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Pathology is Poised for the Digital Revolution

By Monique Brouillette Last year, scientists published a study that analyzed century old viruses preserved in lung samples of patients that died during…

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By Monique Brouillette

Last year, scientists published a study that analyzed century old viruses preserved in lung samples of patients that died during the Spanish flu. The study showed the first ever genetic evidence that the flu virus evolved to become more deadly during the second wave of the pandemic. For virologists, it was an exciting finding, but for pathologists, it was a reminder of just how little their techniques have changed since then.

Despite big advances like digital imaging processing and artificial intelligence, the field of pathology still relies on methods developed one hundred years ago or more. Pathologists today still slice tissues thin, stain them and embed them in paraffin, just like they did a century ago. The methods are time intensive, limit the speed of diagnosis and even hinder the adoption of new advances in AI-driven diagnostics.

In order for pathology to move into the digital century, advances in slide preparation and microscopy will be essential. Pandemic-inspired rollbacks in regulations coupled with new advances in stain-free microscopy, in vivo imaging and even augmented reality could bring the next generation of pathology tools to reality.

Stirrings of change

Although technological advancements have been available, the field of pathology has been slower to adapt than other fields, like radiology, for example, which has rapidly embraced machine learning.

In 2017, the FDA approved the first whole slide imaging system, which allowed pathologists to scan their tissue samples into the computer. For the first time, diagnoses based on histology could be made digitally with machine learning tools. The advance should have catapulted faster digital adoption, but several hurdles stood in the way. Workflow was one. Scanning a slide into the computer adds extra steps and expense into the process. The slide still needs to be created, after all, and many argue in the amount of time it takes to scan a slide a pathologist could make a diagnosis. Simplified and more efficient tissue processing is needed to bring the field forward.

Yair Riverson, CEO
Pictorlabs & Professor, UCLA

“I think there is a greater opening right now for adaptation of these technologies,” says Yair Riverson, a computer engineering professor from UCLA and CEO of Pictorlabs, a company founded in 2020 to develop stain-free technology. “One of the key benefits is that they will  enable us to share slides across multiple platforms and hospitals and other clinical environments.” Riverson said the pandemic really gave the field a boost as pathologists saw the value in working remotely and getting access to digital slides.

Virtual histology 

In 2020 Riverson co-founded Pictorlabs, a company focused on virtual histological staining of tissue samples. The company is one of many that are trying to streamline the slide preparation by eliminating the need for staining. Unlike radiological techniques in which images are collected digitally and seamlessly integrated into a digital workflow, whole slide imaging adds time and additional steps to the process. It also adds costs, like scanners and fancy monitors. For radiology, digital images save money on film. No such savings exist in pathology yet.

But entrepreneurs like Riverson hope that they can improve the workflow using technologies based on autofluorescence that take advantage of naturally fluorescent cell constituents like proteins and fatty acids. The technology hastens slide processing times and makes digital analysis more practical. His company is developing machine learning algorithms that allow the imaging of the tissue without the use of dyes and stains. In a paper published in Nature Biotechnology in 2019, their technique was shown to be equivalent to common histology stains like H&E, Jones attain and Masson’s trichrome in multiple organ tissues.

These “virtual stains” can be overlaid on the image like an instagram filter. Histological features pop out just as clearly if they had been stained with traditional dyes, according to Riverson and the technique saves hours, especially with more complicated assays.

“Radiologists have multiple screens with different views like MRI and CT to correlate data and make their decisions. We hope our technology will enable that experience for pathologists—giving them the multiple views of the same tissue without having to cut more slides and order more assays,” says Riverson.

Slide freedom

Others who are looking to hasten and streamline the pathology workflow want to go a step further even—eliminating the slide entirely. “Histology is fixed in this idea that one can only image tissue if you paraffin-embed it, slice it thin and stick it on a white light microscope,” says Columbia University professor of biomedical engineering, Elizabeth Hillman. “It’s just not compatible with getting data quickly”

Elizabeth Hillman
Elizabeth Hillman, CMD, PhD, CEO
Professor Columbia University

Hillman is developing an approach using light-sheet microscopy, a high-powered type of fluorescent microscopy, that can be used on a patient without having to take a tissue biopsy, fix it in formalin or stain it. In March, Hillman published a paper in Nature Biotechnology detailing the technique’s application in mice and humans. In mice, a hand-held scope was able to image pancreatic tissue in a live mouse undergoing surgery and in human liver biopsied tissue. In humans, the scope was able to identify key diagnostic features like signs of arteriosclerosis and detailed views of the tissue. In addition, the scope was used on a human volunteer to image their tongue. Clear images of the tongue tissue layers were seen up to 200 microns in depth without the need for biopsy or chemical dyes.

Other approaches to get rid of the slide are taking advantage of photoacoustic microscopy, that uses light and ultrasound to generate images, and even ultraviolet light.  “The dream is that in the future, you won’t need to cut the tissue out at all,” says Hillman.

Bridging the gap 

According to Gabe Siegal, CEO of Augmentiqs, an Israeli-based digital pathology start-up, the digital future of the field may still be another 30 years away. In the meantime, his company has found a solution. Augmentiqs builds augmented reality technology that can be plugged into a traditional light microscope. When the pathologist peers through the objective, she will see a glass slide with digital information layered on top, including artificial intelligence-backed tools to measure tumor size, for example. The technology is meant to bridge the gap between the traditional glass slide and next-generation digital processing tools.

Gabe Siegel
Gabe Siegel, CEO, Augmentiqs

“The large-scale transition to digital pathology where everything will be looked at on a screen instead of a microscope is very far from being mainstream,” he says, “this technology offers the seamless integration of the computer with the microscope.”

The augmented reality device, which is added onto a regular light microscope, also connects the user to the full range of machine learning applications. “It’s like the app store for your cell phone,” he says.

 

Monique Brouillette, is a freelance journalist who covers science and health.

The post Pathology is Poised for the Digital Revolution appeared first on Inside Precision Medicine.

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Pharma industry reputation remains steady at a ‘new normal’ after Covid, Harris Poll finds

The pharma industry is hanging on to reputation gains notched during the Covid-19 pandemic. Positive perception of the pharma industry is steady at 45%…

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The pharma industry is hanging on to reputation gains notched during the Covid-19 pandemic. Positive perception of the pharma industry is steady at 45% of US respondents in 2023, according to the latest Harris Poll data. That’s exactly the same as the previous year.

Pharma’s highest point was in February 2021 — as Covid vaccines began to roll out — with a 62% positive US perception, and helping the industry land at an average 55% positive sentiment at the end of the year in Harris’ 2021 annual assessment of industries. The pharma industry’s reputation hit its most recent low at 32% in 2019, but it had hovered around 30% for more than a decade prior.

Rob Jekielek

“Pharma has sustained a lot of the gains, now basically one and half times higher than pre-Covid,” said Harris Poll managing director Rob Jekielek. “There is a question mark around how sustained it will be, but right now it feels like a new normal.”

The Harris survey spans 11 global markets and covers 13 industries. Pharma perception is even better abroad, with an average 58% of respondents notching favorable sentiments in 2023, just a slight slip from 60% in each of the two previous years.

Pharma’s solid global reputation puts it in the middle of the pack among international industries, ranking higher than government at 37% positive, insurance at 48%, financial services at 51% and health insurance at 52%. Pharma ranks just behind automotive (62%), manufacturing (63%) and consumer products (63%), although it lags behind leading industries like tech at 75% positive in the first spot, followed by grocery at 67%.

The bright spotlight on the pharma industry during Covid vaccine and drug development boosted its reputation, but Jekielek said there’s maybe an argument to be made that pharma is continuing to develop innovative drugs outside that spotlight.

“When you look at pharma reputation during Covid, you have clear sense of a very dynamic industry working very quickly and getting therapies and products to market. If you’re looking at things happening now, you could argue that pharma still probably doesn’t get enough credit for its advances, for example, in oncology treatments,” he said.

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Spread & Containment

I created a ‘cosy game’ – and learned how they can change players’ lives

Cosy, personal games, as I discovered, can change the lives of the people who make them and those who play them.

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Cosy games exploded in popularity during the pandemic. Takoyaki Tech/Shutterstock

The COVID pandemic transformed our lives in ways many of us are still experiencing, four years later. One of these changes was the significant uptake in gaming as a hobby, chief among them being “cosy games” like Animal Crossing: New Horizons (2020).

Players sought comfort in these wholesome virtual worlds, many of which allowed them to socialise from the safety of their homes. Cosy games, with their comforting atmospheres, absence of winning or losing, simple gameplay, and often heartwarming storylines provided a perfect entry point for a new hobby. They also offered predictability and certainty at a time when there wasn’t much to go around.

Cosy games are often made by small, independent developers. “Indie games” have long been evangelised as the purest form of game development – something anyone can do, given enough perseverance. This means they can provide an entry point for creators who hadn’t made games before, but were nevertheless interested in it, enabling a new array of diverse voices and stories to be heard.

In May 2020, near the start of the pandemic, the small poetry game A Solitary Spacecraft, which was about its developer’s experience of their first few months in lockdown, was lauded as particularly poignant. Such games showcase a potential angle for effective cosy game development: a personal one.

Personal themes are often explored through cosy games. For instance, Chicory and Venba (both released in 2023) tackle difficult topics like depression and immigration, despite their gorgeous aesthetics. This showcases the diversity of experiences on display within the medium.

However, as the world emerges from the pandemic’s shadow, the games industry is facing significant challenges. Economic downturns and acquisitions have caused large layoffs across the sector.

Historically, restructurings like these, or discontent with working conditions, have led talented laid-off developers to create their own companies and explore indie development. In the wake of the pandemic and the cosy game boom, these developers may have more personal stories to tell.

Making my own cosy game

I developed my own cosy and personal game during the pandemic and quickly discovered that creating these games in a post-lockdown landscape is no mean feat.

What We Take With Us (2023) merges reality and gameplay across various digital formats: a website, a Discord server that housed an online alternate reality game and a physical escape room. I created the game during the pandemic as a way to reflect on my journey through it, told through the videos of game character Ana Kirlitz.

The trailer for my game, What We Take With Us.

Players would follow in Ana’s footsteps by completing a series of ten tasks in their real-world space, all centred on improving wellbeing – something I and many others desperately needed during the pandemic.

But creating What We Take With Us was far from straightforward. There were pandemic hurdles like creating a physical space for an escape room amid social distancing guidelines. And, of course, the emotional difficulties of wrestling with my pandemic journey through the game’s narrative.

The release fared poorly, and the game only garnered a small player base – a problem emblematic of the modern games industry.

These struggles were starkly contrasted by the feedback I received from players who played the game, however.

This is a crucial lesson for indie developers: the creator’s journey and the player’s experience are often worlds apart. Cosy, personal games, as I discovered, can change the lives of those who play them, no matter how few they reach. They can fundamentally change the way we think about games, allow us to reconnect with old friends, or even inspire us to change careers – all real player stories.

Lessons in cosy game development

I learned so much about how cosy game development can be made more sustainable for creators navigating the precarious post-lockdown landscape. This is my advice for other creators.

First, collaboration is key. Even though many cosy or personal games (like Stardew Valley) are made by solo creators, having a team can help share the often emotional load. Making games can be taxing, so practising self-care and establishing team-wide support protocols is crucial. Share your successes and failures with other developers and players. Fostering a supportive community is key to success in the indie game landscape.

Second, remember that your game, however personal, is a product – not a reflection of you or your team. Making this distinction will help you manage expectations and cope with feedback.

Third, while deeply considering your audience may seem antithetical to personal projects, your game will ultimately be played by others. Understanding them will help you make better games.

The pandemic reignited the interest in cosy games, but subsequent industry-wide troubles may change games, and the way we make them, forever. Understanding how we make game creation more sustainable in a post-lockdown, post-layoff world is critical for developers and players alike.

For developers, it’s a reminder that their stories, no matter how harrowing, can still meaningfully connect with people. For players, it’s an invitation to embrace the potential for games to tell such stories, fostering empathy and understanding in a world that greatly needs it.


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Adam Jerrett does not work for, consult, own shares in or receive funding from any company or organisation that would benefit from this article, and has disclosed no relevant affiliations beyond their academic appointment.

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The SNF Institute for Global Infectious Disease Research announces new advisory board

From identifying the influenza virus that caused the pandemic of 1918 to developing vaccines against pneumococcal pneumonia and bacterial meningitis in…

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From identifying the influenza virus that caused the pandemic of 1918 to developing vaccines against pneumococcal pneumonia and bacterial meningitis in the 1970s, combating infectious disease has a rich history at Rockefeller. That tradition continues as the Stavros Niarchos Foundation Institute for Global Infectious Disease Research at Rockefeller University (SNFiRU) caps a successful first year with the establishment of a new advisory board.

Credit: Lori Chertoff/The Rockefeller University

From identifying the influenza virus that caused the pandemic of 1918 to developing vaccines against pneumococcal pneumonia and bacterial meningitis in the 1970s, combating infectious disease has a rich history at Rockefeller. That tradition continues as the Stavros Niarchos Foundation Institute for Global Infectious Disease Research at Rockefeller University (SNFiRU) caps a successful first year with the establishment of a new advisory board.

This international advisory board was created in part to give guidance on how to best use SNFiRU’s resources, as well as bring forward innovative ideas concerning new avenues of research, public education, community engagement, and partnership projects.

SNFiRU was established to strengthen readiness for and response to future health crises, building on the scientific advances and international collaborations forged in the context of the COVID-19 pandemic. Launched with a $75 million grant from the Stavros Niarchos Foundation (SNF) as part of its Global Health Initiative (GHI), the institute provides a framework for international scientific collaboration to foster research innovations and turn them into practical health benefits.

SNFiRU’s mission is to better understand the agents that cause infectious disease and to lower barriers to treatment and prevention globally. To speed this work, the institute launched numerous initiatives in its inaugural year. For instance, SNFiRU awarded 31 research projects in 29 different Rockefeller laboratories for over $5 million to help get collaborative new research efforts off the ground. SNFiRU also supports the Rockefeller University Hospital, where clinical studies are conducted, and brought on board its first physician-scientist through Rockefeller’s Clinical Scholars program. “One of the surprises was the scope of interest from Rockefeller scientists in using their talents to tackle important infectious disease problems,” says Charles M. Rice, Maurice R. and Corinne P. Greenberg Professor in Virology at Rockefeller and director of SNFiRU. “The research topics range from the biology of infectious agents to the dynamics of the immune response to pathogens, and also include a number of infectious disease-adjacent studies.”

In the past 12 months, SNFiRU often brought together scientists studying different aspects of infectious disease as a way to spur new collaborations. In addition to hosting its first annual day-long symposium, SNFiRU initiated a Young Scientist Forum for students and post-doctoral fellows to meet regularly, facilitating cross-laboratory thinking. A bimonthly seminar series has also been established on campus.

Another aim of SNFiRU is to develop relationships with community-based organizations, as well as design and participate in community-engaged research, with a focus on low-income and minority communities. To that end, SNFiRU is helping develop a research project on Chagas disease, a tropical parasitic infection prevalent in Latin America that can cause congestive heart failure and gastrointestinal complications if left untreated. The project will bring together clinicians practicing at health centers in New York, Florida, Texas, and California and basic scientists from multiple institutions to help the communities that are most impacted.

“The SNFiRU international advisory board convenes globally recognized leaders with distinguished biomedical expertise, unrivalled experience in pandemic preparedness and response, and a shared commitment to translating scientific advancements into equitably distributed benefits in real-world settings,” says SNF Co-President Andreas Dracopoulos. “The advisory board will advance the institute’s indispensable mission, which SNF is proud to support as a key part of our Global Health Initiative, and we look forward to seeing breakthroughs in the lab drive better outcomes in lives around the globe.”

The new advisory board will hold its first meeting on April 11th, 2024, following the second annual SNF Institute for Global Infectious Disease Research Symposium at Rockefeller.

Its members are: Rafi Ahmed of Emory University School of Medicine, Cori Bargmann of The Rockefeller University, Yasmin Belkaid of the Pasteur Institute, Anthony S. Fauci, the former director of the National Institute of Allergy and Infectious Diseases, Peter Hotez of Baylor College of Medicine and Texas Children’s Hospital Center for Vaccine Development, Esper Kallas of of the Butantan Institute, Sharon Lewin of the University of Melbourne Doherty Institue, Carl Nathan of Weill Cornell Medicine, Rino Rappuoli of Fondazione Biotecnopolo di Siena and University of Siena, and Herbert “Skip” Virgin of Washington University School of Medicine and UT Southwestern Medical Center.


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