Wednesday, July 21, 2021

Emory team makes finals in Amazon's Alexa Prize for artificial intelligence

The Emory team is led by faculty advisor Jinho Choi (center) and graduate students James Finch (left) and Sarah Finch.

A team of six Emory computer science students made it to the final round for Amazon’s Alexa Prize Socialbot Grand Challenge, a global competition among universities to create a chatbot that advances the field of artificial intelligence. The winner of the 2021 Alexa Prize will be announced in mid-August. At stake is a $500,000 first prize. In addition, $1 million in research funds will be awarded to the winning team if it meets the “grand challenge” criteria, including the ability of its chatbot to engage the judges in conversation for at least 20 minutes. 
 
In addition to Emory, the finalists are Czech Technical University, Prague; SUNY at Buffalo, New York; Stanford University and the University of California Santa Cruz. 
 
The Emory team is headed by graduate students Sarah Finch and James Finch, along with faculty advisor Jinho Choi, assistant professor in the Department of Computer Sciences. Last year, the trio headed a team of 14 Emory students that took first place, winning $500,000 for their chatbot named Emora. They chose the name because it sounds like a feminine version of “Emory” and is similar to a Hebrew word for an eloquent sage. 

This year, they are turning up the heat with an even more advanced version of Emora and new team members, including graduate student Han He and undergraduates Sophy Huang, Daniil Huryn and Mack Hutsell. All the students are members of Choi’s Natural Language Processing Research Laboratory

“I’m extremely proud to have such a talented team of students,” Choi says. “It’s a group of strongly motivated people with the right combination of diverse skills coming together at the right time. They’re working on changing the paradigm for conversational artificial intelligence.” 

“We’re using some established technology but taking a groundbreaking approach in how we combine and execute dialogue management so a computer can make logical inferences while conversing with a human,” adds Sarah Finch. “Ultimately, we’re making Emora even more flexible in how she can interact with people.”


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Monday, July 12, 2021

Using big data to zero in on a mosquito menace

"The ultimate goal is to give public health officials the power to do more effective and efficient mosquito control — even before an epidemic beings," says Gonzalo Vazquez-Prokopec, right, shown with public health technicians in Merida, Mexico.

Scientists from Emory University are leading a new strategy in humanity’s long-running war with the mosquito, using big data to target one species of this tiny disease vector. They have studied the behavior of the Aedes aegypti mosquito, pinpointing where it hangs out in homes. They are mapping cases over time of viral infections that this species can transmit when it bites a human — including dengue fever, Zika, chikungunya and yellow fever. They are zeroing in on high-risk neighborhoods for outbreaks of these diseases in sprawling urban areas of the tropics. 

“We’re working on some of the boldest and biggest changes in decades for the surveillance and control of this mosquito,” says Gonzalo Vazquez-Prokopec, associate professor in Emory's Department of Environmental Sciences
 
The National Institutes of Health’s Division of Microbiology and Infectious Diseases awarded Vazquez-Prokopec a $6.5 million grant to lead a consortium in a randomized clinical trial in Merida, Mexico, as part of the quest to reduce Aedes-borne viral infections. The trial is testing a novel intervention that previous Emory research finds promising: Indoor residual spraying of insecticide, targeted to the places in homes where this mosquito tends to rest. 
 

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Wednesday, July 7, 2021

Mapping dengue hot spots pinpoints risks for Zika and chikungunya

A female Aedes aegypti mosquito takes a blood meal from a human. "The ultimate goal is to give public health officials the power to harness big data and do more effective and efficient mosquito control — even before an epidemic begins," says Emory disease ecologist Gonzalo Vazquez-Prokopec. (Photo by James Gathany / CDC).

By Carol Clark

Data from nine cities in Mexico confirms that identifying dengue fever “hot spots” can provide a predictive map for future outbreaks of Zika and chikungunya. All three of these viral diseases are spread by the Aedes aegypti mosquito. 

Lancet Planetary Health published the research, led by Gonzalo Vazquez-Prokopec, associate professor in Emory University’s Department of Environmental Sciences. The study provides a risk-stratification method to more effectively guide the control of diseases spread by Aedes aegypti

“Our results can help public health officials to do targeted, proactive interventions for emerging Aedes-borne diseases,” Vazquez-Prokopec says. “We’re providing them with statistical frameworks in the form of maps to guide their actions.” 

The study encompassed data for 2008 through 2020 from cities in southern Mexico with a high burden of dengue fever cases during that period, along with cases of the more recently emerged diseases of Zika and chikungunya. The cities included Acapulco, Merida, Veracruz, Cancun, Tapachula, Villahermosa, Campeche, Iguala and Coatzacoalcos. 

The results found a 62 percent overlap of hot spots for dengue and Zika and 53 percent overlap for cases of dengue and chikungunya. In addition, dengue hot spots between 2008 and 2016 were significantly associated with dengue hotspots detected between 2017 and 2020 in five of the nine cities. 

The work builds on a previous study of the spatial-temporal overlap of the three diseases, focused on Merida, a city of one million located in the Yucatan Peninsula. That study showed that nearly half of Merida’s dengue cases from 2008 to 2015 were clustered in 27 percent of the city. These dengue hot spots contained 75 percent of the first chikungunya cases reported during the outbreak of that disease in 2015 and 100 percent of the first Zika cases reported during the Zika outbreak of 2016. 

“In this latest paper, we’ve expanded our analysis in scope and geography and shown that the findings are consistent across these nine cities of different sizes and in different regions,” Vazquez-Prokopec says. “We’ve confirmed that dengue, Zika and chikungunya outbreaks tend to concentrate in small areas of a city, and that these hot spots are predictive of where future cases will concentrate.” 

Mosquito control efforts generally involve outdoor spraying that covers broad swaths of a city, but the Aedes aegypti mosquito has adapted to live inside houses. Work by Vazquez-Prokopec and collaborators has shown that the best way to control these mosquitos and the diseases they spread is by spraying a long-lasting pesticide indoors — on the ceilings, along the bases of walls, and in other areas of homes where the mosquitos tend to cluster. This approach — known as targeted indoor residual spraying — is too expensive and time-consuming to apply across a city. 

The statistical framework in the current paper, however, allows public health officials to concentrate their efforts on previous hot spots for Aedes-borne diseases to better control — and even prevent — outbreaks. 

“The ultimate goal is to give public health officials the power to harness big data and do more effective and efficient mosquito control — even before an epidemic begins,” Vazquez-Prokopec says. 

Vazquez-Prokopec is currently leading a consortium in a randomized clinical trial in Merida to test targeted indoor residual spraying as an intervention against Aedes-borne diseases. The five-year trial, launched in 2020, is funded by a $6.5 million grant from the National Institutes of Health. 

Dengue fever is sometimes called “break-bone fever” due to the excruciating pain that is among its symptoms. More than one third of the world’s population lives in areas at high risk for infection with the dengue virus, a leading cause of illness and death in the tropics and subtropics. Dengue is endemic through most of Mexico, where between 75,000 and 355,000 cases occur annually, translating into an economic cost of between about U.S. $150 million and $257 million annually. 

Chikungunya is rarely fatal but the symptoms can be severe and debilitating. Zika can cause symptoms similar to those of dengue and chikungunya, such as joint pains and fever. While Zika tends to be less debilitating, or even asymptomatic, if a pregnant woman contracts the virus it can have a catastrophic impact on her unborn child, including severe brain defects. 

Co-authors of the Lancet Planetary Health paper include researchers from Mexico’s Ministry of Health; the Autonomous University of the Yucatan; the Autonomous University of Nuevo Leon; Yucatan Health Services; the Mexican Society of Public Health; the National Institute of Public Health in Cuernavaca; the Undersecretary of Prevention and Health Promotion in Mexico City; the Pan American Health Organization; and the U.S. Centers for Disease Control and Prevention. 

The work was funded by USAID, the U.S. Centers for Disease Control and Prevention, the Canadian Institute of Public Health, the state of Yucatan, the National Institutes of Health and Emory University.

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Zeroing in on a mosquito menace

Contact tracing, with indoor spraying, can curb dengue outbreak

Wednesday, June 30, 2021

Genetic risks for nicotine dependence span a range of traits and diseases

"Genetic studies may help reduce some of the stigma society has against substance use disorders, while also making treatment more accessible," says Victoria Risner, first author of the new study on nicotine dependence, who did the work as an Emory undergraduate.

By Carol Clark 

Some people casually smoke cigarettes for a while and then stop without a problem, while others develop long-term, several packs-per-day habits. A complex mix of environmental, behavioral and genetic factors appear to raise this risk for nicotine dependence. 

Studies of groups of twins suggest that 40 to 70 percent of the risk factors are heritable. Until recently, however, studies have only explained about 1 percent of the observed variation in liability to nicotine dependence, using a genetic score based on how many cigarettes a person smokes per day. 

A study led by psychologists at Emory University offers a new model for examining this genetic risk. It leveraged genome wide association studies for a range of different traits and disorders correlated with nicotine dependence and explained 3.6 percent of the variation in nicotine dependence. 

The journal Nicotine & Tobacco Research published the finding. 

Higher polygenetic scores for a risk for schizophrenia, depression, neuroticism, self-reported risk-taking, a high body mass index, alcohol use disorder, along with a higher number of cigarettes smoked per day were all indicators of a higher risk for nicotine dependence, the study found. And polygenetic scores associated with higher education attainment lowered the risk for nicotine dependence, the results showed. 

“If you look at the joint effect of all of these characteristics, our model accounts for nearly 4 percent of the variation in nicotine dependence, or nearly four times as much as what we learn when relying solely on a genetic index for the number of cigarettes someone smokes daily,” says Rohan Palmer, senior author of the study and assistant professor in Emory’s Department of Psychology, where he heads the Behavioral Genetics of Addiction Laboratory. 

“What we’re finding,” Palmer adds, “is that to better leverage genetic information, we need to go beyond individual human traits and disorders and think about how risk for different behaviors and traits are interrelated. This broader approach can give us a much better measure for whether someone is at risk for a mental disorder, such as nicotine dependence.” 

Rohan Palmer heads the Department of Psychology's Behavioral Genetics of Addiction Laboratory that is developing new methods to better understand what makes people vulnerable to substance use disorders.

“All of the traits and diseases we looked at are polygenic, involving multiple genes,” adds Victoria Risner, first author of the study, who did the work as an Emory undergraduate majoring in neuroscience and behavioral biology. “That means that millions of genetic variants likely go into a complete picture for all of the heritable risks for nicotine dependence.” 

The researchers hope that others will build on their multi-trait, polygenetic model and continue to boost the understanding of the risk for such complex disorders. “The more we learn, the closer we can get to one day having a genetic test that clinicians can use to inform their assessment of someone’s risk for nicotine dependence,” Palmer says. 

Although the hazards of smoking are well established, about 14 percent of Americans report daily use of tobacco. Around 500,000 people die each year in the United States from smoking or exposure to smoke, and another 16 million live with serious illnesses caused by tobacco use, including cancer, cardiovascular disease and pulmonary disease. While the toxic chemicals produced during smoking and vaping are what cause harmful health effects, it’s the addictive component of nicotine that hooks people on these habits. 

Risner worked on the current paper for her honors thesis. “Nicotine dependence was interesting to me because the vaping scene was just arriving while I was an undergraduate,” she says. “I saw some of my own friends who were into vaping quickly becoming dependent on it, while some others who were using the same products didn’t. I was curious about the genetic underpinnings of this difference.” 

The project leveraged genome-wide association studies for a range of traits and disorders. The researchers then looked for matching variants in genetic data from a national representative sample of Americans diagnosed with nicotine dependence. The results showed how polygenetic scores for the different traits and disorders either raised or lowered the risk for that dependence. The number of cigarettes smoked per day, self-perceived risk-taking and educational attainment were the most robust predictors. 

The multi-variant, polygenetic model offers a road map for future studies. A clearer picture of heritability for nicotine dependence, for instance, may be gained by adding more risk associations to the model (such as nicotine metabolism) and clusters of polygenic traits (such as anxiety along with neuroticism). 

“As we continue to zero in on who is most at risk for becoming nicotine dependent, and what inter-related factors, whether genetic or environmental, may raise their risk, that could help determine what intervention might work best for an individual,” Palmer says. 

“Just a few decades ago, it was not well understood that nicotine dependence could have a genetic component,” Risner says. “Genetic studies may help reduce some of the stigma society has against substance use disorders, while also making treatment more accessible.” 

Risner graduated from Emory in 2019 and is now in medical school at the University of North Carolina, Chapel Hill. This summer, she’s applying the coding and analytical skills she learned at Emory to conduct research into genetic factors that may raise the risk for pre-term births. 

Emory co-authors of the Nicotine & Tobacco Research article include graduate student Lauren Bertin; post-doctoral fellow Chelsie Benca-Bachman; and Alicia Smith, associate professor in the School of Medicine. Additional authors include researchers from the University of Helsinki; Brown University; the Providence VA Medical Center; the Jackson Laboratory in Bar Harbor, Maine; Purdue University; and the University of Colorado at Boulder. 

The work on the Nicotine & Tobacco Research article was funded by the National Institute on Drug Abuse and the Academy of Finland.

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Heritable traits that appear in teen years raise risk for adult cannabis use

New research aims to understand how genetic differences contribute to addiction

Monday, June 28, 2021

New molecule found in chestnut leaves disarms dangerous staph bacteria

"We're laying the groundwork for new strategies to fight bacterial infections at the clinical level," says Emory ethnobotanist Cassandra Quave, shown gathering samples of chestnut leaves in Italy. "We urgently need these new strategies."

By Carol Clark

Scientists isolated a molecule, extracted from the leaves of the European chestnut tree, with the power to neutralize dangerous, drug-resistant staph bacteria. Frontiers in Pharmacology published the finding, led by scientists at Emory University. 

The researchers dubbed the molecule Castaneroxy A, after the genus of the European chestnut, Castanea. The use of chestnut leaves in traditional folk remedies in rural Italy inspired the research. 

“We were able to isolate this molecule, new to science, that occurs only in very tiny quantities in the chestnut leaves,” says Cassandra Quave, senior author of the paper and associate professor in Emory’s Center for the Study of Human Health and the School of Medicine’s Department of Dermatology. “We also showed how it disarms Methicillin-resistant Staphylococcus aureus by knocking out the bacteria’s ability to produce toxins.” 

Methicillin-resistant Staphylococcus aureus (MRSA) causes infections that are difficult to treat due to its resistance to antibiotics. It is one of the most serious infectious disease concerns worldwide, labeled as a “serious threat” by the Centers for the Disease Control and Prevention. In the United States alone, nearly 3 million antibiotic-resistant infections occur each year, killing more than 35,000 people. 

Antibiotics work by killing staph bacteria, which can lead to greater resistance among those few bacteria that survive, spawning “super bugs.” The Quave lab has identified compounds from the Brazilian peppertree, in addition to the European chestnut tree, that simply neutralize the harmful effects of MRSA, allowing cells and tissue to naturally heal from an infection without boosting resistance. 

“We’re trying to fill the pipeline for antimicrobial drug discovery with compounds that work differently from traditional antibiotics,” Quave says. “We urgently need these new strategies.” She notes that antimicrobial infections kill an estimated 700,000 globally each year, and that number is expected to grow exponentially if new methods of treatment are not found. 

First author of the Frontiers in Pharmacology paper is Akram Salam, who did the research as a PhD student in the Quave lab through Emory’s Molecular Systems and Pharmacology Graduate Program.

The European chestnut, also known as the sweet chestnut, is native to Southern Europe and Asia Minor.

Quave is a medical ethnobotanist, researching traditional plant remedies to find promising leads for new drugs. Although many major drugs are plant-based, from aspirin (the bark of the willow tree) to Taxol (the bark of the Pacific yew tree), Quave is one of the few ethnobotanists with a focus on antibiotic resistance.

The story behind the current paper began more than a decade ago, when Quave and her colleagues researched written reports and conducted hundreds of field interviews among people in rural southern Italy. That pointed them to the European, or sweet, chestnut tree, native to Southern Europe and Asia Minor. “In Italian traditional medicine, a compress of the boiled leaves is applied to the skin to treat burns, rashes and infected wounds,” Quave says. 

Quave took specimens back to her lab for analysis. By 2015, her lab published the finding that an extract from the leaves disarms even the hyper-virulent MRSA strains capable of causing serious infections in healthy athletes. Experiments also showed the extract did not disturb normal, healthy bacteria on skin cells. 

Finally, the researchers demonstrated how the extract works, by inhibiting the ability of MRSA bacteria to communicate with one another, a process known as quorum sensing. MRSA uses this sensing signaling system to make toxins and ramp up its virulence. 

For the current paper, the researchers wanted to isolate these active ingredients from the plant extract. The process is painstaking when done manually, because plant extracts typically contain hundreds of different chemicals. Each chemical must be separated out and then tested for efficacy. Large scale fraction collectors, coupled to high-performance liquid chromatographic systems, automate this separation process, but they can cost tens of thousands of dollars and did not have all the features the Quave lab needed. 

Marco Caputo, a research specialist in the lab, solved the problem. Using a software device from a child’s toy, the LEGO MINDSTORMS robot creator, a few LEGO bricks, and some components from a hardware store, Caputo built an automated liquid separator customized to the lab’s needs for $500. The lab members dubbed the invention the LEGO MINDSTORMS Fraction Collector. They published instructions for how to build it in a journal so that other researchers can tap the simple, but effective, technology. 

The lab's homemade fraction collector.

The Quave lab first separated out a group of molecules from the plant extract, cycloartane triterpenoids, and showed for the first time that this group actively blocks the virulence of MRSA. The researchers then dove deeper, separating out the single, most active molecule from this group, now known as Castaneroxy A. 

“Our homemade piece of equipment really helped accelerate the pace of our discovery,” Quave says. “We were able to isolate this molecule and derive pure crystals of it, even though it only makes up a mere .0019 percent of the chestnut leaves.” 

Tests on mouse skin infected with MRSA, conducted in the lab of co-author Alexander Horswill at the University of Colorado, confirmed the molecule’s efficacy at shutting down MRSA’s virulence, enabling the skin to heal more rapidly. 

Co-author John Bacsa, director of Emory Department of Chemistry’s X-ray Crystallography Center, characterized the crystal shape of Castaneroxy A. Understanding the three-dimensional configuration of the crystal is important for future studies to refine and optimize the molecule as a potential therapeutic.

“We’re laying the groundwork for new strategies to fight bacterial infections at the clinical level,” Quave says. “Instead of being overly concerned about treating the pathogen, we’re focusing on ways to better treat the patient. Our goal is not to kill the microbes but to find ways to weaken them so that the immune system or antibiotics are better able to clear out an infection.” 

Emory co-authors of the paper also include graduate students Caitlin Risener and Lewis Marquez; post-doctoral fellow Gina Porras; and former staff scientist James Lyles. Additional authors from the University of Colorado are Young-Saeng Cho and Morgan Brown. 

The work was funded by the National Center for Complementary and Integrative Health, Emory’s Department of Dermatology, the National Institute of Allergy and Infectious Diseases and the National Institute of General Medical Sciences.

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Brazilian peppertree packs power to knock out antibiotic-resistant bacteria

Major review of plants' role in antibacterial activity clears new paths for drug discovery

Chestnut leaves yield extract that disarms deadly bacteria