Aurelia Butler

Science has the technology to measure the activity of every gene within a single individual cell, and just one experiment can generate thousands of cells worth of data. Researchers at Lund University in Sweden have now revolutionised the way this data is analysed — by using 3D video gaming technology. The study is published in the journal iScience.
Advanced techniques in DNA and RNA sequencing have opened up the possibility of studying individual cells in tissue in a more comprehensive way than was previously possible. The big challenge with these sequencing techniques is that they lead to large amounts of data.
“When you want to distinguish cancer cells from normal cells, for example, you need to examine thousands of cells to get a proper understanding, which translates into enormous amounts of numerical data,” says Shamit Soneji, researcher in computational biology at Lund University.
To make this data comprehensible, each cell is mathematically positioned in three-dimensional space to form a “roadmap” of the cells, and how they relate to each other. However, these maps can be difficult to navigate using a regular desktop computer.
“To be able to walk around your own data and manipulate it intuitively and efficiently gives it a whole new understanding. I would actually go so far as to say that one thinks differently in VR, thanks to the technique’s ability to involve your body in the analysis process,” explains Mattias Wallergård. researcher in interaction design and virtual reality at Lund University.
The Lund University team have developed the software CellexalVR; a virtual reality environment that enables researchers to use intuitive tools to explore all their data in one place. 3D maps of cells that have been calculated from gene activity and other information captured from individual cells can be displayed, and the researcher can clearly see which genes are active when certain cell types are formed.
Using a VR headset, the user has a complete universe of cell populations in front of them, and can more accurately determine how cells relate to one another. Using two hand controllers, they can select cells of interest for further analysis with simple hand gestures as if they were physical objects.
Since space is not an issue, it is possible to have several cellular maps in the same “room” and compare them side by side, something that is difficult on a traditional computer screen. Researchers can also meet in this VR world to analyze data together, despite being in different places geographically.
“Even if you are not familiar with computer programming, this type of analysis is open to everyone. A virtual world is a fast developing area of research that has enormous potential for scientists that need to access and process big-data in a more interactive and collaborative way,” concludes Shamit Soneji.
The software can be downloaded for free at https://www.cellexalvr.med.lu.se/
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The perception that boys are more interested than girls in computer science and engineering starts as young as age six, according to a new study published in Proceedings of the National Academy of Sciences. That may be one reason why girls and women are underrepresented in these STEM career fields, reports study co-author Allison Master, assistant professor at the University of Houston College of Education.
“Gender-interest stereotypes that say ‘STEM is for boys’ begin in grade school, and by the time they reach high school, many girls have made their decision not to pursue degrees in computer science and engineering because they feel they don’t belong,” said Master.
Researchers at UH and the University of Washington surveyed nearly 2,500 students in firstthrough12th grade from diverse racial and socioeconomic backgrounds. The results of those studies were combined with laboratory experiments to provide important insights into how stereotypes impact children’s motivation.
More children believed girls had less interest than boys in key STEM fields. Specifically, 63% of the students believed girls were less interested in engineering than boys were, while 9% believed girls were more interested in the subject. Regarding computer science, 51% thought girls had less interest while 14% thought girls had more interest than boys.
These interest patterns play out in the job market. According to United States Census Bureau statistics, while women make up nearly half of the workforce, they account for only 25% of computer scientists and 15% of engineers.
Researchers say educators, parents and policymakers can help close these gender gaps by introducing girls to high quality computer science and engineering activities in elementary school before stereotype endorsements take root. They also suggest educators who wish to promote girls’ interest and engagement in STEM should consider using inclusive programs designed to encourage girls’ sense of belonging in STEM.
The laboratory experiments gave children a choice between computer science activities. Fewer girls (only 35%) chose a computer science activity they believed boys were more interested in, compared to the 65% of girls who chose an activity for which they believed boys and girls were equally interested.
“It’s time for all stakeholders to be united in sending the message that girls can enjoy STEM just as much as boys do, which will help draw them into STEM activities,” added Master, who directs UH’s Identity and Academic Motivation (I AM) Lab.
Co-authors on the study are Andrew N. Meltzoff of the University of Washington, Seattle’s Institute for Learning & Brain Sciences; and Sapna Cheryan, University of Washington, Seattle’s Department of Psychology.
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Materials provided by University of Houston. Original written by Sara Tubbs. Note: Content may be edited for style and length. More

Every day, cytologists around the world use optical microscopes to analyze and classify samples of bone marrow cells thousands of times. This method to diagnose blood diseases was established more than 150 years ago, but it suffers from being very complex. Looking for rare but diagnostically important cells is both a laborious and time-consuming task. Artificial intelligence has the potential to boost this method — however it needs a large amount of high-quality data to train an AI algorithm.
Largest open-source database for bone marrow cell images
The Helmholtz Munich researchers developed the largest open access database on microscopic images of bone marrow cells to date. The database consists of more than 170,000 single-cell images from over 900 patients with various blood diseases. It is the result of a collaboration from Helmholtz Munich with the LMU University Hospital Munich, the MLL Munich Leukemia Lab (one of the largest diagnostic providers in this field worldwide) and Fraunhofer Institute for Integrated Circuits.
Using the database to boost artificial intelligence
“On top of our database, we have developed a neural network that outperforms previous machine learning algorithms for cell classification in terms of accuracy, but also in terms of generalizability,” says Christian Matek, lead author of the new study. The deep neural network is a machine learning concept specifically designed to process images. “The analysis of bone marrow cells has not yet been performed with such advanced neural networks,” Christian Matek explains, “which is also due to the fact that high-quality, public datasets have not been available until now.”
The researchers aim to further expand their bone marrow cell database to capture a broader range of findings and to prospectively validate their model. “The database and the model are freely available for research and training purposes — to educate professionals or as a reference for further AI-based approaches e.g. in blood cancer diagnostics,” says study leader Carsten Marr.
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Materials provided by Helmholtz Zentrum München – German Research Center for Environmental Health. Note: Content may be edited for style and length. More

A research team at the University of Washington has developed a wearable device to detect and reverse an opioid overdose. The device, worn on the stomach like an insulin pump, senses when a person stops breathing and moving, and injects naloxone, a lifesaving antidote that can restore respiration.
The results demonstrate the proof-of-concept of a wearable naloxone injector system, according to the paper published Nov. 22 in Scientific Reports.
“The opioid epidemic has become worse during the pandemic and has continued to be a major public health crisis,” said lead author Justin Chan, a UW doctoral student in the Paul G. Allen School of Computer Science & Engineering. “We have created algorithms that run on a wearable injector to detect when the wearer stops breathing and automatically inject naloxone.”
Co-author Jacob Sunshine, an associate professor of anesthesiology and pain medicine at the UW School of Medicine, said one of the unique aspects of opioid overdoses is that naloxone, a benign drug, is highly effective and can save lives if it can be administered in a timely fashion.
The UW team is looking to make these devices widely available, which would first require approval by the U.S. Food and Drug Administration. The FDA is currently working to accelerate efforts to address this critical public health problem and has recently published special guidance on emergency-use injectors.
In a multiyear collaboration, the UW investigators worked on the prototype with West Pharmaceutical Services of Exton, Penn, which developed a wearable subcutaneous injector that safely administers medications. More

A team of University of Arizona researchers has developed an ultra-thin wireless device that grows to the surface of bone and could someday help physicians monitor bone health and healing over long periods. The devices, called osseosurface electronics, are described in a paper published Thursday in Nature Communications.
“As a surgeon, I am most excited about using measurements collected with osseosurface electronics to someday provide my patients with individualized orthopedic care — with the goal of accelerating rehabilitation and maximizing function after traumatic injuries,” said study co-senior author Dr. David Margolis, an assistant professor of orthopedic surgery in the UArizona College of Medicine — Tucson and orthopedic surgeon at Banner — University Medical Center Tucson.
Fragility fractures associated with conditions like osteoporosis account for more days spent in the hospital than heart attacks, breast cancer or prostate cancer. Although not yet tested or approved for use in humans, the wireless bone devices could one day be used not only to monitor health, but to improve it, said study co-senior author Philipp Gutruf, an assistant professor of biomedical engineering and Craig M. Berge faculty fellow in the College of Engineering.
“Being able to monitor the health of the musculoskeletal system is super important,” said Gutruf, who is also a member of the university’s BIO5 Institute. “With this interface, you basically have a computer on the bone. This technology platform allows us to create investigative tools for scientists to discover how the musculoskeletal system works and to use the information gathered to benefit recovery and therapy.”
Because muscles are so close to bones and move so frequently, it is important that the device be thin enough to avoid irritating surrounding tissue or becoming dislodged, Gutruf explained.
“The device’s thin structure, roughly as thick as a sheet of paper, means it can conform to the curvature of the bone, forming a tight interface,” said Alex Burton, a doctoral student in biomedical engineering and co-first author of the study. “They also do not need a battery. This is possible using a power casting and communication method called near-field communication, or NFC, which is also used in smartphones for contactless pay.”
Ceramic Adhesive Grows to Bone
The outer layers of bones shed and renew just like the outer layers of skin. So, if a traditional adhesive was used to attach something to the bone, it would fall off after just a few months. To address this challenge, study co-author and BIO5 Institute member John Szivek — a professor of orthopedic surgery and biomedical engineering — developed an adhesive that contains calcium particles with an atomic structure similar to bone cells, which is used as to secure osseosurface electronics to the bone.
“The bone basically thinks the device is part of it, and grows to the sensor itself,” Gutruf said. “This allows it to form a permanent bond to the bone and take measurements over long periods of time.”
For instance, a doctor could attach the device to a broken or fractured bone to monitor the healing process. This could be particularly helpful in patients with conditions such as osteoporosis, since they frequently suffer refractures. Knowing how quickly and how well the bone is healing could also inform clinical treatment decisions, such as when to remove temporary hardware like plates, rods or screws.
Some patients are prescribed drugs designed to speed up bone healing or improve bone density, but these prescriptions can have side effects. Close bone monitoring would allow physicians to make more informed decisions about drug dosage levels.
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Materials provided by University of Arizona College of Engineering. Original written by Emily Dieckman. Note: Content may be edited for style and length. More

Special ferroelectric features offer promise for microelectronics and energy applications.
When a magician suddenly pulls a tablecloth off a table laden with plates and glasses, there is a moment of suspense as the audience wonders if the stage will soon be littered with broken glass. Until now, an analogous dilemma had faced scientists working with special electrical bubbles to create the next generation of flexible microelectronic and energy storage devices.
Scientists at the U.S. Department of Energy’s (DOE) Argonne National Laboratory have discovered a new way to do an atomic-scale version of the tablecloth trick by peeling off heterostructure thin films containing electrical bubbles from a particular underlying material, or substrate, while keeping them fully intact. The discovery may bring us one step closer to a host of applications that rely upon these unusual and brittle structures.
“The bubbles are very fragile and initially need particular underlying materials, called substrates, and specific conditions in order to grow films with them in,” said Argonne materials scientist Saidur Bakaul. “There are many materials of interest to us for which these bubbles could be extremely useful, like plastics. However, we haven’t been able to grow them directly on these materials. Our research is the initial step to make bubbles possible there.”
The electric bubbles are found in a three-layer ultrathin structure with alternating electrical properties: ferroelectric, then dielectric, then ferroelectric again. The bubbles in this multilayer structure are made out of specially ordered dipoles, or twinned electric charges. The orientation of these dipoles is based on the local strain in the material and charges on the surface which cause the dipoles to seek out their relative lowest energy state. Eventually, the electric bubbles (bubble domains) form but only when certain conditions are met. They are also easily distorted by even small forces.
In the experiment, Bakaul’s colleagues at University of New South Wales first grew the bubbles in an ultrathin heterostructure film on a strontium titanate substrate — one of the easiest materials on which to create them. Then, Bakaul faced the challenge of removing the heterostructure from the substrate while retaining the bubbles. “You can think of it like trying to remove a house from its foundation,” he said. “Normally, you would think that the house would collapse, but we found that it retained all of its properties.”
Bubble domains are tiny. They’re only about 4 nanometers in radius — just as wide as a human DNA strand. Therefore, they are difficult to see. In Argonne’s Materials Science division, advanced scanning probe microscopy techniques with Fourier transform analysis allow scientists to not only see them but also quantify their properties in the freestanding films. More

The inherited progressive disorder cystic fibrosis (CF) causes severe damage to the lungs, and other tissues in the body by affecting the cells that produce mucus, sweat, and digestive juices. In individuals carrying mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which encodes an ion channel controlling the flow of ions and water in and out of cells, the mucus in airways and other passageways, which normally is thin and slippery, becomes sticky and thick — thus instead of acting as a lubricant, it becomes a congestant.
Advances in patient screenings and breakthrough therapies allow CF patients now to live into their mid- to late 30s or 40s, sometimes even longer. However, even the ~90% of patients (dependent on continent) with the most common CFTR mutation, called ?F508, who can be treated with available drugs, are still plagued by bacteria settling in their mucus, which causes inflammation in their lungs. The repeated bouts of infection and inflammation, as well as a chronic lower-grade inflammation between infections, gradually weakens and scars patients’ airways, which eventually causes their respiratory systems to fail. For the remaining ~10% of patients with various other CFTR mutations, no targeted treatments even exist yet. A major barrier to developing new and urgently needed treatments is the lack of human in vitro models that recapitulate the CF disease’s pathology.
Now, a multidisciplinary research team at Harvard’s Wyss Institute for Biologically Inspired Engineering led by Wyss Founding Director Donald Ingber, M.D., Ph.D. and supported by a grant from the Cystic Fibrosis Foundation, have developed a microfluidic Organ Chip device the size of a USB memory stick that recapitulates key pathological hallmarks from CF patients more accurately than other in vitro systems have so far. The model replicates CF-specific changes in multiple hallmarks of the disease, including in the airway’s mucus layer, beating of mucus-transporting cilia, pathogen growth, inflammatory molecules, and the recruitment of white blood cells, providing a comprehensive preclinical human model in which to investigate new CF therapies. The findings are published in the Journal of Cystic Fibrosis.
“Now that we are able to accurately model CF pathology, including microbiome and inflammatory responses, in human Airway Chips, we have a way to attack challenges that are important to CF patients,” said Ingber. “The bundled capabilities of this advanced in vitro model can help accelerate the search for drugs that may dampen the exaggerated immune response in patients, treat them with more personalized therapies and, help solve problems that CF patients face every day which cannot be addressed by existing treatments.” Ingber also is faculty lead of the Wyss’ Bioinspired Therapeutics & Diagnostics Platform, as well as the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children’s Hospital, and Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.
To model and compare the microstructure and function of vascularized CF airways, the authors grew lung airway cells obtained from human CF patients or healthy individuals in one of two parallel running hollow channels of a microfluidic device under air, recapitulating the lung’s air-transporting environment. In the second channel, which is separated from the first one by a porous membrane, they recreated a human blood vessel from human lung microvascular cells that was perfused with a blood substitute medium.
“This first microphysiological model of a CF airway closely mimics what we know from airways in CF patients. Maintaining the typical composition of all relevant cell types, it developed a thicker mucus layer, and its ciliated cells exhibit higher densities of cilia that beat at a higher frequency compared to Airway Chips created with airway cells from healthy individuals,” said co-first author and former Postdoctoral Fellow on Ingber’s team Ratnakar Potla, M.B.B.S., Ph.D. “Importantly, these pathological changes were accompanied by an enhanced inflammatory response in the modeled CF bronchial epithelium that is much like the one observed in CF patients.” Potla is now Senior Scientist of complex in vitrosystems at Genentech-Roche.
After culturing the Airway Chips for two weeks, the researchers measured the levels of pro- and anti-inflammatory factors flowing out of the Airway Chip’s vascular channel that are known to be involved in the inflammatory response in the lungs of CF patients. Among other changes, the level of the pro-inflammatory cytokine IL-8 was increased in CF chips compared to those in control Airway Chips. Interestingly, IL-8 is known for its ability to attract the type of white blood cells know as neutrophils that also drive inflammation in the lungs of CF patients.
When the researchers then actually flowed human neutrophils through the vascular channel of the CF Airway Chips, they observed that more of the immune cells spontaneously adhered to the surface of vascular cells, squeezed themselves through the vascular cell layer and porous membrane, and accumulated in the airway epithelial cell layer of the air channel — recapitulating a process known as “transmigration.”
But the CF-mimicking airway tissue not only stimulated immune cell recruitment, it also supported the growth of the bacterium, Pseudomonas aeruginosa, which is present in the microbiome of normal lung but can grow out of control and cause lung infections in human CF patients. Twenty-four hours after they introduced a fluorescently labeled version of P. aeruginosa into the airway channel of chips created with bronchial epithelial cells from CF patients, the team detected higher numbers of the pathogen in CF-specific mucus than in mucus in healthy Airway Chips. As a consequence, the levels of pro-inflammatory cytokines were further increased, thus replicating the infection-inflammation cycle seen in CF patients.
As next steps, the team will further personalize their CF Lung Airway Chip by generating versions in which bronchial epithelial, vascular endothelial, and immune cells all are obtained from the same patient. “For this proof-of-concept study, we have only used CF-specific bronchial airway cells from patients carrying the frequent ?F508 CFTR mutation. But different CFTR mutations may also affect the function of endothelial and immune cells and differ in their effects,” said co-first author Roberto Plebani, Ph.D. “By developing a panel of patient-specific Airway Chips using cells from patients with different mutations, and also by directly measuring the activity of differently compromised CFTR ion channels on-chip, drug responses and efficacies could be investigated in a highly personalized manner.” Plebani worked in Ingber’s lab as a visiting professor from the “G. d’Annnunzio” University of Chieti-Pescara in Italy, and spearheaded the project in Ingber’s group with Potla.
Other authors on the study were former and present members of Ingber’s team, including Mercy Soong, Haiqing Bai, Ph.D., Zohreh Izadifar, Ph.D., Amanda Jiang, Renee Travis, Chaitra Belgur, Alexandre Dinis, Mark Cartwright, Ph.D., Rachelle Prantil-Baun, Ph.D., Pawan Jolly, Ph.D., and Sarah Gilpin, Ph.D.; and Mario Romano, Ph.D. and Professor at the “G. d’Annnunzio” University of Chieti-Pescara in Italy. The study was funded by the Cystic Fibrosis Foundation, Harvard’s Wyss Institute for Biologically Inspired Engineering, and the Programme Operativo Nazionale Ricerca e Innovazione. More