Harvey Kliman, a research scientist in obstetrics, gynecology and reproductive sciences and senior author of the study, developed a new classification system for pregnancy losses based on examining the placentas of babies who passed away. Of the millions of pregnancy losses each year, 40 percent are classified as “unexplained,” leaving families uncertain about the cause. Kliman said he seeks to use his research to help families understand what caused their loss.

“If you don’t know why it happened, invariably, these women feel that they must be responsible,” Kliman said. “Guilt is an understatement. They feel devastatingly responsible for the loss. They are already the mother of this child, and they feel they failed their child.”

The researchers found that the causes of pregnancy loss depend on the phase of the pregnancy, according to Parker H. Holzer GRD ’21, a Yale data science doctoral student and an author of the paper, wrote to the News. With the study, Holzer said the authors hope that doctors can now know what signals to look for at each stage of pregnancy, allowing doctors to hopefully further decrease the rate of pregnancy loss.

To uncover these signals, the researchers analyzed 1,256 placentas from 922 patients. All of these patients’ pregnancies had ended in loss and were referred to Yale’s consult service for evaluation. Of the pregnancies, 70 percent were miscarriages, while 30 percent were stillbirths. 

The researchers attributed the deaths to placental complications including cord accidents, abruptions, thrombotic issues and infections. They attributed other cases to two new categories, which they introduced — “placenta with abnormal development” and “small placenta,” which are placentas below the 10th percentile for gestational age.

  As director of volunteer organization Measure the Placenta, Ann O’Neill works to promote using the Estimated Placental Volume test placenta in prenatal care. The organization is comprised of parents who experienced stillbirths due to an undetected very small or large placenta. She told the News about the guilt she experienced when her baby, Elijah, was born still in 2018. 

“The pressing question that at first I was terrified to ask was ‘Why did he die?’” O’Neill said. “How could this seemingly healthy baby out of nowhere just die?”

When O’Neill turned to pathologists to find answers, she said they provided little help. They labeled Elijah’s passing as unexplained, but his pathology report had one oddity: Elijah, a large baby, had a small placenta. The size difference was so pronounced, according to O’Neill, that pathologists told her the placenta might not be Elijah’s. Though later genetic tests revealed it was his, O’Neill told the News that the pathologists initially wondered whether it might have accidentally been swapped with another placenta. 

O’Neill said she left the meeting with the pathologist feeling disappointed and still seeking answers. Later, O’Neill listened to a podcast in which Kliman discussed the possibility that a small placenta may cause stillbirths. Hoping to find an answer, O’Neill sent Elijah’s physical placenta to Kliman, who attributed Elijah’s death to his small placenta.

“Getting an answer from Kliman was huge in so many ways,” O’Neill said. “Number one, the self-blaming doesn’t happen.”

The study offers additional findings on a larger scale. The study suggests that placental examination can identify the cause behind approximately 99 percent of stillborn cases. The researchers noted that over 60 percent of unexplained stillbirths are due to “placental insufficiency,” or that the placenta is too small in proportion to the baby’s size. Another cause is placental dysmorphia, which describes the placenta’s shape or weight. 

Though the research may help provide closure to these families, Kliman said it will be difficult to translate into clinical changes. The American College of Obstetricians and Gynecologists sets clinical practices in this field. The ACOG requires direct scientific proof that changes to standard treatment, such as measuring the placenta, will result in different outcomes. 

In this case, Kliman said, it is nearly impossible to meet ACOG’s standards. Scientists can never be certain that a treatment will prevent a stillbirth, according to Kliman. Further, he said, it is difficult to change clinical practices because healthcare professionals are not trained in using the EPV test during their residency and fellowship programs. Consequently, Kliman said, some doctors might question the need to incorporate the EPV into their established routines. 

The study encourages clinicians to adopt the EPV tests to manage high-risk pregnancies and make informed decisions about the timing of delivery. If they identify a small placenta, along with other factors, early delivery may mitigate the risk of fetal loss before birth.

Still, the researchers said that the study has limitations. The study lacked comprehensive data on maternal demographics, such as race or ethnicity. Nevertheless, the researchers told the News they recognized that this could be an important point for further research. 

“This study will need to be confirmed by others, however it is likely to change our ability to diagnose the cause of pregnancy loss and potentially help to prevent this tragedy,” Hugh Taylor ’83, a professor of obstetrics, gynecology and reproductive science, wrote to the News. 

Following the study, Kliman said he hopes to explore the genomics underlying pregnancy losses and to delve deeper into the mechanisms that link dysmorphic placentas to pregnancy complications. 

Kliman and Taylor are now conducting an NIH-funded trial that sequences the entire genome of patients who have experienced more than one miscarriage. 

“It’s terrifying to find an answer, but when you do, the emotional guilt is relieved,” O’Neill said. “You have the weight off your shoulders. For future medical care, it’s crucial to understand what caused the previous loss so that in any future pregnancies you can be monitored for those things.”

Stillbirth affects one of every 175 births in the United States.

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The report is among the first to analyze trends in acne clinic visits and treatments around the country broken down by age and sex. The researchers also found that medications known as tetracycline-class antibiotics are the most prescribed therapy in female acne patients.

“Our overall goal with this research was to demonstrate that acne is not only a juvenile problem but something that has and is affecting adult females well into their 40s,” Jungsoo Chang MED ’23, the study’s lead author, wrote to the News. “With this in mind, we also wanted to show different treatments providers have used in the past years.”

The researchers analyzed data from the National Ambulatory Medical Care Survey — a federally administered survey that looks at the use of healthcare services nationwide — to study patterns in acne clinic visits and treatments for females. They also analyzed the acne medications that healthcare providers prescribed, including antibiotics, oral contraceptive pills and gel medications like tretinoin.

The report found that adult women are 2.5 times more likely than men to seek acne care. For Emmy Graber, the president of the Dermatology Institute of Boston who was not involved in the study, the finding mirrors what sees in her own clinic.

The disparity could be for two reasons, Graber said. 

The first possibility is that adult women experience acne at higher rates than men. According to Christopher Bunick, an associate professor of dermatology at the School of Medicine and the study’s senior author, it is likely that there are biological differences in how acne develops in men and women. 

However, Graber also theorized that adult females with acne may be more likely to seek dermatologic care than adult males.

While previous studies have looked at trends in acne care in women, all of them used self-reported data — interviews and questionnaires, the report said, that can be inaccurate. People who are embarrassed about receiving care for acne, for instance, might not accurately disclose details about their treatment.

Both Chang and Bunick noted that there is a stigma surrounding adult acne in older females. Popular media, they added, can promote the idea that it is “abnormal” for adult women to experience acne. 

“Over my career I have seen many 20-50 year-old women come into the Yale Dermatology-Middlebury clinic concerned about their acne and perplexed as to why they have acne at their age,” Bunick wrote to the News. “They commonly say, ‘but I am not a teenager.’ However, my personal experience in the clinic strongly suggested otherwise.”

As a result, Bunick approached Jeffrey Cohen, a dermatology professor at the School of Medicine and a study author, to explore the reality of how often adult women sought care for acne.

“The hope was our work would help adult women suffering from acne feel less isolated, alone, or embarrassed, and provide real impetus for a change in society’s discourse around adult female acne,” Bunick wrote. 

The researchers also found that medications called broad-spectrum tetracycline-class antibiotics were the most commonly prescribed treatment for females. However, they also found that providers are increasingly prescribing the drug spironolactone to treat acne in adult women. 

As an anti-androgen medication, spironolactone is popular because of its ability to reduce “hormonal acne,” Bunick said. Patients also have a lower risk of developing antibiotic resistance while on the drug.

However, Bunick added, after the study period ended, the Food and Drug Administration approved a new medication for acne called sarecycline, which is even less susceptible to antibiotic resistance and has fewer side effects. Based on his own research, Bunick believes that sarecycline should be the go-to medication for acne treatment.

 “We hope that [the study] leads to more research on pathogenic differences in adolescent and adult acne and it helps to improve and expand treatment options including spironolactone and sarecycline,” Chang wrote. 

Graber, though, doesn’t see antibiotics as a long-term solution for acne. 

She said that antibiotics should not be used over long periods of time. 

”If an adult has had acne for many years, it is unlikely to stop in the coming weeks to months and therefore a more appropriate long term chronic therapy should be considered,” Graber said.

Experts are still unsure why acne affects women differently than men. Chang believes that a combination of genetics, stress and cosmetics play a role.

Women may also be impacted by fluctuations in hormone levels, like androgen, estrogen and progesterone throughout adulthood, she added.

“I think this study opens the door for more rigorous investigation into the unique mechanisms driving adult female acne, and creates potential for innovation of targeted therapeutics for this particular group of patients,” Bunick wrote.

The School of Medicine is located at 333 Cedar St.

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With about 250 people registered to compete across 15 teams, the event kickstarted on Feb. 24 with keynote addresses on the hackathon’s theme, which this year was “patient engagement.” Participants heard from Indira Negi, the deputy director of global health at the Bill & Melinda Gates Foundation. 

The purpose of the hackathon was to “provide an opportunity for people who are not clinicians or medical professions to tackle problems in healthcare,” according to Monica Manmadkar, an undergraduate at Columbia University who also served as the hackathon’s advertising and marketing lead. 

“If you create a space of freedom and include a diversity of people, beautiful solutions can arise,” said physician executive Michael O’Brien MED ’16, who served as a mentor for the hackathon. 

Hackathon participants pitched their ideas in fast-paced one-hour meetings on Friday afternoon and Saturday morning. Their projects could fall into one of four tracks related to this year’s theme: personalized therapy, patient monitoring, women’s health or digital therapeutics. Networking and team formation began shortly after. 

In 24 hours, participants came up with project ideas ranging from a webpage that provides educational resources and community support to parents of children facing mental health and substance abuse to customizable journals that commemorate the medical journey of children fighting with cancer.  

Participants came from a wide variety of backgrounds, ranging from high school and undergraduate students to professionals in various fields such as finance, marketing, business operations and academia. 

Hackathon participant Angelin Mathew ’25 said that although her team members came from different parts of the world, they could all testify to how stigma affects patients’ healthcare experiences.

“It was my first hackathon, and it was so exciting to see how much we were able to think through and design in a weekend,” Mathew said. 

Throughout the competition, there were “floating mentors” and a “genius bar” which allowed participants to gain early guidance from a team of multidisciplinary mentors through practice

presentations that took place prior to the final presentation on Sunday. The mentors’ specialities included entrepreneurship, technology, business, medicine, science, design and law.

O’Brien, who worked as a mentor this year, was actually a participant himself in 2020, and said that the hackathon had been “life-changing.” Prior to the event, he had practiced medicine as a physician for about 20 years. He found that the hackathon allowed him to combine his clinical expertise with people with backgrounds drastically different from his own to solve problems that otherwise felt stagnant in healthcare.

O’Brien’s son also joined the hackathon in 2021, which took place virtually due to the pandemic. As a high school student, he was “a master of Google Slides from school and designed the slide deck for his team’s presentation,” according to O’Brien. 

The hackathon sparked O’Brien’s son’s enthusiasm for coding — two years later, he had already participated in the MIT Scratch program and taught himself Python. 

The winning teams were announced on Sunday after participants delivered a three-minute presentation of their project followed by two minutes of questions from the judges. Kyle Feliciano ’26 and Emily Qian ’26, two students from the Yale School of Medicine, won the honorable mention $1,000 prize with their app PlayFit, which aims to help encourage physical activity in youth through video game incentives. 

The app gathers “activity indicators – like step count, heart rate, and general activity level – from the wearable technology a child might already be using,” and then provides the user with an in-game reward “after a certain amount of activity has been accomplished,” according to a description written by the team.

The team that won the $5,000 Rothberg Grand Prize designed “Emma’s Story,” which is “a journal to be created by pediatric oncology patients documenting their journey of cancer treatment, celebratory milestones, and positive memories,” according to team members Jhonatan Nagasako, Zora Luan, Obinna Anosike and Andrea Orane MPH ’92. 

The project idea emerged on Friday after multiple team members recounted their personal stories of battling diseases. They built prototypes of the journal overnight out of cardboard boxes, with cartoonish patterns and vibrant colors. They wanted the journal to appear relatable to a child fighting cancer. 

“Because we were such a small group, everyone’s idea[s] mattered,” Nagasako said.

The team will meet with advisors from CBIT and others from the Yale community to get further feedback on the design.

Mark Saltzman and Maxwell Laurans are the faculty co-directors of the Yale Center for Biomedical Innovation and Technology.

Correction 3/1: A previous version of this article misstated the keynote speaker and O’Brien’s current occupation.

Correction 3/6: A previous version of this article misspelled Luan’s surname. 

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The Poorvu Family Fund for Academic Innovation award is given each year to outstanding junior faculty members who have demonstrated excellence in teaching in undergraduate programs. The award allows faculty to dedicate the summer to research integral to their development as scholars and teachers. This year’s winners were Shirin Bahmanyar, Anastasia Eccles, Amaleah Hartman GRD ’19 and Jim Wood — Bahmanyar and Hartman are both professors in the molecular, cellular and developmental biology department. 

“I can’t think of a better way to be recognized for all the work I put forth,” Hartman told the News. So, thank you to those that nominated me — you made me shed a few tears of happiness in my office.”

Hartman previously facilitated and taught the foundational BIOL 101-104 series of biology courses for Yale undergraduate students. She said the news about the award came as a complete surprise in an email from Yale College Dean Pericles Lewis.

As the lecturer and course coordinator of the introductory biology sequence, Hartman was responsible for organizing the logistics, overseeing the teaching team, addressing student concerns and providing academic advice. She also added science journal clubs and enrichment sessions to encourage active learning. 

Currently, Hartman serves as the lead instructor for Cell Biology and Genetics and Development in the summer, as well as Genetics Lab and Microbiology Lab for upper-level Biology majors.

“While I admittedly miss closely interacting with students in the way the Course Coordinator position afforded […] I have thoroughly enjoyed being the lead instructor and developing course materials for Cell Biology, and it has been an absolute blast to be back at the bench teaching undergraduates how to design experiments and perform many of the techniques we discuss in the biology sequence,” Hartman told the News. 

Shirin Bahmanyar, the second awardee from the department, is an associate professor of MCDB. She teaches two undergraduate courses: one is a core course for the MCDB major, Cell Biology, and the other is a science distributional requirement for non-STEM majors, Biology the World and Us. 

Since the two courses are quite different from each other, Bahmanyar said she “makes a concerted effort to present the material in an accessible manner that is relatable and inclusive” for students in both courses, through methods such as “using props, presenting graphics on the slides and making [herself] accessible to students.”

According to Bahmanyar, the main research interest of the Bahmanyar Lab is to “[understand] how cells are compartmentalized by internal membranes,” with a particular focus on the endoplasmic reticulum, the largest internal membrane system in animal cells.

One of the most significant findings from her lab is that the ER not only serves as a membrane barrier, but also protects the human genome with its unique chemical composition. Bahmanyar received the 2022 Women in Cell Biology Junior Award in Research Excellence for her contributions to cell biology. 

The Poorvu Family Fund for Academic Innovation is administered by the Yale College Dean’s Office. Later this semester, the award recipients will be invited to a celebratory dinner hosted by Dean Lewis. In an email to the News, Lewis emphasized the importance of innovation and teaching.

 “We need to find the best ways to educate students in all fields, and in particular with advances in research, technological changes in how we deliver courses and the recent pandemic, it is clear that we need to be constantly renewing our teaching approaches,” Lewis said.

The Poorvu Family Fund for Academic Innovation was established in 1991.

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The new program quantifies the impact of single-nucleotide variants in cancer proliferation and their survival in humans. The software was developed by Jeffrey Townsend, professor of biostatistics and ecology and evolutionary biology at Yale School of Public Health, Jeffrey Mandell, first author and a doctoral student in Townsend’s lab and Vincent Cannatro, assistant professor of biology at Emmanuel College. 

By organizing data of somatic variants — a mutation that can occur in any cell except for germ cells — facilitating mutational signature analysis and calculating site-specific mutation rates, the researchers confirmed that certain variants exhibit a higher impact of cancer development than most other variants. This software serves as a better predictor of the variant’s effect on cancer than other techniques, which indirectly make predictions based on protein structures or amino acid sequences. 

“In cancer treatment today, one of the big movements is to come up with specific treatments: precision medicine,” Townsend said. “This software examines the mutations that characterize each tumor and quantifies each one to each cancer that an individual has. This prioritizes precision treatment.”

The main question that drove Mandell on this research journey was his attempt to understand which mutations out of thousands of accumulated variants were the most important in cancer development, along with determining what the appropriate targeted treatments are. 

According to Mandell, a patient’s tumor is “easily sequenced” through the advanced technology available today. However, he noted that not all mutations provide the same level of insight to determine the necessary medical treatment.

“The question is then: what tools can we use to prioritize the most relevant genetic mutations?” Mandell said.

The implications of this software are multifaceted. First, it is capable of contributing to “basic science research, academic translational research and pharmaceutical trials,” according to Townsend. He noted that the software will help medical professionals “make better targets when analyzing cancer mutations and making target drugs.” Furthermore, he said that it can aid scientists in deciding what genetic targets to use resources on during clinical trials, which can be “exhaustive.” 

This project has been in development since 2016 when the idea was first proposed, according to Cannatro, who at the time was a postdoc at the Townsend lab. The first version of the software was published in 2018 in the Journal of the National Cancer Institute. Later on, the authors made changes to improve user accessibility, data annotation and expansion in the models of cancer variant selection. The current paper details the final version of the software, which was published in 2022 in Molecular Biology and Evolution. 

“In the literature, there are examples of prevalent variants as a metric of how important the variants are,” Cannatro said. “However, the rate of the occurrence of the variants happens differently.”

For future directions of the research, Townsend said, improvements could be made in quantifying the average effects of the variants across cancer patients and their precise effects on each individual patient. These effects could depend on existing mutations within the patient’s tumor.

Additionally, the current software can only measure somatic single-nucleotide mutations, which constitute the vast majority of mutations in early stages of cancer. However, the software can potentially be programmed to include copy-number mutations and others that occur in later stages of cancer development.  

The first edition of Molecular Biology and Evolution was published in 1983. 

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