Transgender Medical Research and Provider Education Lacking
As a result of the limited transgender medical training offered at medical...
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Samet Co-Authors JAMA Viewpoint on Physician Education in Addiction Medicine
Jeffrey H. Samet
BUSM Professor of Medicine Jeffrey H. Samet, MD and colleagues* recently authored a viewpoint commentary in the Oct. 23 issue of JAMA on physician education in addiction medicine. The commentary explained that there is a “…failure of medical education systems to train physicians in addiction medicine. Despite the enormous burden of disease attributable to addiction in North America, there have traditionally been exceptionally few opportunities for physicians to obtain advanced skills in this area outside of addiction psychiatry.”
The essay concluded, “Ultimately, through the greater incorporation of addiction medicine into the spectrum of medical training, patients will be better served by narrowing the health care quality chasm in addressing substance use disorders. The development of addiction medicine as a formal medical subspecialty also has the potential to begin the slow process of public education required to treat those who are alcohol- or drug-addicted with compassion and care, and to move away from over reliance on punitive approaches that have not served the interests of patients, public health, or taxpayers.”
In addition to serving as Professor of Medicine at BUSM, Samet is Professor of Community Health Sciences at BUSPH, and Chief and Chair of the Section of General Internal Medicine at BMC and BUSM respectively. He also serves as Medical Director of Addictions Prevention, Treatment and Recovery Support Services at the Boston Public Health Commission.
Samet’s research has focused on linkage of substance abuse treatment and primary medical care; addressing substance abuse issues in the primary care setting; the impact of alcohol and drug use in HIV-infected persons, the delay in establishing primary medical care for HIV infection; and HIV prevention strategies in Eastern Europe. He is the principal investigator on several current NIAAA and NIDA-funded studies. He is an internist and has been a primary care physician since 1983.
Read the entire JAMA article.
*Evan Wood, MD, PhD, FRCPC; Jeffrey H. Samet, MD; and Nora D. Volkow, MD, authored the viewpoint.
BUSM Professor, BMC Physician Receives Award for Advancing Research on Tobacco Smoke’s Effect on Lungs
Avrum Spira
Avrum Spira, MD, MSc, the Alexander Graham Bell professor of medicine and chief of the division of computational biomedicine at Boston University School of Medicine, is the recipient of the Alton Ochsner Award Relating Smoking and Disease. The award will be presented to Spira today at the Opening Session of the Annual Meeting of the American College of Chest Physicians in Chicago.
This award recognizes Spira’s seminal research contributions that have enhanced the understanding of the biological response of lung tissue to tobacco smoke, which can cause lung cancer and chronic obstructive lung disease (COPD). Spira has applied innovative approaches to measure gene expression in populations of lung cells damaged by tobacco toxins and was the first to define the reversibility and permanent impact of cigarette smoke on gene activity in the bronchial airway. Spira’s lab has leveraged this genomic response in the airway to develop an early detection biomarker that can enable physicians to diagnose lung cancer earlier among smokers at risk for disease. This has important scientific, clinical and therapeutic implications. More recently, his group has extended this genomic approach to develop molecular biomarkers that can guide treatment decisions in COPD and identify novel therapeutic opportunities for this chronic debilitating disease.
Spira, who also is a physician in the pulmonary, critical care and allergy department at Boston Medical Center, is a graduate of Vanier College, Montreal, Canada, the McGill University Faculty of Medicine, also in Montreal, and Boston University (BU). He also is the Director of the Translational Bioinformatics Program within the Clinical Translational Science Institute of BU.
The Award is named in honor of Doctor Alton Ochsner, co-founder of the Ochsner Clinic in New Orleans. In 1939, Ochsner was the first to publish evidence relating cigarette (tobacco) smoking as the primary cause of lung cancer.
Social Service Barriers Delay Care among Women with Abnormal Cancer Screening
Sarah Primeau, MSW
A recent study performed by researchers at Boston Medical Center (BMC), Boston University School of Medicine (BUSM), Boston University School of Public Health (BUSPH), and Tufts Medical Center found that women with multiple barriers to healthcare, especially those with social barriers such as problems with housing and income, experienced delays in cancer screening follow up compared to those with fewer barriers or no social barriers.
The study, which appears online in the Journal of General Internal Medicine, was led by Sarah Primeau, MSW, research assistant in the department of general internal medicine at BUSM.
Previous studies on healthcare barriers have shown that training individuals from the community, known as patient navigators, to provide emotional and logistical support to patients is an effective way to care for patients in a culturally sensitive way. However, these studies have not addressed whether patient navigators are also effective in addressing social service barriers such as financial problems, employment issues, health insurance, housing constraints and adult and child care.
“Social barriers are more complex than other obstacles to healthcare such as transportation or language and will likely require interventions that healthcare providers and patient navigators aren’t traditionally trained to provide,” said Primeau.
The study looked at 1,493 subjects enrolled in the Boston Patient Navigation Research Program (PNRP), a study performed at BMC from 2007-2010 that used patient navigators to help women with breast and cervical cancer screening abnormalities. The researchers used the data to separate the women into groups based on how many social barriers the navigator was able to identify. They then examined the data to see how long it took for each patient to reach a final diagnosis from the time of the initial abnormal screening test.
Tracy Battaglia, MD
The researchers found that it took longer to achieve a final diagnosis in the patients with multiple barriers to healthcare, and that having one or more social barrier further increased the follow up time. The results of this study indicate that there is a continued need to better understand and overcome complex social obstacles to patient care.
“The findings suggest that not all women benefit equally from patient navigation and there is a need for more research into the innovation of cancer care delivery, and into a possible new model of patient navigation enhanced by legal advocacy,” said senior author, Tracy A. Battaglia, MD, director of the Women’s Health Unit at BMC and associate professor of medicine and epidemiology at BUSM.
Funding for this study was provided in part by the Susan G. Komen Foundation (KG101421).
Researchers Capture Images of Open Channel That Moves Proteins Across Cell Membranes
(This video shows a bacterial ribosome docked onto the SecYEG protein translocation channel, then removes the ribosome as it zooms in to show the channel as a set of ribbons that represent alpha helices of the 3 different channel subunits. The SecY channel is viewed from the plane of the membrane and changes from a closed to an open form and then the nascent (newly forming) protein (in green) from the ribosome, which is not shown in later stages of the video, is modeled within the central pore of the open channel in a looped configuration and additionally, there is a loop of the new protein lying on the top of the channel, before it enters the central pore.)
Similar to passengers on an urban transit system, every protein made in the cell has a specific destination and function. Channels in cell membranes help direct these proteins to their appropriate target. Researchers at Boston University School of Medicine (BUSM) and their colleagues have now captured images of these channels as they open to allow proteins to pass through a membrane, while the proteins are being made. These findings are published as a Letter in Nature (Park, E. et al. 2013).
Christopher W. Akey, PhD, professor of physiology and biophysics at BUSM is a co-senior author of the Letter. In addition, the collaborating institutions include Harvard Medical School (HMS), Baylor College of Medicine (BCM) and Georgia Institute of Technology (GT).
Proteins, which are encoded by genes, are large molecules that perform specific functions. Many proteins such as hormones and growth factors are secreted by the cell and move into the bloodstream. These proteins are made in factories called ribosomes, which interact with a family of channels called Sec61/SecY that provide a path across the membrane. Initially, these nascent, or newly-made, proteins are inserted into channels as the proteins are being made. The channels also aid in inserting nascent proteins into the cell membrane where they function as receptors for drugs and form ion channels that function in vision and in transmitting nerve cell impulses.
This is a summary slide that shows closed and open ribbon models of the SecYEG channel aligned on a cartoon of the membrane and the open form of the channel on the right has a nascent protein in green that is based on our modeling with the density map. The map itself of the open conformation of the channel and ribosome is shown above, as viewed again along the plane of the membrane, wherein the membrane has been modeled with a computer. The small subunit of the ribosome is in gold, the large subunit in blue, the new protein density is shown in green and the segmented channel density is shown in maroon. The original membrane density in the map has been replaced with a model of a membrane generated by a computer for clarity and is rendered so one can see into the lateral gate of the open channel, ie the green density of the newly made protein is visible.
In this study, researchers used samples made in E. coli bacteria to determine the structure of the highly conserved SecY channel. Using an electron microscope and computer analysis, researchers were able to capture images of the SecY channel opening when a nascent protein enters the central pore. In particular, the channel undergoes large movements that enlarge the central pore as a first step in allowing the nascent protein to cross the cell membrane and eventually travel to its destination.
“Similar to train cars that transport passengers through a tunnel, SecY/Sec61 channels help nascent proteins move across the cell membrane to reach their target in the body, and this study provides important insight about the function of these channels,” said Akey.
Funding for this study was provided in part by the National Institutes of Health’s National Institute of General Medical Sciences under grant award number NIH GM45377.
Tom Rapoport, PhD, professor of cell biology, HMS, is a co-senior author. Other collaborators include: Eun Yong Park, PhD, HMS; Jean-François Ménétret, PhD, BUSM; Steven J. Ludtke, PhD, BCM; and JC Gumbart, PhD, GT.
Two BU Profs Inducted into the Institute of Medicine
MED’s Jack, SPH’s Jette earn honor for research, service
MED’s Brian Jack (left) helped develop reengineered discharge steps to reduce hospital readmissions. SPH’s Alan Jette chaired the IOM project that led to the release of a landmark report shaping national priorities in the disability field. Jack photo by Melody Komyerov. Jette photo by Kalman Zabarsky
Two BU professors have been inducted into the Institute of Medicine (IOM), a branch of the National Academy of Sciences (NAS) that confers membership on people in the health and medical fields who combine outstanding professional achievements with a commitment to service. Among the 70 new IOM members nationwide are Brian Jack, a School of Medicine professor and chair of family medicine and chief of family medicine at Boston Medical Center, and Alan Jette, a School of Public Health professor of health policy and management and director of the Health & Disabilities Research Institute. They join IOM’s active membership of just 1,753, a respected body that offers independent analysis and recommendations on important health issues.
“Election to the IOM is considered one of the highest honors in the fields of health and medicine,” says Karen Antman, dean of MED and provost of the Medical Campus, who is also a member. “Dr. Jack has made invaluable contributions to the field of medicine, specifically his extensive research regarding hospital readmissions.” Robert Meenan (MED’72, GSM’89), dean of SPH, who has worked closely with Jette for three decades, lauded his colleague for his longtime leadership in the field of disability. “Through Alan’s insightful studies, disability has become better understood by being more measurable, and his findings have led to important changes in major government policies and programs,” Meenan says.
Although his election came as a pleasant surprise, Jette, who from 1996 to 2004 was dean of Sargent College of Health and Rehabilitation Sciences, has been working with IOM for several years. He chaired the institute’s Future of Disability in America project, which led to the release of a landmark report in 2007 that shaped national priorities in the field of disability. Trained as a physical therapist, he worked with patients in the clinical setting before earning a doctorate in public health, hands-on experience that informs his work helping communities and the Social Security Administration to develop assessment tools. Jette, whose work embraces several fields, recently completed a study of older people who have fractured a hip, and did a clinical trial looking at the benefits of extending traditional rehabilitation.
“We work with social scientists, physicians, nurses, epidemiologists, physical and occupational therapists,” says Jette. He sees the aging of the American population—a major focus of the IOM panel he chaired—as a huge challenge to researchers studying prevention and management of late life disability.
“Election to the IOM is a great honor,” says Jack, whose team has earned international recognition for developing Project RED, a set of 12 detailed steps for reengineered discharge, which reduces hospital readmissions. The IOM membership also recognizes Jack’s work with the Centers for Disease Control and Prevention, which presented him with its External Partner award for his role on a panel on preconception care. Jack has devoted much of his career to improving global health, working on family medicine training programs in Hungary, Romania, Albania, and Lesotho. He believes that preventing “poor maternity outcomes is indeed possible, and in developing family medicine training programs around the world that meet the needs of society, all came about from observations in my clinical work and my reflections on how we can do better.”
The IOM is one of several branches of the National Academy of Sciences, along with the National Academy of Engineering and the National Research Council. It seeks to help both government and the private sector make informed health decisions. Every year, thousands of professionals, IOM members and nonmembers, volunteer their expertise to work on studies launched as specific mandates from Congress or at the request of federal agencies and independent organizations.
This BU Today story was written by Susan Seligson. She can be reached at sueselig@bu.edu.
Transporting Nutrients into Cells without Energy or a Transporter: BUSM Researchers Make a Case for Free Fatty Acids
James Hamilton, PhD
The current global epidemic of obesity-linked diabetes and its associated consequences -cardiovascular, neurological and renal diseases – is a growing public health problem for which therapeutic options are limited.
In obesity, fatty acids, derived mostly from adipose tissue, alter lipid metabolism in other tissues such as liver and skeletal muscles. Both impaired fatty acid metabolism and glucose are hallmarks of diabetes.
In a recent study published in the journal Biochemistry, a research group led by James A. Hamilton, PhD, professor of physiology, biophysics and radiology at Boston University School of Medicine (BUSM), applied novel fluorescent methods to measure the rate by which fatty acids bind to and move across the fatty acid membrane to become metabolized.
“Our study shows that fatty acid entry into cells occurs by diffusion without catalysis by a protein previously described as a fatty acid transport protein. However, this protein promotes intracellular metabolism and storage,” said Hamilton. “With this advance in basic science, new drugs can be designed that target the exact mechanism more precisely than currently available drugs.”
Previous research has shown that glucose transport under the control of insulin is mediated by a transport protein called GLUT4. However, how fatty acids enter into cells has been an important unsolved problem, especially whether there are gatekeeper plasma membrane proteins that regulate fatty acid translocation across the membrane, thereby controlling the supply of fatty acids to the interior of the cell. Although several proteins postulated to be fatty acid transporters have now been shown to have other roles, the mechanistic roles of the protein CD36 have remained elusive and are widely debated.
After measuring the products of fatty acid metabolism over time, the researchers found that CD36 enhances fatty acid metabolism into triglycerides (fat deposits), without increasing fatty acid translocation across the membrane in a cell line that does not normally synthesize triglycerides. Thus, CD36 increases fatty acid uptake by increasing intracellular metabolism, which promotes diffusion of fatty acids into cells.
The work was supported by a grant from the American Diabetes Association. The study’s co-authors are Su Xu, Anthony Jay, Nasi Huang, and Kellen Brunaldi.
MED Student Runs for All, Wants All to Run
Franklin Park Mile race Sunday to strengthen community ties
Owen Kendall (MED’15) leads a group of Rookie Runners and Forest Hills Runners recently. Photos by Cydney Scott
Owen Kendall recalls the shock he felt when two bombs exploded near the finish line of the Boston Marathon last April, killing three people, including Lu Lingzi (GRS’13), and injuring more than 200. The veteran long-distance runner had finished the race in under three hours and was walking through Copley Square to congratulate other runners when the explosions occurred. “I felt helpless, horrified, and frustrated,” he says.
But in the days following the bombings, the 31-year-old Kendall (MED’15) noticed something remarkable. “I saw how close the city became in the wake of that tragedy,” he says. “Boston is a somewhat segregated city, but after the Marathon, it became completely unified. So I really wanted to think of some way to use running to help our community bond like that in the future.”
On Sunday, Kendall will realize his dream: an event billed as the Franklin Park Mile, a one-mile race around Boston’s largest park. The goal, he says, isn’t simply to get people moving, but to instill a sense of community by bringing together residents from the diverse neighborhoods that surround Franklin Park—groups of people who rarely interact.
“We live in a world where people are becoming increasingly disconnected, where there is a massive gulf between the richest and the poorest,” he says. “But running is completely egalitarian, so we felt that we could use that as a way to bring people together and knock down some of the barriers of economic inequality.”
Kendall has spent the last six months planning for Sunday’s race. “We’re reaching out to a different population,” he says. “We’ve been contacting churches and community centers and marketing on a kind of grassroots level, because we don’t want this race to be the same as all the others.”
Kendall supervises an instructional form session.
A veteran triathlete, Kendall has seen firsthand how running can bring a community together. After moving to Jamaica Plain two years ago, he started a free community running group with classmates Kristin Schwarz (MED’14) and Steven Mills (MED’14). Calling themselves the Forest Hills Runners (FHR), they began as a small group of a dozen runners that today is more than 100 strong, with runners of all ages and backgrounds.
“FHR is not like other running groups in that it caters to all runners,” Kendall says, “from people who have been running their whole lives to people who are trying to convince themselves to take their first running steps. Everyone is connected through our shared goal, which is to improve our community as a whole.” He believes that a shared activity like community running can empower an entire population.
And for him, the desire to foster community through running is deeply personal.
“Free community running saved my life,” he says. “When I was going through a separation and divorce, I needed to be around people, and getting my body in motion really helped to stabilize everything else. I knew others were going through similar experiences, and I felt that we could get people connected through this completely human and natural thing.”
Shortly after founding Forest Hills Runners, Kendall, who plans to pursue a career in family medicine, knew he needed to get local youth involved as well. “If you don’t treat the kids and the parents, you can’t make a change,” he says. “If you treat them both, they will help each other by continuing to monitor each other’s behavior.”
Kendall is a mentor to the high school freshmen Rookie Runners.
Kendall teamed up with the Hyde Square Task Force (HSTF), a community-development organization that provides after-school activities for high school students struggling with their grades. HSTF runs dance, music, and theater programs for sophomores, juniors, and seniors, so Kendall partnered with the nonprofit to create a running group for freshmen, called Rookie Runners.
Alexis Agrinsoni (SSW’15) was hired to coordinate the program, which, he says, “teaches students resilience, community development, and leadership skills through running.” Kendall and other MED students volunteer as mentors to the kids. “Owen comes in on a weekly basis to run with us,” Agrinsoni says, “and he reaches the kids on a different level by helping them with reflections about what running means to them.” Kendall says the goal is to help kids stay away from street violence and become youth leaders by promoting healthy lifestyles. Each of the 40 students enrolled in Rookie Runners plans to race in Sunday’s Franklin Park Mile.
Kendall hopes the race will help not only to build stronger ties between communities in Boston, but to serve as a national model for other cities. After graduation, he wants to create a nonprofit that will sponsor free community running groups in cities across the country. “We’re always talking about ways to prevent disease and save money for the American people in the field of medicine,” Kendall says. “Well, here’s a way to do both, while also dramatically improving people’s lives and strengthening community ties. I believe community running has the potential to change the culture of the United States so that it ends up being much more equal and connected, and this race is one of the first steps towards that goal.”
The Franklin Park Mile will be held on Sunday, Oct. 20, at 2 p.m. at the Playstead in Franklin Park (near White Stadium), One Franklin Park Rd., Dorchester. The race entry fee is $10 for adults and free for those under age 16. There will be cash prizes for the fastest overall runners. Whole Foods and Zico will have promotional stands. Bib pickup and race-day sign-up begin at noon, or register in advance here.
This BU Today story was written by Nate Weitzer. He can be reached at nweitzer@bu.edu.
BUSM Investigators Identify Barriers to Implementing Complementary and Integrative Medicine Curricula into Residency Programs
Investigators at Boston University School of Medicine (BUSM) have identified that lack of time and a paucity of trained faculty are perceived as the most significant barriers to incorporating complementary and alternative medicine (CAM) and integrative medicine (IM) training into family medicine residency curricula and training programs.
Paula Gardiner
The study results, which are published online in Explore: The Journal of Science and Healing, were collected using data from an online survey completed by 212 national residency program directors. The study was led by Paula Gardiner, MD, MPH, assistant professor of family medicine at BUSM and assistant director of integrative medicine at Boston Medical Center, and colleagues from the department of Family Medicine.
“This is a part of medicine that has significant impact on patient care,” said Gardiner. “We need to minimize barriers to implementing CAM/IM curricula in order to address these competencies and promote a larger focus on patient centered care.”
According to the current study a majority of family medicine residency program directors felt that CAM and IM were an important part of resident training and, of those, a majority was aware of these recommended competencies. However, a majority of directors also did not have specific learning goals around CAM and IM in their residency programs. Of those directors aware of the competencies, a minority had an adequate evaluation of CAM or IM in their program.
The survey respondents identified “strong” CAM/IM programs as those that incorporated at least one of the following modes of exposing residents to CAM or IM: didactics, clinical rotations or electives. “Weak” programs incorporated none of these modalities. Didactics were the most commonly employed techniques of the strong programs. There were significant differences between the strong and weak programs in perceived access to experts in CAM or IM and faculty training in these modalities.
The study was conducted via an online survey and consisted of six questions on CAM and IM with a focus on awareness, competencies, attitudes toward curricula, barriers to implementation and management techniques.
Given the use of CAM and IM modalities by patients and practicing physicians future directions should include raising awareness around the proposed competencies and identifying solutions to minimize the barriers to incorporating these competencies in residency training programs.
This research was funded in part by a grant from the National Center for Complementary and Alternative Medicine. Study data was provided by the Council of Academic Family Medicine (CAFM) Educational Research Alliance (CERA) Steering Committee.
Researchers Identify an Effective Screening Tool for Detecting Intimate Partner Violence among Women Veterans
Boston University School of Medicine (BUSM) researchers have identified a promising screening tool to detect intimate partner violence (IPV) in females in the VA Boston Healthcare System. The findings, which appear in the current issue of Journal of General Internal Medicine, accurately detected 78 percent of women identified as abused within the past year by a more comprehensive and behaviorally specific scale.
Katherine Iverson
IPV is a major public health issue, particularly among women receiving medical care at VA facilities. The researchers cite “lifetime reports of IPV as high as 74 percent among this population,” reinforcing the critical need for both brief and accurate screening tools. The four-item screening tool studied is named HITS (Hurt/Insult/Threaten/Scream) and can be used in under four minutes. HITS is unique in that it assesses psychological IPV in addition to physical aggression.
The study used a sample of 700 women with data extracted from the Veterans Health Administration electronic health records, with 63.5 percent of those contacted participating. The subjects completed two surveys by mail: the HITS screening test, as well as the Conflict Tactics Scale (CTS-2), considered the gold-standard for measuring IPV. The final study sample included 160 women who reported involvement in an intimate relationship within the prior year.
The study found that nearly 29 percent of women who had been involved in a recent intimate relationship reported physical, sexual and/or severe psychological IPV in the past year. The tool demonstrated good sensitivity and specificity in detecting IPV in this sample. Report of IPV in the past year was associated with higher scores for depression and PTSD. The use of the HITS screening tool was also found to assess sexual IPV with a sensitivity of 87 percent, signifying that very few cases of sexual IPV go undetected.
“Further research is needed to validate questionnaire answers by mail with in-person clinical assessment, however HITS has the potential to effectively and efficiently identify a high proportion of female VHA patients who have experienced past-year IPV,” explained lead author Katherine Iverson, PhD, assistant professor of psychiatry at BUSM and clinical research psychologist at the VA Boston Healthcare System and VA’s National Center for PTSD.
According to Iverson the screening tool has the benefit to quickly identify high-risk patients, and coordinate referrals to more comprehensive support services.
This research was supported by the Department of Veterans Affairs, Veterans Health Administration, Health Services Research and Development (HSR&D) Services as part of Dr. Katherine Iverson’s HSR&D Career Development Award (CDA10-029).
BUSM Awarded $3M NIH Grant to Study Link between Obesity and Breast Cancer in African-American Women
Gerald V.Denis
Gerald V. Denis, PhD, associate professor of pharmacology and medicine at Boston University School of Medicine (BUSM) and Julie Palmer, ScD, professor of epidemiology at the Slone Epidemiology Center at Boston University, have been awarded a five-year, $3M grant from the National Cancer Institute (NCI) to study the implications of obesity on breast cancer in African-American women.
Julie Palmer
“Breast cancer mortality is higher in African-American women in the U.S. when compared to white women and access to care does not fully account for the difference,” said Palmer. “Our hope is that a better understanding of the interplay of obesity with cancer will lead to better outcomes for women with breast cancer.”
Previous research has shown that inflammatory adipose tissue is associated with metabolic status. However, about 28 percent of obese persons remain metabolically healthy. In metabolically-abnormal obese (MAO) individuals who express this inflammation, cardiovascular disease and breast cancer are more prevalent. Until now, MAO and metabolically healthy obese (MHO) individuals have been grouped together. This research will explore the unique immunometabolic features of the MHO subgroup to distinguish important mechanisms that affect cancer risk.
“The American Cancer Society has estimated that the number of American women who will be diagnosed annually with breast cancer may approach double the current 220,000. This increase is attributable solely to the metabolic and immunological complications of insulin-resistant obesity,” said Denis.
Using basic laboratory and epidemiological population data to identify the relationships between co-morbid obesity and cancer and pharmacological solutions, the long term goal of this research is to understand and use the relationships among obesity, inflammation and breast cancer outcomes to reduce the effects of obesity on cancer incidence and mortality.
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number U01CA182898. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
