AI has long been a controversial topic, with some people fearing its potential consequences. This has been exacerbated by popular culture, with movies such as "The Terminator" and "2001: A Space Odyssey" depicting AI systems becoming self-aware and turning against humans. Go back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The evolution of AI: understanding the role of NLP technologies Last updated: 11/04/26 Published: 08/05/23 Artificial intelligence (AI) has long been a controversial topic, with some people fearing its potential consequences. This has been exacerbated by popular culture, with movies such as The Terminator and 2001: A Space Odyssey depicting AI systems becoming self-aware and turning against humans. Similarly, The Matrix portrayed a dystopian future where AI systems had enslaved humanity. Fast forward to the present day- AI has become a normal part of our everyday life, whether we realise it or not. From virtual assistants like Siri and Alexa to personalised movie and product recommendations, AI-powered technologies have revolutionised the way we interact with technology. AI also plays a critical role in industries such as healthcare, finance, and transportation, with algorithms helping to analyse data, identify patterns, and make predictions that lead to better decision-making. As with any industry, the AI industry is very much prone to evolution. In fact, this is especially relevant for the AI industry, given that it engages user habits to learn and redefine its understanding. This has led to the introduction of unforeseen technologies. One of the most studied and developed AI modelling techniques, Natural Language Processing (NLP), has been particularly placed under focus recently with the emergence of technologies such as Open AI’s ChatGPT, Google’s Gemini (formerly Bard) AI and Microsoft’s Bing AI- known as Copilot. ChatGPT in particular, was one of the first technologies of this kind to garner significant fame. Within its first year of release, the GPT-3 model had more than 10,000 registered developers and over 300 applications built on its application programming interface (API). In addition, Microsoft acquired OpenAI's exclusive license to the GPT-3 technology in 2020, further solidifying its position as a leading language model in the industry. ChatGPT works as an advanced artificial intelligence technology designed to understand and process human language. Built on the GPT-3.5 architecture, it uses NLP to comprehend and generate responses that simulate human conversation. ChatGPT is classified as a large language model, which means it has been trained on vast amounts of data and can generate high-quality text that is both coherent and relevant to the input provided. While concerns have been raised about the potential impact of NLP technologies, there are several reasons why we should not fear their emergence. Firstly, NLP has already enabled a wide range of useful applications that have the potential to improve efficiency, convenience, and accessibility. Furthermore, the development and deployment of NLP technologies is subject to ethical considerations and regulations that aim to ensure their responsible use. NLP technologies are not designed to replace humans, but rather to complement and enhance human capabilities. While some jobs may be impacted by automation, new jobs are likely to emerge that require human skills that are not easily replicated by machines. Ultimately, the impact of NLP technologies depends on how they are developed and used. There are always likely to be risks, but by taking a proactive approach to their development and deployment, we can ensure that they are used to benefit society and advance human progress. Written by Jaspreet Mann Related articles: AI: the good, the bad, and the future / Latent space transformations / Markov chains REFERENCES Hirschberg, Julia, and Christopher D. Manning. “Advances in Natural Language Processing.” Science, vol. 349, no. 6245, July 2015, pp. 261–66. DOI.org (Crossref), https://doi.org/10.1126/science.aaa8685. What Is Natural Language Processing? | IBM. https://www.ibm.com/topics/natural-language-processing. Accessed 1 May 2023. Biswas, Som S. “Role of Chat GPT in Public Health.” Annals of Biomedical Engineering, vol. 51, no. 5, May 2023, pp. 868–69. Springer Link, https://doi.org/10.1007/s10439-023-03172-7. Davenport, T.H. (2018). The AI Advantage: How to Put the Artificial Intelligence Revolution to Work. MIT Press. Bird, S., Klein, E., & Loper, E. (2009). Natural Language Processing with Python. O'Reilly Media.

Key facts Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Apocrine carcinoma: a rare form of breast cancer 22/04/25, 15:13 Last updated: Published: 05/09/24, 11:20 Key facts This is article no. 7 in a series on Rare Diseases. Next article: Pseudo-Angelman Syndrome . Previous article: Neuromyelitis optica . Apocrine carcinoma (AC) is a rare form of breast cancer, accounting for approximately 1-4% of all breast cancer cases worldwide. It affects a wide range of patients from 19 to 92 years of age, with the reported mean age varying from 53 to 62 years. AC of the skin - primary cutaneous apocrine carcinoma - is the only other known cancer that arises from apocrine cells. This is a very rare cancer with limited research. AC is commonly classified into two subtypes: triple-negative AC (TNAC) and HER2+ AC. Another receptor not included in the ‘triple negative’ name is the androgen receptor (AR). A ‘pure’ apocrine carcinoma is ER-negative, PR-negative, but AR-positive. Among triple negative ACs, ones that are AR-positive have a better prognosis. AC is often associated with triple-negative breast cancers (TNBC), meaning that it does not express oestrogen receptors (ER) and progesterone receptors (PR), and produces very little to no HER2– all of which play key roles in the reproductive system. AC arises from apocrine metaplastic cells that are commonly located in the lobules of the breast. This disease can be aggressive and can metastasise to the lymph nodes and distant organs (eg. lungs, liver, and bone). What makes AC different is the appearance of cells which have abundant granular eosinophilic or cytoplasm with fine empty vacuoles. Despite its rarity, focal apocrine differentiation is relatively common (reported in approximately 60% of not otherwise specified [NOS] invasive ductal carcinoma) and shows clinical presentation and radiographic findings similar to that of invasive ductal carcinoma NOS. TNBCs are generally aggressive and present a poor prognosis. However, studies show apocrine breast cancer to have a better prognosis and low proliferative nature, despite its poor response to neoadjuvant chemotherapy. Treatment of AC may include surgery, radiation therapy, chemotherapy, hormone therapy, or targeted therapy. The problem with TNACs is that therapies targeting the hormone receptors are ineffective. Conversely, targeted therapy is seen to work relatively well with HER2-positive ACs despite them being more aggressive than TNACs. ACs can be diagnosed through a series of tests—usually a mammogram, ultrasound, biopsy, and finally immunohistochemistry. The latter makes it possible to know the status of the ERs and PRs. As with most breast cancers the earlier the detection and treatment implementation, the better the prognosis for the patient. ACs can be hard to diagnose due to its rarity and non-specific presentation. AC has a low proliferative nature, which is shown in its low Ki-67 index. Ki-67 has a higher presentation in cells that have a high division rate. Slower division rates result in slower growth rates of the tumour, and may imply that there is a better prognosis. This could be one of the reasons why apocrine triple-negative breast cancers have a better prognosis than other types of TNBCs. There is promise in the future for AC, however this is not without its challenges. Due to its rarity there are limited patients to participate in clinical trials which are essential in new treatment development. Written by Henrietta Owen & Sherine A Latheef Related article: Epitheliod hemangioendothelioma REFERENCES Apple, S.K., Bassett, L.W. and Poon, C.M. (2011) ‘Invasive ductal carcinomas’, Breast Imaging, pp. 423–482. doi:10.1016/b978-1-4160-5199-2.00022-9. Bcrf (2024) Types of breast cancer: BCRF, Breast Cancer Research Foundation. Available at: https://www.bcrf.org/blog/types-of-breast-cancer/ (Accessed: 05 June 2024). Hu, T. et al. (2022) ‘Triple-negative apocrine breast carcinoma has better prognosis despite poor response to neoadjuvant chemotherapy’, Journal of Clinical Medicine, 11(6), p. 1607. doi:10.3390/jcm11061607. Suzuki, C., Yamada, A., Kawashima, K., Sasamoto, M., Fujiwara, Y., Adachi, S., Oshi, M., Wada, T., Yamamoto, S., Shimada, K., Ota, I., Narui, K., Sugae, S., Shimizu, D., Tanabe, M., Chishima, T., Ichikawa, Y., Ishikawa, T., & Endo, I. (2023). Clinicopathological Characteristics and Prognosis of Triple-Negative Apocrine Carcinoma: A Case-Control Study. World Journal of Oncology, 14(6), 551-557. Vranic, S., Feldman, R. and Gatalica, Z. (2017) ‘Apocrine carcinoma of the breast: A brief update on the molecular features and targetable biomarkers’, Bosnian Journal of Basic Medical Sciences, 17(1), pp. 9–11. doi:10.17305/bjbms.2016.1811 Xiao, X., Jin, S., Zhangyang, G., Xiao, S., Na, F. and Yue, J. (2022). Tumor-infiltrating lymphocytes status, programmed death-ligand 1 expression, and clinicopathological features of 41 cases of pure apocrine carcinoma of the breast: a retrospective study based on clinical pathological analysis and different immune statuses. Gland Surgery, 11(6), pp.1037–1046. doi:https://doi.org/10.21037/gs-22-248. Project Gallery

Lyra is a prominent constellation, largely due to Vega which forms one of its corners, and is one of the brightest stars in the sky. Interestingly, Vega is defined as the zero point of the magnitude scale - a logarithmic system used to measure the brightness of celestial objects. Technically, the brightness of all stars and galaxies are measured relative to Vega! Go back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Lyrids meteor shower Last updated: 01/03/26 Published: 10/06/23 The Lyrids bring an end to the meteor shower drought that exists during the first few months of the year. On April 22nd, the shower is predicted to reach its peak, offering skygazers an opportunity to witness up to 20 bright, fast-moving meteors per hour which leave long, fiery trails across the sky, without any specialist equipment. The name Lyrids comes from the constellation Lyra - the lyre, or harp - which is the radiant point of this shower, i.e. the position on the sky from which the paths of the meteors appear to originate. In the Northern Hemisphere Lyra rises above the horizon in the northeast and reaches the zenith (directly overhead) shortly before dawn, making this the optimal time to observe the shower. Lyra is a prominent constellation, largely due to Vega which forms one of its corners, and is one of the brightest stars in the sky. Interestingly, Vega is defined as the zero point of the magnitude scale - a logarithmic system used to measure the brightness of celestial objects. Technically, the brightness of all stars and galaxies are measured relative to Vega! Have you ever wondered why meteor showers occur exactly one year apart and why they always radiate from the same defined point in the sky? The answer lies in the Earth's orbit around the Sun, which takes 365 days. During this time, Earth may encounter streams of debris left by a comet, composed of gas and dust particles that are released when an icy comet approaches the Sun and vaporizes. As the debris particles enter Earth’s atmosphere, they burn up due to friction, creating a streak of light known as a meteor. Meteorites are fragments that make it through the atmosphere to the ground. The reason that the Lyrids meteor shower peaks in mid-late April each year is that the Earth encounters the same debris stream at the point on its orbit corresponding to mid-late April. Comets and their debris trails have very eccentric, but predictable orbits, and the Earth passes through the trail of Comet Thatcher in mid-late April every year. Additionally, Earth’s orbit intersects the trail at approximately the same angle every year, and from the perspective of an observer on Earth, the constellation Lyra most accurately matches up with the radiant point of the meteors when they are mapped onto the canvas of background stars in the night sky. The Lyrids meteor shower peaks in mid-late April each year. Image/ EarthSky.org This year, there is a fortunate alignment of celestial events. New Moon occurs on April 20th, meaning that by the time the Lyrids reach their maximum intensity, the Moon is only 6% illuminated, resulting in darker skies and an increased chance to see this dazzling display. Written by Joseph Brennan Related article: L onar Lake

A basic outline Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link An introduction to stem cells and their transformative potential 09/07/25, 11:48 Last updated: Published: 06/09/24, 12:28 A basic outline This is Article 1 in a three-part series on stem cells. Next article: The role of mesenchymal stem cells . Welcome to the first article in a series of three articles about stem cells, where I will introduce stem cells and how they differentiate. Stem cells are a remarkable type of cells that can become other types. They are divided into two main categories: adult stem cells (ASCs) and pluripotent stem cells. ASCs can differentiate into cells of specific tissues and organs. Pluripotent stem cells can differentiate into all cells in the human body and can further be split into embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). ASCs are also known as non-embryonic or somatic stem cells, referring to cells that come from non-reproductive cells, not egg or sperm cells. Some examples of ASCs include mesenchymal cells, epithelial cells and skin cells. These cells are mainly used to replace and repair dead or damaged tissues and organs damaged by disease, injury or ageing. They may stay non-dividing (quiescent) but promptly differentiate in different cell types when needed. ESCs do not come from fertilised eggs but rather from the inner cell mass of a blastocyst. A blastocyst is a group of dividing cells originating from a fertilised egg 3-5 days after fertilisation. After scientists have received informed consent, the cells are fertilised in vitro, outside a living organism, such as in a laboratory. iPSCs are created in a laboratory by mixing ASCs and ESCs. Scientists generate them by transcription-factor transduction, a type of nuclear reprogramming. Nuclear reprogramming and stem cell differentiation Nuclear reprogramming is when the nucleus of a cell is introduced into the cytoplasm of a new cell. The transfer results in changes in gene expression. In 2010, scientists Shinya Yamanaka and Helen M. Blau published a review of three alternative approaches in nuclear reprogramming to restore a cell's pluripotent state: nuclear transfer, cell fusion and transcription-factor transduction. Nuclear transfer involves moving the nucleus from a specialised cell into an egg cell with no nucleus. This can be done with oocytes or fertilised eggs during specific cell cycle phases. The reprogramming factors in the egg cell activate genes in the transferred nucleus, causing the nucleus to express genes typical of embryonic stem cells. Through this process, a specialised cell can adopt the characteristics of embryonic stem cells and potentially develop into any cell type in the body. Cell fusion is when two different cells merge to form a single hybrid cell. During cell fusion, the membranes of the two cells join, allowing their contents to mix. This merging of cells can lead to combining genetic material and cellular components from both cells. Transcription-factor transduction involves introducing specific genes called transcription factors ( Oct4 , Sox2 , Klf4 and c- Myc ) into adult cells to reprogram them into iPSCs. Conclusion Stem cells have a huge potential in medicine and research due to the different types having different functions. While the process of nuclear reprogramming does pose some challenges, such as the difficulty in ensuring that reprogrammed cells are safe and don't develop into tumours, ultimately, a better understanding of the mechanisms behind this process will allow scientists to leverage the potential of these cells, allowing them to be used in regenerative medicine. Watch out for the next article in the series, where I will discuss the role of stem cells in regenerative medicine! Written by Naoshin Haque Related articles: Vertebral stem cells and tumour metastasis / iPSCs and organoids Project Gallery

On the 25th of May, 2020, the world was shocked by the brutal murder of George Floyd, a black American man, by four white police officers. This led to mass outrage among every creed and race and propelled the Black Lives Matter movement to new heights, even in places like Palestine Go Back Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Micro-chimerism: a mother’s intuition and why do men call for their mothers near death? In collaboration with Dr. Aakila Sammy of Publett Last updated: 01/03/26 Published: 08/05/23 On the 25th of May, 2020, the world was shocked by the brutal murder of George Floyd, a black American man, by four white police officers. This led to mass outrage among every creed and race and propelled the Black Lives Matter movement to new heights, even in places like Palestine, a country already drowning in peril. While his last words were “I can’t breathe”, the transcripts revealed that he repeated several times, "Momma, I love you. Tell my kids I love them. I'm dead." As painful as it is to hear these words, especially for his mom, it's not surprising; calling out for your mom when death approaches. Many hospice nurses and soldiers recall that dying men call out for their “Mommy” or “Mama” in their last breath. Some have attributed it to its caregiver familiarity, primal instinct like calling out for your mom as a child or a Mary-Jesus connection. George Floyd (1973-2020). Image/ Publett We know that “the mother” is largely responsible for every life on earth, and most of them have the ability to make everything better, but what if that connection is more than something psychological or spiritual? I know, a physical connection to your mom outside the nine months of her carrying you? Like at this moment? Yes! Scientists call it micro-chimerism, and it may be able to explain why for most, the next greatest pain to losing a child is losing your mom. Micro-chimerism originates from the Greek mythical creature “Chimera”, a monster made up of three animals; a lion, a snake and a goat. In medicine, micro-chimerism was initially described as “alien cells”, and it is simply the circulation of cells from one individual in another genetically distinct individual. A Greek 'Chimera'. Image/ Publett And the culprit? There are several actually; natural cases like pregnancy and breast-feeding and artificial instances like organ or blood transplant. And it goes both ways! It could be responsible for that gut feeling you get when something is wrong with your child, also known as “a mother’s intuition”. And it doesn’t stop there; it has been observed in multiplet pregnancies like twins, which may be why twins have their own intuitive connection. So, in addition to nutrients and waste being exchanged, cells are also trafficked bi-directionally. The embryo/fetus receives cells from the mother and the mother from the fetus, and everyone coexists peacefully, sometimes spanning decades. And the burning question that might be in your mind right now is whether a biological female can have male DNA circulating in her body after carrying a male baby. Yes! Cells are also trafficked bidirectionally. Image/ Publett But what are the limits to this phenomenon? This answer is not clear-cut and varies among individuals and situations. Scientists have found maternal-fetal micro-chimerism is present as early as the embryo stage, and the further along, the more abundant it is. This allows non-invasive tests for genetic abnormalities or gender determination on the fetus using blood drawn from the mother. Another situation where it varies is trauma. We might all be familiar with the fetus releasing stem cells into the mother's circulation, which comes with healing benefits to maintain the well-being of the fetal host – and these cells can be detected up to 27 years after delivery. Even though they sound insignificant, fetal cells aren’t afraid of a challenge. Researchers have found them taking on the role of cancer immune surveillance, clustering around lung tumours in women decades after pregnancy and reducing risk of ovarian cancer in women who have later pregnancies. Now, in the case of abortions and miscarriages, the phenomenon might come as a source of comfort, heartache or both. It is unclear how early fetal cells enter the mother’s circulation; it can be when the placenta attaches around week eight or earlier. Commercial fetal blood tests start at weeks 7-8, but this is when they are abundant enough for testing, so it might very well be earlier. So, what does it mean if you have a miscarriage or abortion before week 8? No fetal cell acquisitions? On the contrary, the trauma of the process, especially in the first trimester, causes a massive acquisition of fetal cells by the mother. It is higher in the case of abortion and even higher in surgical abortions versus chemical abortions. Although the fetus is described as having parasitic nature, this last farewell release of healing benefits to its host is nothing short of pure. While controversy still exists around the role of maternal and fetal microchimeric cells, we still crave answers to questions like: How is the phenomenon affected when the fetus carries genetic abnormalities? Do fetal cells from a previous pregnancy enter the circulation of the fetus sibling in a subsequent pregnancy? It might also result in psychologists reframing questions they ask their male patients; are they worried about becoming your father, or should they be more concerned about becoming their mothers? Plus, we need more on the association between parous women and autoimmune diseases, especially in fetal Y-chromosome carriers. Micro-chimerism is a promising and exciting area of research with much to reveal for many fields. While no concrete evidence exists, we know that these cells are resilient to stress and trauma and offer a new perspective to inter-individual bonds and intuitions. Many scientists believe that individuals are calling out to these cells in times of survival, and maybe that’s why kids call out to their moms first or men their mothers near death. -- Scientia News wholeheartedly thanks Aakila Sammy , co-founder and CEO of Publett , for this fascinating piece of work on a lesser-known genetics topic of micro-chimerism. We hope you enjoyed reading this! Follow them @Dr.Publett on Instagram and/or @Publett Limited on Linkedin for more information. -- Related article: The Y Chromosome Unveiled

It plays a key role in many cancers Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The Hippo signalling pathway 11/07/25, 10:59 Last updated: Published: 06/06/24, 12:35 It plays a key role in many cancers Introduction The Hippo signalling pathway controls tissue growth, and it is also a vital pathway involved in many cancers. It is a serine/threonine kinase pathway, which regulates tissue growth by the control of cell proliferation and apoptosis. It was first discovered in a Drosophila genetic screen and was named Hippo, as a loss of Hippo results in an overgrowth (or hippopotamus) phenotype. When the Hippo pathway is ‘on,’ YAP and TAZ (transcription factors/activators) are degraded in the cytoplasm. This occurs via phosphorylation: Sterile 20-related (MST) kinases are phosphorylated, which in turn phosphorylate Large tumour suppressor 1 and 2 (LATS1/2). LATS phosphorylation then causes phosphorylation of YAP/TAZ. In turn, YAP/TAZ then bind to 14-3-3 proteins in the cytoplasm and are broken down by ubiquitin-dependent degradation (see fig. 1). YAP/TAZ has also been shown to activate transcription of YAP/TAZ regulators, such as LATS1/2, in a negative feedback loop. Conversely, when Hippo is ‘off,’ YAP/TAZ are unphosphorylated and are free to move to the nucleus, where they bind to Transcriptional enhanced associate domain (TEAD). YAP/TAZ-TEAD then are able to bind DNA and be involved in transcription of genes such as Axl, c-Myc, survivin, CTGF , and Cyr61 , which are anti-apoptotic or proliferative. Hippo pathway in cancer YAP/TAZ have been shown to be crucial for cancer initiation, progression, and metastasis. They are known to be involved in many cancers, including prostate, bone, eye, brain, spinal cord, breast, and liver cancers. They are also involved in the rare blood vessel cancer epithelioid hemangioendothelioma (EHE). Interestingly, it appears YAP/TAZ act differently depending on the cell type. YAP/TAZ are oncogenic transcription factors in many solid tumours, but surprisingly, they are thought to act as tumour suppressors in some blood cancers e.g. Multiple myeloma (it is still unknown why this is). Therefore, for YAP/TAZ to behave in a regular manner (i.e. non-oncogenic), they must be tightly regulated. Regulation of the Hippo pathway Hippo signalling is regulated by tight/adherens junctions, mechanical signals, and growth factors/receptors. Tight junctions exist where there is a permeability barrier between adjoining cells, and proteins bind to these membranes for a range of different functions. A protein which binds to these adherens junctions is Merlin (encoded by the gene, NF2 ), which is another regulator of the Hippo pathway and a well-known tumour suppressor. Merlin is known to bind to adherens junction proteins in confluent cells, and loss of Merlin causes a lack of development of adherens junctions. Merlin is also an important component involved in contact inhibition during proliferation. Contact inhibition is where cell growth is inhibited upon contact with other cells. The specific mechanism by which Merlin regulates the Hippo pathway and contact inhibition is still unknown. Another regulator of the Hippo pathway is mechanical signals. Fluid shear stress is the frictional force between flowing blood and endothelial cells lining the blood vessels and is known to cause vascular growth, remodelling and maintenance. This stress can result in changes to endothelial cell shape and cause the activation of transcription factors, leading to gene expression. An additional regulator of the Hippo pathway is growth factors/receptors. Growth factors, such as Sphingosine 1-phosphate (S1P) and lysophosphatidic acid (LPA) are both part of the phospholipids growth factor family. They bind to the S1P receptor and LPA receptor, respectively, inhibiting LATS and causing activation of YAP/TAZ. Whereas molecules, such as glucagon and epinephrine have been shown to suppress YAP/TAZ. Cytokines, vascular endothelial growth factors (VEGF), epidermal growth factors (EGF), Wnt, bone morphogenic protein (Bmp), insulin, and transforming growth factor β (TGF-β) have also been shown to regulate the Hippo pathway, which suggests that regulation of the Hippo pathway is complex and linked to several different other pathways. Conclusion The Hippo pathway is a vitally important pathway regulating tissue growth. YAP/TAZ, which are part of the Hippo pathway, are oncogenic factors in many solid tumours but can act as tumour suppressors in some blood cancers. As YAP/TAZ are involved in transcription in this pathway, they are crucial for cancer initiation, growth and metastasis. Hence, targeting of this pathway could lead to further cancer treatments. For example, TEAD inhibitors may offer a therapeutic avenue of treatment and are currently being investigated. In the future, further research on targeting the Hippo pathway may improve on the current targeted therapeutic landscape, realising the need for diverse treatment options for such a complex disease as cancer. Written by Eleanor R. Markham Related articles: MAPK/ ERK signalling pathway / Epitheliod hemnagioendothelioma Project Gallery

An overview Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Epithelioid hemangioendothelioma (EHE) 09/07/25, 15:05 Last updated: Published: 25/02/24, 14:52 An overview This is article no. 4 in a series on rare diseases. Next article: Unfolding prion disease . Previous article: Herpes vs devastating skin disease . Gene fusion and EHE Epithelioid hemangioendothelioma (EHE) is a rare cancer which arises from the cells lining the blood vessels (endothelial cells). This occurs when two genes fuse together. Generally, there are several different gene fusions which lead to cancer, predominantly in prostate, ovarian, blood, and sarcomas (soft tissue cancer). These arise from two genes which bind together to create a fusion oncogene, such as the classical example of the BCR-ABL1 fusion gene, called the “Philadelphia chromosome,” in chronic myeloid leukaemia . EHE is a rare vascular sarcoma caused by a fusion between two genes, primarily TAZ and CAMTA1. TAZ is part of the Hippo signalling pathway (see below) and is a transcriptional co-activator (it binds to a transcription factor to activate the first step in gene expression, which is the conversion of DNA to RNA). Less is known about CAMTA1, although it is a transcription activator found primarily in the brain. However, there are also a small number of cases (10%) caused by a YAP1-TFE3 fusion. YAP1 is also part of the Hippo pathway, whilst TFE3 is a transcription factor. EHE is a prime example of the importance of gene fusions (and other chromosomal rearrangements) in the genetic origin of many cancers. Therefore, further understanding of this disease may provide clues into the tumourigenesis of other different cancers. EHE is extremely rare at a prevalence of 1 in 1 million and presents more often in females, but it can occur in either sex at any age. It is most common in the liver and lung and has an unusual pathology, as it can present as an aggressive or indolent (slow-growing) cancer. Similarly to many cancers, symptoms can present as any or all the following: a mass, fever, fatigue, pain, and weight loss. It may also have no symptoms and be highlighted by chance whilst undergoing other investigations. Cellular signalling behind EHE: the Hippo pathway The Hippo pathway controls tissue growth and is the signalling mechanism behind EHE. YAP/TAZ are vital members of this pathway and are oncogenic transcription (co-) factors in many solid tumours. They have also been shown to be crucial for cancer initiation, progression, and metastasis. However, surprisingly, certain blood cancers, such as leukaemia, myeloma, and lymphoma, show reduced levels of YAP/TAZ. Therefore, it seems YAP/TAZ behave differently depending on cell type. High expression of YAP/TAZ (or nuclear localization) is related to poor prognosis in breast, colorectal, liver, lung, gastric, pancreatic, ovarian, endometrial, oesophageal, and bladder cancers. YAP/TAZ are phosphorylated and degraded in the cytoplasm when the Hippo pathway is ‘on.’ However, when the Hippo pathway is ‘off,’ YAP/TAZ move to the nucleus, where they are involved in transcription (see the signalling pathway diagram). However, in EHE disease, even when Hippo is ‘on,’ TAZ-CAMTA1/YAP1-TFE3 override this and move to the nucleus to be involved in aberrant (atypical) transcription. YAP/TAZ bind to TEAD ( DNA-binding domain ) in the nucleus, whilst CAMTA1 and TFE3 are thought to be involved in chromatin remodelling. Chromatin consists of tightly packed DNA and histones (proteins). Chromatin remodelling results in the chromatin unwinding and the DNA becoming more accessible for transcription (i.e. ‘switching on’ certain genes). Therefore, this may lead to overexpression and subsequently, cancer. EHE treatment There are no standard treatments for EHE, but indolent cancers are often treated by monitoring, a ‘watch-and-wait’ strategy. Surgery is a common form of treatment for single tumours. Ablation (burning/freezing), isolated limb perfusion (drug treatment to one limb), vascular embolization (blocking tumour blood supply), and radiation therapy are also other forms of possible treatment, along with the mammalian target of rapamycin (mTOR) inhibitors (the mTOR pathway controls cell proliferation/metabolism). Tyrosine kinase inhibitors (tyrosine kinases activate proteins in related pathways) and interferon (immune system modulators) are two other possible treatments. A transplant could also be an option if there is an organ with multiple tumours (most often the liver). However, more effective treatments are needed and research into this disease is currently underway. Summary EHE is a rare cancer which arises from the cells lining the blood vessels. It occurs from gene fusions, primarily TAZ-CAMTA1. TAZ is part of the Hippo signalling pathway, which controls tissue growth. Therefore, Hippo is a vital pathway involved in many cancers, and understanding this pathway in EHE disease may provide clues as to the tumourigenesis of other cancers. Written by Eleanor R. Markham Related articles: The Hippo signalling pathway / Apocrine carcinoma (a rare form of breast cancer) Project Gallery

Integrins are desirable to target cancer Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Biochemistry of cancer: integrins, the desirable targets 20/03/25, 12:01 Last updated: Published: 24/05/23, 09:39 Integrins are desirable to target cancer Every year, eight million people worldwide pass away from cancer, and this number is expected to rise. Cancer can damage a wide range of organs in people of various ages. It is quite honest to say that Cancer is the most common and severe problem in clinical medicine. Cancer's fundamental problems shed light on the biochemical and genetic processes underlying the unchecked expansion of cancer cells. The extracellular matrix (ECM)'s biochemical and biomechanical properties affect how sensitive cells are. Cell health depends on different reactions, such as proliferation, apoptosis, migration, and differentiation. The tumour microenvironment also largely influences cancer metastasis, medication resistance, and recurrence. Transmembrane glycoproteins called integrins mediate connections between cells and the ECM and connect it to the cytoskeleton. They relay the information from the ECM through downstream signalling pathways and can hence control the properties of the cell. Mammals have so far been found to contain 24 different integrin heterodimers, formed by combining 18 α- and 8 β-subunits. A cell's ability to bind to specific ECM elements depends on the pattern of integrin expression, which also affects how a cell recognises and reacts to its surroundings. These same integrin-mediated pathways are used by tumour cells in the context of cancer to boost invasiveness and oncogenic survival as well as to create a host milieu that supports tumour development and metastatic dissemination ( Figure 1 ). Hence, Integrins are interesting targets for cancer therapy due to their role in tumour progression, and several integrin antagonists, including antibodies and synthetic peptides, have been successfully used in clinics for cancer therapy. Unligated integrins may have a detrimental effect on tumour survival. They are generally unligated in adherent cells, which leads to the cleavage of caspase 8, which in turn causes tumour cells to undergo apoptosis through a process known as integrin-mediated death (IMD) ( Figure 2 ). Integrins' precise chemical signals and the mechanical environment of the ECM control how cancer cells behave. A key role is also played by the ECM's physicochemical environment. Chemically altered substrate surfaces have been used to study this interaction, but topology and functionality control are still difficult to achieve. Modifying a cell's local chemical environment does offer a viable method for selectively controlling the behaviour of cancer cells. Together, targeted external cue presentation has the potential to enhance existing intracellular cancer therapy approaches. When combined with other targeted therapies (tyrosine kinase inhibitors, anti-growth factor antibodies) for anticancer treatment, integrin inhibition may be used as a potential target for drug development. However, it needs to be thoroughly evaluated in the pre-clinical phase, possibly taking into account all of the plausible escape mechanisms by which tumour cells can develop. Written by Navnidhi Sharma Related articles: Why whales don't get cancer / Breast cancer and asbestos / MOFs in cancer drug delivery / Anti-cancer metal compounds REFERENCES Hamidi, H., Pietilä, M., & Ivaska, J. (2016). The complexity of integrins in cancer and new scopes for therapeutic targeting. British Journal of Cancer, 115(9), 1017–1023. https://doi.org/10.1038/bjc.2016.312 Jacob, M., Varghese, J., Murray, R. K., & Weil, P. A. (2016). Cancer: An Overview (V. W. Rodwell, D. A. Bender, K. M. Botham, P. J. Kennelly, & P. A. Weil, Eds.). Access Medicine; McGraw-Hill Education. https://accessmedicine.mhmedical.com/content.aspx?bookid=1366§ionid=73247495 Li, M., Wang, Y., Li, M., Wu, X., Setrerrahmane, S., & Xu, H. (2021). Integrins as attractive targets for cancer therapeutics. Acta Pharmaceutica Sinica B. https://doi.org/10.1016/j.apsb.2021.01.004 Yoshii, T., Geng, Y., Peyton, S., Mercurio, A. M., & Rotello, V. M. (2016). Biochemical and biomechanical drivers of cancer cell metastasis, drug response and nanomedicine. Drug Discovery Today, 21(9), 1489–1494. https://doi.org/10.1016/j.drudis.2016.05.011 Zhao, H., F. Patrick Ross, & Teitelbaum, S. L. (2005). Unoccupied αvβ3Integrin Regulates Osteoclast Apoptosis by Transmitting a Positive Death Signal. Molecular Endocrinology, 19(3), 771–780. https://doi.org/10.1210/me.2004-0161 Project Gallery

Tiny solutions for big health problems Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link Nanomedicine 17/07/25, 11:52 Last updated: Published: 17/01/24, 00:07 Tiny solutions for big health problems As the landscape of the healthcare field expands, new advances are coming forth, and one such area of interest is nanomedicine. Existing on a miniature scale called nanometres, nanomedicine and technology provide a revolutionary solution to many modern-day problems faced by the scientific community. Through this article, we’ll aim to explore what exactly nanomedicine is, its importance, its use in medicine, as well as its limitations and future prospects. The nanoscale When mentioning nanomedicine or nanotechnology, we refer to materials and particles existing on the nanoscale. This lies between 1-100 nanometres. For reference, human hair is 80,000-100,000 nanometres wide, so comparatively, the technology is much smaller. Although the technology may seem small, its impact is far too significant to be discredited. Due to their smaller size, the nanoparticles hold several advantages, making them useful in biomedicine, these include providing greater surface area for molecular interactions in the body, and they are much easier to manipulate, allowing for greater control and precision in terms of diagnostics and medicine delivery (Figure 1). Cancer drug delivery systems Nanotechnology in the field of medicine is being widely used and tested with regards to its application as a drug delivery system. More recently, it’s being investigated for its increased precision in delivering anti-cancer drugs to patients. Nanotechnology enables precise drug delivery through the construction of nanoscale infrastructures called nanoparticles. These can be filled with anti-cancer drug treatments, and their outer structure can be further designed to include elements which target folate receptors, such as folic acid (B9 vitamin), thus increasing their affinity for specific receptors in the body. Folate receptors tend to be overexpressed on the surface of many cancers, including pancreas, breast, and lung. So, by increasing selectivity and targeting only the cells which overexpress these receptors, the nanoparticles can deliver chemotherapy drugs with increased precision. This increased accuracy results in decreased cellular toxicity to surrounding non-cancerous tissues whilst also reducing side effects. In current experiments, lipid nanoparticles loaded with the anti-cancer drug edelfosine were tested on mice with mantle cell cancer. Lipid nanoparticles offer several advantages as a drug delivery system, including biocompatibility, greater physical stability, increased tolerability, and controlled release of the encapsulated drug. Lipid nanoparticles are also advantageous for their ability to be size specific to a tumour. In the study, in vivo experimentation using mice that contained mantle cell lymphoma was used, and they were administered 30mg/kg of the encapsulated drug. After administering the edelfosine loaded nanoparticles every 4 days, it was found that the process of metastasis had been removed; this means that cancer cells could not spread to other parts of the body. Additionally, it was also found that because of the way the nanoparticles were absorbed into the lymphatic system, they could accumulate in the thoracic duct providing precise and slow release of the drug over time, thus preventing metastasis (Figure 2). Imaging and diagnostics Another area of use for nanotechnology includes imaging and diagnostics. This area of expertise is regarded as theranostics, which involves using nanoparticles as detectors to help locate the area of the body affected by a disease, such as the location of a tumour, and aid in diagnosing illnesses. With regards to diagnostics, nanoparticles can also help identify what stage of the disease is being observed as well as enable us to garner more information to form a concrete treatment programme for the patient, thus providing a personalised touch to their care. Nanomaterials can be used to engineer different types of nanoparticles, which can enhance contrast on CT and MRI scans so that diseases can be detected more easily by being more visible when compared to traditional scans. In collaboration with Belcher et al., Bardhan worked to collectively develop different formulations of polymers that would be most effective in imagining and detecting cancers earlier. In the figure below, a nanoparticle made of a core shell was used for imaging. It comprises a yellow polymer with a red fluorescent dye to increase imagining contrast of the area and a blue lanthanide nanoparticle. When the lanthanide particles are excited by a light source, fluorescence in the near infrared range (NIR-II) is emitted, allowing for clear contrast and imaging. This can be seen in the figure below. From the colours involved, the tumour being imaged could be investigated more thoroughly in how it was distributed and learn more about its microenvironment in a mouse affected by ovarian cancer (Figure 3). Nanobots In recent times, new investment in the form of nanorobots has been made apparent. Nanorobots are nanoelectromechanical systems whose size is very similar to human organelles and cells, so there are a variety of ways they could be helpful in healthcare, such as in the field of surgery. Traditionally, surgical tools can be limited to work on a small scale. However, with nanorobots, it can be possible to access areas unreachable to surgical tools and catheters whilst also reducing recovery time and infection risk, as well as granting greater control and accuracy over the surgery. In a study conducted by Chen et al. (2020), the researchers manipulated magnetotactic bacterial microrobots to kill a bacteria known as Staphylococcus aureus enabled by magnetic fields to target them. Using a microfluidic chip, the microrobots were guided to the target site and then were programmed to attach themselves to the bacteria. Once connected, the viability of the bacteria was reduced due to the swinging magnetic fields generated by the device. Although this research is promising, further research must be conducted to understand the compatibility of these nanotechnologies with the human body and any implications they may have in side effects (Figure 4). Challenges and safety concerns From the evidence explored above, it is evident that nanotechnology holds much promise in the field of healthcare. However, they are not without their challenges and resignations when introducing their use to human bodies. The human body is incredibly complex, and therefore the complete biocompatibility of nanoparticles, particularly nanobots, is currently under-researched and under reviewed. To extensively use them, it is vital first to understand how safe they are and their efficacy in treatment and diagnosis. Below is a summary of some of the advantages and disadvantages of these nanotechnologies (Figure 5). The future of nanotechnology in biomedicine In conclusion, nanotechnology indicates an extensive and optimistic field at the forefront of changing medical care from diagnosis to treatment. It has the potential to answer many pressing questions in healthcare including decreasing cytotoxicity via a precise drug delivery system, increased accuracy in diagnosis, and possibly becoming a novel tool in surgery. Although it is imperative for there to be new and evolved techniques to increase the quality of care for patients, it is vital not to rush and to be thorough in our approach. This involves undergoing further research, including conducting clinical trials when investigating the use of nanotechnology inside the human body; this will test for tissue compatibility, side effects, efficacy, and even dosage when using nanoparticles for drug delivery. In summary, the transformative role of nanomedicine is undeniable. It offers a path to a more personalised and precise healthcare system, allowing researchers to reshape treatment, diagnosis, and patient well-being, though its limitations are yet to be overcome. Written by Irha Khalid Related articles: Nanoparticles: the future of diabetes treatment? / Semi-conductor manufacturing / Room-temperature superconductor / Silicon hydrogel lenses / Nanoparticles and plant disease / Nanogels / Nanocarriers Project Gallery

Explaining and predicting the behaviour of serial killers Facebook X (Twitter) WhatsApp LinkedIn Pinterest Copy link The new age of forensic neurology 14/07/25, 15:58 Last updated: Published: 23/08/23, 17:16 Explaining and predicting the behaviour of serial killers Background Nobody can argue that true crime has taken the media by storm in recent years. In 2021, the search to find Gabby Petito inflamed social media, with the r/gabbypetito subreddit having 120,000 members at its peak. Tiktok ‘psychics’ would amass millions of views by attempting to predict how the case would progress, with predictably terrible results. A small solace remains, however; the fact that increased media presence of murder cases increases the rate at which research into murderers is published. The increase in both research and media attention toward true crime continued through 2022, invigorated by the release of Monster: the Dahmer Story on Netflix, which was viewed on Netflix for over 1 billion hours by its user base. It could be argued that the popularity of this show and others depicting serial killers also increased the publication of research on the neurology of serial killers. The neurological basis of the serial killer refractory period Dilly (2021) encompasses some very interesting correlational research into the neurological factors at play in the evocation of the serial killer refractory period. Following analysis of the refractory periods of ten American serial killers, a metaanalysis of prior research was performed to establish which prior theory most thoroughly explained the patterns derived. The American serial killers utilised in this investigation were: The Golden State Killer, Joseph James DeAngelo. Jeffrey Dahmer. Ted Bundy. John Wayne Gacy. The Night Stalker, Richard Ramirez. The BTK Killer, Dennis Rader. The I-5 Killer, Randall Woodfield. Son of Sam, David Berkowitz. The Green River Killer, Gary Ridgway. The Co-Ed Killer, Edmund Kemper III. Theory no. 1 While this research is purely speculative due to the lack of real-time neurological imaging of the killers both during refractory periods and their murderous rampages, this research was demonstrated to lend credence to a prior theory proposed by Simkin and Roychowdhury (2014). This research, titled Stochastic Modelling of a Serial Killer , theorised based on their own collated data that the refractory period of serial killers functions identically to that of the refractory period of neurons. This theory is based upon the idea that murder precipitates the release of a powerful barrage of neurotransmitters, culminating in widespread neurological activation. In line with neurological refractory periods, it is believed that this extreme change in state of activation is followed by a period of time wherein another global activation event cannot occur. Theory no. 2 Hamdi et al. (2022) delineates the extent to which the subject’s murderous impulses were derived from Fregoli syndrome, rather than his comorbid schizophrenia. This research elucidated how schizophrenic symptoms can synergise with symptoms of delusional identification syndromes (DIS) to create distinct behaviours and thought patterns that catalyse sufferers to engage in homicidal impulses. DIS include a range of disorders wherein sufferers experience issues identifying objects, people, places or events; Fregoli Syndrome is a DIS characterised by the delusional belief that people around the sufferer are familiar figures in disguise. The subject’s Fregoli Syndrome caused the degeneration of his trust of those around him, which quickly led to an increase in aggressive behaviours. The killer attacked each member of his family multiple times before undertaking his first homicide- excluding his father, whom reportedly ‘scared him very much’. Unsurprisingly then, his victim cohort of choice for murder were older men. The neurobiological explanation of Fregoli Syndrome asserts that the impairment of facial identification, wherein cerebrocortical hyperactivity catalyses delusional identification of unfamiliar faces as familiar ones. Conclusion Forensic neurology has been a key element in expanding the understanding of serial killers, with the research of Raine et al. (1997) popularising the use of neurology to answer the many questions posed by the existence of serial killers. Since Raine, Buchsbaum and LaCasse of the 1997 study first used brain scanning techniques to study and understand serial killers, the use of brain scanning techniques to study this population has become a near-perfect art, becoming ever more of a valid option for use both in understanding and predicting serial killer behaviour. In all likelihood, future innovations in forensic neurology research will continue to bring about positive change, reducing homicidal crime with the invention and use of different methods and systems to predict and stop the crimes before they happen. Summarised from a full investigation. Written by Aimee Wilson Related articles: Serial killers in healthcare / Brain of a bully Project Gallery