AI to make dentists' work easier

New model helps localise the mandibular canals

AALTO UNIVERSITY

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IMAGE: COMPARISON OF THE MODEL SEGMENTATION AND THE GROUND TRUTH, FROM THE SECONDARY TEST DATA ANNOTATIONS, FOR A CBCT SCAN. FOR FURTHER EXPLANATION, SEE THE RESEARCH ARTICLE IN SCIENTIFIC REPORTS. view more 

CREDIT: THE AUTHORS

In order to plan a dental implant operation and the implant size and position, dentists need to know the exact location of the mandibular canal, a canal located in both sides of the lower jaw that contains the alveolar nerve.

The lower jaw is an anatomically complex structure and medical experts use X-ray and computer tomography (CT) models to detect and diagnose such structures. Typically, dentists and radiologists define the location of the mandibular canals manually from the X-ray or CT scans, which makes the task laborious and time-consuming. That is why an automatized way to do this could make their work and placement of dental implants much easier.

To bring a solution to this problem, researchers at the Finnish Center for Artificial Intelligence FCAI, Tampere University Hospital, Planmeca and the Alan Turing Institute developed a new model that accurately and automatically shows the exact location of mandibular canals. The model is based on training and using deep neural networks. The researchers trained the model by using a dataset consisting of 3D cone beam CT (CBCT) scans.

The model is based on a fully convolutional architecture, which makes it as fast and data-efficient as possible. Based on the research results, this type of a deep learning model can localise the mandibular canals highly accurately. It surpasses the statistical shape models, which have thus far been the best, automatized method to localise the mandibular canals.

In simple cases - when the patient does not have any special conditions, such as osteoporosis - the model is as accurate as a human specialist. Most patients that visit a dentist fall into this category. 'In more complex cases, one may need to adjust the estimate, so we are not yet talking about a fully stand-alone system,' says Joel Jaskari, Doctoral Candidate and the first author of the research paper.

Using Artificial Intelligence has another clear advantage, namely the fact that the machine performs the job equally fast and accurately every time. 'The aim of this research work is not, however, to replace radiologists but to make their job faster and more efficient so that they will have time to focus on the most complex cases,' adds Professor Kimmo Kaski.

Planmeca, a Finnish company developing, manufacturing and marketing dental equipment, 2D and 3D imaging equipment and software, collaborates with FCAI. The company is currently integrating the presented model into its dedicated software, to be used with Planmeca 3D tomography equipment.

The research results were recently published in the prestigious publication series Scientific Reports. Link to the research article: https://www.nature.com/articles/s41598-020-62321-3

Improving the treatment of periodontitis

Amoeba linked to severe gum disease

CHARITÉ - UNIVERSITÄTSMEDIZIN BERLIN

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IMAGE: THE PARASITE ENTAMOEBA GINGIVALIS PENETRATES THE GUM TISSUE, FEEDING ON HOST CELLS. view more 

CREDIT: SCHAEFER/ CHARITÉ

For the first time, researchers from Charité - Universitätsmedizin Berlin have shown that a unicellular parasite commonly found in the mouth plays a role in both severe tissue inflammation and tissue destruction. Most patients with severe and recurrent periodontitis (gum disease) showed an increased presence of the amoebaEntamoeba gingivalis inside their oral cavities. The effect of this amoeba is similar to that of Entamoeba histolytica, the parasite responsible for causing amebiasis. Once the parasite has invaded the gingival tissue, it feeds on its cells and causes tissue destruction. According to the researchers' findings, which have been published in theJournal of Dental Research*, the two amoebae show similar mechanisms of tissue invasion and elicit a similar immune response in the host.

Periodontitis, or gum disease, is an inflammation of the gums and supporting structures of the teeth. It is one of the most common chronic diseases in the world. In Germany, approximately 15 percent of people are affected by a particularly severe form of this disease. If left untreated, periodontitis will lead to tooth loss. The disease also increases the risk of arthritis, cardiovascular disease and cancer. In patients with periodontitis, a decrease in the diversity of the oral flora coincides with an increase in the frequency of E. gingivalis. A team of researchers, led by Prof. Dr. Arne Schäfer, Head of the Periodontology Research Unit at Charité's Institute of Dental and Craniofacial Sciences, was able to show that oral inflammation is associated with colonization by the oral parasite E. gingivalis.

Scientists have long been aware of the virulence potential of this genus of amoebae. The gastrointestinal parasite E. histolytica, for instance, causes a disease known as amebiasis, one of the most common causes of death from parasitic diseases worldwide. "We have shown that an amoeba like E. gingivalis, which colonizes the oral cavity, will invade the oral mucosa and destroy gingival tissue. This enables increased numbers of bacteria to invade the host tissue, which further exacerbates inflammation and tissue destruction," says Prof. Schäfer. The international team of researchers was the first to describe precise roles of E. gingivalis in the pathogenesis of inflammation. During their analysis of inflamed periodontal pockets, the researchers detected evidence of the amoeba in approximately 80 percent of patients with periodontitis, but in only 15 percent of healthy subjects. Their observations revealed that, after invading the gums, the parasites move within the tissue, feeding on and killing host cells. Cell culture experiments showed that infection with E. gingivalis slows the rate at which cells grow, eventually leading to cell death.

The researchers concluded that the amoeba's role in inflammation shows distinct parallels to the pathogenesis of amebiasis. "E. gingivalis actively contributes to cell destruction inside the gingival tissue and stimulates the same host immune response mechanisms as E. histolytica during its invasion of the intestinal mucosa," explains Prof. Schäfer. "This parasite, which is transmitted by simple droplet infection, is one potential cause of severe oral inflammation."

Treatment success is often short-lived in patients with periodontitis. This might be due to the high virulence potential of this previously unnoticed, yet extremely common amoeba. Summing up the results of the research, Prof. Schäfer says: "We identified one infectious parasite whose elimination could improve treatment effectiveness and long-term outcomes in patients with gum disease." He adds: "Current treatment concepts for periodontitis fail to consider the possibility of infection by this parasite or its successful elimination." A clinical trial is underway to determine the extent to which the elimination of this amoeba might improve treatment outcomes in patients with periodontitis.

The building blocks of gum disease

OKINAWA INSTITUTE OF SCIENCE AND TECHNOLOGY (OIST) GRADUATE UNIVERSITY

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IMAGE: MOST BACTERIAL CELLS ARE COVERED IN TINY, HAIR-LIKE STRUCTURES CALLED PILI. THEIR DIAMETER IS SMALLER THAN 1/10,000TH OF A HUMAN HAIR. view more 

CREDIT: S. SHIBATA, OIST

Porphyromonas gingivalis is a major bacterial pathogen which leads to periodontitis also known as gum disease. In Japan, 80% of adults aged 35 and over suffer from this disease. What's more, P. gingivalis has also been linked to rheumatoid arthritis, cardiovascular disease, pancreatic cancer, and even Alzheimer's disease.

Periodontitis is an oral inflammatory disease in response to biofilms - a bacterial plaque that accumulates on surfaces like our teeth. Biofilms are primarily created by bacterial cells attaching themselves to the host, and to each other, by sticky hair-like filaments called pili. In serious cases, periodontitis can result in gum erosion and tooth loss.

A team of researchers from the Molecular Cryo-Electron Microscopy Unit at the Okinawa Institute of Science and Technology Graduate University (OIST), alongside the groups of Professor Koji Nakayama at Nagasaki University and Professor Katsumi Imada at Osaka University, have revealed the structure of these adhesive pili and shed light on how they assemble. Their research, published in Nature Microbiology, has provided new insights into bacteriology and is a crucial step towards combatting the diseases this bacterium is associated with.

"Pili are vital for both the survival of the bacteria, and the creation of the biofilms," said Dr. Satoshi Shibata, first author and staff scientist in OIST's Unit, which is led by Associate Professor Matthias Wolf. "By taking a close look at these pili, our research has provided insights into how we can prevent biofilms from forming."

P. gingivalis is a member of the class Bacteroidia. Previous research, led by Professor Nakayama and colleagues at Nagasaki University, found that most bacteria within this class have unique Type V pili. However, until now, the structure and assembly process of these pili were unknown. "Besides periodontal pathogens, Type V pili are seen in major colon bacteria such as Bacteroides and Prevotella species and their Type V pili may contribute to formation of colon microbiota," said Professor Nakayama.

Pili themselves are made up of smaller protein units, called pilins. In the case of P. gingivalispili, most of these are FimA pilins. Although pilins are only linked by weak interactions, they can assemble into very stable pili.

The first step to determining how this assembly occurred was to take a close look at the structure of individual pilins. "Detailed structural information of FimA is very important because pathogenicity of P. gingivalis strains is closely related with the FimA sub-types," said Professor Imada.

Professor Imada and students from Osaka University crystalized FimA pilins, revealing their unassembled state at atomic resolution.

"Based on findings from earlier experiments by the Nakayama group, we theorized that these pilins assembled themselves via a mechanism of protease-mediated strand-exchange," said Dr. Shibata. "So, our next experiment took a close look at fully assembled pili using cryo-electron microscopy."

Associate Prof. Mikio Shoji from the Nakayama group, and Dr. Shibata prepared a genetically engineered version of the FimA pilins, which successfully assembled into pili, after a protease - a protein that cuts other proteins - was added. Dr. Shibata then collected thousands of images on the high-end cryo-electron microscope at OIST and processed the data on the University's "Sango" supercomputer, resulting in a complete three-dimensional atomic model of the assembled pilus structure.

"When we added the protease, the pilins started to assemble into elongated pili like train cars connecting to form a train. This happened because the protease cut a retaining loop and released a protein strand, known as the donor strand, which triggered the assembly to begin," said Professor Wolf. Once released, the donor strand flipped out of the pilin and inserted itself into a neighboring pilins groove, thus connecting the two pilins.

Finally, in a combined team effort, the three groups took a closer look at the amino acid composition at the end of the donor strand and found that it played a critical role in the assembly mechanism. Using biochemistry, crystallography and cryo-EM, they mutated the protein, which prevented the pili from forming and thus proved how these key amino acids contribute to pilin polymerization.

Ultimately, this research is a step towards new anti-bacterial drugs, not just for the diseases caused by P. gingivalis, but for those caused by any bacteria containing Type V pili. "We're now trying to create an inhibitor that prevents pili from assembling," said Dr. Shibata. "This structure serves as a target to create new drugs, which are desperately needed to counter increasing antibiotic resistance. Finding novel antimicrobial compounds is a critical advantage in fighting these pathogens."

Role of fungi in early childhood dental health

CLEMSON UNIVERSITY

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IMAGE: BIOLOGICAL SCIENCES PROFESSOR VINCE RICHARDS AND GRADUATE STUDENT LAUREN O'CONNELL'S DENTAL MYCOBIOME PAPER WAS PUBLISHED ON MARCH 18, 2020, IN APPLIED AND ENVIRONMENTAL MICROBIOLOGY AS A SPOTLIGHT ARTICLE. view more 

CREDIT: CLEMSON COLLEGE OF SCIENCE/PETE MARTIN

CLEMSON, South Carolina -- Although mostly preventable, tooth decay is one of the most common chronic diseases in children worldwide, particularly in developing countries. If left untreated, cavities can be painful and may negatively affect a young child's overall health, development and quality of life.

Clemson University College of Science researchers recently conducted a study that may someday lead to better cavity prevention measures and treatments. Specifically, biological sciences assistant professor Vincent Richards' group examined the oral mycobiome, including all the fungi that might live there.

"This work provides valuable insight into the oral mycobiome and the role fungi play in the mouth as it relates to caries," said Richards. "If we understand that better then researchers can develop better cavity prevention measures. For example, perhaps they can put beneficial fungal species into a pro-biotic treatment."

For years, the dental community has known that tooth decay occurs when the good and bad bacteria in our mouth become imbalanced and forms a biofilm (aka plaque). The biofilm absorbs the sugars we eat and the bacteria catabolize those sugars, turning them into acid, which decalcifies the teeth and causes cavities.

Thanks to advances in genome sequencing technology, scientists recently discovered that there is also a high diversity of fungi in the mouth, albeit in far fewer numbers than bacteria. However, little was known about the fungi's role in cavity formation and caries disease progression.

"The microbiome is a community-based thing and it's very complex," said biological sciences graduate student Lauren O'Connell, the lead author of the study.  "Because fungi are present in the tooth biofilm, they're capable of utilizing these same sugars [as bacteria] and can produce acid, but we don't fully understand their role."

In the study, O'Connell sequenced the DNA from plaque samples of 33 children with varying stages of tooth health, including healthy teeth with no cavities; teeth with enamel lesions, which are indicative of an early-stage cavity; and teeth with dentin lesions, which indicate an advanced-stage cavity requiring either a filling or extraction.

She also examined the condition of the patients' mouths, including a mouth with no cavities or lesions; a mouth with some teeth that have enamel lesions; and a mouth that has some teeth with enamel and dentin lesions.

"By looking at two variables--tooth and mouth health--we are taking a site-specific approach, which enables us to categorize each plaque sample six ways, or along a continuum," said Richards. "This is important because we have found that the bacterial microbiome from a healthy tooth in a diseased mouth is more similar to the microbiome of a diseased tooth. That microbiome has shifted its profile to more of a diseased state."

"We wanted to see how the microbiome community changed as the disease progressed," explained O'Connell. "There's only been one other study that looked at the fungi in relation to cavities, but they examined only healthy teeth and severely diseased teeth."

The research team identified 139 species of fungus that live in human dental plaque, and of those, nine were strongly associated with dental health--in other words they could be contributing to keeping teeth healthy.

The fungi associated with healthy teeth may be producing a compound called xylitol, which has been shown to inhibit the growth of the Streptococcus mutans bacteria that is known to cause cavities. Xylitol is an ingredient in sugarless gum.

"It's possible that the nine fungi are promoting health by creating xylitol and other advanced microbial compounds," said O'Connell. "But we have to do further functional testing to figure out if that is actually what is happening."

The team also discovered interesting things about fungi associated with disease. For example, they learned that Candida dubliniensis was strongly associated with late-stage cavities and was found in abundance as tooth decay progressed, which could make it a potential indicator species of early childhood caries.

According to O'Connell, a second finding related to possible disease-causing fungi was that Candida albicans, the fungus that causes yeast infections, was found in both healthy and diseased plaque samples, which makes its role in dental caries unclear.

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This research was published on March 18, 2020, in Applied and Environmental Microbiology as a spotlight article. The full title of the paper is "Site-specific profiling of the dental mycobiome reveals strong taxonomic shifts during progression of early childhood caries."