Why is Machine Learning Trending in Medical Research but not in Our Doctor’s Offices?

by Melissa Pappas

Illustration of a robot in a white room with medical equipment.Machine learning (ML) programs computers to learn the way we do – through the continual assessment of data and identification of patterns based on past outcomes. ML can quickly pick out trends in big datasets, operate with little to no human interaction and improve its predictions over time. Due to these abilities, it is rapidly finding its way into medical research.

People with breast cancer may soon be diagnosed through ML faster than through a biopsy. Those suffering from depression might be able to predict mood changes through smart phone recordings of daily activities such as the time they wake up and amount of time they spend exercising. ML may also help paralyzed people regain autonomy using prosthetics controlled by patterns identified in brain scan data. ML research promises these and many other possibilities to help people lead healthier lives.

But while the number of ML studies grow, the actual use of it in doctors’ offices has not expanded much past simple functions such as converting voice to text for notetaking.

The limitations lie in medical research’s small sample sizes and unique datasets. This small data makes it hard for machines to identify meaningful patterns. The more data, the more accuracy in ML diagnoses and predictions. For many diagnostic uses, massive numbers of subjects in the thousands would be needed, but most studies use smaller numbers in the dozens of subjects.

But there are ways to find significant results from small datasets if you know how to manipulate the numbers. Running statistical tests over and over again with different subsets of your data can indicate significance in a dataset that in reality may be just random outliers.

This tactic, known as P-hacking or feature hacking in ML, leads to the creation of predictive models that are too limited to be useful in the real world. What looks good on paper doesn’t translate to a doctor’s ability to diagnose or treat us.

These statistical mistakes, oftentimes done unknowingly, can lead to dangerous conclusions.

To help scientists avoid these mistakes and push ML applications forward, Konrad Kording, Nathan Francis Mossell University Professor with appointments in the Departments of Bioengineering and Computer and Information Science in Penn Engineering and the Department of Neuroscience at Penn’s Perelman School of Medicine, is leading an aspect of a large, NIH-funded program known as CENTER – Creating an Educational Nexus for Training in Experimental Rigor. Kording will lead Penn’s cohort by creating the Community for Rigor which will provide open-access resources on conducting sound science. Members of this inclusive scientific community will be able to engage with ML simulations and discussion-based courses.

“The reason for the lack of ML in real-world scenarios is due to statistical misuse rather than the limitations of the tool itself,” says Kording. “If a study publishes a claim that seems too good to be true, it usually is, and many times we can track that back to their use of statistics.”

Such studies that make their way into peer-reviewed journals contribute to misinformation and mistrust in science and are more common than one might expect.

Read the full story in Penn Engineering Today.

The Potential Futures of Neurotech

Roy Hoshi Hamilton, MD, MS, FAAN, FANA

Brain technology offers all kinds of exciting possibilities — from treating conditions like epilepsy or depression, to simply maximizing brain health. But medical ethicists are concerned about potential dangers and privacy concerns. Roy Hamilton, Professor of Neurology in the Perelman School of Medicine,  Director of the Penn Brain Science, Translation, Innovation, and Modulation (BrainSTIM) Center, and member of the Penn Bioengineering Graduate Group, spoke with WHYY about how brain stimulation is being used.

Listen to “Neurotech and the Growing Battle for Our Brains

Two from Penn Bioengineering Graduate Group Elected to the National Academy of Sciences

Four faculty from the University of Pennsylvania have been elected to the United States National Academy of Sciences (NAS). They are David Brainard of the School of Arts & Sciences; Duncan Watts of the Annenberg School of Communication, School of Engineering and Applied Science, and Wharton School; and Susan R. Weiss and Kenneth S. Zaret of the Perelman School of Medicine.

They join 120 members and 23 international members elected by their peers this year to NAS. Recognized for “distinguished and continuing achievements in original research,” this new class brings the total number of active members to 2,565 and of international members to 526.

Brainard and Zaret are members of the Penn Bioengineering Graduate Group.

David Brainard is the RRL Professor of Psychology, director of the Vision Research Center, and associate dean for the natural sciences in the School of Arts & Sciences. His research focuses on human vision, using both experiments and computer modeling of visual processing, to understand how the visual system deciphers information about objects from light entering the eye. Specifically, he and his lab are interested in color vision, conducting psychophysical experiments to investigate how the appearance of color is affected by an object’s surface properties and ambient light, and how color perception aids in identifying objects. Brainard is the recipient of many honors, including the Macbeth Award from the Inter-Society Color Council, Stein Innovation Award from Research to Prevent Blindness, and Edgard D. Tillyer Award from Optica. He is an elected member of the Society of Experimental Psychologists, a Silver Fellow of the Association for Research in Vision and Ophthalmology, and a Fellow of the Association for Psychological Science.

Kenneth Zaret

Kenneth S. Zaret is the Joseph Leidy Professor in the Department of Cell and Developmental Biology at the Perelman School of Medicine, director of the Institute for Regenerative Medicine, and a member of the Cell and Molecular Biology Graduate Program. His research focuses on gene regulation, cell differentiation, and chromatin structure, with a goal of elucidating these phenomena in the context of embryonic development and tissue regeneration. Pinpointing these aspects of development at the cellular level can serve as the basis for developing future therapeutics and experimental models that further scientists’ ability to understand and cure disease. Zaret has been the recipient of many honors, including a MERIT Award from the National Institutes of Health, the Stanley N. Cohen Biomedical Research Award, and election as a fellow of the American Association for the Advancement of Science.

Read the full announcement in Penn Today.

CiPD Fellows Recognized with Research Awards

Members of the inaugural cohort of fellows in the Center for Innovation and Precision Dentistry (CiPD)’s NIDCR T90/R90 Postdoctoral Training Program have been recognized for their research activities with fellows receiving awards from the American Association for Dental, Oral, and Craniofacial Research (AADOCR), the Society for Biomaterials, and the Osteology Foundation. All four of the honored postdocs are affiliated with Penn Bioengineering.

Zhi Ren

Zhi Ren won first place in the Fives-Taylor Award at the AADOCR Mini Symposium for Young Investigators. A postdoctoral fellow in the labs of Dr. Hyun (Michel) Koo at Penn Dental Medicine (and member of the Penn Bioengineering Graduate Group) and Dr. Kathleen Stebe of Penn Engineering, Dr. Ren’s research focuses on understanding how bacterial and fungal pathogens interact in the oral cavity to form a sticky plaque biofilm on teeth, which gives rise to severe childhood tooth decay that affects millions of children worldwide. In his award-winning study, titled “Interkingdom Assemblages in Saliva Display Group-Level Migratory Surface Mobility”, Dr. Ren discovered that bacteria and fungi naturally present in the saliva of toddlers with severe decay can form superorganisms able to move and rapidly spread on tooth surfaces.

Justin Burrell

Justin Burrell won second place in the AADOCR Hatton Competition postdoctoral category for his research. Dr. Burrell has been working with Dr. Anh Le in Penn Dental Medicine’s Department of Oral Surgery/Pharmacology and Dr. D. Kacy Cullen of Penn Medicine and Penn Bioengineering. Together, their interdisciplinary team of clinician-scientists, biologists, and neuroengineers have been developing novel therapies to expedite facial nerve regeneration and increase meaningful functional recovery.

Marshall Padilla

Marshall Padilla earned third place at the Society for Biomaterials Postdoctoral Recognition Award Competition for a project titled, “Branched lipid architecture improves lipid-nanoparticle-based mRNA delivery to the liver via enhanced endosomal escape”. Padilla was also a finalist in the AADOCR Hatton Award Competition, presenting on a separate project titled, “Lipid Nanoparticle Optimization for mRNA-based Oral Cancer Therapy”. Both projects employ lipid nanoparticles, the same delivery vehicles used in the mRNA COVID-19 vaccine technology. A postdoctoral fellow in the lab of Dr. Michael J. Mitchell of Penn’s Department of Bioengineering, Dr. Padilla’s research focuses on developing new ways to enhance the efficacy and safety of lipid nanoparticle technology and its applications in dentistry and biomedicine. He has been working in collaboration with Dr. Shuying (Sheri) Yang and Dr. Anh Le in Penn Dental Medicine.

Dennis Sourvanos

Dennis Sourvanos (GD’23, DScD’23) was the recipient of the Trainee Travel Grant award through the Osteology Foundation (Lucerne Switzerland). Dr. Sourvanos will be presenting his research related to medical dosimetry and tissue regeneration at the International Osteology Symposium in Barcelona, Spain (April 27th – 29th 2023). He also presented at the 2023 AADOCR/CADR Annual Meeting for his project titled, “Validating Head-and-Neck Human-Tissue Optical Properties for Photobiomodulation and Photodynamic Therapies.” Dr. Sourvanos has been working with Dr. Joseph Fiorellini in Penn Dental Medicine’s Department of Periodontics and Dr. Timothy Zhu in the Hospital of the University of Pennsylvania’s Department of Radiation Oncology and the Smilow Center for Translational Research (and member of the Penn Bioengineering Graduate Group).

Read the full announcement in Penn Dental Medicine News.

More 2023 SFB STAR Awards for Penn Bioengineering Students

Following up on our recent announcement of two Student Travel Achievement Recognition (STAR) Awards from the Society for Biomaterials (SFB) for members of the lab of Mike Mitchell, we are pleased to announce that two more Penn Bioengineering students also received STAR Awards!

Matthew Aronson and Alexandra Dumas are both members of the lab of Riccardo Gottardi, Assistant Professor in Pediatrics in the Perelman School of Medicine and in Bioengineering in the School of Engineering and Applied Science. Both presented their work at the recent 2023 SFB Annual Meeting and Exposition in San Diego, California in April 2023 and were honored with STAR Awards for their research.

The Gottardi Bioengineering and Biomaterials Laboratory studies treatment and function restoration for children with otolaryngologic disorders through the Children’s Hospital of Philadelphia  (CHOP) in the Division of Otolaryngology.

Matthew Aronson

Matthew Aronson is a third-year Ph.D. student in Bioengineering, an Ashton Fellow, and a NSF Fellow. His doctoral research focuses on studying pediatric airway diseases and disorders. More specifically, he is interested in how bacteria of the upper airway are responsible for the development and progression the disease subglottic stenosis, narrowing of the airway. In addition to understanding this devastating disease in the context of pediatric patients at CHOP, he also designed a novel drug-eluting endotracheal tube to deliver a selective antimicrobial peptide to function as a treatment modality for the prevention of the disease.

Alexandra Dumas

Alexandra Dumas is a rising fourth-year undergraduate in Bioengineering from Durban, South Africa. She is a PURM Fellow and a University Scholar. Her recent work in the Gottardi Lab focuses on using decellularized cartilage scaffolds to repair the meniscus and airway. After her undergraduate degree, she hopes to pursue a Ph.D. or M.D.-Ph.D. in bioengineering to pursue the design of new biomaterials for low-resource communities.

 

Read more stories featuring Gottardi and his team here.

Penn Medicine and Independence Blue Cross Eliminate Preapprovals for Imaging Tests

Brian Litt, MD

Brian Litt, Professor in Bioengineering in Penn Engineering and in Neurology in the Perelman School of Medicine, spoke to Neurology Today about the advances in technology for detecting and forecasting seizures.

The Litt Lab for Translational Neuroengineering translates neuroengineering research directly into patient care, focusing on epilepsy and a variety of research initiatives and clinical applications.

“Dr. Litt’s group is working with one of a number of startups developing ‘dry’ electrode headsets for home EEG monitoring. ‘They are still experimental, but they’re getting better, and I’m really optimistic about the possibilities there.'”

Read “How Detecting, Identifying and Forecasting Seizures Has Evolved” in Neurology Today.

Read more stories featuring Litt in the BE Blog.

2023 Senior Design Project Competition Winners Announced

Each year, Penn Engineering’s seniors present their Senior Design projects, a year-long effort that challenges them to test and develop solutions to real-world problems, to their individual departments. The top three projects from each department go on to compete in the annual Senior Design Competition, sponsored by the Engineering Alumni Society, which involves pitching projects to a panel of judges who evaluate their potential in the market.

We are proud that two of the four awards went to Penn Bioengineering teams!

This year’s panel included over forty judges, and each winning team received a $2,000 prize, generously sponsored by Penn Engineering alumnus Kerry Wisnosky.

Congratulations to all of the 2023 participants and winners!

Technology & Innovation Award

This award recognized the team whose project represents the highest and best use of technology and innovation to leverage engineering principles.

Team BAMBI poses with Dean Vijay Kumar.

Winner: Team BAMBI
Department: Bioengineering
Team Members: Ria Dawar, Pallavi Jonnalagadda, Jessica Ling, Grace Qian
Mentor: Erin Anderson
Instructors: Erin Berlew, Sevile Mannickarottu, and David Meaney
Abstract: BAMBI (Biointelligent Apnea Monitor for Bradycardia-Prone Infants) is a tripartite system that leverages machine learning and automated mechanical stimulation to detect and treat apnea of prematurity in the NICU.

Judges’ Choice Award

Team StablEyes poses with Dean Vijay Kumar.This award recognizes the group whose all-around presentation captures the best of the senior design program’s different facets:  ideation, scope of project, team problem-solving, execution and presentation.

Winner: Team StablEyes
Department: Bioengineering
Team Members: Ella Atsavapranee, Jake Becker, Ruoming Fan, Savan Patel
Mentor: Erin Anderson, Dr. Drew Scoles and Dr. Tomas Aleman (Children’s Hospital of Philadelphia, Penn Medicine)
Instructors: Erin Berlew, Sevile Mannickarottu, and David Meaney
Abstract: StablEyes consists of a stabilization mount that provides fine, motorized control of the handheld OCT to improve ease of use for physicians and machine learning-based software to aid in diagnosis from retinal images.

Read the full list of SEAS Senior Design Competition Award winners in Penn Engineering Today.

Read more about all the Class of 2023 Penn Bioengineering Senior Design Teams in the Penn BE Labs website.

Study Reveals New Insights on Brain Development Sequence Through Adolescence

by Eric Horvath

3D illustration of a human brain
Image: Courtesy of Penn Medicine News

Brain development does not occur uniformly across the brain, but follows a newly identified developmental sequence, according to a new Penn Medicine study. Brain regions that support cognitive, social, and emotional functions appear to remain malleable—or capable of changing, adapting, and remodeling—longer than other brain regions, rendering youth sensitive to socioeconomic environments through adolescence. The findings are published in Nature Neuroscience.

Researchers charted how developmental processes unfold across the human brain from the ages of 8 to 23 years old through magnetic resonance imaging (MRI). The findings indicate a new approach to understanding the order in which individual brain regions show reductions in plasticity during development.

Brain plasticity refers to the capacity for neural circuits—connections and pathways in the brain for thought, emotion, and movement—to change or reorganize in response to internal biological signals or the external environment. While it is generally understood that children have higher brain plasticity than adults, this study provides new insights into where and when reductions in plasticity occur in the brain throughout childhood and adolescence.

The findings reveal that reductions in brain plasticity occur earliest in “sensory-motor” regions, such as visual and auditory regions, and occur later in “associative” regions, such as those involved in higher-order thinking (problem solving and social learning). As a result, brain regions that support executive, social, and emotional functions appear to be particularly malleable and responsive to the environment during early adolescence, as plasticity occurs later in development.

“Studying brain development in the living human brain is challenging. A lot of neuroscientists’ understanding about brain plasticity during development actually comes from studies conducted with rodents. But rodent brains do not have many of what we refer to as the association regions of the human brain, so we know less about how these important areas develop,” says corresponding author Theodore D. Satterthwaite, the McLure Associate Professor of Psychiatry in the Perelman School of Medicine, and director of the Penn Lifespan Informatics and Neuroimaging Center (PennLINC).

Read the full story in Penn Medicine News.

N.B.: Theodore Satterthwaite in a member of the Penn Bioengineering Graduate Group.

2023 Solomon R. Pollack Awards for Excellence in Graduate Bioengineering Research

The Solomon R. Pollack Award for Excellence in Graduate Bioengineering Research is given annually to the most deserving Bioengineering graduate students who have successfully completed research that is original and recognized as being at the forefront of their field. This year, the Department of Bioengineering at the University of Pennsylvania recognizes the stellar work of four graduate students in Bioengineering.

Margaret Billingsley

Dissertation: “Ionizable Lipid Nanoparticles for mRNA CAR T Cell Engineering”

Maggie Billingsley

Margaret earned a bachelor’s degree in Biomedical Engineering from the University of Delaware where she conducted research in the Day Lab on the use of antibody-coated gold nanoparticles for the detection of circulating tumor cells. She conducted doctoral research in the lab of Michael J. Mitchell, J. and Peter Skirkanich Assistant Professor in Bioengineering. After defending her thesis at Penn in 2022, Margaret began postdoctoral training at the Massachusetts Institute of Technology (MIT) in the Hammond Lab where she is investigating the design and application of polymeric nanoparticles for combination therapies in ovarian cancer. She plans to use these experiences to continue a research career focused on drug delivery systems.

“Maggie was an absolutely prolific Ph.D. student in my lab, who pioneered the development of new mRNA lipid nanoparticle technology to engineer the immune system to target and kill tumor cells,” says Mitchell. “Maggie is incredibly well deserving of this honor, and I am so excited to see what she accomplishes next as a Postdoctoral Fellow at MIT and ultimately as a professor running her own independent laboratory at a top academic institution.”

Victoria Muir

Dissertation: “Designing Hyaluronic Acid Granular Hydrogels for Biomaterials Applications”

Victoria Muir

Victoria is currently a Princeton University Presidential Postdoctoral Research Fellow in the lab of Sujit S. Datta, where she studies microbial community behavior in 3D environments. She obtained her Ph.D. in 2022 as an NSF Graduate Research Fellow at Penn Bioengineering under the advisement of Jason A. Burdick, Adjunct Professor in Bioengineering at Penn and Bowman Endowed Professor in Chemical and Biological Engineering at the University of Colorado, Boulder. She received a B.ChE. in Chemical Engineering from the University of Delaware in 2018 as a Eugene DuPont Scholar. Outside of research, Victoria is highly active in volunteer and leadership roles within the American Institute of Chemical Engineers (AIChE), currently serving as Past Chair of the Young Professionals Community and a member of the Career and Education Operating Council (CEOC). Victoria’s career aspiration is to become a professor of chemical engineering and to lead a research program at the interaction of biomaterials, soft matter, and microbiology.

“Victoria was a fantastic Ph.D. student,” says Burdick. “She worked on important projects related to granular materials from the fundamentals to applications in tissue repair. She was also a leader in outreach activities, a great mentor to numerous undergraduates, and is already interviewing towards an independent academic position.”

Sadhana Ravikumar 

Dissertation: “Characterizing Medial Temporal Lobe Neurodegeneration Due to Tau Pathology in Alzheimer’s Disease Using Postmortem Imaging”

Sadhana Ravikumar

Sadhana completed her B.S. in Electrical Engineering at the University of Cape Town, South Africa in 2014 and her M.S. in Biomedical Engineering from Carnegie Mellon University in 2017. Outside of the lab, she enjoys spending time in nature and exploring restaurants in Philadelphia with friends. She focused her doctoral work on the development of computational image analysis techniques applied to ex vivo human brain imaging data in the Penn Image Computing and Science Laboratory of Paul Yushkevich, Professor of Radiology at the Perelman School of Medicine and member of the Penn Bioengineering Graduate Group. She hopes to continue working at the intersection of machine learning and biomedical imaging to advance personalized healthcare and drug development.

“Dr. Sadhana Ravikumar’s Ph.D. work is a tour de force that combines novel methodological contributions crafted to address the challenge of anatomical variability in ultra-high resolution ex vivo human brain MRI with new clinical knowledge on the contributions of molecular pathology to neurodegeneration in Alzheimer’s disease,” says Yushkevich. “I am thrilled that this excellent contribution, as well as Sadhana’s professionalism and commitment to mentorship, have been recognized through the Sol Pollack award.”

Hannah Zlotnick

Dissertation: “Remote Force Guided Assembly of Complex Orthopaedic Tissues”

Hannah Zlotnick

Hannah was a Ph.D. candidate in the lab of Robert Mauck, Mary Black Ralston Professor in Orthopaedic Surgery and in Bioengineering. She successfully defended her thesis and graduated in August 2022. During her Ph.D., Hannah advanced the state-of-the-art in articular cartilage repair by harnessing remote fields, such as magnetism and gravity. Using these non-invasive forces, she was able to control cell positioning within engineered tissues, similar to the cell patterns within native cartilage, and enhance the integration between cartilage and bone. Her work could be used in many tissue engineering applications to recreate complex tissues and tissue interfaces. Hannah earned a B.S. in Biological Engineering from the Massachusetts Institute of Technology (MIT) in 2017 during which time she was also a member of the women’s varsity soccer team. At Penn, Hannah was also involved in the Graduate Association of Bioengineers (GABE) intramurals & leadership, and helped jumpstart the McKay DEI committee. Since completing her Ph.D., Hannah has begun her postdoctoral research as a Schmidt Science Fellow in Jason Burdick’s lab at the University of Colorado Boulder where she looks to improve in vitro disease models for osteoarthritis.

“Hannah was an outstanding graduate student, embodying all that is amazing about Penn BE – smart, driven, inventive and outstanding in every way,” says Mauck. “ I can’t wait to see where she goes and what she accomplishes!”

Congratulations to our four amazing 2023 Sol Pollack Award winners!

Puneeth Guruprasad Wins 2023 Penn Prize for Excellence in Teaching by Graduate Students

Front, from left to right: Lucy Andersen, Vice Provost for Education Karen Detlefsen, Derek Yang, Ann Ho, and Arianna James. Back, from left to right: Ritesh Isuri, Adiwid (Boom) Devahastin Na Ayudhya, Oualid Merzouga, and Puneeth Guruprasad.

Ten winners of the 2023 Penn Prize for Excellence in Teaching by Graduate Students were announced at a ceremony held April 13 at the Graduate Student Center. The recipients, who represented five of Penn’s 12 schools, were recognized among a pool of 44 Ph.D. candidates and master’s students nominated primarily by undergraduates—a quality unique to and cherished about this Prize.

“It’s a particularly authentic expression of gratitude from undergraduates, and that’s really the pleasure [of presenting these awards],” says Vice Provost for Education Karen Detlefsen, who was present to announce the winners and award them with a certificate. (They also receive a monetary award.) “I’m so proud of our students: Our undergraduates, for taking the time to recognize what it is our graduate students contribute to the student body, and the graduate students who are contributing to the life of the University.

“Students are the lifeblood of the University and without them, we wouldn’t be here.”

The Prize began in the 1999-2000 academic year under former Penn President Judith Rodin. It was spearheaded by then-doctoral-candidate Eric Eisenstein and has been issued every year since. Nominations for the Prize often mention how graduate teaching assistants were able to take a complex subject and make it relatable or craft a course like philosophy or mathematics into an enjoyable—even highly anticipated—experience for students.

“Many nominations show how much students value a TA or a graduate instructor of record who shows that they care for their learning and for them as people, and who makes themself readily available to assist,” says Ian Petrie, director of graduate student programming for the Center for Teaching and Learning, who organizes the selection committee for the Prize. “Typically, however, committee members are also interested in seeing nominations that really point to how a graduate student instructor taught or gave feedback—not just how responsive they were to emails or how many office hours they had.”

He also emphasizes that many winners this year were not just teachers, but mentors—often helping undergraduates or new graduate students navigate not only the course but also Penn as an institution.

Puneeth Guruprasad

One of the winners, Puneeth Guruprasad, hails from Penn Bioengineering. Guruprasad is a fourth-year Ph.D. student in Bioengineering who conducts research in the lab of Marco Ruella, Assistant Professor of Medicine in the Division of Hematology/Oncology in the Perelman School of Medicine. Ruella is also a member of the Center for Cellular Immunotherapies (CCI) and the Penn Bioengineering Graduate Group.

Guruprasad studies mechanisms of resistance to chimeric antigen receptor (CAR) T cell therapy for cancer. He has served as a teaching assistant for five semesters: three for Intro to Biotransport Processes (BE 3500) taught by Alex Hughes, Assistant Professor in Bioengineering, and two for Cellular Engineering (BE 3060), taught by Daniel Hammer, Alfred G. and Meta A. Ennis Professor in Bioengineering and in Chemical and Biomolecular Engineering. Both courses are a part of the core curriculum for undergraduate bioengineering students. His doctoral thesis focuses on how a specific interaction between CAR T cells and tumor cells limits their function across a range of cancers.

“I make myself approachable outside the classroom, and I think that’s one aspect of being a TA: having responsibilities that extend beyond the classroom,” says Guruprasad. “Dozens of times, I’ve spoken to students over coffee, or over some lunch, about what direction they want to take in their life, what they want to do outside of the course, and give them my two cents of advice. I try to individualize.”

This post was adapted from an original story by Brandon Baker in Penn Today. Read the full story and list of 2023 winners here.