Study finds large language models (LLMs) use stigmatizing language about individuals with alcohol and substance use disorders

Mass General Brigham

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Recommended Non-Stigmatizing Language for Alcohol and Substance Use Communications 

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Credit: Mass General Brigham

As artificial intelligence is rapidly developing and becoming a growing presence in healthcare communication, a new study addresses a concern that large language models (LLMs) can reinforce harmful stereotypes by using stigmatizing language. The study from researchers at Mass General Brigham found that more than 35% of responses in answers related to alcohol- and substance use-related conditions contained stigmatizing language. But the researchers also highlight that targeted prompts can be used to substantially reduce stigmatizing language in the LLMs’ answers. Results are published in The Journal of Addiction Medicine.

“Using patient-centered language can build trust and improve patient engagement and outcomes. It tells patients we care about them and want to help,” said corresponding author Wei Zhang, MD, PhD, an assistant professor of Medicine in the Division of Gastroenterology at Mass General Hospital, a founding member of the Mass General Brigham healthcare system.  “Stigmatizing language, even through LLMs, may make patients feel judged and could cause a loss of trust in clinicians.”

LLM responses are generated from everyday language, which often includes biased or harmful language towards patients. Prompt engineering is a process of strategically crafting input instructions to guide model outputs towards non-stigmatizing language and can be used to train LLMs to employ more inclusive language for patients. This study showed that employing prompt engineering within LLMs reduced the likelihood of stigmatizing language by 88%.

For their study, the authors tested 14 LLMs on 60 generated clinically relevant prompts related to alcohol use disorder (AUD), alcohol-associated liver disease (ALD), and substance use disorder (SUD). Mass General Brigham physicians then assessed the responses for stigmatizing language using guidelines from the National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism (both organizations’ official names still contain outdated and stigmatizing terminology).

Their results indicated that 35.4% of responses from LLMs without prompt engineering contained stigmatizing language, in comparison to 6.3% of LLMs with prompt engineering. Additionally, results indicated that longer responses are associated with a higher likelihood of stigmatizing language in comparison to shorter responses. The effect was seen across all 14 models tested, although some models were more likely than others to use stigmatizing terms.

Future directions include developing chatbots that avoid stigmatizing language to improve patient engagement and outcomes. The authors advise clinicians to proofread LLM-generated content to avoid stigmatizing language before using it in patient interactions and to offer alternative, patient-centered language options. The authors note that future research should involve patients and family members with lived experience to refine definitions and lexicons of stigmatizing language, ensuring LLM outputs align with the needs of those most affected. This study reinforces the need to prioritize language in patient care as LLMs become increasingly used in healthcare communication.

 

Authorship: In addition to Zhang, Mass General Brigham authors include Yichen Wang, Kelly Hsu, Christopher Brokus, Yuting Huang, Nneka Ufere, Sarah Wakeman, and James Zou.

Disclosures: None.

Funding: This study was funded by grants from the May Center Clinic for Digital Health in partnership with the Mayo Clinic Office of Equity, Inclusion, and Diversity and Dalio Philanthropies.

Paper cited: Wang, Y. et. al. “Stigmatizing Language in Large Language Models for Alcohol and Substance Use

Disorders: A Multi-Model Evaluation and Prompt Engineering Approach” DOI: 10.1097/ADM.0000000000001536

 

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About Mass General Brigham

Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.

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Journal

Journal of Addiction Medicine

DOI

10.1097/ADM.0000000000001536 

Method of Research

Randomized controlled/clinical trial

Subject of Research

People

Article Title

Study Finds Large Language Models (LLMs) Use Stigmatizing Language About Individuals with Alcohol and Substance Use Disorders

Article Publication Date

24-Jul-2025

National study finds healthcare provider stigma toward substance use disorder varies sharply by condition and provider

Emergency medicine physicians show highest stigma—but also play crucial role in linking patients to treatment

Columbia University's Mailman School of Public Health

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A new national study from Columbia University Mailman School of Public Health, with colleagues at the University of Miami Miller School of Medicine, University of Chicago, National Opinion Research Center, and Emory University finds that stigma toward patients with substance use disorders (SUD) remains widespread among U.S. healthcare providers—and varies significantly across types of substances. The findings are published in the journal Addiction.

The study is the first national analysis to compare provider stigma across opioid (OUD), stimulant, and alcohol use disorders (AUD) with other chronic but often-stigmatized conditions like depression, HIV, and Type II diabetes. Researchers also assessed how stigma influences whether providers screen for SUD, offer referrals, or deliver treatment.

“While we've made progress in expanding access to evidence-based SUD treatment, stigma remains a profound barrier—often embedded in the clinical encounter itself,” said Carrigan Parish, DMD, PhD, assistant professor in the Department of Sociomedical Sciences at Columbia Mailman School of Public Health. “Our findings show that many providers still feel uncomfortable treating patients with substance use disorders and that hesitancy leads directly to missed opportunities for care. In particular, emergency departments often serve as the first—and sometimes only—point of care for people with substance use disorders. We need to leverage those moments, not miss them.”

The study, conducted from October 2020 to October 2022, surveyed 1,081 primary care providers (PCPs), 600 emergency medicine providers (EMPs), and 627 dentists using a nationally representative random sample licensed from the American Medical and Dental Associations. Participants rated their agreement with 11 standardized stigma statements and reported their screening, referral, and treatment practices for six conditions: three SUDs (opioids, stimulants, alcohol) and three comparison medical conditions (Type II diabetes, depression, HIV).

Key findings:

• Stigma score toward stimulant use disorders was highest (36.3 points, followed by OUD (35.6 points) and AUD (32 points).
• For comparison, stigma scores were far lower for depression (26.2 points, HIV (25.8 points), and Type II diabetes (23.2 points), where providers also reported higher levels of compassion and treatment.
• More than 30 percent of providers said they prefer not to work with patients with OUD or stimulant use disorders—compared to just 2 percent for diabetes, and 9 percent for both HIV and depression.
• Emergency medicine physicians (EMPs) expressed the highest levels of stigma toward SUD, yet were also the most active in providing clinical care:
  • 28.4 percent reported providing drug use treatment
  • 27.2 percent prescribed medications for opioid use disorder (MOUD) compared to just 12 percent and 10 percent of primary care physicians (PCPs) for drug use treatment and prescribing medications, respectively. 
• Dentists reported the lowest stigma levels toward all queried conditions—which may be due to greater clinical and moral distance from SUD treatment and viewing SUD-related practices as outside their scope of practice
• Stigma scores did not significantly differ by provider race, age, gender, region, or rurality, indicating that these attitudes span the healthcare workforce

“Overall, providers were less likely to feel they could effectively help patients with stimulant or opioid use disorders. In fact, 22 percent of providers said, ‘there is little I can do to help patients like this’—a response we almost never saw for other conditions,” said Daniel Feaster, PhD and professor of Biostatistics and one of the lead investigators at University of Miami.

“This isn’t just a matter of attitude—it’s about access. If a provider doubts treatment efficacy or holds stigmatizing beliefs, they’re less likely to screen or refer a patient. That becomes a system failure.”

The study also highlighted key institutional barriers that may reinforce stigma, including:

• Time constraints 
• Lack of training
• Limited referral resources
• Discomfort discussing SUD with patients
• Legal concerns
• Minimal privacy in clinical settings

Senior author Lisa R. Metsch, professor of Sociomedical Sciences at Columbia Mailman School and Dean of the School of General Studies at Columbia University added, “We heard over and over that providers feel unequipped or unsupported to treat SUD—despite being on the frontlines. That’s especially true in primary care settings, where time pressures and limited resources are a daily challenge.” Metsch also added, “Notably, the majority of health providers agreed that insurance plans should cover patients with SUD at the same degree as they cover patients with other health conditions.” 

Dentists, although typically less involved in treating SUD, are well-positioned to recognize oral signs of substance use and refer patients to appropriate care—but they, too, face gaps in training and systemic support. 

“Going forward, we should strive to be more cognizant of the many treatment and provider roles we have distinguished in this study. By unpacking all the variations, we can start to build smarter interventions—tailored by specialty, setting, and substance,” said Parish. 

Other co-authors are Viviana E. Horigian, University of Miami Miller School of Medicine; Harold A. Pollack, University of Chicago School of Social Work; Xiaoming Wang and Petra Jacobs, National Institute of Drug Abuse; Christina Drymon and Elizabeth Allen, National Opinion Research Center; Carlos del Rio, Emory University School of Medicine; and Margaret R. Pereyra and Lauren Gooden, Columbia Mailman School.

The study was supported by the National Institute on Drug Abuse Treatment Clinical Trials Network, grant 5UG1DA013720-23.

Columbia University Mailman School of Public Health

Founded in 1922, the Columbia University Mailman School of Public Health pursues an agenda of research, education, and service to address the critical and complex public health issues affecting New Yorkers, the nation and the world. The Columbia Mailman School is the third largest recipient of NIH grants among schools of public health. Its nearly 300 multi-disciplinary faculty members work in more than 100 countries around the world, addressing such issues as preventing infectious and chronic diseases, environmental health, maternal and child health, health policy, climate change and health, and public health preparedness. It is a leader in public health education with more than 1,300 graduate students from 55 nations pursuing a variety of master’s and doctoral degree programs. The Columbia Mailman School is also home to numerous world-renowned research centers, including ICAP and the Center for Infection and Immunity. For more information, please visit www.mailman.columbia.edu.

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Journal

Addiction

DOI

10.1111/add.70122 

Article Title

Healthcare provider stigma toward patients with substance use disorders

International study reveals sex and age biases in AI models for skin disease diagnosis

Health Data Science

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Scientists from ShanghaiTech University compared the performance of large language models (LLMs), like ChatGPT-4 and LLaVA, in diagnosing skin diseases among male and female patients across different age groups. The findings point to potential biases across age and sex groups, that must be addressed before clinical deployment.

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Credit: Zhiyu Wan, Health Information Safety and Intelligence Research Lab, ShanghaiTech University (generated with the help of ChatGPT-4o)

An international research team led by Assistant Professor Zhiyu Wan from ShanghaiTech University has recently published groundbreaking findings in the journal Health Data Science, highlighting biases in multimodal large language models (LLMs) such as ChatGPT-4 and LLaVA in diagnosing skin diseases from medical images. The study systematically evaluated these AI models across different sex and age groups.

Utilizing approximately 10,000 dermatoscopic images, the study focused on three common skin diseases: melanoma, melanocytic nevi, and benign keratosis-like lesions. Results revealed that while ChatGPT-4 and LLaVA outperformed most traditional deep learning models overall, ChatGPT-4 showed greater fairness across demographic groups, whereas LLaVA exhibited significant sex-related biases.

Dr. Wan emphasized, “While large language models like ChatGPT-4 and LLaVA demonstrate clear potential in dermatology, we must address the observed biases, particularly across sex and age groups, to ensure these technologies are safe and effective for all patients.”

The team plans further research incorporating additional demographic variables like skin tone to comprehensively evaluate the fairness and reliability of AI models in clinical scenarios. This research provides critical guidance for developing more equitable and trustworthy medical AI systems.

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Journal

Health Data Science

DOI

10.34133/hds.0256 

Article Title

Evaluating Sex and Age Biases in Multimodal Large Language Models for Skin Disease Identification from Dermatoscopic Images

ABOLISH THEM

Delinking PBM compensation from drug list prices could unleash major savings

Reforming payments to PBMs and other pharmacy middlemen could lower annual U.S. drug spending by nearly $100 billion, analysis finds

University of Southern California

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Net drug spending vs. scenario with fixed intermediary fees

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Credit: USC Schaeffer Center

Breaking the link between prescription drug list prices and compensation to middlemen like pharmacy benefit managers (PBMs) could cut a significant portion of the nation’s annual drug tab, finds a new analysis from the USC Schaeffer Center for Health Policy & Economics.

PBMs, who negotiate drug benefits on behalf of insurers and employers, are typically paid based on a percentage of a drug’s list price before rebates and other discounts are applied. Federal and state policymakers have proposed delinking PBM compensation from list prices in response to evidence that PBMs often steer patients toward higher-priced drugs — even when cheaper alternatives are available — to boost their own profits.

Shifting instead to a transparent, fixed payment model for PBMs and other intermediaries in the prescription drug supply chain would reduce annual net drug spending by $95.4 billion (or nearly 15%) without undermining pharmaceutical innovation, according to research from Schaeffer Center Director of Health Policy Geoffrey Joyce published July 24 in Health Affairs Scholar.

Fair Compensation

The U.S. spent $650 billion on prescription drugs in 2023 after factoring in discounts, with about one-third ($215 billion) flowing to PBMs, wholesalers and pharmacies — though the exact division of these costs is unclear. However, using simplified estimates, Joyce finds spending on these intermediaries would have dropped to $119.6 billion under fair and transparent compensation models.

Here’s how those costs break down:

• PBMs: A fixed administrative fee of $4 per claim would result in total costs of $27.6 billion in 2023. Payments to PBMs could be reasonably adjusted for hitting cost and quality targets.
• Wholesalers: Entities that purchase drugs from manufacturers in bulk add about a 3% markup on average to the list price before selling to pharmacies, hospitals and long-term care facilities. Applying that markup to net prices instead would yield $19.5 billion in total revenues, less than the $27.5 billion these firms reported in 2023.
• Pharmacies: A $10.50 per prescription dispensing fee would have generated gross venues of $72.5 billion. That rate is commonly used by state Medicaid programs and aligns with the pricing model used by Mark Cuban’s Cost Plus Drug Company.

Reform Implications

A proposal to delink PBM compensation from list prices was included in earlier drafts of sweeping domestic policy legislation before it was dropped from the final version that was recently enacted. However, policymakers have expressed continued interest in reforming PBM practices amid growing evidence that these firms use their considerable market power to artificially inflate drug prices and restrict access to essential medications.

Joyce warns that some commonly proposed reforms, such as those aimed at curbing consolidation and increasing PBM transparency, are too modest to meaningfully change PBM behavior given how quickly the industry has shifted tactics in the face of heightened scrutiny.

“Delinking compensation from list prices is the clearest and most effective way to tackle the warped incentives in the prescription drug supply chain that drive up costs for patients without adversely affecting manufacturers’ incentive to innovate,” says Joyce, who is also chair of the Department of Pharmaceutical and Health Economics at the USC Mann School of Pharmacy and Pharmaceutical Sciences.

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Journal

Health Affairs Scholar

DOI

10.1093/haschl/qxaf126 

COI Statement

No conflicts declared

 

Naval Research hydrogen tech goes tactical

The Hydrogen Small Unit Power (H-SUP) prototype offers a low-signature solution for electric power production, up to 1.2 kW of continuous power, in a ruggedized package

Naval Research Laboratory

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U.S. Naval Research Laboratory Principal Investigator Kevin Cronin (left) and U.S. Marine Corps Expeditionary Energy Office Science and Technology Analyst Capt. Joshua Ashley (right) train Marines with Combat Logistics Company 33 on the warfighting utility of hydrogen fuel cell systems during an exercise at Marine Corps Training Area Bellows, Hawaii, March 4, 2024. (Photo by DIU Energy)

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Credit: Photo by DIU Energy

WASHINGTON, D.C. – U.S. Naval Research Laboratory (NRL) has prototyped a Hydrogen Small Unit Power (H-SUP) system to reduce detectability and improve readiness of Marine Corps in expeditionary warfare operations.

NRL’s H-SUP is a portable fuel cell electric generator with greater energy per weight than batteries and lower audible and thermal signatures than combustion generators.

“This is more than a power system. It’s a capability that supports distributed operations and extends mission range. That’s strategic value,” said NRL Principal Investigator Kevin Cronin. “At NRL, we champion long-term modernization while working hand in glove with end-users across the services. Our investment today with the Marines in low-signature power intends to shape the future of how Marines fight – more independently, more efficiently, and with less logistical burden.”

The use of hydrogen in key applications can lead to increased electrical efficiency and energy density, increased operational range, reduced thermal and audible signature, and reduced maintenance requirements; ultimately increasing lethality of the force and decreasing logistical sustainment requirements.

“Warfighter feedback is a critical component of the technology development process and will be used to inform requirement definition and future research and development activities,” said Capt. Joshua Ashley, U.S. Marine Corps, Expeditionary Energy Office (E2O) Science and Technology Analyst. “The E2O serves as the link between the warfighter and the lab, providing feedback to refine the system and accelerate acquisition.”

The Marine Corps established the E2O to conduct research and development in technologies, which can be the difference between mission success and failure, while reducing energy consumption with the goal of increasing reach, persistence, and lethality. E2O works closely with the combat and technology development communities and serves as the proponent for Expeditionary Energy in the force development process.

“H-SUP isn’t just innovative – it increases lethality by keeping us powered and hard to find,” Ashley said. “We ensure this technology meets the needs of Marines on the ground – quiet, efficient, and reliable power that supports expeditionary operations.”

By evaluating H-SUP in operational scenarios, the team is reducing risk and accelerating requirements development of technology that increases endurance and improves the autonomy of small units.

H-SUP was field tested at Marine Corps Base Camp Lejeune in July 2022, Marine Corps Air Station Yuma in February 2025, Marine Corps Training Area Bellows in March 2025, an Army event at Fort Polk with the 101st Airborne in May 2025, and most recently at Marine Corps Air Ground Combat Center Twentynine Palms in May 2025.

“Our mission at NRL is to advance science that solves today’s problems while anticipating tomorrow’s threats,” Cronin said. “Hydrogen fuel cells fit both categories.”

NRL and E2O are translating feedback from Marines to refine the system for usability, survivability, and integration. This leads to adoption, not just prototypes.

“My role at NRL is to turn advanced science into operational capability,” Cronin said. “We built H-SUP not just to work in the lab, but to serve Marines in the field. Through collaboration with partners and direct feedback from users, we’re pushing this from prototype to practical.”

The fuel cell system in H-SUP was originally developed for use in unmanned vehicles. The high specific energy content of hydrogen enables increased range and endurance for those systems. This has been demonstrated in the Naval Air Warfare Center Aircraft Division’s H2 Stalker program, where this same fuel cell was integrated into the Stalker VXE30.

H2 Stalker provides greater combined power and energy to weight than alternate Stalker VXE30 configurations, enabling improved range, endurance, and dash metrics compared to the baseline VXE30. H2 Stalker successfully completed multiple flight tests and demonstrations in various environmental conditions.

“We’re pushing technology into the hands of warfighters through real partnerships with industry and acquisition commands,” Cronin said. “In addition, the fuel cell in the H-SUP can also be used to power unmanned aerial vehicles to extend mission endurance. Lastly, fuel cells can support multiple aspects of the U.S. Marine Corps concept of Expeditionary Advanced Base Operations.”

NRL has developed fuel cell technology and the H-SUP system with sponsorship from the Office of Naval Research, Office of the Secretary of Defense Manufacturing Science and Technology Program, Naval Air Systems Command, and the USMC E2O; in addition to collaboration with industry partners, Northwest UAV and Noble Gas Systems.

U.S. Naval Research Laboratory Principal Investigator Kevin Cronin (left) trains Marines from Marine Wing Support Squadron 371 on the operation of the Hydrogen Small Unit Power (H-SUP) at Marine Corps Air Station Yuma, Arizona, Feb. 19, 2025. (U.S. Navy photo)

Credit

U.S. Navy Photo

About the U.S. Naval Research Laboratory

NRL is a scientific and engineering command dedicated to research that drives innovative advances for the U.S. Navy and Marine Corps from the seafloor to space and in the information domain. NRL is located in Washington, D.C. with major field sites in Stennis Space Center, Mississippi; Key West, Florida; Monterey, California, and employs approximately 3,000 civilian scientists, engineers and support personnel.

For more information, contact NRL Corporate Communications at (202) 480-3746 or nrlpao@us.navy.mil. Please reference package number at top of press release.

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BUILD A GIANT BEACH UMBRELLA

USC teams up with ShadeLA coalition to cool Los Angeles ahead of 2028

ShadeLA, a new USC-led initiative, unites civic, academic and community partners to expand urban tree canopy and shade infrastructure — building lasting heat resilience for Angelenos well beyond 2028.

University of Southern California

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Extreme heat is the most dangerous climate threat facing Los Angeles — one that’s growing more severe each year. (Graphic/USC Brand Creative)

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Credit: (Graphic/USC Brand Creative)

USC on Wednesday announced ShadeLA, a bold new collaborative effort to cool Los Angeles by expanding tree canopy and shade infrastructure in key public and community spaces.

With major sporting events like the 2026 FIFA World Cup, 2027 Super Bowl and the 2028 Olympic and Paralympic Games on the horizon — and as climate change drives more frequent and intense heat waves — ShadeLA aims to keep Angelenos and visitors safe while leaving a lasting legacy of resilience.

ShadeLA is led by USC Dornsife Public Exchange in collaboration with UCLA Luskin Center for Innovation, and with participation by the city of Los Angeles, County of Los Angeles Chief Sustainability Office, L.A. Metro and the Los Angeles Organizing Committee for the 2028 Olympic and Paralympic Games (LA28). The campaign is powered by a growing list of community-based organizations who have led on-the-ground shade projects across Los Angeles and the region, helping ensure solutions are locally driven and responsive to neighborhood priorities. ShadeLA builds on the city’s leadership on tree canopy equity and its longstanding partnership with USC’s Urban Trees Initiative.

“For years, USC Dornsife Public Exchange has been leading the way on sustainable urban forestry,” USC Interim President Beong-Soo Kim said. “Now, we’re proud to be spearheading ShadeLA, an important initiative that leverages our cutting-edge research to improve quality of life for all of us in Los Angeles.”

“Extreme heat continues to impact the lives of the people of Los Angeles, and this partnership empowers our communities to come together, build resilience and cool our neighborhoods,” L.A. Mayor Karen Bass said. “As we prepare to welcome the world, this initiative will leave a lasting legacy for Angelenos for years to come.”

ShadeLA: Tackling the deadliest climate threat of our time

Extreme heat is the most dangerous climate threat facing Los Angeles — one that’s growing more severe each year. The city’s dense population, concrete infrastructure and uneven tree cover amplify temperatures, especially in vulnerable neighborhoods. Extreme heat leads to an estimated 1,500 excess daily emergency room visits per “heat day” across L.A. County. By 2050, the number of extreme heat days is projected to increase by 31%, placing even greater strain on low-income communities and communities of color, who face higher risks of heat-related illness and limited access to cooling and care.

Shade is one of the most effective, low-cost ways to reduce heat risk. Whether from a tree, canopy, awning or bus shelter, shaded areas can feel between 35 degrees Fahrenheit to 70 degrees Fahrenheit cooler than in the sun. It’s simple, scalable and can be integrated into everyday spaces where people live, work and move.

Los Angeles County has less shade than the national average. Urbanized areas of the county only have an average of 21% shade at noon when the sun is directly overhead, compared with the national average of 27%, according to the UCLA Luskin Center for Innovation and their National Shade Map that is part of American Forests’ Tree Equity Score.

“ShadeLA is about more than trees and structures — it’s about people,” said Monica Dean, climate and sustainability practice director at USC Dornsife Public Exchange. “This campaign addresses heat not just as an environmental issue, but as a public health, infrastructure and community challenge. We’re designing solutions to protect lives — during major events and every day.”

What ShadeLA will do

The campaign focuses on four key goals:

• Add shade: ShadeLA is working with public agencies, schools, businesses and community organizations to bring new shade to the places people need it most — on schoolyards, sidewalks, parks and other everyday spaces.
• Protect existing shade: Maintaining the shade we already have — whether from mature trees or built structures — is critical to keeping communities cool. ShadeLA supports local caretakers, provides guidance and training, and works with public agencies to clarify responsibilities and secure funding for ongoing upkeep.
• Use science to inform decisions: Research, data and planning tools are used to pinpoint where shade is most needed, evaluate which solutions will have the greatest impact and track results over time. This evidence-based approach helps ensure that shade projects are not only well-placed, but also aligned with public health, climate and community priorities — turning research insights into real-world action.
• Make it easy to act: Adding shade shouldn’t be complicated — but too often, it is. ShadeLA works to streamline the process by offering practical tools, clear guidance and technical support for residents, businesses, schools and agencies. Many resources are already available, but confusion and misperceptions can stand in the way. By addressing these barriers head-on, the campaign empowers more people to take part in building a cooler Los Angeles.

These efforts will evolve and be developed in coordination with local communities and organizations across Los Angeles. Together, they aim to build a more comfortable and livable L.A., one shaded space at a time.

“We are committed to helping residents keep their cool as climate impacts intensify,” said Rita Kampalath, chief sustainability officer for Los Angeles County. “Creating more built and natural shade will not only benefit visitors, but will pay dividends for vulnerable residents for generations to come.”

From planting trees to building shade

USC Dornsife Public Exchange and the UCLA Luskin Center for Innovation bring considerable experience to ShadeLA. Public Exchange leads the USC Urban Trees Initiative, a multi-year, data-driven effort to help the city of Los Angeles prioritize tree planting in areas of greatest need. That work combines environmental, public health and equity data to guide tree planting efforts and contributed to the planting and care of nearly 1,000 trees in South and East Los Angeles.

UCLA is demonstrating how trees and other forms of shade affect people’s heat experiences and measuring the impact of shade in places such as homes, schools and streetscapes. For example, the new National Shade Map, developed by the UCLA Luskin Center for Innovation and American Forests, empowers communities to see when and where they have shade, providing decision-makers the first accessible, comprehensive opportunity to identify “shade deserts” and prioritize investments to mitigate the impacts of heat.

While trees are essential, they aren’t always feasible — especially in dense, paved or transit-heavy areas where space, soil and infrastructure constraints limit planting. ShadeLA builds on this foundation by expanding the focus to include built shade solutions like canopies, awnings and modular structures.

“We’re at a critical juncture as L.A. gets hotter, and we are thrilled to partner with USC, to lead with evidence, and to collectively envision a livable future for our region,” said Edith de Guzman, water and adaptation policy cooperative extension specialist at the UCLA Luskin Center for Innovation.

To launch the campaign, ShadeLA is introducing a set of activities to spark innovation, engage the public and guide smart investments. In the weeks ahead, new survey data from LABarometer, based at USC Dornsife’s Center for Economic and Social Research, will offer insights into how residents experience heat and value shade in their neighborhoods.

A global spotlight on Los Angeles

L.A. will soon welcome the world for major global sporting events. In 2026, SoFi Stadium will host eight FIFA World Cup matches, including the U.S. men’s national team opener. In 2028, Los Angeles will host the Olympic and Paralympic Games.

“LA28 is committed to incorporating sustainable solutions throughout the Games’ footprint,” said Becky Dale, vice president of sustainability at LA28. “ShadeLA supports not only keeping spectators cool during the Games, but also leaving a legacy of a cooler, greener Los Angeles for all Angelenos.”

By expanding shade and modeling collaborative climate action, ShadeLA aims to show how a major global city can tackle extreme heat while creating safer, healthier public spaces for everyone — now and for decades to come.

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For more information, see the ShadeLA Fact Sheet.

 

One billion-year-old rules of protein stability revealed

Huge experiment reveals rules governing protein stability, paving way to faster drug and enzyme design

Center for Genomic Regulation

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The core (gold and black) and surface (silver) residues that were randomised

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Credit: Albert Escobedo/Centro de Regulación Genómica

Proteins are life’s molecular workhorses, doing everything from turning sunlight into food to fighting viruses. They are built from 20 different types of amino acid molecules, so even a small protein made of 60 amino acids in length can, in theory, be constructed in a quinquavigintillion, or 10⁷⁸, different ways. That’s about as many atoms there are in the entire universe. 

How did evolution choose the handful of amino acid combinations that result in proteins which fold, stay stable and get the job done? And can we learn these rules to help protein engineers design better medicines and greener catalysts? A study published today in the journal Science has taken an important step toward answering both questions. 

Proteins have a core that keeps the structure from collapsing, while the surface does most of the work, such as binding with other molecules. For decades, biologists assumed that altering the core was like removing a load-bearing wall: one wrong move and the whole structure collapses. Because buried amino acids are packed tightly, it seemed logical that any alteration can force neighbouring amino acids to shift, resulting in unpredictable domino effects that ripple throughout the protein. 

With this classical picture of protein stability, most changes to the building blocks of a protein would set off hidden booby traps and threaten to knock the entire structure out of shape. Given the sheer number of combinations possible, the odds of evolution stumbling onto a safe route to create new proteins seems very small. 

The study turns this idea on its head. Researchers at the Centre for Genomic Regulation (CRG) in Barcelona and the Wellcome Sanger Institute in Hinxton, UK, studied a human protein domain (the functional bit of a protein) called FYN-SH3, making hundreds of thousands of variants and testing which ones still folded and worked. 

The experiments revealed that SH3 retained its shape and function across thousands of different core and surface combinations. Only a few true, load-bearing amino acids existed in the protein’s core. 

“Our data challenges the dogma of proteins being a delicate house of cards. The physical rules governing their stability is more like Lego than Jenga, where a change to one brick threatening to bring the entire structure down is a rare, and crucially, predictable phenomenon,” explains Dr. Albert Escobedo, first author of the study and postdoctoral researcher at the Centre for Genomic Regulation.  

The team used the large amount of data generated by their experiments to test whether learning the rules from one protein could help explain the evolution of all related proteins that exist in Nature. They fed the data into a machine-learning algorithm, which helped them create a tool that can predict whether an SH3 sequence will stay stable. 

SH3 domains have been diversifying since early multicellular life, roughly one billion years ago. The researchers compared their model against 51,159 natural SH3 sequences found in public databases spanning the entire tree of life, including bacteria, plants, insects and humans. The algorithm correctly flagged almost all SH3 domains as stable, even when a test sequence shared less than a quarter of the sequence with the human version.  

“Evolution didn’t have to sift through an entire universe of sequences. Instead, the biochemical laws of folding create a vast, forgiving landscape for natural selection,” says Dr. Escobedo. 

Implications for protein engineering 

The field of protein engineering currently relies on companies screening thousands of protein variants with minimal changes, inching forward a few changes at a time and making the design of new enzymes, drugs and vaccines slow and expensive. 

The confirmation that protein stability follows simpler rules than previously thought can slash the trial-and-error phase for protein design, saving significant time and effort for developing proteins with medical or industrial applications, such as greener catalysts or longer-lasting medicines.  

For example, therapeutic enzymes often fail because their surfaces trigger immune flare-ups. Resurfacing these proteins is labour intensive, requiring lots of trial and error to avoid the scaffold from collapsing and sabotaging a promising design. Now, protein engineers can propose bolder designs, including dozens of simultaneous changes, on computers and walk into the lab already knowing which variants are most likely to survive both folding and functional tests.  

“The ability to predict and model protein evolution opens the door to designing biology at industrial speed, challenging the conservative pacing of protein engineering,” explains ICREA Research Professor Ben Lehner, corresponding author of the study with dual affiliation at the Centre for Genomic Regulation (CRG) and the Wellcome Sanger Institute. 

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Journal

Science

DOI

10.1126/science.adq3948 

Article Title

Genetics, energetics, and allostery in proteins with randomized cores and surfaces

Article Publication Date

24-Jul-2025