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Brain cancer in children is notoriously hard to treat – a new mRNA cancer vaccine triggers an attack from within

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theconversation.com – Christina von Roemeling, Assistant Professor of Neurosurgery, University of Florida – 2024-05-01 10:01:09

How cancer vaccines are delivered into the body influences their effectiveness.

Liuhsihsiang/iStock via Getty Images Plus

Christina von Roemeling, University of Florida and John Ligon, University of Florida

Brain cancers remain among the most challenging tumors to treat. They often don’t respond to traditional treatments because many chemotherapies are unable to penetrate the protective barrier around the brain. Other treatments like radiation and surgery can leave patients with lifelong debilitating side effects.

As a result, brain cancer is the leading cause of cancer-related death in children. Brain tumors in children frequently do not respond to treatments developed for adults, likely due to the fact that pediatric brain cancers are not as well-studied as adult brain cancers. There is an urgent need to develop new treatments specific to children.

We developed a new messenger-RNA, or mRNA, cancer vaccine, described in newly published research, that can deliver treatments more effectively in children who have brain cancer and teach their immune systems to fight back.

Close-up of child's hand with IV line placed held by adult's hand

Cancer treatments designed for adults may not necessarily work as well in children.

Virojt Changyencham/Moment via Getty Images

How do cancer vaccines work?

The immune system is a complex network of cells, tissues and organs whose primary function is to continuously surveil the body for threats posed by foreign invaders – pathogens that damage tissues and make you sick. It accomplishes this by recognizing antigens, or abnormal proteins or molecules, on pathogens. T cells that recognize these antigens seek out and destroy the pathogens.

Your immune system also protects you from domestic threats like cancer. Over time, your cells sustain DNA damage from either internal or external stressors, leading to mutations. The proteins and molecules produced from mutated DNA look quite different from the ones cells typically produce, so your immune system can recognize them as antigens. Cancer develops when cells accumulate mutations that enable them to continue to grow and divide while simultaneously going undetected by the immune system.

In 1991, scientists identified the first tumor antigen, helping lay the framework for modern-day immunotherapy. Since then, researchers have identified many new tumor antigens, facilitating the development of cancer vaccines. Broadly, cancer vaccines deliver tumor antigens into the body to teach the immune system to recognize and attack cancer cells that display those antigens. Although all cancer vaccines conceptually work very similarly, they each significantly vary in the way they are developed and the number and combination of antigens they carry.

Cancer vaccines help the immune system differentiate between healthy cells and tumor cells.

One of the biggest differences among cancer vaccines is how they are created. Some vaccines use protein fragments, or peptides, of tumor antigens that are directly given to patients. Other vaccines use viruses reengineered to express cancer antigens. Even more complex are vaccines where a patient’s own immune cells are collected and trained to recognize cancer antigens in a laboratory before being delivered back to the patient.

Currently, there is a lot of excitement and focus among researchers on developing mRNA-based cancer vaccines. Whereas DNA is the blueprint of which proteins to make, mRNA is a copy of the blueprint that tells cells how to build these proteins. Thus, researchers can use mRNA to create blueprint copies of potential antigens.

mRNA cancer vaccines

The COVID-19 pandemic brought significant attention to the potential of using mRNA-based vaccines to stimulate the immune system and provide protection against the antigens they encode for. But researchers have been investigating the use of mRNA vaccines for treating various cancers since before the pandemic.

Our team of scientists in the Brain Tumor Immunotherapy Program at University of Florida has spent the past 10 years developing and optimizing mRNA vaccines to treat brain cancer.

Cancer vaccines have faced significant challenges. One key hurdle is that these vaccines may not always trigger a strong enough immune response to eradicate the cancer completely. Moreover, tumors are not made up of one type of cancer cell, but rather a complex mix of cancer cells that each harbors its own unique cocktail of mutations.

Our cancer vaccine seeks to address these issues in a number of ways.

Diagram of lipid molecules formed a spherical shell around single-stranded mRNAs

Lipid nanoparticles can carry therapeutic mRNA into the body.

Buschmann et al. 2021/ Wikimedia Commons, CC BY-SA

First, we designed our vaccines by using the RNA of a patients’ own cancer cells as a template for the mRNA inside our nanoparticles. We also packaged our cancer vaccine inside of nanoparticles made up of specialized lipids, or fat molecules. We maximized the amount of mRNA packaged within each nanoparticle by sandwiching them between lipid layers like the layers of an onion. In this way, we increase the likelihood that the mRNA molecules in our nanoparticles produce enough tumor antigens from that patient’s cancer to activate an immune response.

Also, instead of injecting nanoparticles into the skin, muscle or directly into the tumor, as is commonly done for many therapeutic cancer vaccines, our mRNA nanoparticles are injected into the bloodstream. From there, they travel to organs throughout the body involved in the immune response to teach the body to fight against the cancer. By doing so, we’ve found that the immune system launches a near immediate and powerful response. Within six hours of receiving the vaccine, there is a significant increase in the amount of blood markers connected to immune activation.

Looking to the future

Our mRNA-based vaccines are currently undergoing early-phase clinical trials to treat real patients with brain cancer.

We administered our mRNA-based vaccine to four adult patients with glioblastoma who had relapsed after previous treatment. All patients survived several months longer than the expected average survival at this advanced stage of illness. We expect to treat children with a type of brain tumor called pediatric high-grade glioma by the end of the year.

Importantly, mRNA vaccines can be developed to treat any kind of cancer, including childhood brain tumors. Our Pediatric Cancer Immunotherapy Initiative focuses on developing new immune-based therapies for children afflicted with cancer. After developing an mRNA vaccine for glioma in chidren, we will expand to treat other kinds of pediatric brain cancers like medulloblastoma and potentially treat other kinds of cancers like skin cancer and bone cancer.

We are hopeful that mRNA-based vaccines may lead to more children being cured of their brain tumors.The Conversation

Christina von Roemeling, Assistant Professor of Neurosurgery, University of Florida and John Ligon, Assistant Professor of Hematology, University of Florida

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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Hundreds of 19th-century skulls collected in the name of medical science tell a story of who mattered and who didn’t

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theconversation.com – Pamela L. Geller, Associate Professor of Anthropology, University of Miami – 2024-11-14 07:23:00

Hundreds of 19th-century skulls collected in the name of medical science tell a story of who mattered and who didn’t

Illustration of just one of almost a thousand skulls Morton and colleagues collected.

Crania Americana by Samuel Morton, CC BY

Pamela L. Geller, University of Miami

When I started my research on the Samuel George Morton Cranial Collection, a librarian leaned over my laptop one day to share some lore. “Legend has it,” she said, “John James Audubon really collected the skulls Morton claimed as his own.” Her voice was lowered so as not to disturb the other scholars in the hushed archive.

As my work progressed, I uncovered no evidence to substantiate her whispered claim. Audubon had collected human skulls, several of which he then passed on to Morton. But birds and ornithology remained Audubon’s passion.

Nevertheless, the librarian’s offhanded comment has proven useful – a touchstone of sorts that continues to remind me of the controversy and confusion long surrounding the Morton Collection.

Morton was a physician and naturalist who lived in Philadelphia from 1799 until the end of his life in 1851. A lecture he delivered to aspiring doctors at the Philadelphia Association for Medical Instruction outlined the reasons for his cranial compulsion:

“I commenced the study of Ethnology in 1830; in which year, having occasion to deliver an introductory lecture on Anatomy, it occurred to me to illustrate the difference in the form of the skull as seen in the five great races of men … When I sought the materials for my proposed lecture, I found to my surprise that they could be neither bought nor borrowed.”

He would go on to acquire almost 1,000 human skulls.

Morton used these skulls to advance an understanding of racial differences as natural, easily categorizable and able to be ranked. Big-brained “Caucasians,” he argued in the 1839 publication “Crania Americana,” were far superior to small-skulled American Indians and even smaller-skulled Black Africans. Many subsequent scholars have since thoroughly debunked his ideas.

Certainly, condemnation of Morton as a scientific racist is warranted. But I find this take represents the man as a caricature, his conclusions as foregone. It provides little insight into his life and the complicated, interesting times in which he lived, as I detail in my book “Becoming Object: The Sociopolitics of the Samuel George Morton Cranial Collection.”

My research demonstrates that studies of skulls and diseases undertaken by Morton and his medical and scientific colleagues contributed to an understanding of U.S. citizenship that valued whiteness, Christianity and heroic masculinity defined by violence. It is an exclusionary idea of what it means to be American that persists today.

Yet, at the same time, the collection is an unintended testament to the diversity of the U.S. population during a tumultuous moment in the nation’s history.

Pen and ink portrait of a 19th century white man

Samuel Morton wasn’t a lone voice on the fringe of medicine.

‘Memoir of the life and scientific labors of Samuel George Morton’ by Henry S. Patterson, CC BY

Men of science and medicine

As a bioarchaeologist who has studied the Morton Collection for many years, I have sought to better understand the social, political and ideological circumstances that led to its creation. From my work – analyzing archival sources including letters, laws, maps and medical treatises, as well as the skulls themselves – I’ve learned that, over a lifetime, Morton fostered a professional network that had far-reaching tentacles.

He had plenty of help amassing the collection of skulls that bears his name.

The physician connected with medical colleagues – many of whom, like him, received degrees from the University of Pennsylvania – gentleman planters, enslavers, naturalists, amateur paleontologists, foreign diplomats and military officers. Occupational differences aside, they were mostly white, Christian men of some financial means.

Their interactions took place during a pivotal moment in American history, the interlude between the nation’s revolutionary consolidation and its violent civil unraveling.

Throughout this stretch of time, Morton and his colleagues catalyzed biomedical interventions and scientific standards to more effectively treat patients. They set in motion public health initiatives during epidemics. They established hospitals and medical schools. And they did so in the service of the nation.

Not all lives were seen as worthy of these men’s care, however. Men of science and medicine may have fostered life for many, but they also let others die. In “Becoming Object,” I track how they represented certain populations as biologically inferior; diseases were tied to nonwhite people, female anatomy was pathologized, and poverty was presumed inherited.

From person to specimen

Such representations made it easier for Morton and his colleagues to regulate these groups’ bodies, rationalize their deaths and collect their skulls with casual cruelty from almshouse dissecting tables, looted cemeteries and body-strewn battlefields. That is, a sizable portion of the skulls in Morton’s collections were not culled from ancient graves but belonged to those of the recently alive.

It is no coincidence that Morton began his scientific research in earnest the same year Andrew Jackson signed the Indian Removal Act of 1830. Men of science and medicine benefited from the expansionist policies, violent martial conflicts and Native displacement that underpinned Manifest Destiny.

line drawing of a skull from three angles, with text beneath about how it was collected from battle

A drawing from Morton’s book of the skull of a Seminole man killed by American troops. A bullet hole is visible on the left side of the man’s head.

‘Crania Americana’ by Samuel George Morton, CC BY

The collection reveals these acts of nation-building as necropolitical strategies – techniques used by sovereign powers to destroy or erase certain, often already vulnerable, populations from the national consciousness. These skulls attest to precarious existences, untimely deaths and trauma experienced from cradle to beyond the grave.

In the specific case of Native Americans, skeletal analysis testifies to the violent effects of U.S. military campaigns and forced removal. Native skulls that Morton labeled “warriors” have evidence of unhealed fractures and gunshot wounds. Children’s skulls bear the marks of compromised health; such pathology and their young ages at death are evidence of long-standing malnutrition, poverty and deprivation or stress.

To effectively transform subjects into objects – human beings into specimens – collected crania were ensconced in the institutional spaces of medical school lecture halls and museum storage cabinets.

There, Morton first numbered them sequentially. These numbers along with information about race, sex, age, “idiocy” or “criminality,” cranial capacity and provenance were inked on skulls and written in catalogs. Very rarely was the person’s name recorded. If used as teaching tools, Morton drilled holes to hang the skulls for display and notated them with the names of skeletal elements and features.

As dehumanizing as this process was, the Morton Collection does contain evidence of resilience and heterogeneous lives. There are traces of people with mixed-race backgrounds such as Black Indians. Several people may have also bent gender to navigate dire conditions or in keeping with social norms, such as native Beloved Women, who were active in warfare and political life.

stone monument in a graveyard

In contrast to those whose skulls ended up in his collection, Samuel Morton’s own grave was memorialized with a monument.

Pamela L. Geller

What these bones mean today

As anthropologists now recognize, it is through the repatriation of the remains of the people in the Morton Collection to their descendants, among other types of reparations, that current practitioners may begin to atone for the sins of intellectual forebears. Indeed, all institutions housing legacy collections must contend with this issue.

There are other, valuable lessons – about diversity and suffering – that the Morton Collection has to impart in today’s interesting times.

The collection demonstrates that the American body politic has always been a diverse one, despite efforts of erasure by men like Morton and his colleagues. Piecing together the stories of past, disenfranchised lives – and acknowledging the silences that have made it difficult to flesh them out – counters past white nationalism and xenophobia and their current resurgence.

The collection, I believe, also urges the repudiation of violence, casual cruelty and opportunism as admirable attributes of masculinity. Valorizing men who embody these qualities has never served America well. Particularly in the mid-1800s, when Morton amassed skulls, it led to a nation divided and hardened to suffering, an unfathomable death count and the increasing fragility of democracy.The Conversation

Pamela L. Geller, Associate Professor of Anthropology, University of Miami

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Weight loss plans are less effective for many Black women − because existing ones often don’t meet their unique needs

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theconversation.com – Loneke Blackman Carr, Assistant Professor of Community and Public Health Nutrition, University of Connecticut – 2024-11-13 07:24:00

People who are obese or overweight are at higher risk of developing several chronic diseases.
andreswd/E+ via Getty Images

Loneke Blackman Carr, University of Connecticut and Jameta Nicole Barlow, George Washington University

The popularity of weight loss drugs such as Ozempic and Mounjaro continue to reflect Americans’ desire to slim down. While these new drugs have offered a solution for people struggling with obesity, many eligible patients – especially Black adults – cannot afford the high price.

These drugs are also not a one-stop solution for better health, as healthy eating and regular exercise are also key to losing weight. But current weight loss interventions based on lifestyle changes largely fail to meet the needs of Black women.

As community health researchers, we wondered why scientists have been unable to craft a lifestyle-based weight loss solution that works for Black women.

So we reviewed 10 years of research on weight loss interventions based on lifestyle changes. We found that only a few studies focused on Black women, and those that did often resulted in only small amounts of weight loss and were inconsistent in how they approached weight loss. Why is that?

Missing the mark for Black women

Obesity increases the risk of developing weight-related conditions such as Type 2 diabetes, heart disease and some types of cancer. Nearly 60% of Black women in the U.S. are obese, placing them at greater risk of developing these conditions.

Lifestyle interventions focusing on healthy diet and increased physical activity are proven to help most people lose weight, typically resulting in a 5% to 10% weight reduction that also reduces the risk of chronic disease. However, these lifestyle interventions usually result in only a 2% to 3% weight loss in Black women.

Our review suggests that lifestyle-based weight loss has been stymied among Black women because they often aren’t included in this research. Because their lived experiences aren’t considered in these studies, these interventions might not meet their specific needs. Of the 138 studies we assessed, Black women made up at least half of the participants in only eight studies.

Research on why lifestyle interventions are often less effective for Black women is lacking. However, some studies highlight the effects of race and gender on their daily lives as potential factors.

Person sitting on couch, pinching skin between eyebrows
The ‘strong’ Black woman is compelled to ignore her physical and emotional needs to take care of others.
PixelsEffect/E+ via Getty Images

The superwoman role

Black women exposed to the persistent stress of navigating everyday racism and sexism face the additional burden of what researchers call the superwoman role. Not only do Black women have to weather their own experiences of race- and gender-based inequalities, they’re also expected to be invulnerable, hyperindependent and suppress their emotions in order to seem strong to their family and community. Many minimize their vulnerabilities and overstress their capabilities in order to fulfill an overwhelming obligation to take care of other people.

Many famous names have spoken about the effects of being the strong superwoman. Actress Taraji P. Henson has pointed to how the need to display strength can lead to ignoring the physical and emotional needs of Black women.

Rapper Megan Thee Stallion spoke about the emotional toll of the superwoman role after being shot by rapper Tory Lanez. “As a Black woman … people expect me to take the punches, take the beating, take the lashings, and handle it with grace. But I’m human.”

The superwoman role levies a heavy tax on Black women, leaving little room to prioritize their health. To cope with the stress, some engage in emotional eating or binge eating. The constant demands of playing multiple caregiver roles can also disrupt physical activity.

Naturally, these challenges make it difficult to adopt healthier eating habits and a consistent exercise routine. Even when working toward weight loss, some Black women continue to gain weight.

Improving weight loss for Black women

Lifestyle interventions that fully integrate the lived experiences of Black women into treatment may be key to improving weight loss. We argue that Black Feminism and Womanism, which focus on the experiences of women of color, can guide researchers to rebuild and reframe weight loss interventions to be more effective for Black women.

Black Feminism and Womanism are approaches guiding Black women and girls to surviving and thriving, specifically by always considering the role that gender and race play in different issues. These frameworks focus on multiple areas of health and wellness, including physical, mental and emotional health, arguing that self-care and wellness practices are acts of social change.

Focusing on the full context of Black women’s lives can lead to better overall health. Obesity, specifically, is influenced by multiple factors, and treating obesity requires a focus on holistic health and well-being. This includes addressing Black women’s economic needs, incorporating faith practices central to Black life, attending to emotional and mental health, and building an environment that makes acquiring healthy food and engaging in daily exercise an easy choice.

Three people walking down a tree-lined trail, smiling at each other
Lifestyle changes are easier to incorporate when they’re tailored to your everyday life.
FG Trade/E+ via Getty Images

Current weight loss interventions vary widely in which elements of Black women’s lives they focus on. For example, some emphasize spirituality, while others concentrate on emotional health. Approaches to weight loss that respond to individual needs and move away from one-size-fits-all will be critical to addressing the various aspects of Black women’s lives that affect their wellness.

If health care providers and researchers begin listening to and working with Black women to redesign weight loss interventions, they will likely find that their efforts at addressing obesity among Black women are more effective.The Conversation

Loneke Blackman Carr, Assistant Professor of Community and Public Health Nutrition, University of Connecticut and Jameta Nicole Barlow, Associate Professor of Writing, Health Policy & Management and Women’s, Gender and Sexuality Studies,, George Washington University

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Can AI chatbots boost human creativity?

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theconversation.com – Jaeyeon Chung, Assistant Professor of Business, Rice University – 2024-11-13 07:26:00

AI chatbots can give helpful suggestions.

Carol Yepes/Moment via Getty Images

Jaeyeon Chung, Rice University

Think back to a time when you needed a quick answer, maybe for a recipe or a DIY project. A few years ago, most people’s first instinct was to “Google it.” Today, however, many people are more likely to reach for ChatGPT, OpenAI’s conversational AI, which is changing the way people look for information.

Rather than simply providing lists of websites, ChatGPT gives more direct, conversational responses. But can ChatGPT do more than just answer straightforward questions? Can it actually help people be more creative?

I study new technologies and consumer interaction with social media. My colleague Byung Lee and I set out to explore this question: Can ChatGPT genuinely assist people in creatively solving problems, and does it perform better at this than traditional search engines like Google?

Across a series of experiments in a study published in the journal Nature Human Behavour, we found that ChatGPT does boost creativity, especially in everyday, practical tasks. Here’s what we learned about how this technology is changing the way people solve problems, brainstorm ideas and think creatively.

ChatGPT and creative tasks

Imagine you’re searching for a creative gift idea for a teenage niece. Previously, you might have googled “creative gifts for teens” and then browsed articles until something clicked. Now, if you ask ChatGPT, it generates a direct response based on its analysis of patterns across the web. It might suggest a custom DIY project or a unique experience, crafting the idea in real time.

To explore whether ChatGPT surpasses Google in creative thinking tasks, we conducted five experiments where participants tackled various creative tasks. For example, we randomly assigned participants to either use ChatGPT for assistance, use Google search, or generate ideas on their own. Once the ideas were collected, external judges, unaware of the participants’ assigned conditions, rated each idea for creativity. We averaged the judges’ scores to provide an overall creativity rating.

One task involved brainstorming ways to repurpose everyday items, such as turning an old tennis racket and a garden hose into something new. Another asked participants to design an innovative dining table. The goal was to test whether ChatGPT could help people come up with more creative solutions compared with using a web search engine or just their own imagination.

two adults and two small children play with an arrangement of cardboard boxes in a brightly lit room with hard flooring

ChatGPT did well with the task of suggesting creative ideas for reusing household items.

Simon Ritzmann/DigitalVision via Getty Images

The results were clear: Judges rated ideas generated with ChatGPT’s assistance as more creative than those generated with Google searches or without any assistance. Interestingly, ideas generated with ChatGPT – even without any human modification – scored higher in creativity than those generated with Google.

One notable finding was ChatGPT’s ability to generate incrementally creative ideas: those that improve or build on what already exists. While truly radical ideas might still be challenging for AI, ChatGPT excelled at suggesting practical yet innovative approaches. In the toy-design experiment, for example, participants using ChatGPT came up with imaginative designs, such as turning a leftover fan and a paper bag into a wind-powered craft.

Limits of AI creativity

ChatGPT’s strength lies in its ability to combine unrelated concepts into a cohesive response. Unlike Google, which requires users to sift through links and piece together information, ChatGPT offers an integrated answer that helps users articulate and refine ideas in a polished format. This makes ChatGPT promising as a creativity tool, especially for tasks that connect disparate ideas or generate new concepts.

It’s important to note, however, that ChatGPT doesn’t generate truly novel ideas. It recognizes and combines linguistic patterns from its training data, subsequently generating outputs with the most probable sequences based on its training. If you’re looking for a way to make an existing idea better or adapt it in a new way, ChatGPT can be a helpful resource. For something groundbreaking, though, human ingenuity and imagination are still essential.

Additionally, while ChatGPT can generate creative suggestions, these aren’t always practical or scalable without expert input. Steps such as screening, feasibility checks, fact-checking and market validation require human expertise. Given that ChatGPT’s responses may reflect biases in its training data, people should exercise caution in sensitive contexts such as those involving race or gender.

We also tested whether ChatGPT could assist with tasks often seen as requiring empathy, such as repurposing items cherished by a loved one. Surprisingly, ChatGPT enhanced creativity even in these scenarios, generating ideas that users found relevant and thoughtful. This result challenges the belief that AI cannot assist with emotionally driven tasks.

Future of AI and creativity

As ChatGPT and similar AI tools become more accessible, they open up new possibilities for creative tasks. Whether in the workplace or at home, AI could assist in brainstorming, problem-solving and enhancing creative projects. However, our research also points to the need for caution: While ChatGPT can augment human creativity, it doesn’t replace the unique human capacity for truly radical, out-of-the-box thinking.

This shift from Googling to asking ChatGPT represents more than just a new way to access information. It marks a transformation in how people collaborate with technology to think, create and innovate.The Conversation

Jaeyeon Chung, Assistant Professor of Business, Rice University

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