Scientists Get Closer to a Better PSA Test

Dennis Thompson wrote . . . . . . . . .

The most common screening test for prostate cancer so often returns a false positive result that it’s no longer recommended for men older than 70, and it’s offered as a personal choice for younger men.

But researchers think they’ve found a way to make the blood test for prostate-specific antigen (PSA) accurate enough to significantly reduce overdiagnosis and better predict dangerous cancers.

By calibrating PSA levels to each man’s genetics, doctors could control for other factors that might cause levels to be elevated, according to researchers at Stanford Medicine, in California.

The researchers envisioned combining the regular blood-based PSA test with an additional genetic analysis that detects inherited genetic variants that can affect PSA levels.

Elevated PSA levels can be a sign of prostate cancer, but levels can also be high due to other issues like inflammation, infection, an enlarged prostate or just old age, the study authors said in background notes.

“Some men have higher PSA levels due to their genetics,” senior researcher John Witte, a Stanford professor of epidemiology and population health, said in a university news release. “They don’t have cancer, but the higher PSA level leads to a cascade of unnecessary medical interventions like biopsy.”

By one estimate, less than one-third of men with elevated PSA levels were confirmed by a biopsy to have prostate cancer, the researchers reported. Moreover, 15% of men with normal PSA levels were later found to have prostate cancer.

But health experts are reluctant to write off the PSA test completely, given that prostate cancer rates are on the rise in the United States.

Prostate cancer rates rose by 3% a year between 2014 and 2019 after two decades of decline, and advanced prostate cancers increased by about 5% a year, the latest American Cancer Society statistics show.

The problem is that the signal delivered by current PSA screening — a man’s risk of prostate cancer — is too often mixed with background noise, the researchers explained.

“To improve the signal, which is the variation in PSA levels caused by a prostate tumor, we subtract out the noise, which in this case comes from genetics,” said lead researcher Linda Kachuri, an assistant professor of epidemiology and population health at Stanford.

For this study, the investigators looked at the genomes and PSA levels of nearly 96,000 men without prostate cancer to better understand the genetics behind normal variation in PSA levels. The data had been collected as part of earlier studies and included mostly men of European ancestry.

Through this analysis, the researchers estimated that 30% to 40% of the variation found in each man’s PSA levels constitutes “noise,” determined by genetic factors unrelated to cancer.

“Specifically, what we’re trying to capture are the genetic determinants of normal PSA variation,” Kachuri explained.

“This is different from our usual research deciphering the genetic basis of cancer,” Witte said. “We want to remove the non-cancer-related part that’s making PSA a less specific biomarker.”

The researchers identified 128 specific sites in the genome that can affect a man’s PSA level, and then developed a means to account for these normal genetic variations when calculating what they called a PSA polygenic score.

“A polygenic score is a quantitative way of summarizing someone’s genetic predisposition for a trait in a single value,” Kachuri said.

The researchers then tested their PSA polygenic score against data from a separate group of nearly 32,000 men without prostate cancer.

They found that the score could predict close to 10% of variation in PSA levels. However, it was much more effective among men of European ancestry than among men of East Asian or African ancestry.

Next, the researchers applied their score to a mixed group of men with and without prostate cancer, as confirmed by biopsy. The results showed that their PSA test could have spared roughly 30% of those men a biopsy.

The adjusted PSA levels particularly improved detection of the more aggressive forms of prostate cancer, although the benefit was noticeable only in men of European ancestry, according to the report.

“What we’re really worried about are those aggressive cases, so the fact that we’re able to show that genetically adjusted PSA is more predictive of aggressive disease is really promising,” Kachuri said.

Unfortunately, the adjusted PSA levels also would have missed approximately 9% of positive biopsies, the findings showed.

The majority of these missed cases were slow-growing tumors, which are not as dangerous and may not even require treatment. However, the misclassifications point to room for improving the score, the study authors said.

The team next plans a larger study that will include more men from diverse populations, to better improve the accuracy of the test.

“Ideally, we want to come up with a single score that works well for everybody, across the spectrum of ancestry,” Kachuri said.

Even a small improvement in screening could save lives, given that one in nine men in the United States will be diagnosed with prostate cancer and one in 40 will die from it, the researchers said.

The new study was published in Nature Medicine.

Source: HealthDay

 

 

 

 

Advertisement

NASA Looks to Spice Up Astronaut Menu with Deep Space Food Production

Steve Gorman wrote . . . . . . . . .

In the 2015 sci-fi film “The Martian,” Matt Damon stars as an astronaut who survives on a diet of potatoes cultivated in human feces while marooned on the Red Planet.

Now a New York company that makes carbon-negative aviation fuel is taking the menu for interplanetary cuisine in a very different direction. Its innovation has put it in the finals of a NASA-sponsored contest to encourage development of next-generation technologies for meeting the food needs of astronauts.

Closely held Air Company of Brooklyn has pioneered a way of recycling carbon dioxide exhaled by astronauts in flight to grow yeast-based nutrients for protein shakes designed to nourish crews on long-duration deep-space missions.

“It’s definitely more nutritious than Tang,” said company co-founder and Chief Technology Officer Stafford Sheehan, referring to the powdered beverage popularized in 1962 by John Glenn when he became the first American to orbit Earth.

Sheehan, who has a doctorate in physical chemistry from Yale University, said he originally developed his carbon-conversion technology as a means of producing high-purity alcohols for jet fuel, perfume and vodka.

The NASA-sponsored Deep Space Food Challenge prompted Sheehan to modify his invention as a way of producing edible proteins, carbohydrates and fats from the same system.

TASTES LIKE … SEITAN

The resulting single-cell protein drink entered in NASA’s contest has the consistency of a whey protein shake, Sheehan said. Sheehan compared its flavor with that of seitan, a tofu-like food made from wheat gluten that originated in East Asian cuisine and has been adopted by vegetarians as a meat substitute.

“And you get that sweet-tasting, almost malted flavor to it,” Sheehan said in an interview.

Apart from protein drinks, the same process can be used to create more carbohydrate-heavy substitutes for breads, pastas and tortillas. For the sake of culinary variety, Sheehan said he sees his smoothie being supplemented on missions by other sustainably produced comestibles.

The company’s patented AIRMADE technology was one of eight winners announced by NASA this month in the second phase of its food competition, along with $750,000 in prize money. A final round of the competition is coming up.

Other winners included: a bioregenerative system from a Florida lab to raise fresh vegetables, mushrooms and even insect larvae to be used as micronutrients; an artificial photosynthesis process developed in California to create plant- and fungal-based ingredients; and a gas-fermentation technology from Finland to produce single-celled proteins.

Up to $1.5 million in prize money will be divvied up among the eventual final winners of the contest.

While few if any are likely to earn a place in the Michelin Guide for fine dining, they represent a big leap forward from Tang and the freeze-dried snacks consumed by astronauts in the earliest days of space travel.

The new food-growing schemes are also more appetizing, and promise to be far more nutritious, than Matt Damon’s fictional poop-fertilized potatoes in “The Martian.”

“That was taking an idea to an extreme for a Hollywood movie,” said Ralph Fritsche, space crop production manager at NASA’s Kennedy Space Center in Florida, adding that human waste alone “is not the complete nutrient source that plants need to grow and thrive.”

Keeping astronauts well nourished for extended periods within the limited, zero-gravity confines of space vehicles in low-Earth orbit long has posed a challenge for NASA. For the past two decades, crews aboard the International Space Station have lived on a diet mostly of packaged meals with some fresh produce delivered on regular re-supply missions.

ISS teams also have experimented with growing a number of vegetables in orbit, including lettuce, cabbage, kale and chile peppers, according to NASA.

But the imperative for self-contained, low-waste food production requiring minimal resources has become more pronounced as NASA sets its sights on returning astronauts to the moon and eventual human exploration of Mars and beyond.

Advances in space-based food production also have direct applications for feeding Earth’s ever-growing population in an era when climate change is making food more scarce and harder to produce, Fritsche said.

“Controlled environment agriculture, the first modules we deploy on the moon, will have some similarity to the vertical farms that we’ll have here on Earth,” Fritsche said.

Sheehan’s system starts by taking carbon dioxide gas scrubbed from the air breathed by astronauts and blending it with hydrogen gas extracted from water by electrolysis. The resulting alcohol-and-water mixture is then fed into a small quantity of yeast to grow a renewable supply of single-celled proteins and other nutrients.

In essence, Sheehan said, the carbon dioxide and hydrogen form an alcohol feedstock for the yeast, “and the yeast is the food for the humans.”

“We’re not re-inventing products,” Sheehan said, “we’re just making them in a more sustainable way.”

Source: Reuters

 

 

 

 

Company Rolls Out First CRISPR-Edited Produce to U.S. Restaurants

Michael Wolf wrote . . . . . . . . .

Pairwise, a startup specializing in developing gene-edited produce, today announced the launch of its first product, a CRISPR-developed mustard green. The new product, the Conscious Greens Purple Power Baby Greens Blend, will launch into the restaurant/food service channel in partnership with the food service specialist Performance Food Group.

The launch of gene-edited produce by Pairwise comes almost three years after the company got the sign-off from the USDA for its gene-edited mustard green. Mustard greens aren’t usually found on menus due to their pungent smell and bitter taste, but with changes engineered by CRISPR, Pairwise hopes to create a nutritious alternative to kale and Brussels sprouts that also tastes good.

While the Conscious Foods blend with Pairwise’s mustard greens will be the first publicly announced CRISPR-edited produce available in the US market, the product follows the launch of gene-edited tomatoes in Japan in late 2021. That product was produced by Sanatech Seed, which used CRISPR to increase the amount of γ-aminobutyric acid (GABA) in the tomatoes, a supplement that researchers claim can reduce blood pressure and improve moods.

The release of the Sanatech Seed tomatoes came roughly the same time gene-edited fish became commercially available in Japan. In late 2021, Kyoto-based Regional Fish Co., Ltd. started selling genome-edited “Madai” red sea bream and “22-seiki fugu” tiger puffer fish which were edited to grow bigger.

In the US, large ag conglomerates like Simplot have been working with CRISPR since 2018, developing the technology to reduce bruising and black spots in potatoes or extend the life of the strawberry. However, as of this point, Simplot and other firms working with the technology haven’t announced the public availability of their products.

Pairwise, which showcased its CRISPR-edited produce for one of the first times earlier this year at The Spoon’s CES food tech happy hour, plans to roll out its Conscious Foods product into grocery stores later in 2023.

Source: The Spoon

 

 

 

 

How Does Baking Powder Affect My Cookies?

Stella Parks wrote . . . . . . . . .

What Is Baking Powder?

Baking powder is a two-in-one chemical leavening that combines a powdered alkali (sodium bicarbonate) with a powdered acid (originally, tartaric acid). When moistened in a dough or batter, a chemical reaction takes place that produces carbon dioxide gas, inflating cookies, cakes, and pancakes. Because baking powder combines both an acid and a base, it eliminates the need for ingredients like buttermilk or sour cream to activate the sodium bicarbonate, allowing milk or even water to set off the reaction.

Long before the internet, folks at home knew how to do the exact same thing with baking soda and cream of tartar, so baking powder didn’t prove an instant commercial success. To make baking powder more affordable than DIY alternatives, manufacturers lowered the cost by replacing expensive tartaric acid (an imported by-product of winemaking) with monocalcium phosphate (domestically produced from calcium and phosphorus).

Even so, baking powder didn’t truly take off until the 1890s, when companies introduced “double-acting” formulas by adding sodium aluminum sulfate. Though acidic by nature, this insoluble crystalline powder refuses to interact with sodium bicarbonate unless fully melted, delaying any reaction until it’s warmed above 140°F.

So why use two acids? In double-acting formulas, the moisture-sensitive acid is meant to prime (not leaven!) the dough, seeding it with carbon dioxide. Then the heat-sensitive acid kicks in right as cakes and cookies need it most—about midway through the baking process, when softly set batters and doughs threaten to collapse.

Don’t Bother With Homemade Baking Powder

It’s that one-two punch that makes modern baking powder so effective, and why I don’t recommend DIY alternatives at home. Totally better than nothing at all, but according to the Handbook of Food Products Manufacturing, such “single-acting” baking powders expend 75% of their carbon dioxide before even reaching the oven.

That said, cookies are far more forgiving than cakes, in part because their comparatively low moisture content prevents sodium bicarbonate and acid from truly interacting until the butter melts (hence, cookie dough is happy to chill in the fridge). In double-acting formulas, there’s no need to fear; worst-case scenario, the first dose of carbon dioxide is wasted, but the second hits the oven rarin’ to go.

Barring some sort of cookie crisis that necessitates MacGyvering (or MacGrubering) through a recipe, single-acting baking powders are all but obsolete. When cookies call for baking powder, the “double-acting” part should go without saying.

How Much Baking Powder Do My Cookies Need?

The exact amount a recipe will need varies depending on how long the cookies bake, i.e., how long the supply of carbon dioxide needs to last. Expect about one teaspoon per five ounces of flour; thin and crispy cookies may need a little less, thick and chewy cookies may need a little more.

Even without baking powder, a well-aerated dough will still puff with steam. If that supply cuts off before the cookies set, a soft dough will collapse in on itself. If it continues until the end, the air pockets are preserved as the cookie’s crumb.

Baking powder simply adds carbon dioxide to the equation, providing a more forceful pressure that encourages a dough to spread up and out. Without the well-developed elasticity of a bread dough, the strands of gluten in cookies would sooner snap than stretch, cracking along the surface. That gives cookies their familiar appearance, but if you keep pushing the dough with more carbon dioxide, those cracks will only deepen.

In this series of photos, you can see that as we increase the baking powder, the cookies tend to rise a little more, but only to a certain point. Eventually, the reaction is so strong and violent that it will actually cause those air pockets to rupture and collapse, delivering a denser, squatter cookie.

So, contrary to popular belief, it’s not excess baking powder that makes a cookie cakey. Baking powder just regulates how air cells expand—whether or not a dough can handle that expansion depends on gluten. Recipes that are relatively acidic, lean, low in sugar, and high in moisture favor gluten development. Recipes that are relatively alkaline, rich, high in sugar, and low in moisture don’t. You can’t change that with baking powder—you can only cram a dough with more chemicals than it can burn off in a given time, leaving a funky taste behind.

With Baking Powder, Brand Doesn’t Matter

The brand of double-acting baking powder you use isn’t that important. Different companies use different blends of starches, alkalis, and acids, and some may offer various certifications (gluten-free, kosher, etc.), but they’re all formulated to produce a two-stage reaction to a relatively equivalent degree.

I keep Clabber Girl at home, but I don’t owe it any particular allegiance (it’s what they sell at Sam’s Club, my one-stop chemical shop). It has the same blend of ingredients that popularized baking powder 120 years ago, so I figure it’s tried and true.

When comparing labels, keep in mind that the ingredients in baking powder are meant to fuel a chemical reaction. Unless something goes awry, those ingredients aren’t in the final product. For example, it’s impossible to taste sodium aluminum sulfate in cookies because it’s not there: It reacts with sodium bicarbonate to evolve into carbon dioxide, sodium, water, and aluminum hydroxide—an odorless mineral. Meanwhile, what’s touted as a tastier alternative, sodium acid pyrophosphate, produces carbon dioxide, water, and trisodium pyrophosphate—an inherently bitter acid.

Store Your Baking Powder Cool and Dry

Whatever kind you choose, store your baking powder someplace cool and dry. Packages generally indicate a six-month shelf life, but there’s little concern of being ambushed by bad powder.

Baking powder’s chief ingredients, cornstarch and sodium bicarbonate, are outrageously stable even in abusive storage conditions, and its most important acid is defined by an inability to react with water. Hypothetically, the moisture-sensitive acid could be activated prematurely, but liquid water would be created as a by-product of that reaction, causing the cornstarch to visibly cake, clump, and pill.

Bad Cookies? It’s Probably Not the Baking Powder’s Fault

My personal theory is that a lack of aeration (from under-creaming or ultra-soft butter) is the real reason trusted recipes sometimes fall flat.

Check it out—both sugar cookies contain the exact same amount of baking powder. I made the batch on the left with room-temperature butter, using a stand mixer to stir rather than cream in the sugar. I made the batch on the right by creaming cool butter and sugar until light and fluffy.

With proper creaming to incorporate countless tiny pockets of air for the carbon dioxide to expand, my sugar cookies puffed up light. Without aeration to provide a foothold in the dough, the carbon dioxide simply tunneled out, erupting in ugly wormholes. See those dark spots?

If you didn’t understand the importance of creaming or the fact that squishy butter won’t retain air, it’d be easy to blame “bad” baking powder. So, instead of tossing out a perfectly good tin, check your technique instead. In a lifetime of baking, 10 years of professional kitchen work, five years of troubleshooting recipes online, and the formal recipe-testing process that goes into writing a cookbook, I’ve yet to encounter a single baking powder–based failure.

Then again, I’ve never been struck by lightning. It could technically happen, but the odds are not, as the kids say, ever in your favor.

If you’re still worried, put a tablespoon of double-acting baking powder into the bottom of a tall drinking glass, add three ounces of boiling water, and watch it foam to the top. If it doesn’t, check the date on the package and shoot me an email—I’m trying to determine the real-world upper limit, but haven’t found it yet.

Source: Serious Eat

 

 

 

 

A Simple Paper Test Could Offer Early Cancer Diagnosis

Anne Trafton wrote . . . . . . . . .

MIT engineers have designed a new nanoparticle sensor that could enable early diagnosis of cancer with a simple urine test. The sensors, which can detect many different cancerous proteins, could also be used to distinguish the type of a tumor or how it is responding to treatment.

The nanoparticles are designed so that when they encounter a tumor, they shed short sequences of DNA that are excreted in the urine. Analyzing these DNA “barcodes” can reveal distinguishing features of a particular patient’s tumor. The researchers designed their test so that it can be performed using a strip of paper, similar to an at-home Covid test, which they hope could make it affordable and accessible to as many patients as possible.

“We are trying to innovate in a context of making technology available to low- and middle-resource settings. Putting this diagnostic on paper is part of our goal of democratizing diagnostics and creating inexpensive technologies that can give you a fast answer at the point of care,” says Sangeeta Bhatia, the John and Dorothy Wilson Professor of Health Sciences and Technology and of Electrical Engineering and Computer Science at MIT and a member of MIT’s Koch Institute for Integrative Cancer Research and Institute for Medical Engineering and Science.

In tests in mice, the researchers showed that they could use the sensors to detect the activity of five different enzymes that are expressed in tumors. They also showed that their approach could be scaled up to distinguish at least 46 different DNA barcodes in a single sample, using a microfluidic device to analyze the samples.

Bhatia is the senior author of the paper, which appears today in Nature Nanotechnology. Liangliang Hao, a former MIT research scientist who is now an assistant professor of biomedical engineering at Boston University, is the lead author of the study.

DNA barcodes

For several years, Bhatia’s lab has been developing “synthetic biomarkers” that could be used to diagnose cancer. This work builds on the concept of detecting cancer biomarkers, such as proteins or circulating tumor cells, in a patient’s blood sample. These naturally occurring biomarkers are so rare that it’s nearly impossible to find them, especially at an early stage, but synthetic biomarkers can be used amplify smaller-scale changes that occur within small tumors.

In previous work, Bhatia created nanoparticles that can detect the activity of enzymes called proteases, which help cancer cells to escape their original locations, or settle into new ones, by cutting through proteins of the extracellular matrix. The nanoparticles are coated with peptides that are cleaved by different proteases, and once these peptides are released into the bloodstream, they can then be concentrated and more easily detected in a urine sample.

The original peptide biomarkers were designed to be detected based on small engineered variations in their mass, using a mass spectrometer. This kind of equipment might not be available in low-resource settings, so the researchers set out to develop sensors that could be analyzed more easily and affordably, using DNA barcodes that can be read using CRISPR technology.

For this approach to work, the researchers had to use a chemical modification called phosphorothioate to protect the circulating DNA reporter barcodes from being broken down in the blood. This modification has already been used to improve the stability of modern RNA vaccines, allowing them to survive longer in the body.

Similar to the peptide reporters, each DNA barcode is attached to a nanoparticle by a linker that can be cleaved by a specific protease. If that protease is present, the DNA molecule is released and free to circulate, eventually ending up in the urine. For this study, the researchers used two different types of nanoparticles: one, a particle made from polymers that have been FDA-approved for use in humans, and the other a “nanobody” — an antibody fragment that can be designed to accumulate at a tumor site.

Once the sensors are secreted in the urine, the sample can be analyzed using a paper strip that recognizes a reporter that is activated by a CRISPR enzyme called Cas12a. When a particular DNA barcode is present in the sample, Cas12a amplifies the signal so that it can be seen as a dark strip on a paper test.

The particles can be designed to carry many different DNA barcodes, each of which detects a different type of protease activity, which allows for “multiplexed” sensing. Using a larger number of sensors provides a boost in both sensitivity and specificity, allowing the test to more easily distinguish between tumor types.

Disease signatures

In tests in mice, the researchers showed that a panel of five DNA barcodes could accurately distinguish tumors that first arose in the lungs from tumors formed by colorectal cancer cells that had metastasized to the lungs.

“Our goal here is to build up disease signatures and to see whether we can use these barcoded panels not only read out a disease but also to classify a disease or distinguish different cancer types,” Hao says.

For use in humans, the researchers expect that they may need to use more than five barcodes because there is so much variety between patients’ tumors. To help reach that goal, they worked with researchers at the Broad Institute of MIT and Harvard led by Harvard University Professor Pardis Sabeti, to create a microfluidic chip that can be used to read up to 46 different DNA barcodes from one sample.

This kind of testing could be used not only for detecting cancer, but also for measuring how well a patient’s tumor responds to treatment and whether it has recurred after treatment. The researchers are now working on further developing the particles with the goal of testing them in humans. Glympse Bio, a company co-founded by Bhatia, has performed phase 1 clinical trials of an earlier version of the urinary diagnostic particles and found them to be safe in patients.

Source: MIT News