More recently, however, cancer surgeons have discovered that CLND has the potential to cause more problems than it solves. In most cases, patients do better on immunotherapy alone than they do when their surgery involves removal of the lymph nodes, due to potential complications from lymph node surgery.

In a paper published in February in the Annals of Surgical Oncology, University of Colorado (CU) Cancer Center members Martin McCarter, MD, Camille Stewart, MD, Karl Lewis, MD, William Robinson, MD, Ana Gleisner, MD, PhD, and Rene Gonzalez, MD — along with CU School of Medicine resident Robert Torphy, MD, PhD — reviewed their patient data to determine if immunotherapy alone resulted in better outcomes than CLND.

“In the few years prior to immunotherapy being available, some surgical trials were done asking if regional node dissection by itself improves overall survival for the patients,” says McCarter, a professor of surgical oncology at the CU School of Medicine. “And the answer came back: no, it did not improve survival. That had been the standard forever, because we didn’t have other effective therapies, but once the definitive trials were done, we learned that CLND wasn’t helping, it wasn’t improving survival. Subsequent trials demonstrated that immunotherapy can improve survival in metastatic melanoma.”

Better outcomes with immunotherapy

For the study, Torphy, working with McCarter and the other researchers, looked at data on 90 patients who underwent sentinel lymph node biopsy (a procedure to determine if a skin melanoma has spread microscopically) only for stage III melanoma but did not undergo CLND. Of those patients, 56 received immunotherapy and 34 did not. Those who received immunotherapy had better rates of distant metastasis-free survival, meaning their cancer was less likely to come back.

“As treatments for melanoma have evolved, the standard of care may be evolving as well,” McCarter says. “This study took a look at the patients who had a sentinel lymph node biopsy, so we knew the patient had a positive melanoma metastasis to their regional node. Those folks historically used to go on and get the completion lymph node dissection, but recently, people started to forego doing that lymph node dissection, which did not improve survival, and instead moved directly to immunotherapy, which did improve survival in other clinical trials. We proved that this is acceptable, that we’re not causing more harm to patients by doing it, and that those who do go on to get the immunotherapy seem to benefit from it.”

The de-escalation movement

Forgoing CLND is part of a recent movement in cancer treatment known as de-escalation (or de-implementation) — giving patients only the surgery absolutely necessary to treat their immediate disease. It’s especially important when it comes to lymph node surgery, McCarter says, as on top of the risks inherent to all surgeries, CLND has a 20% to 30% risk of permanent lymphedema, potentially harmful tissue swelling caused by an accumulation of protein-rich fluid that’s usually drained through the body’s lymphatic system.

“If you could avoid that complication and not compromise a patient’s survival, that would be beneficial,” McCarter says. “That’s what we guessed was happening outside of definitive clinical trial evidence, and that’s what we were able to show. We know that we often overtreat patients, and this fits in that paradigm of finding ways to de-escalate unnecessary therapies, which has been done in breast cancer and other cancers as well.”

Changing course

The CU researchers hope the study begins to move the needle for cancer surgeons for whom CLND is still routine, despite the earlier studies showing that the additional surgery was not improving survival.

“Previous clinical trials with the use of adjuvant immunotherapy for melanoma had required a CLND,” McCarter says. “This study used real-world data from our stage III melanoma patients who were treated with immunotherapy without having a prior CLND.

“It takes years to change people’s practice patterns. I still have conversations with community surgeons who treat melanoma, asking me, ‘Should I be doing these regional node dissections?’ even though this data has been out for five to 10 years now,” McCarter continues. “They’re afraid to give up what they used to do, and they’re afraid that they are doing a disservice to the patients or not giving them the best chance, when in reality, our understanding of cancer biology has evolved. We now have effective immunotherapy, which is overcoming some of the limitations of surgery while improving outcomes.”

Dr. Cynthia Hipwell is studying friction at the finger-device level, while Dr. Jonathan Felts is researching friction in the interaction between single skin cells and the glass of the touchscreen interface. The two are bringing together their respective areas of expertise to apply friction principles at the microscopic level to finger-device interaction mechanics.

Hipwell highlighted the significance of the pursuit by comparing it to the technologies currently available for conveying immersive and accurate information through high-fidelity audio and video.

“We can view digitally recorded or remotely transmitted audio and video on a screen with great detail,” said Hipwell, Oscar S. Wyatt, Jr. ’45 Chair II professor. “We do not yet have that same capability with touch on a touchscreen. Imagine you could feel the skin of a snake that lives on another continent or the fabric of clothes you want to buy online.”

Another application of this technology, which has received high levels of interest recently, is the augmentation of immersive virtual environments, such as the proposed metaverse.

“The touch sensations that would be required to really immerse yourself into a reality that is fully digital requires huge advancements in touch perception,” said Felts, associate professor and Steve Brauer, Jr. ’02 Faculty Fellow. “What we’ve done is essentially created an entirely new way to modulate the perception of touch that hasn’t existed before.”

The team is working to show that it is possible to mimic the unique mechanical and thermal sensations associated with different surface textures and shapes. Their recent publication in the journal Science Robotics demonstrates the potential for translating these sensations on a touchscreen by using temperature variation alone, rather than expressing them through ultrasonic vibrations or electroadhesion methods.

“We were actually surprised by the magnitude of the friction increase we were able to achieve,” Hipwell said. “Its magnitude is competitive with current surface haptic devices, meaning that there is another option for friction modulation in surface-haptic device rendering.”

Another exciting development, Hipwell said, is that their research has shown that it is possible to localize the friction to the outer layer of the skin and, at least at swipe speeds, control friction without making the device feel hot.

As the research continues, Felts said many of the questions remaining involve how readily the approach can be incorporated into consumer devices and commercialized.

“Can it be scaled down? Can it respond quickly enough? Can it mimic a wide range of surfaces? Can it be affordable? We think these are fair criticisms, yet we look forward to using this phenomenon to improve our basic understanding of haptic feedback and pursuing miniaturization and commercialization avenues,” he said.

The team is continuing their work to address challenges facing the approach by further exploring the complexities of the finger-device interface and variations that occur due to environmental and skin-property differences. They also hope to look at design improvements for miniaturization and integration into touchscreens.

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Materials provided by Texas A&M University. Original written by Steve Kuhlmann. Note: Content may be edited for style and length.

This scenario is not as impossible as it seems. Too small to withstand a rhythmic strum or sliding bowstring, DNA is a powerhouse for storing audio files and all kinds of other media.

“DNA is nature’s original data storage system. We can use it to store any kind of data: images, video, music — anything,” said Kasra Tabatabaei, a researcher at the Beckman Institute for Advanced Science and Technology and a coauthor on this study.

Expanding DNA’s molecular makeup and developing a precise new sequencing method enabled a multi-institutional team to transform the double helix into a robust, sustainable data storage platform.

The team’s paper appeared in Nano Letters in February 2022.

In the age of digital information, anyone brave enough to navigate the daily news feels the global archive growing heavier by the day. Increasingly, paper files are being digitized to save space and protect information from natural disasters.

From scientists to social media influencers, anyone with information to store stands to benefit from a secure, sustainable data lock box — and the double helix fits the bill.

“DNA is one of the best options, if not the best option, to store archival data especially,” said Chao Pan, a graduate student at the University of Illinois Urbana-Champaign and a coauthor on this study.

Its longevity rivaled only by durability, DNA is designed to weather Earth’s harshest conditions — sometimes for tens of thousands of years — and remain a viable data source. Scientists can sequence fossilized strands to uncover genetic histories and breathe life into long-lost landscapes.

Despite its diminutive stature, DNA is a bit like Dr. Who’s infamous police box: bigger on the inside than it appears.

“Every day, several petabytes of data are generated on the internet. Only one gram of DNA would be sufficient to store that data. That’s how dense DNA is as a storage medium,” said Tabatabaei, who is also a fifth-year Ph.D. student.

Another important aspect of DNA is its natural abundance and near-infinite renewability, a trait not shared by the most advanced data storage system on the market today: silicon microchips, which often circulate for just decades before an unceremonious burial in a heap of landfilled e-waste.

“At a time when we are facing unprecedented climate challenges, the importance of sustainable storage technologies cannot be overestimated. New, green technologies for DNA recording are emerging that will make molecular storage even more important in the future,” said Olgica Milenkovic, the Franklin W. Woeltge Professor of Electrical and Computer Engineering and a co-PI on the study.

Envisioning the future of data storage, the interdisciplinary team examined DNA’s millennia-old MO. Then, the researchers added their own 21st-century twist.

In nature, every strand of DNA contains four chemicals — adenine, guanine, cytosine, and thymine — often referred to by the initials A, G, C, and T. They arrange and rearrange themselves along the double helix into combinations that scientists can decode, or sequence, to make meaning.

The researchers expanded DNA’s already broad capacity for information storage by adding seven synthetic nucleobases to the existing four-letter lineup.

“Imagine the English alphabet. If you only had four letters to use, you could only create so many words. If you had the full alphabet, you could produce limitless word combinations. That’s the same with DNA. Instead of converting zeroes and ones to A, G, C, and T, we can convert zeroes and ones to A, G, C, T, and the seven new letters in the storage alphabet,” Tabatabaei said.

Because this team is the first to use chemically modified nucleotides for information storage in DNA, members innovated around a unique challenge: not all current technology is capable of interpreting chemically modified DNA strands. To solve this problem, they combined machine learning and artificial intelligence to develop a first-of-its-kind DNA sequence readout processing method.

Their solution can discern modified chemicals from natural ones, and differentiate each of the seven new molecules from one another.

“We tried 77 different combinations of the 11 nucleotides, and our method was able to differentiate each of them perfectly,” Pan said. “The deep learning framework as part of our method to identify different nucleotides is universal, which enables the generalizability of our approach to many other applications.”

This letter-perfect translation comes courtesy of nanopores: proteins with an opening in the middle through which a DNA strand can easily pass. Remarkably, the team found that nanopores can detect and distinguish each individual monomer unit along the DNA strand — whether the units have natural or chemical origins.

“This work provides an exciting proof-of-principle demonstration of extending macromolecular data storage to non-natural chemistries, which hold the potential to drastically increase storage density in non-traditional storage media,” said Charles Schroeder, the James Economy Professor of Materials Science and Engineering and a co-PI on this study.

DNA literally made history by storing genetic information. By the looks of this study, the future of data storage is just as double-helical.

Additional UIUC collaborators include Aleksei Aksimentiev, the Center for Biophysics and Quantitative Biology; and Alvaro Hernandez, the Roy J. Carver Biotechnology Center. Partner institutions include the University of Massachusetts at Amherst and Stanford University. For a full list of collaborators and their affiliations, please consult the published work.

The double-blind study is the first of its kind to investigate the effectiveness of rTMS in treating CUD in people with schizophrenia, and was supported by the U.S. National Institute on Drug Abuse (NIDA) and the CAMH Foundation.

“People with schizophrenia have very high rates of cannabis use disorder compared to the general population, and there is strong evidence that cannabis use worsens psychiatric symptoms and quality of life in these people,” said senior author CAMH clinician scientist Dr. Tony George. “Despite the known harmful effects, there is currently no approved treatment for CUD with or without schizophrenia. These results indicate rTMS may be a safe and effective way to reduce cannabis among people with schizophrenia.”

Until relatively recently, brain stimulation technologies like rTMS were used primarily for treatment-resistant depression. However, studies have now found rTMS to be effective in reducing drug use and cravings for several substance use disorders in the general population.

Study participants were given rTMS treatment at the Temerty Centre for Therapeutic Brain Intervention at CAMH five times a week for four weeks targeting the brain’s the dorsolateral prefrontal cortex (DLPFC), which is associated with the brain’s reward system and executive function.

Those who were given rTMS reported a reduction in cannabis use by up to 60 per cent after 28 days as well as reduced cravings, compared to controls receiving sham rTMS.

The authors state that one of the reasons there is currently no effective treatment for CUD in people with schizophrenia is that people with schizophrenia or other mental illnesses are usually excluded from CUD clinical trials. Dr. George says that CAMH is uniquely positioned to do this kind of research:

“In addition to our ability to conduct clinical trials with brain stimulation at the Temerty Centre, CAMH also has one of the largest schizophrenia outpatient clinics in North America as well as state-of-the-art addiction treatment programs,” said Dr. George. “All those factors make CAMH one of the few places in the world that can lead a study like this.”

“It was a difficult study to recruit for given the intensity of time commitment required by patients,” said study lead author Dr. Karolina Kozak Bidzinski. “However, the awareness patients had of the negative effects cannabis was having on their lives, the expected benefits of reducing their use and noticing the various positive outcomes that would surface throughout the duration of the trial, enabled such a high number of patients to complete the study. Hopefully this work paves the way for more research into investigating the effects of rTMS as a treatment for cannabis use disorder in people with schizophrenia.”

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Materials provided by Centre for Addiction and Mental Health. Note: Content may be edited for style and length.