New ICGC DACO website offers improved access to cancer data

A new online data access application will provide cancer researchers with a more streamlined and secure way to access important information about tumour mutations.

On May 16, the International Cancer Genome Consortium (ICGC) Data Access Compliance Office (DACO) launched a new website that gives researchers access to ICGC’s controlled data sets.

ICGC’s catalogue of tumour-specific data is freely available to the scientific community, offering key insights into cancer biomarkers that can inform the next generation of diagnostics and therapies. But to minimize the risk of identifying donors, ICGC DACO developed a simple yet secure authorization process for research teams wanting to access the data.

The new site replaces the original ICGC DACO website, an innovative data access application that has been harnessed by about 1,500 researchers since it launched in 2011.

The redesigned website offers better usability, including an improved application form that guides applicants through the process. Under a new data access agreement, the revamped site allows researchers to be approved for two years of access to IGCC controlled data, instead of just one year under the legacy system.

Data security is paramount in the new website, which offers even stronger security to ensure that only known, authorized users can access the data sets. New security features include a single sign-on identification system through Google based authentication.

The legacy ICGC DACO website has now been retired, so approved research teams are strongly encouraged to copy over the relevant information from their legacy application to a new application in the new website.

“We are proud to offer a more streamlined website that is easier to manage and reduces the risk of data loss,” says Kim Cullion, Senior UX/UI Designer for OICR’s Genome Informatics team. “We thank our talented team of engineers, architects and everyone who contributed to the project, and are excited for the first batch of applications to be approved soon.”

Visit the new ICGC DACO website at daco.icgc-argo.org

OICR launches new Patient Partnership Plan

OICR has taken a major step to integrate patient perspectives across its research programs by launching a new Patient Partnership Plan.

Co-created with the OICR Patient and Family Advisory Council (PFAC), the Patient Partnership Plan will guide OICR’s activities over the coming three years to ensure they benefit from the lived experience of cancer patients and their families.

OICR believes partnering closely with patients will help align research priorities with patient needs, strengthen cancer research in Ontario and ultimately improve cancer care.

The new Plan establishes several goals for involving patients in research and sets out activities to achieve them. These activities are underpinned by three priorities:

Bringing the patient voice to OICR research
Building capacity for patient partnership
Sharing knowledge

Launching the Plan marks the next stage in OICR’s work to put patients at the centre of its research programs. OICR launched the PFAC in early 2021 and has since incorporated patients into its funding review process, supported research teams to form patient partnership plans and embedded patient partners in key advisory roles.

Moving forward, OICR will evaluate its progress toward the Plan’s objectives and use what it learns to strengthen patient partnership activities.

OICR thanks members of the PFAC for their contributions to the Plan and acknowledges founding PFAC chair Antonia Palmer for working with OICR to initiate these activities. Antonia recently stepped down from her role and OICR welcomed Diana Lemaire as new PFAC chair.

See our Patient Partnership Plan

Perspectives

“OICR PFAC members and staff have undertaken a thoughtful and collaborative process to develop our first Patient Partnership Plan. The PFAC is excited to work with staff and researchers to make patient partnership integral to OICR as we move cancer research forward together.”
Diana Lemaire, OICR Patient and Family Advisory Council Chair

“This plan is the culmination of so much hard work from dedicated patient partners and OICR staff. Yet it’s also a new beginning, and I’m excited to see the impact patient perspectives will have on the future of cancer care in Ontario.”
Rebecca Tamarchak, OICR Senior Director, Strategy and Governance

“Working closely with patient partners has been a tremendous learning experience for everyone at OICR. Their insights have shaped our research for the better, and we look forward to continuing our partnership to solve cancer together. I would like to thank our PFAC and all our patient partners for their time and dedication in working with us to strengthen OICR’s impact.”
Dr. Laszlo Radvanyi, OICR President and Scientific Director

Innovative MRI shines new light on cancer

Synthetic correlated diffusion imaging detects tumours and their margins by capturing the movement of water through tissue.

Cancer can be tough to distinguish from the healthy tissue around it, especially in the black-and-white image from a standard MRI.

But new MRI technology is harnessing one of cancer’s unique properties — its irregular density — to ‘light up’ cancerous tissue and pinpoint where it is located.

Synthetic correlated diffusion imaging uses MRI signals and a sophisticated algorithm to capture how water molecules move through tissue at different levels. Cancer cells are packed less uniformly than other tissues, and so the irregular movement of water indicates the presence of cancer.

The system generates an image that resembles a heat map — the more intense the irregular movement of water in one area, the brighter it appears. Cancerous tissue shows up as bright red spots, which researcher Dr. Alexander Wong says makes it easier to see tumours among the surrounding tissue.

“By having the tumour light up in red, we can better localize and detect it, and also get a clearer picture of the margins around it,” says Dr. Wong, an OICR Affiliate and Canada Research Chair in Artificial Intelligence and Medical Imaging at the University of Waterloo.

Dr. Wong and his colleagues spent six years developing synthetic correlated diffusion imaging, hoping to create a cancer-targeted alternative to the standard MRI, which produces images where cancer can be difficult to see.

In addition to Dr. Wong, Dr. Masoom Haider, Professor of Radiology at the University of Toronto and an OICR Clinician Scientist, and University of Waterloo graduate students Hayden Gunraj and Vignesh Sivan, were the core members of the research team. They collaborated with experts at OICR and multiple Toronto hospitals.

Their preliminary study was published in Scientific Reports and describes how synthetic correlated diffusion imaging accurately detected tumours and their margins in 200 patients with prostate cancer. They are also conducting another study testing their new MRI system with breast cancer patients, and Dr. Wong says results are similarly promising.

These studies show that synthetic correlated diffusion imaging has the potential to strengthen early detection, which is crucial to surviving both prostate cancer and breast cancer. It could also help track tumour growth and inform more precise surgeries and therapies.

“I can see a lot of different areas where this could be really important,” Dr. Wong says. “It could help a lot of people get earlier treatment as well as more personalized, targeted treatment.”

Encouraged by the positive results, Dr. Wong says the research team hopes to do a much larger study to refine and validate their technology. They are also exploring how to best integrate synthetic correlated diffusion imaging into clinical practice.

Because it uses the same technology as standard MRI, but with different pulse sequences and specialized software to process data, integration could be relatively seamless.

“That’s the beauty — the physical piece of hardware doesn’t change,” says Dr. Wong. “We designed it so that it can easily fit within the imaging workflow.”

He says it’s also important that results are delivered in a way that resonates with clinicians and helps them make informed care decisions.

“At the end of the day, this is a tool,” Dr. Wong says. “It needs to be something that clinicians can effectively leverage in order to have an impact on what matters most: the health and wellness of patients.”

New research asks if clinical trials are losing sight of what matters most to cancer patients

Dr. Bishal Gyawali says research into new cancer drugs should focus on outcomes like quality of life and overall survival.

Cancer therapies should help people live longer or live better, and ideally they should do both.

“That’s just common sense,” says medical oncologist Dr. Bishal Gyawali.

But Dr. Gyawali’s research shows that clinical trials for new cancer drugs don’t always prioritize outcomes like quality of life and overall survival. And he worries oncology is losing sight of what matters most to cancer patients.

“What patients care about is how long they’ll live and how well they’ll live,” says Dr. Gyawali, an OICR Clinician Scientist and Associate Professor at Queen’s University. “But unfortunately, these outcomes are frequently not measured or even discussed in clinical trials.”

Dr. Gyawali’s latest research explores how quality-of-life outcomes are reported in clinical trials for new cancer drugs. He worked with colleagues at Queen’s University — including quality of life experts — to conduct a cohort study of recent Phase III trials and published their findings in JAMA Oncology.

To start, they had to exclude a large proportion of trials because the papers didn’t report on quality of life at all. Of studies that did, less than a quarter of therapies actually improved patients’ quality of life. That wasn’t surprising to Dr. Gyawali, who found in a 2018 study that just 42 per cent of cancer clinical trials reported on quality-of-life outcomes, and ones that did mostly reported no improvement.

What surprised Dr. Gyawali in his new study was that when drugs failed to improve quality of life, results were often presented with a favourable spin. Unchanged quality of life was described as “maintained” or “not worsened” in some journal articles, while decreases in quality of life were sometimes written off as “not clinically significant.”

“A patient wants their quality of life to improve,” Dr. Gyawali says. “How can I tell a patient that if you take this drug your quality of life will ‘not be worse?’”

Instead of focusing on quality-of-life outcomes, many studies reported on progression-free survival (PFS), a measure of how much tumours grow or shrink over a period of time. But Dr. Gyawali and colleagues found that improvements in PFS were not necessarily associated with improvements in quality of life. In fact, some cancer therapies that slowed the growth of tumours actually made patients’ quality of life worse and had no effect on how long they survived. Yet, these trials were still framed as successful.

Dr. Gyawali says that raises major questions about the value of PFS as an endpoint. “If a drug delays the growth of the tumour but does not improve survival and worsens quality of life, then we should call that drug harmful,” Dr. Gyawali says.

The JAMA Oncology study reinforces much of Dr. Gyawali’s recent work, which has taken a hard look at oncology research in the hopes of making it more patient-centred.

His interest in this area began shortly after he became a medical oncologist in 2017. He says his medical education in Nepal focused mainly on “textbook medicine,” and he didn’t initially question the evidence behind his textbooks. But studying oncology in Japan opened his eyes to evidence-based medicine, and he started digging deeper into the clinical trials underlying the drugs he was supposed to prescribe.

He says he found flaws in how some trials were structured and reported, which led to expensive cancer drugs that offered little benefit to patients being approved and prescribed. “It was like an epiphany when I first noticed this,” he says. “Then I started seeing it everywhere, and it became my major research theme.”

He approaches this research from various angles, looking at medical education, research processes and policy decisions to see why oncology research can sometimes “forget the bigger picture” of its impact on patients.

And this April, he and his Queen’s University collaborator Dr. Christopher Booth described some overarching problems in a Nature Medicine paper titled “Cancer treatments should benefit patients: a common-sense revolution in oncology.”

“Our overall theme is that cancer treatments should benefit patients and we’re losing sight of that,” Dr. Gyawali says. “So how can we bring the system back in line with what matters to patients?”

Among many recommendations, Drs. Gyawali and Booth suggest changes to medical education to improve doctors’ ability to critically assess literature, changes to clinical trials to focus more on patient-centred outcomes like quality of life and overall survival, and changes to the journal publishing process to ensure that studies are reported without hype or bias.

These and other changes could help ensure oncology is focused on what’s most important, Dr. Gyawali says, and make sure patients and their doctors have the best information to make decisions about their health. “I want a society where patients are more and more aware of these issues,” he says. “Their lives and well-being are literally at stake.”

Dr. Gyawali knows his research is sometimes seen as controversial, and says he gets mixed reactions from colleagues when his papers are published. But he doesn’t think it’s revolutionary to say that cancer therapies should benefit cancer patients.

“If cancer drugs can’t improve a patient’s chance of surviving or improve their quality of life, then we shouldn’t be using those drugs,” he says. “That shouldn’t be controversial.”

Building evidence for the landmark U.S. ban on menthol cigarettes

OICR Senior Investigator Dr. Geoffrey Fong’s research helped inform the newly proposed tobacco control policy.

When the U.S. Food and Drug Administration (FDA) announced in April 2022 that it was moving forward with a ban on menthol cigarettes, FDA Commissioner Dr. Robert Califf said the ban would help smokers quit, stop young people from starting smoking, and save lives.

He knows that in part because of OICR Senior Investigator Dr. Geoffrey Fong.

Dr. Fong is widely renowned for his research into the impact of policies to curb tobacco smoking — the greatest cause of preventable cancer in Ontario, in Canada and around the world. As Chief Principal Investigator of the International Tobacco Control Policy Evaluation Project (ITC Project) at the University of Waterloo, he led an evaluation of Canada’s recent menthol cigarette ban that was cited by the FDA as it explored a U.S. menthol ban.

Canada became one of the first countries to ban menthol cigarettes when all provinces introduced bans between 2015 and 2018, and then became the first country where a menthol ban has been evaluated on whether it leads smokers to quit.

Smoking kills about 45,000 Canadians every year, and public health authorities including the World Health Organization have long advocated for banning menthols, which have added flavouring and are popular among young smokers, women and some minority groups.

In their initial analysis published in April 2021, Dr. Fong and his ITC Project colleagues showed that banning menthol cigarettes made Canadian menthol smokers significantly more likely to quit than those who smoked non-menthol cigarettes. He presented these findings to colleagues at the FDA. Three weeks later, the FDA announced that it would develop a rule to ban menthol, citing the ITC study.

Now, on the same week of the FDA’s latest announcement, Dr. Fong and colleagues published a new analysis in Tobacco Control that projects the U.S. ban could lead 1.3 million American smokers to quit.

“This is an enormous, landmark decision by the FDA,” says Dr. Fong, who spoke about the decision with several major U.S. news outlets including the New York Times, Washington Post and NBC News. “It’s a major step in tackling the number one preventable cause of cancer and non-communicable diseases.”

This newest study builds on the ITC Project’s previous work by combining ITC data across 7 provinces with data from another project that also evaluated the impact of the menthol ban only in Ontario. Together, they found that 22.3 per cent of menthol smokers quit following the ban, compared to 15 per cent of non-menthol smokers. Applying that 7.3 per cent difference to the more than 18 million menthol smokers in the U.S. gave Dr. Fong and colleagues their 1.3 million estimate.

The menthol ban is likely to have a major impact on the health of Black Americans, who smoke menthols at much higher rates than other Americans and who have been targeted by aggressive menthol tobacco marketing. Dr. Fong’s research estimates that more than 381,000 Black smokers are likely to quit following the ban.

Although the policy has been formally proposed, it may take years before a ban comes into force. The proposal still needs to be finalized and will likely face strong pushback from tobacco companies.

The tobacco industry has a long history of suing countries that try to implement stronger policies, often attempting to discredit the evidence behind those policies. That’s why having comprehensive, population-level studies like Dr. Fong’s is particularly important to the success of these measures.

“Our study is the most complete evaluation of Canada’s menthol cigarette ban,” Dr. Fong said. “I think it can stand up to the challenges that will be coming.”

Predicting cancer evolution with deep learning algorithms

New proof-of-concept approach offers faster, more accurate inferences about tumour populations.

The prevalence of mutations in a tumour can provide clues about how the cancer has grown or evolved and how best to treat it.

But making predictions about the evolution of mutated tumours using a single DNA sequenced biopsy requires complex estimates, and current methods are either slow, or don’t always consider why certain subpopulations of cells proliferate more than others.

This led a pair of researchers at the Ontario Institute for Cancer Research (OICR) to develop a new method for understanding and predicting cancer evolution that harnesses modern deep learning algorithms and incorporates evolutionary modeling.

TumE is a deep learning approach that analyzes the frequency of mutations in a biopsy — known as the variant allele frequency — to identify which subpopulation of mutated cells that are most “fit” and thus most likely to make a tumour stronger.

“We’re taking deep learning tools into the cancer genomic space and trying to find optimal methods for predicting and understanding cancer evolution,” says lead researcher Tom Ouellette, a PhD student at OICR based in Dr. Philip Awadalla’s lab.

TumE’s algorithm uses evolutionary modeling to distinguish between cases where highly “fit” cellular subpopulations are driving tumour growth versus cases where no one cell or subpopulation has a detectable advantage. This helps it make predictions about how many subpopulations are observed in a tumour biopsy, and which subpopulations and mutations will eventually take over.

Understanding which mutations will increase in frequency can provide insight for therapeutic intervention or for quantifying the aggressiveness of tumour growth.

TumE builds on two other methods for inferring the evolution of mutations — approximate Bayesian computation and mixture models — which have been used for several years but have limitations. When tested with simulated data and 88 whole genome sequence samples, as reported in PLOS Computational Biology, TumE generated inferences that were faster than approximate Bayesian computation and more accurate than mixture models.

Though it’s still at the proof-of-concept stage, Ouellette says that TumE offers a good foundation for quickly understanding the link between mutations and the evolutionary dynamics that drive cancer. With access to more data, he says the approach could be scaled up to make more complex predictions.

“With high-quality data and with minimal computational cost, we could use methods like TumE to find patterns and start making statistical estimates of which mutations lead to worse outcomes,” he says.

The advantage of deep learning is that, once something like TumE has been developed, it can be re-tuned to predict different things without having to start from scratch. Eventually, Ouellette says deep learning could be used to determine which mutations or subpopulation of cells are most deadly and should be targeted with precision cancer treatments, ultimately leading to better outcomes for patients.

“We’re trying to find methods that can be used quickly and concurrently with patient care,” he says. “I think this is a stepping stone to get there.”

TumE is publicly available for use at https://github.com/tomouellette/TumE

Two OICR innovations bolstered by investments from FACIT

Investments will support high-profile work led by Dr. Rima Al-awar and Dr. Lincoln Stein.

Groundbreaking projects in OICR’s Drug Discovery and Adaptive Oncology research themes are receiving support to advance made-in-Ontario innovations thanks to investments from FACIT.

The investments announced on April 27 will support work led by OICR’s Head of Therapeutic Innovation and Drug Discovery Dr. Rima Al-awar and Head of Adaptive Oncology Dr. Lincoln Stein.

Dr. Al-awar’s Drug Discovery team is working on a therapeutic platform that targets members of the WD40 repeat domain family of proteins, research that has garnered a lot of attention for its potential to enable new drug discoveries and intellectual property.

Dr. Stein’s team is applying deep data analytics, network association and informatics to better understand the cancer genome. Funding from FACIT will help researchers validate and optimize proprietary technology that helps prioritize tumour targets.

“Congratulations to Dr. Al-awar and Dr. Stein on receiving critical seed capital from FACIT,” says Dr. Laszlo Radvanyi, President and Scientific Director of OICR. “Our world-leading Drug Discovery and Informatics teams are in a unique position to leverage an organic partnership and develop their integrated, competitive platform technologies.”

These new investments come through FACIT’s Prospects Oncology Fund, which provides seed-stage capital for Ontario-based innovations in oncology. FACIT’s review of Prospects Oncology Fund investments are complemented by third party expert reviews to support the best innovations in the province.

“The FACIT team is pleased to support these internationally renowned scientists and invest in product platforms with serious potential for the treatment of cancer,” FACIT President Dr. David O’Neill says.

FACIT and OICR are collaborators in translating cancer research discoveries to patients. Learn more about OICR and FACIT.

Adding another dimension to breast cancer screening

3D ultrasound prototype shows promise as point-of-care screening tool for women with dense breasts.

Researchers at Western University are hoping their 3D ultrasound system can help close a gap in breast cancer screening for the nearly 40 per cent of women with dense breasts.

Mammography is the gold standard in breast cancer imaging, and regular mammograms can help detect breast cancer early when it is most treatable. But dense breast tissue can ‘mask’ tumours in a mammogram, increasing the chances that early stage cancers are missed.

Ultrasound is a potentially more effective screening option for women with dense breasts. Producing higher contrast images than mammography, standard 2D ultrasound images can help spot cancer independent of breast density. And new developments in 3D ultrasound technology could provide an even more detailed picture.

Western University’s Claire Park is first author of a paper in Medical Physics describing a 3D ultrasound prototype for whole-breast imaging. The method involves adding a clinician-controlled robotic arm to an existing 2D ultrasound system, taking 2D photos at different angles, and using custom software to synthesize them into 3D.

“By adding that three-dimensional information, we can better detect cancer, and better characterize the cancer we see,” says Park, a PhD candidate in Medical Biophysics at Western University’s Robarts Research Institute under Dr. Aaron Fenster, who is also Co-Director of OICR’s Imaging Program. “It also opens the possibility for imaging in auxiliary regions of the breast where other systems can’t see.”

Because the prototype is adaptable to any existing 2D ultrasound system — one of the most widely accessible imaging technologies — it has the potential to be rolled out widely and cost-effectively. It also performed well in early testing, producing highly accurate 3D images in volunteers and tissue-mimicking phantoms.

“The results were really encouraging,” Park says. “They show that our system could be used as an accurate alternative [to mammography].”

The study also demonstrated the system’s potential for point-of-care imaging. The prototype is small, fitting onto a medical cart, and Park says it could ultimately be portable enough to screen high-risk women at the bedside.

Though promising, this work is still in early stages. The research team is currently using what it learned from testing to optimize the prototype, working to reduce errors and iterating components to improve workflow. Ultimately, researchers hope to develop a robust protocol for whole-breast imaging and would ultimately like conduct a clinical trial.

For now, Park and her colleagues are encouraged by what their system could mean for a large number of women.

“There is an unmet clinical need for women with dense breasts,” says Park. “A system like ours that harnesses technology that is already readily available in the clinic could really address that need.”

Claire Park was one of six Ontario trainees working in cancer research to receive a 2022 Rising Stars Award.

Up-and-coming research trainees receive OICR Rising Stars awards

Winners of the 2022 awards are working on a range of cancer research projects across Ontario.

The Ontario Rising Stars in Cancer Research Network has recognized six outstanding research trainees with the 2022 Rising Stars Awards.

Supported by OICR, Rising Stars is a pan-Ontario network for trainees in cancer research at the graduate and postdoctoral levels. Its annual awards recognize Ontario trainees who demonstrate a high standard of scholarly achievement in cancer research as well as community engagement and leadership.

This year’s award winners are:

Master’s students

Aline Atallah, Queen’s University
Aline’s research is focused on characterizing the tumour immune microenvironment in bladder cancer to better understand the role of innate immune memory acquisition in the response to Bacillus Calmette-Guérin immunotherapy, with the ultimate goal of improving patient outcomes.

Anisha Hundal, University of Toronto
Anisha’s research investigates whether breast cancer cells deficient in homology-directed DNA double-strand break (DSB) repair employ microtubule-driven nuclear envelope invaginations to repair DSBs, and whether this mechanism may be exploited to limit cancer cell growth and survival.

PhD students

Nabanita Nawar, University of Toronto
Nabanita applies a multi-disciplinary drug discovery approach for therapeutic intervention of HDAC6, to explain its numerous and often contrasting roles in diseases, and design small molecules that can inhibit HDAC6 activity, and alleviate disease phenotypes.

Claire Park, Western University
Claire’s research is focused on developing systems to improve diagnostic and image-guided interventions for women at high-risk of developing breast cancer using PEM and (2D and 3D) ultrasound

Postdoctoral fellow

Dr. Emma Bell, Princess Margaret Cancer Centre (UHN)
As a bioinformatician, Emma combines biology, statistics, and information engineering, to ask biologically and clinically meaningful questions of genomics data. They aim to improve gynaecological healthcare outcomes for women, non-binary and trans people.

Dr. David Cook, Lunenfeld-Tanenbaum Research Institute
Residual disease following treatment remains a challenge for effective cancer treatment. David applies single-cell genomics to understand how cancer cells adapt to treatment and learn to tolerate therapies.

Award-winning co-op student makes her mark on pancreatic cancer research

Undergrad Laura Bumbulis was named the University of Waterloo Faculty of Mathematics Co-op Student of the Year for her work with OICR.

In just four months as a co-op student with OICR’s Pancreatic Cancer program (PanCuRx), Laura Bumbulis helped identify gene mutations in pancreatic cancer and make tumour analysis more efficient.

Not bad for someone who hadn’t studied biology since Grade 11.

Bumbulis joined OICR in the summer of 2021 as an undergraduate student from the University of Waterloo’s Faculty of Mathematics.

“I wasn’t always interested in health sciences, but my interest grew from wanting to have a positive impact on society,” says Bumbulis, who is studying for a double major in statistics and combinatorics/optimization.

At OICR, Bumbulis was tasked with learning how to analyze genome sequencing data and automate PanCuRx’s data analysis workflow. She finished that with time to spare ⁠— while helping streamline the team’s data analysis process ⁠— and was given the more challenging job of studying genetic mutation patterns in tumour samples that were exposed to chemotherapy.

Bumbulis excelled once again, implementing a new algorithm that identified mutation patterns the team hadn’t previously been able to find, providing new insight on how pancreatic adenocarcinoma develops. This work will be written up and submitted for publication and Bumbulis will be named as an author.

Bumbulis’ ability to learn on the fly and apply her knowledge of informatics to solve complex problems earned praise from her supervisors.

“Laura far exceeded our expectations during her work term,” says Dr. Faiyaz Notta, who co-leads the PanCuRx program with Dr. Steven Gallinger. “She worked on highly technical projects that are far beyond what can usually be accomplished in a co-op term.”

Her achievements also earned her recognition from her university, which named her the Faculty of Mathematics Co-op Student of the Year.

Bumbulis is proud she was able to quickly brush up on the science, despite not having a background in biology, and contribute to the program’s important work. She credits the PanCuRx team for supporting her and helping build her confidence.

She expects to complete her undergraduate program in 2023 and then plans to pursue a research-based master’s degree, and she says her experience at OICR will serve her well.

“It was really exciting to have that view into cancer research,” she says, “and it was inspiring to see how everyone’s work was making an impact on people’s lives.”

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