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Young Scientists Journal - Peer-reviewed scientific research by young people across the globe. TOMORROW'S SCIENTISTS, TODAY The Young Scientists Journal is the largest and oldest journal of its kind. We are an internationally peer-reviewed science journal, written, reviewed and produced by students aged 12 to 20. Since 2006, we have connected students from over 50 countries. Find out more ABOUT US “I was amazed and delighted at the high quality of the science, the enthusiasm of the young scientists and the confidence with which they presented their research. They were inspirational. The world has a bright future with young scientists like these.” Professor Sir Martyn Poliakoff University of Nottingham Relive #ysjconf 2024 Talks & More Find Out More Recent Posts Sep 22, 2024 12 min read Navigating Bioethical Waters: The ethical landscape behind stem cell research Sep 16, 2024 3 min read Medicine Overview of Brain Imaging Techniques Sep 16, 2024 3 min read How Music Affects the Brain

Join us for the Young Scientists Journal Conference 2024 at The King's School, Canterbury. Empower tomorrow's scientists today. Young Scientists Journal CONFERENCE 2024 Wednesday 13th November Thanks For Coming! 2024 Annual conference The Young Scientists Journal's annual conference is a platform for young minds to showcase their diverse studies, from Biology to Psychology, Maths to Geology. The event features illuminating lectures by world-leading scientists, inspiring the next generation. Held at the historic King's School, the conference fosters a spirit of inquiry, collaboration, and curiosity, providing a space for young minds to flourish. Tomorrow's scientists, today Relive the action via our YouTube Livestream. Click Here! *Please note that the final panel session has no audio due to technical difficulties. No events at the moment Guest speakers We are absolutely thrilled to announce the incredible guest speakers for this year's conference. Each one brings a treasure trove of experience that they can't wait to share with all of you. Dr Amy Barker Oxford Biomedica Principal Scientist Dr Barker is a biologist who has worked on a variety of rare diseases and is developing gene therapies for cancer Dr Mark Basham The Rosalind Franklin Institute Science Director, Head of AI Dr Basham’s primary research contributions have focused on the removal of barriers between image processing techniques in different scientific domains. Dr Alexandre Paschoal The Rosalind Franklin Institute Group Leader, AI Dr. Paschoal's primary research lies in building cut-edge AI techniques to translate biological/life science data into solutions using bioinformatics expertise to guide decision-making. James Clarke Rothamsted Research Director of Communications and Engagement James Clarke has more than a decade of experience producing science radio programmes for the BBC, and has worked in a number of communication roles abroad. He has had a career long interest in popularising science for varied audiences across multiple media outlets and through high profile events. Vanessa Madu Imperial College London PhD Student Vanessa Madu is a PhD student on the EPSRC CDT in Modern Statistics and Statistical Machine Learning at Imperial College London and Oxford University. She is an "Oceanographically-enabled Mathematical Statistician" who is interested in statistical machine-learning methods for predicting ocean surface currents. Rewatch The Livestream: 2024 Poster Competition (Now Closed) Just like our last 10 years of conferences, students aged 12-20 will have the opportunity to submit their original research projects in poster form. All posters submitted will be printed in-house and go on display at our conference. There is no need to bring your poster with you if you are unable to! All those who submit are welcomed to book their free ticket using the event page above. Judges will be walking around looking at posters so it is in your best interest to be there to answer any questions or submit a video presentation of your poster to maximise your chances of a prize. Prizes Available: Certificate from the Young Scientists Journal Publication on the Young Scientists Journal Website STEM Books (courtesy of the Butrous Foundation) DEADLINE: 1st NOVEMBER 2024 Needing Some Inspiration? Take a look at the entry of a previous finalist!

Explore the possibilities of publishing with us! Join our journal and share your unique content with a global audience. Let your voice be heard. Publish with us Make your mark on the world of science 01 Types of articles Original Research: Scientific investigation which has never been done before Review Articles: A summary and your take on the research done, drawing from previously published articles and papers. Blog or Magazine Article: An opinion piece or news story, sharing your view on a scientific topic. It can include interviews and profiles. 03 Step-by-step process Data Check Initial Review by a Junior Editor Academic Review by an Academic Advisor Final Review by a Senior Editor Publication by the Production Team Please be aware publication can take months, as the Journal is run completely by volunteers 02 Before you publish Plagirsim is forbidden. Chicago Style references only. British English spelling throughout. Please use All Guides below before submitting. Author's Guide Reference Guide Marking Grid 04 Publishing The YSJ prides publishes a variety of work done by young people. We are the largest Journal of our kind, drawing in thousands of readers. If you want your work showcased, continue reading. You must be between the ages of 12-20 at the time of submission. SUBMIT YOUR ARTICLE

Co-authors: Huaxuan Chen, Adithya Chakravarthy, Rachel Woo First published: June 2020 Abstract The Zika virus is a mosquito-borne virus that has affected 65 countries since 2015. There are currently no cures for the virus, so at-risk populations rely solely on preventative methods such as nets and insecticide sprays, with limited effectiveness. COBWEB, a computer simulation software, was used to determine the effectiveness of an introduction of the insecticide “permethrin” in the Brazilian city of Olaria, where the Zika virus is particularly virulent. Due to its flexibility and wide array of parameters, COBWEB was also able to model the effects of permethrin resistance on Zika transmission. The result was that permethrin significantly reduced fatality rates from the Zika virus and permethrin with resistance was still comparatively better than the control. This information is helpful, as it can be applied to other areas where the Zika virus is especially virulent, and serve as a potential solution to this emerging disease. Introduction Vector-borne infectious diseases are human illnesses caused by vectors, which are carriers of diseases or medicine. Vectors do not cause disease, but they spread infection when they’re passed from one organism to another. These vector-borne diseases are typically transmitted by animal hosts, and they make up a significant portion of the world’s disease burden. Indeed, nearly half of the global population is infected with at least one type of vector-borne disease pathogen.[1] Mosquitoes are the most common disease vector, and they spread pathogens by ingesting them from an infected host during a blood meal and then injecting them into a new host.[2] The Zika virus has spread rapidly across Eastern Brazil and Mexico by mosquitoes since its first identification in Africa in 1947. As of 22 June 2016, 61 countries and territories have reported continuing Zika transmission.[2] In Brazil alone, there have been an estimated 440 000 – 1 300 000 cases of Zika[3]. Propagated by the vector Aedes aegypti, or the yellow fever mosquito, the Zika virus can result in a number of symptoms, ranging from rashes and joint pain to total body paralysis.[4] When pregnant women are infected with Zika, their fetuses often display birth defects such as microcephaly, a rare neurological condition resulting in abnormal head sizes; in Paraiba, a province in Northeastern Brazil, the health ministry released statistics revealing that 114 babies per every 10,000 live births were born with suspected microcephaly – more than 1% of all newborns.[5] Since there are no solutions to the Zika virus as of now, preventative measures such as nets are used to prevent undue exposure to the disease vector. Permethrin is a synthetic form of the naturally occurring insecticide, pyrethrum, which comes from Chrysanthemums. It is an insecticide to mosquitoes, ticks and other insects.[6] Its usage is highly effective, and it was shown through a study by the Institute of Medicine Forum on Microbial Threats that when lightweight uniforms from the military are treated until moist (approximately 4.5 oz) of permethrin (concentration 0.5%), it gives them 97.7% protection from mosquito bites.[1] Using the large-scale biological simulation software “COBWEB”, the effectiveness of the insecticide “permethrin” in reducing the spread of Zika was modelled. This simulation focuses on the city of Olaria, Brazil, where the Zika virus is especially virulent. Furthermore, the study examines the growing trend of permethrin resistance in the Aedes aegypti vector, which affects the efficacy of insecticides in preventing further spread of Zika. Three different simulations were created for comparison purposes; one was the control, one had the application of permethrin, and one had permethrin with the added factor of insecticide resistance. In comparing the three simulations, the research team was able to determine the best way of dealing with the emerging disease. Methods and Materials COBWEB, which stands for Complexity and Organized Behaviour Within Environmental Bounds, is an agent-based, Java coded software, used to study interconnected and interdependent components of complex systems in numerous fields of study. COBWEB explores how components, such as mosquito and human populations, change and adapt as different variables are manipulated. It is used to create virtual laboratories and facilitate the study of how different populations of agents are influenced by various environmental changes. This permits the assessment of growth, decline, or sustainability of the populations within their environment over time. Additionally, abiotic factors such as permethrin can be included to study the effects of its introduction in the virtual laboratory. The effect of human migration on Zika transmission rate can be simulated using COBWEB by translating population and treatment circumstances into agents and environmental factors. Based on data by the World Health Organization, the Zika virus has been prevalent in Brazil. However, not all areas of Brazil have reported evidence of the Zika virus. The city of Olaria was selected as the environment because it has the highest concentration of the virus; in the 0.79 area covering the average flight range of Aedes mosquitoes, it was found that there were 3,505 and 4,828 female mosquitoes in the MosquiTrap and aspirator, respectively, totalling 8,333.[7] By applying Olaria’s population to transmission rates, the population variance upon addition of the pesticide was observed. A. Setting up COBWEB: Assumptions and/or arbitrary figures Some arbitrary numbers and assumptions were made for a few parameters in COBWEB. In the environment tab in COBWEB, three Agent types were chosen (Figure 1). Agent 1 was assigned to represent the human population of Olaria, while Agent 2 was set to represent mosquitos; Agent 3 represents the permethrin, which is a control factor in the experiment. Additionally, it was decided that the environment would be 180 x 180 in dimensions. By increasing the environment and space for the various components to interact, more reliable data is produced. All other parameters were kept in their default state. Figure 1: This is where the desired simulation is configured. This can exemplify a number of systems such as a section of a forest, ocean, city or body part that the user wants to study. The environment is represented on a 2D grid. This represents the city of Olaria. This experiment had three simulations. The first (the control) was a simulation featuring just humans and the vector. The second (Simulation 2) featured humans, the vector, and the insecticide permethrin. The last (Simulation 3) featured humans, the insecticide-resistant vector, and permethrin. For ease of explanation, this paper will first explain the Control, Simulation 2, followed by Simulation 3 (Figures 2 – 7). Several tabs on the COBWEB software were used. The “resources”, “agents”, “food web”, and “diseases” tabs were the main factors that were manipulated for the purposes of this study. The “resources” tab was used to sustain the various populations (in this case, mosquitos, humans, and permethrin) and ensure that they had the ‘resources’ to function in the experiment. The “agents” tab was used to model the various populations and their respective roles within the environment. In order to ensure accuracy, the population of Olaria and the mosquito count were determined and inputted as the agent counts. The “food web” function was used to control the interactions and interrelationships between the agents. Finally, the “disease” function was used to study the effects of Zika on the fatality rates in Olaria and the transmission of microcephaly. The contact transmission rate, child transmission rate, and use of permethrin as a “vaccine” with a specific effectiveness were used to study the effects that permethrin has on the simulation and the effects that Zika has on future populations. The tick number at the top of the screen represents the time period in which a simulation runs. This number, which was kept constant in all three models, is relative and is representative of a sample time period. The numerical time is not the most important, as the trend over a constant period of time provides the most conclusive and useful results. However, for the purposes of this simulation, the tick number was chosen to represent days, so each tick represented one day of the year. CONTROL: Vector and Humans, with no Permethrin Figure 2A: In the “Resources” tab of COBWEB, certain resource amounts were allotted to the different agents to ensure they have enough ‘food’ to function and progress through the experiment. “Agent 1” corresponds to the human population and “Agent 2” corresponds to the mosquito population. Figure 2B: In the “Agents” tab of COBWEB, the counts of the different agents, which were determined from research, were inputted to ensure reliability of the results. The other factors were determined upon experimentation and done in ratios to depict the patterns of the agents. Figure 2C: In the “Food Web” tab of COBWEB, the interconnectedness between the two agents was depicted. For instance, “Agent 2” has a checkmark for “Agent 1” because the mosquito population affects the human population. Figure 2D: In the “Disease” tab of COBWEB, the infected fraction and the child transmission rate (as of 2015) were inputted. Since the Zika virus leads to microcephaly, a birth defect, the percentage of children who have parents infected with the virus and that acquire the condition was inputted. SIMULATION 2: Vector with Permethrin Figure 3: To reiterate, the food web function was employed to depict the interactions between the agents and the three varieties of food. Agent 3 (permethrin) “consumes” mosquitoes to signify that it kills them. Food 1 represents food both mosquitoes and humans need to survive; this mostly signifies water since it is the resource that both agents need to the greatest extent to survive. Food 2 represents food just meant for mosquitoes. “Food 3” is there to simply keep permethrin levels relatively consistent throughout the simulation’s progress; it can be seen as a source of permethrin. Figure 4: The next step was setting the agent parameters. Agent 1 represents the human population of 1893 in Olaria, Brazil[8], Agent 2 is the mosquito population of 2500, or the average of the female population size[9], and Agent 3 is the control group, or in this case the insecticide. The breed energy is higher for Agent 1 to signify that ‘more energy’ is required to reproduce, concluding that birth rates of humans are lower than that of mosquitos. Figure 5 : The initially infected fraction was approximately 7%[9], the contact transmission rate was set as the default, and the child transmission rate was 15%, as not all babies exposed to the Zika virus would be infected; the average was taken of the predicted 10-20% chance of infection.[5] For agent 2, the factors were all kept constant. This was also seen for agent 3 but with exception to the effectiveness rate of 97.7%, as the pesticide gives 97.7% protection from mosquito bites. As seen in Figure 3, agent 3 ‘eats’ agent 2, so the contact transmission rate is translated in that respect. SIMULATION 3: Insecticide-Resistant Vector with Permethrin Figure 6: All the factors are identical to that of the second simulation, except in the third where the vector’s resistance to permethrin is modelled in under the “vaccine effectiveness” tab. According to various experiments that have studied insecticide resistance of Aedes aegypti vector, the vector can show resistance ranging from 90% to 95% of its interactions with permethrin.[10] The vaccine effectiveness was averaged as 93% to represent the mean and most common resistance statistic. Results To effectively compare the three simulations, the tick count (i.e. the time step in the model) was consistently kept at 800. Since this number is quite large, it ensures an observable trend; there could be significant changes in an ecosystem over short periods of time which may skew the findings and thus, the results. CONTROL: In the control simulation, it was seen that there was a rapid growth in the mosquito population and a rapid decrease in the human population. This can be attributed to the fact that without interference, there is exponential growth in the number of mosquitos, and thus an exponential growth in the interactions between mosquitoes and humans. Figure 7A : The control simulation examined the effects of the Zika virus in Olaria without permethrin. In this simulation, the tick count number was 800, which was representative of 800 days. The graph above depicts the population of humans over time, which is steadily decreasing. Figure 7B: The graph above depicts the population of mosquitoes over time, which increases and then decreases after the population reaches 7000. SIMULATION 2: The second simulation also had a tick count of 800 for consistency. In this simulation, the human population experienced an initial decrease in population, followed by a steady increase by about 4 times the initial population (Figure 5). The mosquito population rapidly declined and then levelled out at zero after around 411 days (Figure 6). Once the mosquito population hit zero, there was an observable spike in the human population, as expected. The supply of permethrin was made to be steady and constant over time to maximize its influence on the population. Figure 8 : This graph shows the increase in human population over a time span of 800 days. Figure 9. This graph shows the decrease in the Aedes aegypti population over a span of 800 days. SIMULATION 3: The third simulation, which also had a tick count of 800 days, displayed the resistance development of the Aedes species mosquito with insecticide. Because mosquitos “learn” and eventually develop resistance to certain treatments, it is important to study their effects over time and to what degree the resistance impinges on the effectiveness of permethrin. Figure 10 : The population of Aedes aegypti vector spikes before declining to zero unlike the second simulation (Figure 5), where the mosquito population declines without spiking; this is attributable to the implementation of insecticide resistance. Figure 11: The graph above depicts the trend of the human population in Olaria when the city is under the subjection of permethrin-resistant mosquitoes. The human population rises steadily, but at a slower rate than the second simulation (Figure 5). Discussion From the study, it is evidenced that Zika is best controlled with permethrin. Although the consideration and inclusion of permethrin resistance created a deviance from the results with sole permethrin application, the results were still comparatively better than the control; the human population increased and the mosquito population decreased to a greater extent when permethrin was applied. Additionally, in comparing the graphs depicting simulation 3 and the control, it can be seen that simulation 3 yields a smaller fatality rate for humans and a greater fatality rate for mosquitos. However, in consideration of insecticide resistance, the results and trends were not as significant as those without. For instance, the population of the Aedes aegypti spiked before declining to zero. This was likely due to insecticide resistance, which allowed the initial population of mosquitoes to further propagate before declining, as expected. Also, the human population in the third simulation rose steadily but at a slower rate than in the simulation without insecticide resistance. This was likely due to insecticide resistance, which could’ve made it easier for mosquitoes to infect humans and thus, slowed population growth. Although care was taken to ensure error was minimized, there are a few inevitable errors that could have affected the data from this study. Firstly, the model does not account for certain environmental factors such as differences in temperature, humidity, and elevation, all of which could influence the reproductive and survival rates of the Aedes aegypti vector. More specifically, the rise of global temperatures as a result of climate change would undoubtedly significantly affect the vector populations. As the crisis is affecting the viability of populations, it can affect the results of the survivability and reproduction of mosquitoes. Extreme weather can also drastically influence the populations of humans and mosquitoes, making the data less reliable. These factors could be included in the next iteration of this work. Besides environmental factors being neglected from the study, numerous socio-economic factors were not factored into the study. The methods assumed that women and men were equally susceptible to Zika, because biologically speaking, their chances of contracting the virus were equal. However, in many rural areas such as Olaria, the city in question, a significant number of women work in the fields and in adverse conditions, thereby increasing their chances of exposure to the vector; about 70% of rural people in Brazil engage in agricultural employment, and female-headed households, which are becoming increasingly common, make up 27% of the poor rural population. Thus, had these environmental and socio-economic elements been factored into the simulation, the simulation results could have been different. Another potential source of error was with the averaging of the effectiveness of permethrin, which created a sample rate as opposed to a range. However, the average was the most prevalent among the tests, so it was used to find the main and most prevalent occurrence in the range of possibilities. Furthermore, in the real world, a small population of mosquitoes may survive because of insecticide resistance, and pass on the disease; in this way, the number of mosquitoes who can transmit the Zika virus could grow exponentially. However, the COBWEB software isn’t able to factor that circumstance into the simulation, so the model features all mosquitoes dying out. This additional factor would have affected the mosquito populations over time, but the model does give a guideline and approximate trend for the reduction of mosquitoes. Although there may have been discrepancies with the data, COBWEB still had the ability to produce results similar to the data provided by the WHO. In the future, factors such as the impact of climate change and the migration of people who have the disease could be studied, and comparisons can be made between Permethrin and other solutions for mitigating the spread of the Zika virus. Conclusion There is potential for more studies to be performed using the current Zika models in COBWEB. The insecticide permethrin has shown promising ability to decrease the population affected by Zika in Olaria. This can be applied to all of Brazil, and extend to other countries where Zika is virulent. This research explicates permethrin as an effective barrier to the initial interaction of humans and mosquitoes. This study suggests an alternative solution to the existing options of nets and human reproduction practices. The next step is to explore how climate change can affect these agents, and how encouraging governments to mitigate the effects of the changing climate can impact the population\’s health and well-being. Another area of future study deals with the effectiveness of a Zika vaccine, as a study has shown 17 out of 18 tests on monkeys to be effective. Overall, permethrin was shown to be effective in reducing the interactions between humans and mosquitoes, and concurrently reducing the cases of Zika. This research can be applied to other countries, such as Ecuador, where the Zika virus is also very virulent. Acknowledgements : A great thank you to Dr. Brad Bass, a status professor at the University of Toronto and Nobel Peace Prize Co-recipient, for developing the COBWEB software and for mentoring the team along the way. References : Threats, Institute. 2008. \”Summary And Assessment\”. Ncbi.Nlm.Nih.Gov . https://www.ncbi.nlm.nih.gov/books/NBK52939/ . \”Zika Situation Report\”. 2016. World Health Organization. http://www.who.int/emergencies/zika-virus/situation-report/23-june-2016/en/ . Bogoch, Isaac, Oliver Brady, Moritz Kraemer, Matthew German, Marisa Creatore, and Manisha Kulkarni. 2016. \”Anticipating The International Spread Of Zika Virus From Brazil\”. Europe PMC. http://europepmc.org/articles/pmc4873159 . \”What We Know About Zika\”. 2018. CDC. https://www.cdc.gov/zika/about/ . \”More Brazilian Babies Born With Defects\”. 2018. BBC News. http://www.bbc.co.uk/news/world-latin-america-35368401 . Bloomington, Indiana, Indiana Bloomington, IU Bloomington, and Indiana University. 2018. \”Insect Precautions – Permethrin, Deet, And Picaridin: IU Health Center\”. Healthcenter.Indiana.Edu . http://healthcenter.indiana.edu/answers/insect-precautions.shtml . Massad, Eduardo, Marcos Amaku, Francisco Countinho, Claudio Struchiner, Luis Lopez, Annelies Wilder-Smith, and Marcelo Burattini. 2018. Estimating The Size Of Aedes Aegypti Populations From Dengue Incidence Data: Implications For The Risk Of Yellow Fever Outbreaks. Ebook. Accessed November 18. https://arxiv.org/pdf/1709.01852.pdf . \”Olaria (Municipality, Brazil) – Population Statistics, Charts, Map And Location\”. 2018. Citypopulation.De . https://www.citypopulation.de/php/brazil-regiaosudeste-admin.php?adm2id=3145406 . Maciel-de-Freitas, Rafael, Alvaro Eiras, and Ricardo Lourenco-de-Oliveira. 2008. \”Calculating The Survival Rate And Estimated Population Density Of Gravid Aedes Aegypti (Diptera, Culicidae) In Rio De Janeiro, Brazil\”. http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-311X2008001200003 . Rodriguez, Maria, Juan Bisset, and Ditter Fernandez. 2007. \”Home\”. Bioone.Org . http://www.bioone.org/doi/abs/10.2987/5588.1 . About the Authors Huaxuan Chen is a student who is extremely passionate about global health, law, chemistry, and development. She is also an SDGs advocate who was a Canadian Youth Representative at the Commission on the Status of Women Youth Forum and PGA High Level Event on Education; she focuses mainly on climate action, gender equality, and education. She enjoys using her knowledge and skills to help others. She is now studying statistics at Duke University. Adithya Chakravarthy is currently a third-year student at the University of Toronto in the Engineering Science Program. He is very passionate about computer modeling of complex systems. Apart from science, he is also deeply involved in debating, representing Canada on the Canadian National Debate Team at the 2018 World Schools Debating Championships in Zagreb, Croatia. He is also a vocalist in the Indian Classical music tradition, having performed in many concerts across North America and India. Rachel Woo is starting her Masters in Public Health at Waterloo in Fall 2020. Her research interests include data visualization, and games for health.

Author: Kai Sun Yiu Abstract The summer of 1996 sparked the beginnings of limitless, scientific potential. Dolly the sheep was born from her surrogate mother, after being cloned by Sir Ian Wilmut and his team from a six-year-old Finn Dorset sheep [1]. Dolly was formed through genetic material, extracted from a Finn Dorset Sheep, being placed into an enucleated egg cell [2]. An embryo was formed following a series of meiotic divisions, and 148 days (about 5 months) after being implanted into the surrogate mother’s uterus, Dolly was born [3]. However, Dolly wasn’t the first mammal to be cloned, with that title being held by two other sheep, Megan and Morag, who had been cloned a year earlier from embryonic and fetal cells [2]. However, this didn’t undermine her significance, through being the first mammal cloned from an adult cell, rather than an embryonic cell. Dolly’s existence disproved past assumptions that specialized cells could only do a certain job, with Dolly being born from a specialized mammary cell which somehow held the genetic information to create an entirely new sheep [4]. This sparked new potential for medicine and biology through the development and research of personalized stem cells, which will be explored within this article through the differences between embryonic stem cells and adult stem cells.  Introduction Human cloning can be defined as the creation of a ‘genetically identical copy of a previously existing human,’ or the reproduction of cloned cells / tissue from that individual [5]. Through human cloning, we can gain stem cells from the cloned blastocyst and treat these cells to differentiate into any cells we need for medical purposes. However, this understandably has ethical complications which have made it difficult for scientists to carry out lots of stem cell research.  This article focuses on the more complex ethical standpoints around stem cell research through some forms of therapeutic cloning, using SCNT (Somatic cell nuclear transfer) and iPSCs (Induced pluripotent stem cells). While SCNT uses embryonic stem cells, iPSCs utilizes the adult stem cells we possess in our bodies to repair damaged cells and tissues. However, both types of cells contain major ethical complications through their uses, allowing this article to tackle the conflict between stem cells' infinite possibilities against their downsides and ethical considerations.  An insight into modern stem cell research - SCNT and iPSCs Somatic cell nuclear transfer (SCNT) refers to the process used by both reproductive and therapeutic cloning to produce a cloned embryo. SCNT was first used by Sir Ian Wilmut and his team when cloning Dolly, the sheep: The nucleus which contains the organism’s genetic material (DNA) of a somatic cell is removed The nucleus from the somatic cell is then inserted into the cytoplasm of an enucleated egg cell The egg which contains the nucleus stimulated with electric shocks to encourage mitotic division After many mitotic divisions, the cell forms a blastocyst, which divides further until it eventually forms an embryo [6] SCNT is utilized by scientists and researchers worldwide in an attempt to obtain stem cells from the cloned embryo, and use it through regenerative medical practices [6]. A common use of stem cells in regenerative medicine would include the treatment of Parkinson’s disease, where stem cells can restore the production of dopamine in the brain. The in-depth process includes gaining undifferentiated stem cells from the embryo and treating them to differentiate intro dopamine producing nerve cells to treat Parkinsons [7].  With the use of SCNT, autologous cells can be formed. Autologous cells are formed from the stem cells of the same individual, meaning the therapeutic material is cloned from the patient, allowing there to be no need for immunosuppressive treatments when differentiated cells are injected into the body [7]. This is due to the autologous cells not being foreign cells, therefore resulting in no probability of the immune system rejecting and damaging the newly introduced stem cells into their body. With stem cell’s ability to ‘treat many human afflictions, including ageing, cancer, diabetes, blindness and neurodegeneration,’ why is there such a lack of breakthrough research on stem cell therapy [8]? Induced pluripotent stem cells (iPSCs) refer to cells that have been derived and reprogrammed from adult somatic cells (normally taken from a patient bone marrow) [9]. These cells have been altered through the introduction of genes and other factors into the cells to make them pluripotent; this arguably makes them like embryonic stem cells, so they similarly carry the same ethical problems [9].  iPSCs are not only seen as unethical, but also take 3-4 weeks of careful lab work to form [10]. The process is extremely slow and inefficient and has a success rate lower than 0.1% [10]. Nonetheless, there are limitless applications for iPSCs such as regenerative medicine, disease modeling and gene therapy.  Similarly to SCNT, the main advantage of iPSCs is the ability to eliminate any possibility of immune system rejection. The iPS cells are directly generated from the somatic cell of the person’s own body, so there can’t be an immune response to them, as the cells are genetically tailored precisely for the patient they are taken from [12]. The main problem of iPSC is the risk of mutation during the reprogramming of the somatic cells, which can lead to the formation of a cancerous tumor [11]. However, we still need to explore the ethical standpoints in the formation of pluripotent stem cells for research and regenerative science.  The ethics - SCNT Through the process of SCNT, we can gain embryonic stem cells from a three-day old embryo. The extraction of the stem cells destroys the blastocyst, a 3-5 day old embryo which can be observed as a cluster of around 180 cells growing within a petri dish, before it fully forms into a fetus [13]. The blastocyst is used as it is at such an early stage of the formation of the fetus, so the cells have not yet differentiated so is arguably ‘not alive’ [13].  The ethical argument against the extraction of stem cells is the fact that the destruction of an embryo is arguably killing a fully developed human being. We can look at the position of Senator Sam Brownback, who saw ‘a human embryo...as a human being just like you and me. [13]’ The ethical standpoint around the destruction of embryos is so varied, with George Bush using his veto when US Congress passed a controversial bill, which permitted more funding towards research that used embryonic stem cells [14]. All these ethical considerations surrounding the formation of stem cells are difficult to forget, yet we still need to remember the immense medical and research potential they carry.  Embryonic Stem Cell Research around the Globe - SCNT  Map Explanation [15] Dark Brown = ‘permissive’ - Allows various embryonic stem cell research techniques such as SNCT. Light Brown = ‘flexible’ - Lots of restrictions, with embryos only being used under extreme conditions. SCNT is completely banned with human reproductive cloning not allowed.  Yellow = no policy or restricted policy - Outright prohibition of embryonic stem cell research Black Dots - Leading genome sequencing research centers in the world  The map above illustrates the flexibility around the globe when it comes to the use of embryos during stem cell research. Even in the very few countries which have leading facilities and institutions, there are massive restrictions on the usage of embryos. Even looking at Britain, who managed to vote on the easing of restrictions on the use of embryonic stem cells in 2001, we still have only 7 laboratories across the country [16], [17].  The various ethical considerations around the destruction of an embryo makes stem cell research difficult to legalize and even fund. However, the use of stem cells can be arguably seen as the most promising research done for regenerative medicine in the last century. Imagine the ability to cure diseases through replacing cells damaged by infection or being able to grow organs from stem cells to transplant into the thousands of patients waiting for an organ donor.  What if there was a way to form somatic stem cells without the destruction of an embryo? The ethics - iPSCs  Pluripotent stem cells have the ability to form all three of the basic layers in our body (ectoderm/endoderm/mesoderm), which allows them to potentially produce any cell or tissue needed [18]. There are four types of pluripotent human stem cells [19]: Embryonic stem cells Nuclear Transplant stem cells Parthenote stem cells Induced stem cells All pluripotent human stem cells, apart from Induced stem cells, require human eggs to create. This means that the use of pluripotent human stem cells is limited by ethical considerations; however, induced pluripotent stem cells are different in the way they don’t require the destruction and harm of an embryo.  These iPSC were discovered over ten years ago by Shinya Yamanaka. The Nobel Prize winner managed to revolutionize biological research by developing a technique to convert adult mature cells into stem cells using the four key genes OCT3/4, SOX2, KLF4, MYC, which are now known as the ‘Yamanaka factors [20].’ iPSCs as a research area has been greatly explored by thousands of researchers around the world, due to the production of the cells being non-controversial in their ability to be derived straight from adult cells rather than embryonic cells. There have been numerous applications of iPSCs in therapeutic medicine. In 2014, RIKEN (The largest scientific research institution in Japan), treated the first patient with iPSC derived retinal sheets, which were able to help with visual function [21]. 2 years later, Cynata Therapeutics (A biotech company), produced iPSC derived product for the treatment of GvHD (Graft versus host disease) [21]. GvHD is a life-threatening disease which can occur when there are complications during stem cell and bone marrow transplants [21]. When the grafted cells are transplanted into the patient, they begin to produce antibodies which interact with the host antigens. This triggers an immune response which may result in an inflammatory cascade, which can cause irreversible organ dysfunction and even death [22].  The unlimited medical possibilities iPSCs unlock, paired with the lack of ethical problems they face, makes IPSCs the perfect way to bring stem cell therapy to the masses.  However, it is not so simple, with the main issue of iPSCs is the need for retrovirus to form these stem cells [23]. The retroviruses used in forming the iPSCs can insert their DNA anywhere in the human genome and trigger cancerous gene expression when transplanted into the patient [23]. Furthermore, the success rate of reprogramming somatic cells into iPSCs is around 0.1%. Not only this, but iPSCs have a strange tendency to not always differentiate, making them much less reliable and successful than embryonic stem cells [23].  Nonetheless, research into iPSCs has developed rapidly over the past few years, with scientists and researchers slowly making stem cell therapy using iPSCs available to the public.  The Pros and Cons of Embryonic Stem Cells and Induced Pluripotent Stem Cells  Embryonic Stem Cells Induced Pluripotent Stem Cells   Pros Can maintain and grow for 1 year or more in culture Established protocols for maintenance in culture ESCs are pluripotent cells that can generate most cell types By studying ESCs, more can be learned about the process of development Abundant somatic cells of donor can be used Issues of histocompatibility with donor/recipient transplants can be avoided Very useful for drug development and developmental studies Information learned from the “reprogramming” process may be transferable for in vivo therapies to reprogram damaged or diseased cells/tissues  Cons Process to generate ESC lines is inefficient Unsure whether they would be rejected if used in transplants. Therapies using ESC avenues are largely new and much more research and testing is needed If used directly from the ESC undifferentiated culture prep for tissue transplants, they can cause tumors (teratomas) or cancer development  Methods for ensuring reproducibility and maintenance, as differentiated tissues are not certain. Viruses are currently used to introduce embryonic genes and has been shown to cause cancers in mouse studies  Ethical Concerns To acquire the inner cell, mass the embryo is destroyed Risk to female donors being consented iPS cells have the potential to become embryos if exposed to the right conditions A comparative table between Embryonic Stem cells and Induced Pluripotent Stem Cells [26] Stem Cell Therapy Today  Although no one has been cured of Parkinson's disease (PD) yet, the research from institutions around the world have shown significant development in recent years with ‘experimental treatment.’ On the 13th of February 2023, embryonic stem cells (most likely obtained through SCNT) derived healthy, dopamine producing nerve cells, which were transplanted into a patient with Parkinson’s at Skåne University Hospital, Sweden [24]. This marks an important milestone for all stem cell research, with the transplantation of the nerve cells being performed perfectly, shown by magnetic resonance imaging (MRI) [24].  The STEM - PD trial at Lund University (The first in-human trial to test the safety of stem cells for Parkinsons) is continuing to replace lost dopamine cells with healthy ones, manufactured from embryonic stem cells [24]. Parkinson's disease slowly affects the nervous system, due to the loss of nerve cells in the substantia nigra in the brain. Nerve cells are crucial for the production of dopamine, so the implantation of nerve cells helps regulate brain activity and function by secreting regular levels of dopamine. STEM - PD aims to move from their first human trial all the way to global treatment around the world [24]. This latest success in the use of embryonic stem cells further pushes researchers around the world, with stem cells soon to unlock cures for multiple diseases, in addition to aiding with the worldwide shortage of organs.  In Early 2023, researchers were able to differentiate neurons from induced pluripotent stem cells (iPSCs) [25]. The usage of iPSCs made it an arduous task, with the team needing to firstly differentiate the iPSCs into motor neurons, before placing them into coatings of synthetic nanofibers containing rapidly moving dancing molecules [25]. These mature neurons help aid the body’s nervous system, through sending rapid electrical signals around our body through tiny structures known as nerves. Within the near future, researchers believe that these mature neurons can be transplanted into those suffering with spinal cord injuries as well as neurodegenerative diseases (ALS, Parkinsons, Alzheimer's, Sclerosis) [25]. This new advancement in the usage of iPSCs allows scientists to research ethically sound ways of using stem cells for the treatment of all diseases. Conclusion Use of stem cells in repairing damaged cells/tissues, research into understanding diseases and testing for new drugs gives them incredible value in research and regenerative medicine. As the research for regenerative medicine improves, the success rate in the use of stem cells will gradually grow, which will hopefully loosen the tight legal grasp over the use of ESC (embryonic stem cells) and iPSCs due to their ethical problems (As seen in the table above), in either destroying and embryo or theoretically being from an embryo in iPSCs as they can be derived into an embryo.  Researcher and scientists should strive to refine existing stem cell formation techniques, and through the difficult legal ties, battle their way to the final aim of having stem cells with the ability to differentiate into any cell needed to cure any disease, form any organs to be used in transplants, and research into greater depth the difficulty in battling certain diseases.  References [1] Weintraub, Karen. “20 Years after Dolly the Sheep Led the Way-Where Is Cloning Now?” Scientific American, July 1, 2016.  https://www.scientificamerican.com/article/20-years-after-dolly-the-sheep-led-the-way-where-is-cloning-now/ [2] “The Life of Dolly.” Dolly the Sheep. Accessed November 26, 2023. https://www.ed.ac.uk/roslin/about/dolly/facts/life-of-dolly [3] “Dolly and Polly.” Encyclopedia Britannica. Accessed November 26, 2023. https://www.britannica.com/biography/Ian-Wilmut/Dolly-and-Polly [4] Natural World 5 min read. “Dolly the Sheep.” National Museums Scotland. Accessed November 26, 2023.  https://www.nms.ac.uk/explore-our-collections/stories/natural-sciences/dolly-the-sheep/ [5] “Human Cloning.” ScienceDaily. Accessed November 26, 2023. https://www.sciencedaily.com/terms/human_cloning.htm [6] “Somatic Cell Nuclear Transfer.” Somatic_cell_nuclear_transfer. Accessed November 26, 2023. https://www.bionity.com/en/encyclopedia/Somatic_cell_nuclear_transfer.html [7] “Therapeutic Cloning.” Therapeutic Cloning - an overview | ScienceDirect Topics. Accessed November 26, 2023.  https://www.sciencedirect.com/topics/engineering/therapeutic-cloning [8] Watt, Fiona M, and Ryan R Driskell. “The Therapeutic Potential of Stem Cells.” Philosophical transactions of the Royal Society of London. Series B, Biological sciences, January 12, 2010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2842697/#:~:text=Almost%20every%20day%20there%20are,%2C%20diabetes%2C%20blindness%20and%20neurodegeneration [9] Ye, Lei, Cory Swingen, and Jianyi Zhang. “Induced Pluripotent Stem Cells and Their Potential for Basic and Clinical Sciences.” Current cardiology reviews, February 1, 2013.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584308/ [10] Ghaedi, Mahboobe, and Laura E Niklason. “Human Pluripotent Stem Cells (Ipsc) Generation, Culture, and Differentiation to Lung Progenitor Cells.” Methods in molecular biology (Clifton, N.J.), 2019.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976544/#:~:text=To%20generate%20the%20iPSCs%2C%20each,low%20as%00.01–0.1%20%25 [11] “Why IPSC Research Is so Important (and so Tough).” Tecan. Accessed November 27, 2023. https://www.tecan.com/blog/why-ipsc-research-is-soimportant#:~:text=For%20example%2C%20iPSC%20are%20used,specific%20cell%20types%20and%20tissues [12] Lowden, Olivia. Advantages and disadvantages of induced pluripotent stem cells, November 10, 2023.  https://blog.bccresearch.com/advantages-and-disadvantages-of-induced-pluripotent-stem-cells [13] “Examining the Ethics of Embryonic Stem Cell Research.” Harvard Stem Cell Institute (HSCI). Accessed November 28, 2023.  https://hsci.harvard.edu/examining-ethics-embryonic-stem-cell-research [14] Lenzer, Jeanne. “Bush Says He Will Veto Stem Cell Funding, despite Vote in Favour in Congress.” BMJ (Clinical research ed.), June 16, 2007.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1892464/ [15] Stem cell policy: World stem cell map. (Image: William Hoffman, MBBNet) Accessed November 29, 2023.   https://www.mbbnet.umn.edu/scmap.html [16] Lachmann, P. “Stem Cell Research--Why Is It Regarded as a Threat? An Investigation of the Economic and Ethical Arguments Made against Research with Human Embryonic Stem Cells.” EMBO reports, March 2001.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1083849/ [17] Stem cell processing, Cellular and Molecular Therapies - NHS Blood and Transplant. Accessed November 29, 2023. https://www.nhsbt.nhs.uk/cellular-and-molecular-therapies/products-and-services/stem-cell-processing/ [18] Stem Cell Program, Pluripotent Stem Cell Research. Accessed November 29, 2023. https://www.childrenshospital.org/research/programs/stem-cell-program-research/stem-cell-research/pluripotent-stem-cell-research#:~:text=What%20makes%20pluripotent%20stem%20cells,body%20needs%20to%20repair%20itself [19] Beford Research Foundation. ‘What are Induced Pluripotent Stem Cells? (iPS Cells)’ Apr 23, 2011 https://www.youtube.com/watch?v=i-QSurQWZo0 [20] Dana G. ‘Reflecting on the Discovery of the Decade: Induced Pluripotent Stem Cells.’ Accessed November 29, 2023. https://gladstone.org/news/reflecting-discovery-decade-induced-pluripotent-stem-cells ‌[21] Cade Hildreth. Induced Pluripotent Stem Cell (iPS Cell) Applications in 2023. Accessed December 3, 2023. https://bioinformant.com/ips-cell-applications/ [22] Clopton, David. n.d. “Graft versus Host Disease | Radiology Reference Article | Radiopaedia.org .” Radiopaedia.  https://radiopaedia.org/articles/graft-versus-host-disease?lang=gb [23] Dr. Surat, and Dr. Tomislav Mestrovic. Induced Pluripotent Stem (iPS) Cells: Discovery, Advantages and CRISPR Cas9 Gene Editing. 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Author : Steffi Kim Brain imaging techniques allow neurologists and researchers alike to measure brain activity, diagnose medical and psychiatric conditions, and gain insight into the brain’s interconnected webs and complex structures. While psychologists once had to rely entirely on observable behavior and could only guess at the workings of the brain, new technologies can reveal the brain’s structure and function in astonishing detail. Each brain scanning technology has specific purposes and limitations. As such, researchers may choose a specific technique or combination of techniques depending on the circumstances and what is being measured. EEG (Electroencephalogram) The EEG was first developed in 1924 by Hans Berger, a German psychiatrist, making it one of the oldest brain imaging technologies. EEG measures the frequency and location of brain waves through a series of small electrodes placed across the scalp. Every time neurons in the brain fire, an electrical field is produced. By measuring electrical activity, the electrodes can effectively assess neuronal firing. The electrodes are commonly attached to a cap and are wired to a monitor that graphs the frequency of brain waves. Different brain waves—gamma, beta, alpha, theta, and delta—signal varying levels of brain alertness and functioning. Abnormal brain wave patterns could be the result of a neurological condition, and EEG is commonly used to test for epilepsy and sleep disorders. fMRI (Functional Magnetic Resonance Imaging) fMRI involves tracking the movement of blood and oxygen through the brain to analyze functioning and structure. Highly active brain regions require more oxygen, and greater blood flow in an area is associated with increased brain activity. To perform an fMRI scan, patients are placed into the tunnel of an MRI scanner, which utilizes strong magnetic fields and radio waves. The magnetic field of the scanner alters the positioning of hydrogen protons in the water of the blood, causing the hydrogen atoms to rotate and release energy. The scanner measures the magnetic signals produced by hydrogen to develop detailed images of the brain. fMRI is widely used in studies, where participants may perform tasks while in the MRI scanner to allow researchers to observe which brain regions are involved. PET (Positron Emission Tomography) PET scans track blood flow in the brain via a radioactive tracer substance. The radioactive substance, which is either injected, swallowed, or inhaled, binds to glucose in the blood. The blood then travels up to the brain and through various regions, emitting gamma waves from positrons in the radioactive tracer interacting with electrons. Neurons utilize glucose as their main energy source, and areas with more glucose indicate higher brain activity. The radioactive substance appears on images in bright, multicolored patches, where red symbolizes the highest level of glucose metabolism and activity, while purple and black represent low levels of function. PET scans, which reveal how well the brain is working on a cellular level, are often used to measure Alzheimer's and seizures, as well as medical conditions. CT (Computerized Tomography) CT scans splice together multiple X-rays to create cross-sectional images or 3D models of the brain. CT scans reveal more information about the brain tissues and skull than typical X-rays and are ideal for assessing fractures, brain injuries, and damage after strokes. References: Bosquez, Taryn. “Neuroimaging: Three Important Brain Imaging Techniques.” ScIU, February 5, 2022. https://blogs.iu.edu/sciu/2022/02/05/three-brain-imaging-techniques/. “Brain Imaging: What Are the Different Types?” BrainLine, April 22, 2011. https://www.brainline.org/slideshow/brain-imaging-what-are-different-types. Genetic Science Learning Center. "Brain Imaging Technologies." Learn.Genetics. June 30, 2015. https://learn.genetics.utah.edu/content/neuroscience/brainimaging/. Lovering, Nancy. “Types of Brain Imaging Techniques.” Psych Central, October 22, 2021. https://psychcentral.com/lib/types-of-brain-imaging-techniques. “Scanning the Brain.” American Psychological Association, August 1, 2014. https://www.apa.org/topics/neuropsychology/brain-form-function.