Publisher Health

As smoke from wildfires crosses state and international borders more frequently, tracking and studying it is increasingly important for shaping air quality and health measures around the world.An upcoming study from researchers at Stanford University offers a new way to trace far-flung smoke and pollution back to individual wildfires of origin.What’s burning in a wildfire determines what kind of pollution is in the smoke. A forest fire burns differently from a fire in a swamp, or a fire that burns buildings. As smoke travels, its chemical composition may change with time and distance.The findings could help officials to determine which wildfires are likely to have the biggest health consequences for the greatest number of people, and to allocate firefighting resources accordingly.“We don’t find that fire suppression resources are often spent on the fires that are most damaging from a health perspective,” said Jeff Wen, a Ph.D. candidate in Earth system science at Stanford and the study’s lead author.Others have done similar research before, but at a much smaller scale. The new study, not yet peer reviewed, would be the first to cover the whole contiguous United States, according to the authors.“Historically, we haven’t really been able to study those types of questions at a broad spatial, temporal scale,” Mr. Wen said.It’s clear that wildfires have become more frequent and intense in recent years, fueled in part by climate change’s role in drying out many landscapes. Less clear to scientists has been how smoke from these fires has changed over time. The new study shows that as fires have worsened, so has their smoke: From 2016 to 2020, the U.S. population experienced double the smoke pollution that it did 10 years earlier, from 2006 to 2010. While the study focused on historical data, some of its methods can also be used to predict where smoke from a new fire will travel in the future.The researchers focused on a pollutant called particulate matter, made of very small solid particles floating in the air, which can enter people’s lungs and blood and lead to problems such as difficulty breathing, inflammation and damaged immune cells.A helicopter survey of wildfires burning near Mistissini, Quebec, this month.Canadian Forces, via ReutersUsing their new method, Mr. Wen and his team ranked all of the wildfires observed in the United States from April 2006 to December 2020 by the resulting smoke exposure. They found that the worst fire by smoke exposure during this period was the 2007 Bugaboo Fire, which burned more than 130,000 acres in and around the Okefenokee Swamp, straddling Georgia and Florida.This initially surprised the researchers, since Western states tend to have more large fires. But the Eastern Seaboard is more densely populated, so smoke from the Bugaboo Fire didn’t have to go far to affect many millions of people. Peatlands like the Okefenokee Swamp also tend to burn slowly, Mr. Wen said, releasing more particulate matter into the air.The worst fires in their ranking did not match up very well with the worst fires in traditional rankings, such as acres burned or buildings and infrastructure lost. More firefighting resources were not necessarily deployed to the smokiest fires, either.“We often suppress fires mainly because of structures and immediate threat to life,” said Bonne Ford, an atmospheric scientist at Colorado State University who was not involved in this study. While it’s important to save lives and help rural communities in immediate harm’s way, it’s “short-term thinking” to focus only on those immediately dangerous fires and ignore others that may harm many people farther away through smoke exposure.Dr. Ford and others have studied wildfire smoke patterns, as well as the resulting exposure to particulate matter pollution. But the Stanford researchers have pulled off something new by putting the two together, she said, especially over so many years and so much land area.One aspect of the study Dr. Ford took issue with was treating all human exposure to particulate matter in smoke the same, no matter where it happened. Some people are more vulnerable to air pollution, she said, depending on their age, pre-existing health conditions, other environmental factors and whether they can take precautions such as wearing face masks outside and using air filters inside. Future research could combine Dr. Wen’s methods with existing vulnerability indexes, Dr. Ford said.There are also more precise ways to track and predict where smoke travels, according to John Lin, an atmospheric scientist at the University of Utah who was not involved in the study. Aside from that, Dr. Lin thought the Stanford study would be very useful in figuring out the real human toll of wildfire smoke.Smoke traveling long distances is “the new normal,” he said. This reality challenges the ways governments have historically dealt with air quality, through regulations like the Clean Air Act. Now that pollution is increasingly crossing borders, Dr. Lin said, the way that people manage air quality should evolve accordingly.

With an aging global population comes a need for new sensor technologies that can help clinicians and caregivers remotely monitor a person’s health. New smart pants based on fiber optic sensors could help by offering a nonintrusive way to track a person’s movements and issue alerts if there are signs of distress.
“Our polymer optical fiber smart pants can be used to detect activities such as sitting, squatting, walking or kicking without inhibiting natural movements,” said research team leader Arnaldo Leal-Junior from the Federal University of Espirito Santo in Brazil. “This approach avoids the privacy issues that come with image-based systems and could be useful for monitoring aging patients at home or measuring parameters such as range of motion in rehabilitation clinics.”
In the Optica Publishing Group journal Biomedical Optics Express, the researchers describe the new smart pants, which feature transparent optical fibers directly integrated into the textile. They also developed a portable signal acquisition unit that can be placed inside the pants pocket.
“This research shows that it is possible to develop low-cost wearable sensing systems using optical devices,” said Leal-Junior. “We also demonstrate that new machine learning algorithms can be used to extend the sensing capabilities of smart textiles and possibly enable the measurement of new parameters.”
Creating fiber optic pants
The research is part of a larger project focused on the development of photonic textiles for low-cost wearable sensors. Although devices like smartwatches can tell if a person is moving, the researchers wanted to develop a technology that could detect specific types of activity without hindering movement in any way. They did this by incorporating intensity variation polymer optical fiber sensors directly into fabric that was then used to create pants.

The sensors were based on polymethyl methacrylate optical fibers that are 1 mm in diameter. The researchers created sensitive areas in the fibers by removing small sections of the outer cladding fiber core. When the fiber bends due to movement, this will cause a change in optical power traveling through the fiber and can be used to identify what type of physical modification was applied to the sensitive area of the fiber.
By creating these sensitive fiber areas in various locations, the researchers created a multiplexed sensor system with 30 measurement points on each leg. They also developed a new machine learning algorithm to classify different types of activities and to classify gait parameters based on the sensor data.
Classifying activities
To test their prototype, the researchers had volunteers wear the smart pants and perform specific activities: slow walking, fast walking, squatting, sitting on a chair, sitting on the floor, front kicking and back kicking. The sensing approach achieved 100% accuracy in classifying these activities.
“Fiber optic sensors have several advantages, including the fact that they are immune to electric or magnetic interference and can be easily integrated into different clothing accessories due to their compactness and flexibility,” said Leal-Junior. “Basing the device on a multiplexed optical power variation sensor also makes the sensing approach low-cost and highly reliable.”
The researchers are now working to connect the signal acquisition unit to the cloud, which would enable the data to be accessed remotely. They also plan to test the smart textile in home settings.
This work was performed in LabSensors/LabTel in the scope of assistive technologies framework funded by Brazilian agencies FINEP and CNPq.

A groundbreaking study led by researchers at the Faculty of Dentistry of the University of Hong Kong (HKU), in collaboration with multiple international institutions has successfully demonstrated the use of artificial intelligence (AI) in detecting gum inflammation, also known as gingivitis, from intraoral photographs.
This cutting-edge technology can revolutionise early detection and prevention of oral and systemic diseases linked to gum inflammation, such as tooth loss, cardiovascular diseases, and diabetes.
The study, published in the International Dental Journal, an official journal of the World Dental Federation (FDI), shows that AI algorithms can analyse patients’ intraoral photographs to detect signs of inflammation like redness, swelling, and bleeding along the gum margin with over 90% accuracy, matching the visual examination of a dentist. This innovative technology enables population-wide monitoring of gum health and paves the way for more personalised dental care.
The study was conducted by researchers from the HKU Faculty of Dentistry, the Department of Computer Science at Hong Kong Chu Hai College, the School of Information Engineering at Guangdong University of Technology, and the Faculty of Dentistry at The National University of Malaysia. It involved developing and testing an AI model using a dataset of over 567 images of gums with varying degrees of inflammation and is one of the first to explore the use of AI in detecting gum inflammation.
Dr Walter Yu-Hang Lam, the study’s leading HKU researcher, emphasises the significance of the findings for the early detection and management of gum disease.
“Many patients do not attend regular dental check-ups, and they only seek dentists to alleviate pain when their teeth are at the end stage of dental diseases, in which tooth loss is inevitable, and only expensive rehabilitative treatments are available. Our study shows that AI can be a valuable screening tool in detecting and diagnosing gum disease, one of the key indicators of periodontal disease, allowing earlier intervention and better health outcomes for the population.” He said.
The use of AI in dentistry has been gaining momentum in recent years, with researchers exploring various applications of the technology, from detecting cavities to predicting treatment outcomes to biomimetic design of artificial teeth. The use of AI in gum inflammation detection is a promising development that could revolutionize how gum disease is detected, treated, and even prevented.
Dr. Reinhard Chun-Wang Chau, an HKU co-investigator of the team, pointed out the benefits of using intraoral photographs in conjunction with AI technology and said: “Based on these intraoral photographs, patients can address the area that they did not clean well and seek dentist’ help at an earlier stage.”
The collaborative nature of this study is a testament to the power of interdisciplinary research and knowledge exchange. By bringing together experts from different fields and regions, the researchers can develop an AI model that could accurately detect gum inflammation, with important implications for public health and wellbeing.
For the project’s next stage, Dr Lam plans to utilize the AI system for community services, making the technology more accessible to elderly and underserved communities, with the aim of improving oral health outcomes and reducing health disparities.

A research team led by Professor Kelvin Yeung from the Department of Orthopaedics and Traumatology, School of Clinical Medicine, LKS Faculty of Medicine, the University of Hong Kong (HKUMed) has designed a new microneedle patch to offer a highly-effective non-antibiotic approach for the treatment of skin infection. In brief, the design engineered with ultrasound-responsive zinc-based metal-organic framework (MOF) antibacterial nanoparticles promises pain-free delivery to treat bacterial infection on skin tissue and facilitate skin repair at the same time. The novel microneedle is around 50 microns in diameter, similar to a typical hair. The findings have been published in Science Advances.
Acne is a common skin disease worldwide that upsets more than 80 % of teenagers and young adults.1 The primary cause can attribute to excessive lipid secretion that clogs the hair follicles, thereby establishing a hypoxic microenvironment in skin tissue. This undesirable condition particularly favours to the proliferation of Propionibacterium acnes (P. acnes) bacteria. Infected pimple, regarding as one of skin infections, is mainly caused by P. acnes bacteria that affects millions of people worldwide. It not only causes the patients with significant physical and emotional distress, but may also develop into chronic inflammatory condition without proper treatment. The clinical management normally includes non-prescription treatment (i.e., benzoyl peroxide and salicylic acid), or the administration of antibiotics orally or topically. However, such treatments can be ineffective or have unpleasant side effects.
In general, the first-line treatment for infected pimple is antibiotics administered either oral or topical. However, the therapeutic effect of topical antibiotic treatment is concerning, particularly when the drugs pass through the skin tissue. Also, the treatment becomes less effective, when bacteria are drug resistant or when they migrate to subcutaneous tissue. Especially, P. acnes bacteria can secrete extracellular polysaccharides to form biofilm that blocks out the attacks initiated by antibacterial agents or immune cells.
Even most microneedle products on the market mainly use pharmaceutical ingredients to treat acne. However, repeated applications of antibiotics may reduce the sensitivity of bacteria to drugs. Patients who have been affected by acne for a long time will know that the effects of the same treatment products can be significantly reduced after long-term use.
HKUMed team has invented a new microneedle patch that facilitates the transdermal delivery of ultrasound-responsive antibacterial nanoparticles to treat the infection induced by P. acnes at minimal invasive approach. In the current design, ultrasound-responsive antibacterial nanomaterials are introduced to the microneedle patch that responds to bacterial infection quickly and efficiently. The use of drugs is avoided in the treatment of acne. The modified nanoparticles comprised of ZnTCPP and ZnO are able to produce a substantial amount of reactive oxygen species (ROS) subject to ultrasound stimulation that can effectively oxidize the key cellular macromolecules of bacteria. The results demonstrate that the killing of P. acnes bacteria mediated by ROS can reach to 99.73% after 15 minutes of ultrasound stimulation. Also, the levels of inflammatory markers, including tumour necrosis factor-a (TNF-α), interleukins (ILs), and matrix metalloproteinases (MMPs) are significantly reduced. Furthermore, the zinc ions released can elevate the DNA replication-related genes, thereby augmenting more fibroblasts towards superior skin repair.
Professor Kelvin Yeung Wai-kwok, remarked, ‘The new microneedle patch enabling ROS generation upon ultrasound stimulation, regarding as a non-antibiotic and transdermal approach, can not only effectively address the infection induced by P. acnes bacteria, but also facilitates the skin repair due to zinc ion release. Due to the specific killing mechanism of ROS, we believe that this design is also able to address the other skin infections induced by fungi, parasites, or viruses, such as tinea pedis (namely “Athlete’s Foot” or “Hong Kong Foot” in slang).’
This research study was led by Professor Kelvin Yeung Wai-kwok, Department of Orthopaedics and Traumatology, School of Clinical Medicine, HKUMed. The first author Xiang Yiming is the PhD candidate under Professor Yeung’s supervision. The research interests of Professor Yeung’s team include orthopaedic biomaterials, musculoskeletal tissue regeneration and anti-bacterial infection.
This work was jointly supported by the National Key R&D Programmes of China (2018YFA0703100), the General Research Fund of Hong Kong Research Grants Council (Nos. 17207719 and 17214516), the Health Bureau Health and Medical Research Fund (Nos.19180712, 20190422 and 21200592), the Innovation and Technology Fund Partnership Research Programme (PRP/030/30FX), the National Science Fund for Distinguished Youth Scholars (No. 51925104), Shenzhen Science and Technology Programme (Nos. JSGG20180507183242702 and JCYJ20210324120009026), and the Shenzhen’s Sanming Project of Medicine — ‘Team of Excellence in Spinal Deformities and Spinal Degeneration’ (SZSM201612055).

Johns Hopkins Medicine scientists say they have developed a nanoparticle — an extremely tiny biodegradable container — that has the potential to improve the delivery of messenger ribonucleic acid (mRNA)-based vaccines for infectious diseases such as COVID-19, and vaccines for treating non-infectious diseases including cancer.
Results of tests in mice, reported June 20 in the Proceedings of the National Academy of Sciences, show that the degradable, polymer-based nanoparticle carrying an mRNA-based vaccine, when injected into the bloodstream of mice, was able to travel to the spleen and activate certain cancer-fighting immune cells in a targeted way.
The researchers also found that mice with melanoma survived twice as long, and twice the number of mice with colorectal cancer survived long-term, following an injection of the Johns Hopkins-made nanoparticles compared with mice that received control treatments.
In addition, the scientists found that throughout the mice, about half of the specialized immune cells responsible for recognizing and destroying unhealthy cells such as those infected with viruses or cancer, had been activated and primed to recognize the specific invading cancer cells.
Nanoparticles made from lipids (a type of fatty acid) are the basis for mRNA COVID-19 vaccines. Such lipid-based, preventive vaccines are typically injected into muscle.
However, while muscle contains many cells capable of expressing mRNA that can lead to an antibody response, there are relatively few dendritic cells — immune cells that teach the rest of the immune system, in particular T-cells, to seek and destroy cancer cells. Scientists may be able to improve cancer treatment-focused vaccines by enhancing their ability to reach dendritic cells with their mRNA instructions.

Injecting lipid-based vaccines into the bloodstream has proved difficult because the vaccines tend to travel directly to the liver, where they are degraded.
“Our goal was to develop a nanoparticle that wouldn’t be sent directly to the liver and could effectively teach immune system cells to seek and destroy the appropriate target,” says Jordan Green, Ph.D., professor of biomedical engineering at the Johns Hopkins University School of Medicine.
Green explains that to make stronger vaccines for infectious disease and for noninfectious disease, such as cancer, the nanoparticle’s mRNA contents are needed to reach, enter and be expressed in dendritic cells. After the mRNA is expressed in dendritic cells, it is quickly degraded, and the resulting immune cell response can last much longer after the mRNA and nanoparticles are long gone, say the researchers.
Customarily, scientists have accomplished this cell targeting by attaching proteins to a nanoparticle that bind specifically, like a lock and key, to a target cell’s surface. However, in laboratory tests of this approach, only a small percentage of nanoparticles reach the target cell, and the scientists say there are manufacturing challenges with such approaches.
Green and his team tested various materials and ultimately decided to encase a desired mRNA in a polymer-based vessel. Polymers are repetitive groups of small molecules that form a tightly bonded chain to create a larger molecule, and they can be designed to biodegrade back to small molecules in the body. Green’s team engineered the nanoparticle’s ratio of water-loving to water-phobic molecules just right — a key to making the nanoparticle more apt to encapsulate mRNA, and making it easier to enter the target cell.

Then, Green’s team used disulfide bonds to make the nanoparticles degrade quickly inside the target cell. The polymers used to construct the nanoparticles contained end-capping molecules that have an affinity for a specific tissue type.
Finally, Green and his team added a “helper,” also known as an adjuvant, to the nanoparticle. The adjuvant helps activate the dendritic cell.
In experiments of cells grown in the laboratory, the researchers found that the nanoparticle configuration they developed was taken up by primary dendritic cells at levels about fifty-fold higher than mRNA by itself. In mice, nearly 80% of cells in the spleen that the nanoparticles reached were the target dendritic cells.
In one set of experiments, the researchers used mice with immune cells genetically engineered to glow red if the nanoparticle was opened to reveal its mRNA contents. They found that 5% to 6% of all dendritic cells in the spleen successfully took up, opened and processed the nanoparticle, and that this happened mostly in dendritic cells compared with other immune cells including macrophages, monocytes, neutrophils and T-cells.
“The immune system is designed to work through an amplified response, where dendritic cells teach other immune cells what to look for in the body,” says Green.
Later experiments showed that half of mice with colorectal cancer survived long-term after receiving two injections of the new nanoparticle formulation plus an immunotherapy drug, compared with 10% to 30% that survived after treatment with other nanoparticle formulations and an immunotherapy drug or the immunotherapy drug alone.
Of the long-term surviving mice with colorectal cancer, all of them lived without additional treatment when the researchers gave them additional colorectal cancer cells, suggesting a long-term immunological response that prevented the cancer from returning.
The researchers also found that 21 days after treatment with the new nanoparticle, 60% of the cell-killing T-cells in the mice were armed to recognize and attack the colorectal cells. Similarly, in mice with melanoma, about half of the same type of T-cells were primed to attack melanoma.
“The nanoparticle delivery system was able to create an army of T-cells that can recognize cancer-linked antigen,” says Green.
“This new nanoparticle delivery system may improve the way vaccines are given for infectious disease, and it may open a new avenue for treating cancer as well,” Green says.
Other contributors to the research are Elana Ben-Akiva, Johan Karlsson, Shayan Hemmati, Hongzhe Yu, Stephany Tzeng at Johns Hopkins, and Drew Pardoll at the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy and the Kimmel Cancer Center.
This work was supported in part by grants from the National Institutes of Health (R01CA228133, P41EB028239, R37CA246699, F31CA250367), the Goldhirsh-Yellin Foundation, the Swedish Research Council international postdoctoral grant, and the Johns Hopkins Bloomberg-Kimmel Institute for Cancer Immunotherapy.
Ben-Akiva, Karlsson, Tzeng and Green are coinventors on patents the Johns Hopkins University filed on technologies related to this research.
Green and Tzeng are founders and hold shares of stock in OncoSwitch Therapeutics. Both Green and Tzeng serve as board of director members to OncoSwitch Therapeutics. Green is a founder, equity holder and paid consultant for Cove Therapeutics LLC. Green is a founder, equity holder and serves on the board of directors for WyveRNA. The results of the study discussed in this news release could affect the value of OncoSwitch Therapeutics, Cove Therapeutics and WyveRNA. Under licensing agreements between Cove Therapeutics and the Johns Hopkins University and WyveRNA and the Johns Hopkins University, Green and Tzeng are entitled to royalty distributions related to technology described in the study discussed in the news release.

How do cells become cancerous, multiply uncontrollably, and form into tumors? And what role do aberrant embryonic stem cells play? These are big questions explored by medical researchers since the embryonic theory of cancer was first proposed in the 19th century.
Now, in an exciting new study adding to the global pool of knowledge about the roots of human cancers, researchers are establishing a clear link between different types of cancers and their embryonic origins. They also identify new concepts that can be considered in future drug discovery projects and used in standard chemotherapeutics in the clinic.
Published in Cell Chemical Biology, the rigorous study is a collaborative effort by researchers at the uOttawa Faculty of Medicine, McMaster University, and the University of Calgary. Dr. Yannick Benoit is the paper’s co-first author along with Dr. Luca Orlando, a postdoctoral researcher in the lab of Dr. Mick Bhatia at McMaster.
Dr. Benoit says that because cancer typically uses blueprints borrowed from embryonic stem cells to promote its propagation in the body, the team first sought to identify drugs that can force human embryonic stems cells to acquire adult tissue specification.
What they observed was highly compelling. They saw that drugs stimulating the formation of the embryonic nervous system were the most effective against brain tumors. Molecules promoting the acquisition of primitive gut features were best at blocking the formation of colon tumors. And drugs pushing embryonic cells toward becoming fetal blood cells were the most effective at killing leukemia.
“Ultimately, we observed that tumors in tissues with the same embryonic ancestry share similar molecular networks that can be targeted to eliminate cancer more effectively,” says Dr. Benoit, a principal investigator and assistant professor in the Faculty’s Cellular and Molecular Medicine (CMM) department.

It’s taken over a decade for the study to be completed and published. The research began in 2012, and Dr. Benoit worked on portions of the project at McMaster before being recruited to uOttawa in 2017.
This is deeply ambitious research. Essentially, the team was searching for drugs that trigger the specialization of embryonic stem cells toward specific paths of human development. Along the way, they uncovered molecules more effective at re-educating cancer cells based on a path once followed by the affected organ during its fetal life.
“While this concept has been previously proposed over the ages based on observing dissected tumor tissues and inferred through modern computational analyses, our study is the first to provide an experimental demonstration of its applicability in cancer drug discovery,” says Dr. Benoit, who last year was recognized by the Gairdner Foundation for his exceptional research achievements and his future potential.
“Our discovery re-emphasizes that cancer is not a single disease, but hundreds of different ones regrouped under the same name. At the end of our journey, we will not find ‘the cure’ for cancer. Instead, it will be distinct therapeutic avenues with variable chances of success, depending on the type of cancer afflicting a specific patient,” he says.
His lab at uOttawa — which aims to create novel anticancer agents that can target epigenetic features of colorectal cancer stem cells — developed the capacity to measure the effect of certain drugs on cancerous stems cells within colon tumor samples. The McMaster and University of Calgary groups were oriented on leukemia and brain tumors.
Together, the team was able to generalize their findings to 30 tumor types and their healthy tissue counterparts with the aid of data sets generated by researchers across the globe and available to the scientific community.
What are the next steps for Dr. Benoit’s uOttawa lab as the research team explores questions suggested by this study?
“My lab keeps running searches for candidate drugs to destroy cancer stem cell populations in colon tumors,” he says. “Most of our projects start with testing on human embryonic stem cells to see if our compounds of interest alter molecular signatures of early human development.”

A new study led by researchers at The University of Texas MD Anderson Cancer, University of California, Irvine and Baylor College of Medicine has created the world’s largest and most comprehensive map of normal breast tissue, providing an unprecedented understanding of mammary biology that may help identify therapeutic targets for diseases such as breast cancer.
The Human Breast Cell Atlas, published today in Nature, used single-cell and spatial genomic methods to profile more than 714,000 cells from 126 women. The breast atlas highlights 12 major cell types and 58 biological cell states, and identifies differences based on ethnicity, age and the menopause status of healthy women.
“We are thrilled to see the completion of this monumental seven-year project,” said senior corresponding author Nicholas Navin, Ph.D., chair of Systems Biology at MD Anderson. “We were able to leverage many technologies to define, in a very granular way, all the different cell types and cell states in each of the main areas of the breast. We expect this tool will be highly useful for anyone studying breast cancer and other diseases such as mastitis, as well as breast development and lactation failure.”
This team-science effort was led by Navin; Kai Kessenbrock, Ph.D., and Devon Lawson, Ph.D., of UC Irvine; and Bora Lim, M.D., and Alastair Thompson, M.D., of Baylor College of Medicine. The project is part of the global Human Cell Atlas consortium supported by the Chan Zuckerberg Initiative (CZI), which uses recent technologies to generate cellular reference maps for every organ system in the human body.
The human body contains roughly 200 different cell types, 12 of which are found in normal breast tissue. Previous studies on breast tissue have focused primarily on epithelial cells, given that these are known to give rise to cancer, but non-epithelial cell types have not been studied in depth using genomic approaches.
Modern tools, such as single-cell sequencing and spatial mapping, allowed the researchers to perform a highly detailed classification of 12 major cell type clusters, including three types of epithelial cells, lymphatic cells, vascular cells, T cells, B cells, myeloid cells, adipocytes, mast cells, fibroblasts and perivascular cells.

For this study, researchers collected and examined 220 breast tissue samples from 132 women undergoing breast reduction or mastectomy surgery. Of these women, 46% were Caucasian, 41% were African American, 7% were Hispanic, and 6% were of unknown ethnicity. Samples were collected across four institutions, including MD Anderson, UC Irvine, Baylor College of Medicine and St. Luke’s Hospital.
This wide-ranging dataset of normal breast cell types and their diverse states across females also takes into account individual factors including ethnicity, age, BMI, obesity, menopause status, pregnancy and number of births, providing a wealth of information that serves as a powerful resource for the research community.
Spatial mapping highlights four major cell regions, unexpected immune cell populations Spatial mapping techniques, which create a map of the cells within the tissue environment, allowed researchers to look at the RNA and protein composition of the samples to understand how and where the different cell types reside.
These techniques resolved the composition of known cell types and new cell states in the four main regions currently known in the breast, including lobular milk-producing areas, ductal areas that transport milk, connective tissue composed of fibroblasts, and adipose areas made up primarily of fatty tissue.
The researchers were surprised to learn that 16.7% of all cells found in normal breast tissue were composed of immune cells, including the three major types: myeloid, natural killer (NK) T cells and B cells. Scientists previously thought that few immune cells would be found in normal tissue.

Additionally, these immune cells were located primarily around ducts and lobules in three of the four major tissue regions. Understanding the nuances of these different immune cells could help in developing more effective immunotherapies for some subtypes of breast cancer, Navin explained, and in defining their role in breast cancer progression.
The researchers also found an unexpectedly high amount (7.4%) of perivascular cells, including pericytes, which regulate blood flow from capillaries into tissues, and vascular smooth muscle cells, which regulate contractions of the arteries.
Age, menopause and ethnicity play roles in different cell types and cell states The study revealed significant differences in breast tissue composition and cell states that were dependent upon ethnicity, age and menopause status.
For example, African American women are disproportionally affected by aggressive breast cancer subtypes, such as triple-negative breast cancer and inflammatory breast cancer, but little is known about the underlying causes of this disparity. The differences seen in baseline cell states in breast tissues from African American women and Caucasian women could, with further research, highlight potential markers for cancer risk prediction.
Additionally, there were significant differences in the breast tissues from women over the age of 50 compared to younger women, as well as differences in cell states dependent on menopause status. Obesity, body-mass index, pregnancy status and breast density also showed some smaller differences in changes of cell types and cell states.
The authors point out that more studies are needed to further understand the functional role of many of these cell states and to focus on other factors that may significantly advance the knowledge of human breast biology and disease.
The Human Breast Cell Atlas project is ongoing and is actively recruiting participants to build upon and improve the datasets, but the data is freely available now for researchers to access.
This work was supported by the Chan Zuckerberg Initiative, the National Cancer Institute (RO1CA240526, RO1CA236864, 1R01CA234496, F30CA243419), the Cancer Prevention and Research Institute of Texas (CPRIT) Single Cell Genomics Center (RP180684), the American Cancer Society, the Rosalie B. Hite Fund for Cancer Research Fellowship, and the California Institute for Regenerative Medicine (CIRM) Training Grant.

A study of more than 22,000 people with multiple sclerosis (MS) has for the first time identified a genetic variant associated with faster progression of the disease, an accumulation of disability that can rob patients of their mobility and independence over time.
Multiple sclerosis begins as an autoimmune disease where the immune system attacks the brain and the spinal cord, resulting in symptom flares, called relapses, as well as longer-term degeneration known as progression. Despite the development of effective treatments for the inflammatory autoimmune disease, none can prevent increased disability during the neurodegenerative phase of the disease.
The new study, which includes researchers from Yale and was published in Natureon June 28, is the first to identify a genetic variant that increases disease severity, an advance that the authors say offers a key step toward understanding and eventually fighting this progressive form of MS.
“While we have identified genetic variants that are predominantly immune related associated with risk of developing MS, this is the first study to identify neuronal genetic variants associated with the neurodegenerative aspects of the disease,” said Dr. David Hafler, the William S. and Lois Stiles Edgerly Professor of Neurology and Professor of Immunobiology at Yale School of Medicine, chair of the Department of Neurology, and an author of the study.
The work was the result of a large international collaboration of the International MS Genetics Consortium (IMSGC), which consists of more than 70 institutions from around the world. Hafler is a co-founder of the IMSGC.
Previous studies have shown that MS susceptibility, or risk, stems in large part from dysfunction in the immune system. Some of this dysfunction can be treated, slowing the progression of the disease.

But “these risk factors don’t explain why, 10 years after diagnosis, some MS patients are in wheelchairs while others continue to run marathons,” said Sergio Baranzini, a professor of neurology at University of California, San Francisco and co-senior author of the study.
For the first part of the new study, researchers combined data from more than 12,000 people with MS to complete a genome-wide association study (GWAS), a research approach that uses statistics to carefully link genetic variants to particular traits. In this case, the traits of interest were related to MS severity, including the years it took for each individual to advance from diagnosis to a certain level of disability.
After sifting through more than 7 million genetic variants, the scientists found one that was associated with faster disease progression. The variant sits between two genes with no prior connection to MS, called DYSF and ZNF638.
They found that MS patients with two copies of the gene variant, located near the two genes that help repair damaged cells and one that helps control viral infection, experienced faster disease progression. The location of the variant suggests a possible mechanism for accelerated progression.
“Inheriting this genetic variant from both parents accelerates the time to needing a walking aid by almost four years,” Baranzini said.

“These genes are normally active within the brain and spinal cord, rather than the immune system,” said Adil Harroud, assistant professor of neurology at the Montreal Neurological Institute and lead author of the study. “Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies.”
The findings give the field its first significant leads to address the nervous system component of MS.
To confirm their findings, the scientists investigated the genetics of nearly 10,000 additional MS patients. Again, they found that those with two copies of the variant became disabled faster.
“This gives us a new opportunity to develop new drugs that may help preserve the health of all who suffer from MS,” Harroud said.
This work was supported in part by funding from the National Institute of Neurological Disorders and Stroke (which is part of the National Institutes of Health), the European Union’s Horizon 2020 Research and Innovation Funding Programme, and the Multiple Sclerosis Society of Canada.
Hafler is a Yale Cancer Center member in the Yale Cancer Immunology Research Program.

Scientists identify the first genetic marker for MS severity, opening the door to preventing long-term disability.
A study of more than 22,000 people with multiple sclerosis has discovered the first genetic variant associated with faster disease progression that can rob patients of their mobility and independence over time. Multiple sclerosis (MS) is the result of the immune system mistakenly attacking the brain and the spinal cord, resulting in symptom flares known as relapses as well as longer-term degeneration known as progression. Despite the development of effective treatments for relapses, none can reliably prevent the accumulation of disability. The breakthrough findings, published in Nature on June 28, 2023, point to a genetic variant that increases the disease’s severity and provide the first real progress in understanding and eventually fighting this aspect of MS.
“Inheriting this genetic variant from both parents accelerates the time to needing a walking aid by almost four years,” said Sergio Baranzini, PhD, professor of neurology at the University of California, San Francisco (UCSF) and co-senior author of the study. The work was the result of a large international collaboration of more than 70 institutions from around the world, led by researchers from UCSF and the University of Cambridge. “Understanding how the variant exerts its effects on MS severity will hopefully pave the way to a new generation of treatments that are able to prevent disease progression,” said Stephen Sawcer, a professor at Cambridge and the other co-senior author of the study.
A renewed focus on the nervous system
To address the mystery of MS severity, two large MS research consortia joined forces: The International Multiple Sclerosis Genetics Consortium (IMSGC) and The MultipleMS Consortium. This enabled MS researchers from around the world to pool the resources needed to begin to identify the genetic factors influencing MS outcomes. Previous studies have shown that MS susceptibility, or risk, stems in large part from dysfunction in the immune system, and some of this dysfunction can be treated, slowing down the disease. But “these risk factors don’t explain why, 10 years after diagnosis, some MS patients are in wheelchairs, while others continue to run marathons,” explained Baranzini.
The two consortia combined data from more than 12,000 people with MS to complete a genome-wide association study (GWAS), which uses statistics to carefully link genetic variants to particular traits. In this case, the traits of interest were related to MS severity, including the years it took for each individual to advance from diagnosis to a certain level of disability. After sifting through more than 7 million genetic variants, the scientists found one that was associated with faster disease progression. The variant sits between two genes with no prior connection to MS, called DYSF and ZNF638. The first is involved in repairing damaged cells, and the second helps to control viral infections. The variant’s proximity to these genes suggests that they may be involved in the disease’s progression.

“These genes are normally active within the brain and spinal cord, rather than the immune system,” said Adil Harroud, MD, lead author of the study and former postdoctoral researcher in Baranzini’s lab. “Our findings suggest that resilience and repair in the nervous system determine the course of MS progression and that we should focus on these parts of human biology for better therapies.” The findings give the field its first leads to address the nervous system component of MS.”Although it seems obvious that your brain’s resilience to injury would determine the severity of a disease like MS, this new study has pointed us towards the key processes that underlie this resilience,” Sawcer said. To confirm their findings, the scientists investigated the genetics of nearly 10,000 additional MS patients. Those with two copies of the variant became disabled faster.
Netherlands Institute for Neuroscience
But how do we know how relevant this DNA variant actually is? That’s where the Dutch Brain Bank steps in. A team of researchers from the Netherlands Institute for Neuroscience (Aletta van den Bosch, Jeen Engelenburg, Dennis Wever, Jorg Hamann, Inge Huitinga and Joost Smolders), within the International MS Genetics Consortium (IMSGC), looked at the genetic architecture underlying the course of MS, using donor brains.
Joost Smolders (aside from his employment at the Netherlands Institute for Neuroscience, also working as a neurologist at Erasmus MC Rotterdam and member of the IMSGC): ‘In terms of treatment, there’s already a lot that we can do for people with MS, but we can’t yet predict the speed at which their health deteriorates. For this we need more insight into underlying mechanisms, with the discovery of the SNP being an important first step. A SNP is a variation in the DNA of a single DNA building block. At the Netherlands Institute for Neuroscience, we can perform the second step, which involves looking into the brain tissue to see the effect of this SNP. At the Brain Bank, we have brains from deceased donors with MS who already have an entire disease history behind them, all available for research. We asked ourselves whether carriers of the genetic abnormality had more severe MS-related changes in their brains.’
‘Our results show that homozygous carriers of the risk allele (rs10191320), or double carriers of the gene, have almost twice as many MS abnormalities in their gray and white matter than MS donors without this genetic variation. This is very important, because it allows us to validate that this SNP may really be relevant to people with MS. This also illustrates the strength of the Brain Bank: you can look at the pathology very closely. The effect of such a SNP is magnified far more in the pathology than in the effect it has on someone’s experience with MS. Something that would typically require tens of thousands of people with MS for living measurements can be confirmed with a hundred or so of these particular MS brain donors.’
Next steps
Further work will be necessary to determine exactly how this genetic variant affects DYSF, ZNF638, and the nervous system more generally. The researchers are also collecting an even larger set of DNA samples from people with MS, expecting to find other variants that contribute to long-term disability. “This gives us a new opportunity to develop new drugs that may help preserve the health of all who suffer from MS,” said Harroud. Could we say instead, “treatments to prevent long-term disability”?

A multi-faceted device for effectively treating deep, non-compressible, and irregularly-shaped wounds has been engineered by the scientists at the Terasaki Institute for Biomedical Innovation (TIBI). As outlined in their recent paper in Advanced Science, the device provides rapid hemorrhage management, has minimal inflammatory effects, and provides infection control. It also has tunable biodegradation rates, making it usable for both internal and external use, and features sensing capabilities for long-term hemorrhage monitoring. This versatile device is highly beneficial for timely alerts and control of bleeding from surgical wounds, traumatic injuries, and critical illnesses.
There are currently many hemorrhage control products available such as cotton or gauze bandages, powders, and tourniquets. These are usually used with compression on shallow, more uniformly shaped wounds, and they cannot simultaneously detect bleeding and control hemorrhage. Newer, highly absorbent shape-memory sponges treat deep, irregularly shaped wounds while retaining their structure and original dimensions; after blood absorption, these sponges also naturally apply pressure to the wound and promote coagulation. Cellulose-based shape-memory sponges are adequate but not biodegradable as gelatin-based versions are, and neither have the ability for hemorrhage detection.
To create a versatile hemorrhage management device, the TIBI team turned to silk fibroin, a protein produced by the Bombyx mori silkworm. Silk fibroin is a biodegradable material with optimum anti-inflammatory and mechanical properties and can be engineered into porous, highly absorbent memory-shaped sponges. These sponges can also promote coagulation and tissue regeneration. The tunable degradation rates of the sponges allow longer-term use in the body as well as the possibility of integration with sensors that can monitor bleeding over time.
The TIBI team leveraged these capabilities and developed a unique, all-in-one hemorrhage management device. The device consists of two silver nanowire layers positioned above and below a hemostatic sponge layer. The nanowires function as hemorrhage detection sensors as well as antibacterial agents.
The TIBI team carried out a comprehensive evaluation of the device, including testing mechanical properties, biocompatibility, and biodegradation. Mechanically, the SF sponges showed outstanding elasticity and absorptive powers, along with excellent retention of pore size, shape, and size when tested against water and blood; optimum hemorrhage control could be obtained by tuning the silk fibroin concentrations to match the mechanical properties of surrounding wound tissue. Favorable biocompatibility and minimal anti-inflammatory responses in both the sponge and nanowire layers were shown by good cellular viability and proliferation when tested with connective tissue samples. Further tests showed that the degradation rate of the sponge could be slowed both by increasing the silk fibroin concentration and by employing a methanol wash step during fabrication.
Next, the device and a commercial gelatin-based anti-hemorrhage device were evaluated in rat models via below-the-skin implantation. The commercial sponge completely degraded after four weeks, while the silk fibroin nanowire device maintained its structure. In addition, the implanted sponge showed minimal inflammatory responses and posed no adverse effects on the organs and the behavior of the rats. Also, the silk fibroin device outperformed the commercial sponge in hemorrhage control tests, with a two-fold higher level of hemorrhage control in a rat bleeding model.
In addition to providing hemorrhage management, the device also includes a nanowire-based capacitive sensor for bleeding detection. During bleeding, the sponge absorbs the blood, which increases its capacitance without affecting its shape. The increase in capacitance is detectable and directly correlates to the amount of blood absorbed, thus providing a way to monitor bleeding in real time. Tests showed that the device could selectively monitor blood absorption against other bodily fluids it might encounter in the wound.
“This multifunctional device offers many attractive features for hemorrhage control and wound monitoring and is highly adaptable for different types of wounds and tissues,” said Ali Khademhossein, Ph.D., TIBI’s Director and CEO. “And the hemorrhage monitoring feature also opens up several possibilities for integrative biosensing and additional therapeutics.”
Authors are: Reihaneh Haghniaz, Ankit Gangrade, Hossein Montazerian, Fahimeh Zarei, Menekse Ermis, Zijie Li, Yuxuan Du, Safoora Khosravi, Natan Roberto de Barros, Kalpana Mandal, Ahmad Rashad, Fatemeh Zehtabi, Jinghang Li, Mehmet R. Dokmeci, Han-Jun Kim, Ali Khademhosseini, Yangzhi Zhu.
This work was partially supported by the National Institutes of Health (AR074234, AR073135, HL140618, HL137193, GM126571, GM126831).