The research is published in Nature Communications, a peer-reviewed, open access, scientific journal published by Nature Research.

Instead of using chemicals or radiation, immunotherapy is a type of cancer treatment that helps the patient’s immune system fight cancer. T cells are a type of white blood cell that are of key importance to the immune system. Cytotoxic T cells are like soldiers who search out and destroy the targeted invader cells.

While there has been success in using immunotherapy for some types of cancer in the blood or blood-producing organs, a T cell’s job is much more difficult in solid tumors.

“The tumor is sort of like an obstacle course, and the T cell has to run the gauntlet to reach the cancer cells,” said Paolo Provenzano, the senior author of the study and a biomedical engineering associate professor in the University of Minnesota College of Science and Engineering. “These T cells get into tumors, but they just can’t move around well, and they can’t go where they need to go before they run out of gas and are exhausted.”

In this first-of-its-kind study, the researchers are working to engineer the T cells and develop engineering design criteria to mechanically optimize the cells or make them more “fit” to overcome the barriers. If these immune cells can recognize and get to the cancer cells, then they can destroy the tumor.

In a fibrous mass of a tumor, the stiffness of the tumor causes immune cells to slow down about two-fold — almost like they are running in quicksand.

“This study is our first publication where we have identified some structural and signaling elements where we can tune these T cells to make them more effective cancer fighters,” said Provenzano, a researcher in the University of Minnesota Masonic Cancer Center. “Every ‘obstacle course’ within a tumor is slightly different, but there are some similarities. After engineering these immune cells, we found that they moved through the tumor almost twice as fast no matter what obstacles were in their way.”

To engineer cytotoxic T cells, the authors used advanced gene editing technologies (also called genome editing) to change the DNA of the T cells so they are better able to overcome the tumor’s barriers. The ultimate goal is to slow down the cancer cells and speed up the engineered immune cells. The researchers are working to create cells that are good at overcoming different kinds of barriers. When these cells are mixed together, the goal is for groups of immune cells to overcome all the different types of barriers to reach the cancer cells.

Provenzano said the next steps are to continue studying the mechanical properties of the cells to better understand how the immune cells and cancer cells interact. The researchers are currently studying engineered immune cells in rodents and in the future are planning clinical trials in humans.

While initial research has been focused on pancreatic cancer, Provenzano said the techniques they are developing could be used on many types of cancers.

“Using a cell engineering approach to fight cancer is a relatively new field,” Provenzano said. “It allows for a very personalized approach with applications for a wide array of cancers. We feel we are expanding a new line of research to look at how our own bodies can fight cancer. This could have a big impact in the future.”

In addition to Provenzano, the study’s authors included current and former University of Minnesota Department of Biomedical Engineering researchers Erdem D. Tabdanov (co-author), Nelson J. Rodríguez-Merced (co-author), Vikram V. Puram, Mackenzie K. Callaway, and Ethan A. Ensminger; University of Minnesota Masonic Cancer Center and Medical School Department of Pediatrics researchers Emily J. Pomeroy, Kenta Yamamoto, Walker S. Lahr, Beau R. Webber, Branden S. Moriarity; National Institute of Biomedical Imaging and Bioengineering researcher Alexander X. Cartagena-Rivera; and National Heart, Lung, and Blood Institute researcher Alexander S. Zhovmer, who is now at the Center for Biologic Evaluation and Research.

The research was funded primarily by the National Institutes of Health (NIH) and University of Minnesota Physical Sciences in Oncology Center, which receives funding from NIH’s National Cancer Institute. Additional funding was provided by the American Cancer Society and the Randy Shaver Research and Community Fund. The University of Minnesota Imaging Center provided additional staff expertise. Some of the researchers also are part of the University of Minnesota Center for Genome Engineering and the University’s Institute for Engineering in Medicine.

Mullen designed a maze game that could be played in both virtual reality and conventional formats, then the research team recruited 41 UC Santa Cruz undergraduate students to test the game. Participants played in both formats, with researchers randomizing which version of the game each student started with. Both versions were essentially the same, but the mazes in each varied slightly so that there was no repetition between formats.

Participants were asked to stop playing the game whenever they felt like five minutes had passed. Since there were no clocks available, each person had to make this estimate based on their own perception of the passage of time.

Prior studies of time perception in virtual reality have often asked participants about their experiences after the fact, but in this experiment, the research team wanted to integrate a time-keeping task into the virtual reality experience in order to capture what was happening in the moment. Researchers recorded the actual amount of time that had passed when each participant stopped playing the game, and this revealed a gap between participants’ perception of time and the reality.

The study found that participants who played the virtual reality version of the game first played for an average of 72.6 seconds longer before feeling that five minutes had passed than students who started on a conventional monitor. In other words, students played for 28.5 percent more time than they realized in virtual reality, compared to conventional formats.

This time compression effect was observed only among participants who played the game in virtual reality first. The paper concluded this was because participants based their judgement of time in the second round on whatever initial time estimates they made during the first round, regardless of format. But if the time compression observed in the first round is translatable to other types of virtual reality experiences and longer time intervals, it could be a big step forward in understanding how this effect works.

While there are many informal descriptions of time compression in virtual reality from people who have experienced it first-hand, it’s still an active area of research. One particularly well-known prior study applied virtual reality time compression to shorten the perceived duration of treatment for chemotherapy patients, but that experiment didn’t compare virtual reality with conventional screen formats.

“This is the first time we can really isolate that it’s not just that you’re playing a video game, or the content of whatever you’re seeing,” Mullen said. “It’s really the fact that it is virtual reality versus a conventional screen that contributes to this time compression effect.”

Time compression could be useful in some situations — like enduring an unpleasant medical treatment or passing the time on a long flight — but in other circumstances, it could have harmful consequences.

“As virtual reality headsets get more comfortable to wear for longer periods of time, and as more immersive games are made for this format, I think it would be good to avoid having it become like a virtual casino, where you end up playing more because you don’t realize how much time you’re spending,” Mullen said.

Research on game addiction shows that losing track of time during gameplay can negatively affect a player’s sleep cycle and mood. These effects could be more pronounced in virtual reality, but Mullen says game designers can help to minimize the risk, perhaps by integrating a clock that would appear at regular intervals during gameplay.

It will also be important to discover why virtual reality seems to contribute to time compression. In the paper, Mullen describes one possibility, which relates to the fact that, in virtual reality, a player has less body awareness. Psychology Professor Nicolas Davidenko, a coauthor and advisor on the paper, explained why this might be important.

“In virtual reality, when you look down, you might see nothing where your body normally would be, or you might see a schematic of a body, but it won’t feel like your body,” Davidenko said. “There are theories that we may rely on our heartbeat and other bodily rhythms to help our brain track the passage of time, so if you have a less vivid sense of your body in virtual reality, you might be missing the pulses of this timekeeping mechanism.”

Future experiments to test this theory could yield new insights to help designers maximize benefits and minimize harm from time compression as virtual reality technology continues to grow.

SARS-CoV-2 spreads mainly through respiratory droplets, and dental procedures are known to produce an abundance of aerosols — leading to fears that flying saliva during a cleaning or a restorative procedure could make the dentist’s chair a high-transmission location.

Ohio State University researchers set out to determine whether saliva is the main source of the spray, collecting samples from personnel, equipment and other surfaces reached by aerosols during a range of dental procedures.

By analyzing the genetic makeup of the organisms detected in those samples, the researchers determined that watery solution from irrigation tools, not saliva, was the main source of any bacteria or viruses present in the spatter and spurts from patients’ mouths.

Even when low levels of the SARS-CoV-2 virus were detected in the saliva of asymptomatic patients, the aerosols generated during their procedures showed no signs of the coronavirus. In essence, from a microbial standpoint, the contents of the spray mirrored what was in the office environment.

“Getting your teeth cleaned does not increase your risk for COVID-19 infection any more than drinking a glass of water from the dentist’s office does,” said lead author Purnima Kumar, professor of periodontology at Ohio State.

“These findings should help us open up our practices, make ourselves feel safe about our environment and, for patients, get their oral and dental problems treated — there is so much evidence emerging that if you have poor oral health, you are more susceptible to COVID,” Kumar said.

The study was published Wednesday, May 12, in the Journal of Dental Research.

Previous research has shown that dental-procedure aerosols tend to land on providers’ faces and the patient’s chest, and can travel as far as 11 feet. But the studies, catching the spray in petri dishes placed on people, equipment and around the room, found only that bacteria existed — they rarely identified the organisms and never determined where they came from. Saliva has been the presumptive source for a long time.

When saliva was considered potentially deadly at the start of the pandemic, Kumar decided a long-term answer was needed to settle the question of whether saliva is the source of dental aerosols.

For the study, the team enrolled 28 patients receiving dental implants and restorations using high-speed drills or ultrasonic scaling procedures in Ohio State’s College of Dentistry between May 4 and July 10, 2020. Researchers collected samples of saliva and irrigant (the water-based cleaning solutions used to flush out the mouth) before each procedure and, 30 minutes after the procedure, aerosol remnants — condensate — from providers’ face shields, the patient’s bib and an area 6 feet away from the chair.

Kumar and colleagues then put genome sequencing technology to use that wasn’t available in the petri-dish days. This allowed them to first characterize the microbial mix in pre-procedure saliva and irrigants, which they could then compare to organisms in the aerosol samples collected later.

With the analytical method they used, the researchers did not need to characterize the microbes — they instead looked for variations in sequences that provided enough information to identify the family of bacteria or viruses to which they belonged.

“Some species that live in your mouth can closely resemble those in water and the environment. Using this method, we don’t even have to know the names of these organisms — you can tell whether they are exactly genetically identical or genetically different,” Kumar said. “If you use this granular approach to see these very nuanced differences in the genetic code, you can very accurately identify where they’re coming from.”

No matter the procedure or where the condensate had landed, microbes from irrigants contributed to about 78% of the organisms in aerosols while saliva, if present, accounted for 0.1% to 1.2% of the microbes distributed around the room.

Salivary bacteria were detected in condensate from only eight cases and of those, five patients had not used a pre-procedural mouth rinse. The SARS-CoV-2 virus was identified in the saliva of 19 patients, but was undetectable in aerosols in any of the cases.

The findings are reassuring, but also make sense, Kumar said: Irrigant dilutes saliva — a “thick, viscous” substance — by an estimated 20- to 200-fold, and the research is validated by a 2020 study that reported a less than 1% COVID-19 positivity rate among dentists.

Kumar noted that dentistry has long been at the forefront of infection-control practices in health care. During the pandemic, new protocols have included strengthened ventilation systems, extra aerosol suction equipment, N95 masks and face shields on top of goggles, and extended downtime between patients. She is hopeful this study’s findings will make practitioners and patients feel at ease about being in the dentist’s office — with continued stringent protection in place.

“Dental surgeons and hygienists are always at the forefront of the war against bacteria in the mouth, and they of course did not feel safe because they are front-line workers surrounded by aerosol,” said Kumar, who has a periodontology practice of her own and was one of the procedure operators in the study.

“Hopefully this will set their mind at rest because when you do procedures, it is the water from the ultrasonic equipment that’s causing bacteria to be there. It’s not saliva. So the risk of spreading infection is not high,” she said. “However, we should not lose sight of the fact that this virus spreads through aerosol, and speaking, coughing or sneezing in the dental office can still carry a high risk of disease transmission.”

Co-authors of the study include Archana Meethil, Shwetha Saraswat and Shareef Dabdoub of Ohio State and Prem Prashant Chaudhary of the National Institute of Allergy and Infectious Diseases.

It is difficult for us to succeed in whatever we set out to do if we lack motivation. We usually need it as a driving force to achieve both short- and long-term goals, from household chores to getting a degree. However, because of the ongoing pandemic, our lifestyles have been subjected to drastic and dynamic changes, and many work- and study-related activities are now carried out online exclusively. This, among other complex factors, have made it difficult for some people to stay focused and motivated, and psychology researchers are trying to find effective and widely applicable solutions to address such problems.

In a recent study published in BMC Psychology, researchers from Ritsumeikan University and the National Institute of Information and Communications Technology (NICT), Japan, have explored a simple strategy to increase motivation in college students by nurturing a positive emotion: gratitude. Many studies have shown that even short “gratitude interventions,” which are activities that increase an individual’s awareness of feelings of gratitude, can have a lasting positive effect on that person’s mood, satisfaction, and well-being. However, based on previous studies, the available evidence on the effect of such interventions on academic motivation is somewhat inconclusive. This prompted the researchers to test the effects of a different type of gratitude intervention: daily gratitude journaling.

“Our main hypothesis was that engaging in an online gratitude journal by writing down up to five things one felt grateful for each day could make students be more aware of their academic opportunities — their ‘blessings’ — and help them re-evaluate their motives and goals, ultimately improving their motivation,” explains Dr. Norberto Eiji Nawa from NICT, first author of the study. They recruited 84 participants, all Japanese college students, and divided them into a control group and an intervention group. Over the course of two weeks, students in both groups had to evaluate aspects of their daily life through online questionnaires each day, but only the intervention group had to keep the online daily gratitude journal. At the start of the intervention and after 1, and 2 weeks, and 1 and 3 months, the participants had to complete the Academic Motivation Scale (AMS), a tried-and-tested tool for measuring different aspects of academic motivation.

The results were certainly promising; through statistical analyses, the researchers found that the gratitude intervention through daily journaling significantly increased the students’ academic motivation. Most notably, this robust positive effect was not restricted only to the two-week period of the intervention, as the increased level of academic motivation was maintained even after three months. In addition, through an exploratory analysis, the researchers established that the enhancement in academic motivation was mostly driven by a decrease in “amotivation scores.” Amotivation, in this context, refers to the state in which a person perceives that their own actions are irrelevant to the resulting outcomes, leading to feelings of helplessness and incompetence.

Academic motivation can be one of the primary determinants of both academic achievements and satisfaction with school life, and developing widely applicable intervention strategies is critical to foster student growth. “Online interventions have the advantage of being more accessible, scalable and affordable to large portions of the population. Gathering solid evidence to support their deployment will be essential to unleash their true potential in the future,” concludes Professor Noriko Yamagishi from Ritsumeikan University. Fortunately, it appears that the positive impact of gratitude interventions extends well beyond the already-documented effects on individual well-being.

This study was partly supported by a research grant from the Ritsumeikan Inamori Philosophy Research Center. This Center aims to promote multidisciplinary research on the management philosophy advocated by Dr. Kazuo Inamori, a prominent Japanese entrepreneur and renowned philanthropist. With this major goal in mind, Professor Yamagishi, alongside Dr. Nawa, have been working on the scientific elucidation of the emotions of “altruism” and “gratitude” from the perspective of cognitive psychology and neuroscience. This particular study was conducted as part of this more overarching research. Until the day these human emotions become clearer, we can safely give this piece of advice: remember to count your blessings.

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Materials provided by Ritsumeikan University. Note: Content may be edited for style and length.