified in Hepatitis core antigen (PF00906) Large envelope protein S (PF00695), X protein (PF00739), DNA polymerase (viral) N-terminal domain (PF00242) and Protein P (Pf00336). In HBV genome, seven RCC identified that found in hepatitis core antigen, large envelope protein S and DNA polymerase proteins and proteins structures of TrEMBL entries sequences that reported in Sherlocc program outputs are not complete. Based on situation of RCC in structure of HBV proteins, it suggested those RCCs are important in HBV life cycle. We hoped that this study provide a new and deep perspective in protein research and drug design for treatment of HBV.

Keywords: rare codon clusters, hepatitis B virus, bioinformatic study, infectious disease

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Authors: Mohammad Hassanzadeh

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As far as incidental vocabulary learning is concerned, the basic contention of the Involvement Load Hypothesis (ILH) is that retention of unfamiliar words is, generally, conditional upon the degree of involvement in processing them. This study examined input modality and incidental vocabulary uptake in a task-induced setting whereby three variously loaded task types (marginal glosses, fill-in-task, and sentence-writing) were alternately assigned to one group of students at Allameh Tabataba’i University (n=2l) during six classroom sessions. While one round of exposure was comprised of the audiovisual medium (TV talk shows), the second round consisted of textual materials with approximately similar subject matter (reading texts). In both conditions, however, the tasks were equivalent to one another. Taken together, the study pursued the dual objectives of establishing a litmus test for the ILH and its proposed values of ‘need’, ‘search’ and ‘evaluation’ in the first place. Secondly, it sought to bring to light the superiority issue of exposure to audiovisual input versus the written input as far as the incorporation of tasks is concerned. At the end of each treatment session, a vocabulary active recall test was administered to measure their incidental gains. Running a one-way analysis of variance revealed that the audiovisual intervention yielded higher gains than the written version even when differing tasks were included. Meanwhile, task 'three' (sentence-writing) turned out the most efficient in tapping learners' active recall of the target vocabulary items. In addition to shedding light on the superiority of audiovisual input over the written input when circumstances are relatively held constant, this study for the most part, did support the underlying tenets of ILH.

Keywords: Keywords— Evaluation, incidental vocabulary learning, input mode, Involvement Load Hypothesis, need, search.

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Authors: Kahlouche Amal, Touzene F. Zohra, Betatache Fatihaet Nouani Abdelouahab

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The development of the world production of the cheese these last decades, as well as agents' greater request cheap coagulants, accentuated the search for new surrogates of the rennet. What about the interest to explore the vegetable biodiversity, the source well cheap of many naturals metabolites that the scientists today praise it (thistle, latex of fig tree, Cardoon, seeds of melon). Indeed, a big interest is concerned the search for surrogates of vegetable origin. The objective of the study is to show the possibility of extracting a protease coagulant the milk from the cake of Sunflower, available raw material and the potential source of surrogates of rennet. so, the determination of the proteolytic activity of raw extracts, the purification, the elimination of the pigments of tint of the enzymatic preparations, a better knowledge of the coagulative properties through study of the effect of certain factors (temperature, pH, concentration in CaCl2) are so many factors which contribute to value milk particularly those produced by the small ruminants of the Algerian dairy exploitations. Otherwise, extracts coagulants of vegetable origin allowed today to value traditional, in addition, although the extract coagulants of vegetable origin made it possible today to develop traditional cheeses whose Iberian peninsula is the promoter, but the test of 'pressed paste not cooked' cheese manufacturing led to the semi-scale pilot; and that, by using the enzymatic extract of sunflower (Helianthus annus) which gave satisfactory results as well to the level of outputs as on the sensory level,which, statistically,did not give any significant difference between studied cheeses. These results confirm the possibility of use of this coagulase as a substitute of rennet commercial on an industrial scale.

Keywords: characterization, cheese, Rennet, sunflower

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Authors: Sally Kafelghazal

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Introduction: Arab Americans, who include immigrants, refugees, or U.S. born persons of Middle Eastern or North African descent, may experience significant difficulties during acculturation to Western society. Influential stressors include relocation, loss of social support, language barriers, and economic factors, all of which can impact mental health. There is limited research investigating the effects of acculturation on the mental health of the Arab American population. Objectives: The purpose of this study is to identify ways in which acculturation impacts the mental health of Arab Americans, specifically the development of depression and anxiety. Method: A literature search was conducted using PubMed and PsycArticles (ProQuest), utilizing the following search terms: “Arab Americans,” “Arabs,” “mental health,” “depression,” “anxiety,” “acculturation.” Thirty-nine articles were identified and of those, nine specifically investigated the relationship between acculturation and mental health in Arab Americans. Three of the nine focused exclusively on depression. Results: Several risk factors were identified that contribute to poor mental health associated with acculturation, which include immigrant or refugee status, facing discrimination, and religious ideology. Protective factors include greater levels of acculturation, being U.S. born, and greater heritage identity. Greater mental health disorders were identified in Arab Americans compared to normative samples, perhaps particularly depression; none of the articles specifically addressed anxiety. Conclusion: The current research findings support the potential association between the process of acculturation and greater levels of mental health disorders in Arab Americans. However, the diversity of the Arab American population makes it difficult to draw consistent conclusions. Further research needs to be conducted in order to assess which subgroups in the Arab American population are at highest risk for developing new or exacerbating existing mental health disorders in order to devise more effective interventions.

Keywords: arab americans, arabs, mental health, anxiety, depression, acculturation

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Authors: Daniela V. Bavaresco, Tamy Colonetti, Antonio Jose Grande, Francesc Colom, Joao Quevedo, Samira S. Valvassori, Maria Ines da Rosa

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Objective: Performed a systematic review and meta-analysis to evaluated the potential effect of the cyclo-oxygenases (Cox)-2 inhibitor Celecoxib adjunct treatment in Bipolar Disorder (BD), through of randomized controlled trials. Method: A search of the electronic databases was proceeded, on MEDLINE, EMBASE, Scopus, Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, Web of Science, IBECS, LILACS, PsycINFO (American Psychological Association), Congress Abstracts, and Grey literature (Google Scholar and the British Library) for studies published from January 1990 to February 2018. A search strategy was developed using the terms: 'Bipolar disorder' or 'Bipolar mania' or 'Bipolar depression' or 'Bipolar mixed' or 'Bipolar euthymic' and 'Celecoxib' or 'Cyclooxygenase-2 inhibitors' or 'Cox-2 inhibitors' as text words and Medical Subject Headings (i.e., MeSH and EMTREE) and searched. The therapeutic effects of adjunctive treatment with Celecoxib were analyzed, it was possible to carry out a meta-analysis of three studies included in the systematic review. The meta-analysis was performed including the final results of the Young Mania Rating Scale (YMRS) at the end of randomized controlled trials (RCT). Results: Three primary studies were included in the systematic review, with a total of 121 patients. The meta-analysis had significant effect in the YMRS scores from patients with BD who used Celecoxib adjuvant treatment in comparison to placebo. The weighted mean difference was 5.54 (95%CI=3.26-7.82); p < 0.001; I2 =0%). Conclusion: The systematic review suggests that adjuvant treatment with Celecoxib improves the response of major treatments in patients with BD when compared with adjuvant placebo treatment.

Keywords: bipolar disorder, Cox-2 inhibitors, Celecoxib, systematic review, meta-analysis

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Authors: Anda-veronica Gherman, Dimitrios Varthalitis

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Neurosurgery, like many surgical specialties, undoubtedly exhibits a significant gender gap, particularly in leadership positions. While increasing women representation in neurosurgery is important, it is crucial to increase their presence in leadership positions. Across the globe and Europe there are concerning trends of only 4% of all neurosurgical departments being chaired by women. This study aims to explore the situation regarding gender disparities in leadership in the United Kingdom and to identify possible contributing factors as well as discussing future strategies to bridge this gap. Methods: A literature review was conducted utilising PubMed as main database with search keywords including ‘female neurosurgeon’, ‘women neurosurgeon’, ‘gender disparity’, ‘leadership’ and ‘UK’. Additionally, a manual search of all neurosurgical departments in the UK was performed to identify the current female department leads and training director leads. Results: The literature search identified a paucity of literature addressing specifically leadership in female neurosurgeons within the UK, with very few published papers specifically on this topic. Despite more than half of medical students in the UK being female, only a small proportion pursue a surgical career, with neurosurgery being one of the least represented specialties. Only 27% of trainee neurosurgeons are female, and numbers are even lower at a consultant level, where women represent just 8%.Findings from published studies indicated that only 6.6% of leadership positions in neurosurgery are occupied by women in the UK. Furthermore, our manual searches across UK neurosurgical departments revealed that around 5% of department lead positions are currently held by women. While this figure is slightly higher than the European average of 4%, it remains lower compared to figures of 10% in other North-West European countries. The situation is slightly more positive looking at the training directors, with 15% being female. Discussion: The findings of this study highlight a significant gender disparity in leadership positions within neurosurgery in the UK, which may have important implications, perpetuating the lack of diversity on the decision-making process, limiting the career advancement opportunities of women and depriving the neurosurgical field from the voices, opinions and talents of women. With women representing half of the population, there is an undeniable need for more female leaders at the policy-making level. There are many barriers that can contribute to these numbers, including bias, stereotypes, lack of mentorship and work-like balance. A few solutions to overcome these barriers can be training programs addressing bias and impostor syndrome, leadership workshops tailored for female needs, better workplace policies, increased in formal mentorship and increasing the visibility of women in neurosurgery leadership positions through media, speaking opportunities, conferences, awards etc. And lastly, more research efforts should focus on the leadership and mentorship of women in neurosurgery, with an increased number of published papers discussing these issues.

Keywords: female neurosurgeons, female leadership, female mentorship, gender disparities

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Authors: Soumi Banerjee

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In this research paper we will go deep into understanding Benedict Anderson’s definition of the nation as an imagined community and we will analyze why and how national identities were created through long and complex processes, and how there can exist strong emotional bonds between people within an imagined community, given the fact that these people have never known each other personally, but will still feel some form of imagined unity. Such identity construction on the part of an individual or within societies are always in some sense in a state of flux as imagined communities are ever changing, which provides us with the ontological foundation for reaching on this paper. This sort of identity crisis among individuals living in the Western world, who are in search for psychological comfort and security, illustrates a possible need for spatially dislocated, ontologically insecure and vulnerable individuals to have a secure identity. To create such an identity there has to be something to build upon, which could be achieved through what may be termed as ‘homesteading’. This could in short, and in my interpretation of Kinnvall and Nesbitt’s concept, be described as a search for security that involves a search for ‘home’, where home acts as a secure place, which one can build an identity around. The next half of the paper will then look into how populism and identity have played an increasingly important role in the political elections in the so-called western democracies of the world, using the U.S. as an example. Notions of ‘us and them’, the people and the elites will be looked into and analyzed through a social constructivist theoretical lens. Here we will analyze how such narratives about identity and the nation state affects people, their personality development and identity in different ways by studying the U.S. President Donald Trump’s speeches and analyze if and how he used different identity creating narratives for gaining political and popular support. The reason to choose narrative analysis as a method in this research paper is to use the narratives as a device to understand how the perceived notions of 'us and them' can initiate huge identity crisis with a community or a nation-state. This is a relevant subject as results and developments such as rising populist rightwing movements are being felt in a number of European states, with the so-called Brexit vote in the U.K. and the election of Donald Trump as president are two of the prime examples. This paper will then attempt to argue that these mechanisms are strengthened and gaining significance in situations when humans in an economic, social or ontologically vulnerable position, imagined or otherwise, in a general and broad meaning perceive themselves to be under pressure, and a sense of insecurity is rising. These insecurities and sense of being under threat have been on the rise in many of the Western states that are otherwise usually perceived to be some of the safest, democratically stable and prosperous states in the world, which makes it of interest to study what has changed, and help provide some part of the explanation as to how creating a ‘them’ in the discourse of national identity can cause massive security crisis.

Keywords: identity crisis, migration, ontological security(in), nation-states

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Authors: Enes Gunaltili, Burak Dam

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The airplane history started with the Wright brothers' aircraft and improved day by day. With the help of this advancements, big aircrafts replace with small and unmanned air vehicles, so in this study we design this type of air vehicles. First of all, aircrafts mainly divided into two main parts in our day as a rotary and fixed wing aircrafts. The fixed wing aircraft generally use for transport, cargo, military and etc. The rotary wing aircrafts use for same area but there are some superiorities from each other. The rotary wing aircraft can take off vertically from the ground, and it can use restricted area. On the other hand, rotary wing aircrafts generally can fly lower range than fixed wing aircraft. There are one kind of aircraft consist of this two types specifications. It is named as VTOL (vertical take-off and landing) type aircraft. VTOLs are able to takeoff and land vertically and fly horizontally. The VTOL aircrafts generally can fly higher range from the rotary wings but can fly lower range from the fixed wing aircraft but it gives beneficial range between them. There are many other advantages of VTOL aircraft from the rotary and fixed wing aircraft. Because of that, VTOLs began to use for generally military, cargo, search, rescue and mapping areas. Within this framework, this study answers the question that how can we design VTOL as a small unmanned aircraft systems for search and rescue application for benefiting the advantages of fixed wing and rotary wing aircrafts by eliminating the disadvantages of them. To answer that question and design VTOL aircraft, multidisciplinary design optimizations (MDO), some theoretical terminologies, formulations, simulations and modelling systems based on CFD (Computational Fluid Dynamics) is used in same time as design methodology to determine design parameters and steps. As a conclusion, based on tests and simulations depend on design steps, suggestions on how the VTOL aircraft designed and advantages, disadvantages, and observations for design parameters are listed, then VTOL is designed and presented with the design parameters, advantages, and usage areas.

Keywords: airplane, rotary, fixed, VTOL, CFD

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Authors: Mikiyas Adugna

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Effort estimation is among the activities carried out in software development processes. An accurate model of estimation leads to project success. The method of agile effort estimation is a complex task because of the dynamic nature of software development. Researchers are still conducting studies on agile effort estimation to enhance prediction accuracy. Due to these reasons, we investigated and proposed a model on LASSO and Elastic Net regression to enhance estimation accuracy. The proposed model has major components: preprocessing, train-test split, training with default parameters, and cross-validation. During the preprocessing phase, the entire dataset is normalized. After normalization, a train-test split is performed on the dataset, setting training at 80% and testing set to 20%. We chose two different phases for training the two algorithms (Elastic Net and LASSO) regression following the train-test-split. In the first phase, the two algorithms are trained using their default parameters and evaluated on the testing data. In the second phase, the grid search technique (the grid is used to search for tuning and select optimum parameters) and 5-fold cross-validation to get the final trained model. Finally, the final trained model is evaluated using the testing set. The experimental work is applied to the agile story point dataset of 21 software projects collected from six firms. The results show that both Elastic Net and LASSO regression outperformed the compared ones. Compared to the proposed algorithms, LASSO regression achieved better predictive performance and has acquired PRED (8%) and PRED (25%) results of 100.0, MMRE of 0.0491, MMER of 0.0551, MdMRE of 0.0593, MdMER of 0.063, and MSE of 0.0007. The result implies LASSO regression algorithm trained model is the most acceptable, and higher estimation performance exists in the literature.

Keywords: agile software development, effort estimation, elastic net regression, LASSO

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Authors: Kofi Nkonkonya Mpuangnan, Samantha Govender, Hlengiwe Romualda Mhlongo

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Educational leaders are skilled architects crafting a vibrant environment where growth, creativity, and adaptability can flourish within schools. Their journey is one of transformation, urging them to explore administrative strategies that align seamlessly with evolving educational models and cater to the specific needs of students, educators, and stakeholders. Through this committed effort to innovate, they seek to enhance the effectiveness and influence of educational systems, paving the way for a more inclusive and forward-thinking educational environment. In this context, the authors explored the concept of transforming educational leadership with administrative strategies in alignment with the following research objectives. To find the strategies that can be adopted by transformation leaders to promote effective administrative practices in an educational setting and to explore the roles of educational leaders in promoting collaboration in education. To find answers to these questions, a systematic literature review underpinned by the transformational leadership model was adopted. Therefore, concepts integrated from a variety of outlets, including academic journals, conference proceedings, and reports found within SCOPUS, WoS, and IBSS databases. A search was aided using specific themes like innovative administrative practices, the roles of educational leaders, and interdisciplinary approaches to administrative practices. The process of conducting the search adhered to the five-step framework, which was subjected to inclusion and exclusion of studies. It was found that transformational leadership, agile methodologies, employee wellbeing, seminars and workshops could foster a culture of innovation and creativity among teachers and staff to transform administrative practices in education settings. It was recommended that professional development programs be organized periodically for educational leaders in educational institutions to help them revitalize their knowledge and skills in educational administration.

Keywords: educational leadership, innovative strategies, administrative practices, professional development, stakeholder engaement, student outcome

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Authors: M. L. Mangena, N. Mokoena, K. Rashamuse, M. G. Tlou

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Tertiary alcohol ester (TAE) hydrolases are a group of esterases (EC 3.1.1.-) that catalyze the kinetic resolution of TAEs and as a result, they are sought-after for the production of optically pure tertiary alcohols (TAs) which are useful as building blocks for number biologically active compounds. What sets these enzymes apart is, the presence of a GGG(A)X-motif in the active site which appears to be the main reason behind their activity towards the sterically demanding TAEs. The genome of Pseudomonas syringae pv. maculicola (Psm) comprises a multitude of genes that encode esterases. We therefore, hypothesize that some of these genes encode TAE hydrolases. In this study, Psm was screened for TAE hydrolase activity using the linalyl acetate (LA) plate assay and a positive reaction was observed. As a result, the genome of Psm was screened for esterases with a GGG(A)X-motif using the motif search tool and two potential TAE hydrolase genes (PsmEST1 and 2, 1100 and 1000bp, respectively) were identified, PsmEST1 was amplified by PCR and the gene sequenced for confirmation. Analysis of the sequence data with the SingnalP 4.1 server revealed that the protein comprises a signal peptide (22 amino acid residues) on the N-terminus. Primers specific for the gene encoding the mature protein (without the signal peptide) were designed such that they contain NdeI and XhoI restriction sites for directional cloning of the PCR products into pET28a. The gene was expressed in E. coli JM109 (DE3) and the clones screened for TAE hydrolase activity using the LA plate assay. A positive clone was selected, overexpressed and the protein purified using nickel affinity chromatography. The activity of the esterase towards LA was confirmed using thin layer chromatography.

Keywords: hydrolases, tertiary alcohol esters, tertiary alcohols, screening, Pseudomonas syringae pv., maculicola genome, esterase activity, linalyl acetate

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Authors: Cyril Kaplan

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26 participants played 4 EEG neurofeedback (NF) games encouraged to find their strategies to control the specific NF parameter. Mixed method analysis of performance in the games and post-session interviews led to the identification of states of consciousness that correlated with success in the game. We found that increase in left frontal beta activity was facilitated by evoking interest in observed surroundings, by wondering what is happening behind the window or what lies in a drawer in front.

Keywords: EEG neurofeedback, states of consciousness, frontal beta activity, mixed methods

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Authors: Zhipeng Yan, Janice Wing-Tung Kwong, Ching-Lung Lai

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Background: Advanced melanoma accounts for the majority of skin cancer death due to its poor prognosis. Nivolumab and ipilimumab are monoclonal antibodies targeting programmed cell death protein 1 (PD-1) and cytotoxic T-lymphocytes antigen 4 (CTLA-4). Nivolumab and ipilimumab combination therapy has been proven to be effective for advanced melanoma. This systematic review and meta-analysis are to evaluate its clinical efficacy and adverse events. Method: A systematic search was done on databases (Pubmed, Embase, Medline, Cochrane) on 21 June 2020. Search keywords were nivolumab, ipilimumab, melanoma, and randomised controlled trials. Clinical trials fulfilling the inclusion criteria were selected to evaluate the efficacy of combination therapy in terms of prolongation of progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The odd ratios and distributions of grade 3 or above adverse events were documented. Subgroup analysis was performed based on PD-L1 expression-status and BRAF-mutation status. Results: Compared with nivolumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR in combination therapy were 0.64 (95% CI, 0.48-0.85; p=0.002), 0.84 (95% CI, 0.74-0.95; p=0.007) and 1.76 (95% CI, 1.51-2.06; p < 0.001), respectively. Compared with ipilimumab monotherapy, the hazard ratios of PFS, OS and odd ratio of ORR were 0.46 (95% CI, 0.37-0.57; p < 0.001), 0.54 (95% CI, 0.48-0.61; p < 0.001) and 6.18 (95% CI, 5.19-7.36; p < 0.001), respectively. In combination therapy, the odds ratios of grade 3 or above adverse events were 4.71 (95% CI, 3.57-6.22; p < 0.001) compared with nivolumab monotherapy, and 3.44 (95% CI, 2.49-4.74; p < 0.001) compared with ipilimumab monotherapy, respectively. High PD-L1 expression level and BRAF mutation were associated with better clinical outcomes in patients receiving combination therapy. Conclusion: Combination therapy is effective for the treatment of advanced melanoma. Adverse events were common but manageable. Better clinical outcomes were observed in patients with high PD-L1 expression levels and positive BRAF-mutation.

Keywords: nivolumab, ipilimumab, advanced melanoma, systematic review, meta-analysis

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