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Machine Learning Helps Define New Subtypes of Parkinson’s Disease

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Weill Cornell Medicine investigators used AI to discern subtypes of Parkinson's disease from diverse data sources. Credit: Shutterstock

Researchers at Weill Cornell Medicine have used machine learning to define three subtypes of Parkinson’s disease based on the pace at which the disease progresses. In addition to having the potential to become an important diagnostic and prognostic tool, these subtypes are marked by distinct driver genes. If validated, these markers could also suggest ways the subtypes can be targeted with new and existing drugs.

The research was published on July 10 in npj Digital Medicine.

“Parkinson’s disease is highly heterogeneous, which means that people with the same disease can have very different symptoms,” said senior author Dr. Fei Wang , a professor of population health sciences and the founding director of the Institute of AI for Digital Health (AIDH) in the Department of Population Health Sciences at Weill Cornell Medicine. “This indicates there is not likely to be a one-size-fits-all approach to treating it. We may need to consider customized treatment strategies based on a patient’s disease subtype.”

The investigators defined the subtypes based on their distinct patterns of disease progression. They named them the Inching Pace subtype (PD-I, about 36% of patients) for disease with a mild baseline severity and mild progression speed, the Moderate Pace subtype (PD-M, about 51% of patients) for cases that have mild baseline severity but advance at a moderate rate, and Rapid Pace subtype (PD-R), for cases with the most rapid symptom progression rate.

They were able to identify the subtypes by using deep learning-based approaches to analyze deidentified clinical records from two large databases. They also explored the molecular mechanism associated with each subtype through the analysis of patient genetic and transcriptomic profiles with network-based methods. For example, the PD-R subtype had activation of specific pathways, such as those related to neuroinflammation, oxidative stress and metabolism. The team also found distinct brain imaging and cerebrospinal fluid biomarkers for the three subtypes.

Dr. Wang’s lab has been studying Parkinson’s since 2016, when the group participated in the Parkinson's Progression Markers Initiative (PPMI) data challenge sponsored by the Michael J. Fox Foundation. The team won the challenge on the topic of deriving subtypes , and since then has received funding from the foundation to continue this work. They employed the data collected from the PPMI cohort as the primary subtype development cohort in their research and validated them with National Institute of Neurological Disorders and Stroke (NINDS) Parkinson's Disease Biomarkers Program (PDBP) cohort.

The researchers used their findings to identify possible drug candidates that could be repurposed to target the specific molecular changes seen in the different subtypes. They then used two large-scale, real-world databases of patient health records to confirm these drugs could help ameliorate Parkinson’s progression. These databases, the INSIGHT Clinical Research Network, based in New York, and the OneFlorida+ Clinical Research Consortium, are both part of the National Patient-Centered Clinical Research Network (PCORnet). INSIGHT is led by Dr. Rainu Kaushal , senior associate dean for clinical research at Weill Cornell Medicine and chair of the Department of Population Health Sciences at Weill Cornell Medicine and NewYork-Presbyterian/Weill Cornell Medical Center.

“By examining these databases, we found that people taking the diabetes drug metformin appeared to have improved disease symptoms—especially symptoms related to cognition and falls—compared with those who did not take metformin,” said first author Dr. Chang Su , an assistant professor of population health sciences and also a member of the AIDH at Weill Cornell Medicine. This was especially true in those with the PD-R subtype, who are most likely to have cognitive deficits early in the course of their Parkinson’s disease.

“We hope our research will lead other investigators to think about using diverse data sources when conducting studies like ours,” Dr. Wang said. “We also think that translational bioinformatics investigators will be able to further validate our findings, both computationally and experimentally.”

A number of collaborators contributed to this work, including scientists at the Cleveland Clinic, Temple University, University of Florida, University of California at Irvine, University of Texas at Arlington as well as doctoral candidates from the computer science program at Cornell Tech and the computational biology program at Cornell University’s Ithaca campus.

Many Weill Cornell Medicine physicians and scientists maintain relationships and collaborate with external organizations to foster scientific innovation and provide expert guidance. The institution makes these disclosures public to ensure transparency. For this information, see profile for Dr. Fei Wang .

This work was supported in part by the National Institute on Aging, the National Institute of General Medical Sciences, and the National Institute of Neurological Disorders and Stroke, all part of the National Institutes of Health, through grant numbers RF1AG072449, R01AG080991, R01AG076234,R01AG076448, U01AG073323, R21AG083003, R01AG066707, R01AG082118, RF1AG082211, RF1NS133812, 3R01AG066707, 3R01AG066707, R56AG074001, R01AG053798, P30AG072959, R35AG71476, AG083721,  P20GM109025  and U01NS093334.

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Kamala Harris aims to define herself by campaigning across the country

Deepa Shivaram

Steve Inskeep

Vice President Harris is off and running. She will be in Indianapolis Wednesday, after her first big event in Milwaukee on Tuesday. Get caught up on the rapid-fire launch of this campaign.

Copyright © 2024 NPR. All rights reserved. Visit our website terms of use and permissions pages at www.npr.org for further information.

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The fight to define Harris is on. And for now, Republicans are dominating Democrats on the airwaves

Vice President Kamala Harris arrives at Indianapolis International Airport, Wednesday, July 24, 2024 in Indianapolis. Harris is in Indianapolis to give a keynote speech at Zeta Phi Beta Sorority, Inc.'s Grand Boul’ event. (Brendan Smialowski/Pool via AP)

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NEW YORK (AP) — Just days into her new role as the Democratic Party’s likely presidential nominee , Kamala Harris is already facing a wave of Republican-backed attack ads questioning her personality, her progressive record and what she knew about President Joe Biden’s decline.

But for now, at least, Democrats have yet to engage in the summertime advertising fight. And in a sharp reversal from much of the year, Republicans are suddenly dominating the airways.

Follow AP’s live coverage of the 2024 presidential race.

Overall, Trump and his allies are outspending Harris’ team 25-to-1 on television and radio advertising — more than $68 million for Republicans compared to just $2.6 million for Democrats — in the period that began on Monday, the day after Biden stepped aside , through the end of August, according to an AP analysis of data compiled by the media tracking firm AdImpact.

The stunning disparity reflects actual spending for this week and reservations for subsequent weeks, which will almost certainly change in the coming days. But for now, the numbers highlight a dangerous imbalance for Democrats at the very moment that millions of voters are re-shaping their opinions of the vice president, who has spent much of the last four years in Biden’s shadow.

Some Harris allies are already sounding the alarm.

“Public opinion is like cement. It’s soft at first and then it hardens,” said Sarah Longwell, co-founder of Republican Voters Against Trump. “The next three weeks are definitive. She needs to define herself before Trump defines her.”

To be sure, Harris only earned Biden’s endorsement on Sunday. And in the days since, friends and foes agree that she’s benefited from a flood of so-called “earned” news media coverage, much of it positive. Trump pollster Tony Fabrizio described it as “Harris’ honeymoon” in a memo on Tuesday that predicted a surge in the polls for the Democratic vice president.

Asked about the advertising disparity, Harris spokesperson Kevin Munoz said the vice president “will make her case aggressively alongside a campaign infrastructure designed to win close elections.”

“In just 24 hours, Kamala Harris put abortion rights front and center for voters, broke fundraising records, and spun Donald Trump out into a manic and public breakdown — because he knows she is best-equipped to prosecute the case against a convicted felon like himself,” he said.

Harris’ team has the money to launch a robust advertising campaign whenever it wants to.

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Her campaign raised a jaw-dropping $100 million between Sunday afternoon as of Monday night alone. And allies, led by the super PAC Future Forward, received donor commitments of $150 million in the first 24 hours after Biden left the race.

“Obviously, advertising is important and will pick up, but it’s not the only factor,” said Democratic strategist Josh Schwerin. “With Harris taking over as the presumptive nominee, she’s getting wall-to-wall largely positive coverage. ... You always need to take in the context of the entire media ecosystem.”

Still, some of the Harris attack ads may be beginning to shape the narrative.

Biden allies privately raised concerns about a new ad from Pennsylvania Republican Senate candidate Dave McCormick that describes Harris as “the most liberal nominee ever.” The ad highlights her progressive positions on immigration, policing, energy and health care. It ends with audio of Harris’ loud laugh, which has been a frequent Republican focus.

Trump’s campaign has been largely silent on the airwaves since he emerged as his party’s presumptive presidential nominee this spring. The delay in ad spending reflected, in part, the former president’s financial challenges following an expensive primary and overwhelming legal bills. Backed by allied super PACs that are running tens of millions in ads this summer, however, the Trump campaign can also afford to wait until more voters are paying attention this fall to pour money into advertising.

The pro-Trump Preserve America super PAC, backed by casino magnate Miriam Adelson, has reserved $45 million worth of advertising through the end of August. MAGA Inc. has booked another $23 million.

Democrats, meanwhile, just halted its advertising spending after devoting enormous sums to boost Biden in the weeks and months before he dropped out.

Overall, Biden’s campaign spent more than $138 million on advertising between Jan. 1 of this year through Sunday, when he announced his decision to step aside. While much of the advertising went after Trump, the ads also featured Biden, who is no longer a candidate and largely viewed as a political liability for Harris.

It is only a matter of time, days perhaps, before Harris and her allies ramp up their advertising plans.

While AdImpact found only about $2.6 million in Democratic-backed ad reservations through the end of August, the pro-Biden super PAC Future Forward is set to begin rolling out a $129 million advertising campaign in September.

But for now, voters are only seeing presidential ads that knock Harris.

One of them, from MAGA Inc., blames the vice president for “a border invasion, runaway inflation,” and the death of the American dream.

“Kamala knew Joe couldn’t do the job, so she did it,” says the narrator in the spot that started running Sunday across Pennsylvania, Georgia and Arizona. “They created this mess. They — no, Kamala — owns this failed record.”

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home•work

An assignment is a task that someone is given to do, usually as part of their job.

An assignment is also a piece of academic work given to students.

In American English, an assignment is also a piece of work given to students to do at home.

Work given to schoolchildren to do at home is also called homework .

Be Careful! Homework is an uncountable noun. You do not talk about 'homeworks' or 'a homework'. Note that you do not say ' I have made my homework '. You say 'I have done my homework'.

Homework is work that school pupils are given to do at home. You say that pupils do homework. Don't say that they ' make homework '.

Housework is work such as cleaning or washing that is done in a house.

Be Careful! Both homework and housework are uncountable nouns. Don't talk about ' a homework ' or ' houseworks '.

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Definition of homework – Learner’s Dictionary

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• Go upstairs and do your homework.
• For your homework, please do exercise 3 on page 24.
• When I finish my homework, can I watch TV?
• Get on with your homework.
• She was trying to duck out of doing her homework.

(Definition of homework from the Cambridge Learner's Dictionary © Cambridge University Press)

Translations of homework

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a hollow object, such as a box or a bottle, that can be used for holding something, especially to carry or store it

Putting a spanner in the works – Idioms in The Guernsey Literary and Potato Peel Pie Society

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New York Stars Define 'Liberty Basketball'

Geoff magliocchetti | jul 26, 2024.

• New York Liberty

When fourth quarter rallies at Barclays Center are interrupted by media timeouts, the New York Liberty's hype team leads fans in the team's pop-inspired fight song. It's a tune carried over from the franchise's Madison Square Garden days, one armed with a chorus that spells out the team's nickname.

That perhaps saves fans a trip to the dictionary, where they'll never find the definition of "liberty" adjusted for New York's seafoam savants. Those leading the way took a stab at it through a fateful week, one that set a countdown on the first halves of the 2024 WNBA season.

The concept of "Liberty basketball" came through one of New York's rare misfires this season, when a fourth quarter slump and history from rookie sensation Caitlin Clark led to a defeat in Indianapolis. Point guard Sabrina Ionescu, the longest-tenured New Yorker, was asked by Jackie Powell of The Next if Clark and the Indiana Fever took away the sense of "Liberty basketball" that had sustained the team over the first literal half of the season, one that yielded a franchise record 17 victories.

Ionescu insisted that New York indeed played Liberty basketball and simply fell short in a "Super Bowl game" for the developing Fever. That begs the question: what exactly Liberty basketball, and how is it defined in this fateful journey?

Reigning WNBA MVP needed but one word to pull off the feat.

"My definition of liberty basketball is just toughness," Stewart said. "No matter what the challenge is, no matter the adversity we face, like having three back-to-backs, what it is, we continue to fight through. We don't want to take any excuses."

New York's top representatives took a stab at such clarity in the final pre-Olympic quartet, updating the term as they closed on a league-best record that would ensure that the path to the championship primarily ran through Barclays Center ... whose visitors play an equally vital role in opposing shutdowns.

"I think we're playing really good basketball," Jonquel Jones said. "I think we're playing hard and I think that when teams come in here, they know that it's going to be a tough place to play, not just because of us but because of the fans. I think New York basketball in general is just being tough and doing whatever needs to be done to kind of win and in being resilient no matter what you're going through. I think, so far, our team has kind of embodied that."

"I think playing 40 minutes of tough, gritty basketball is really kind of what we hang our hat on on both sides of the floor, making sure we play the right way," Ionescu later offered. "I think (that Indiana game) was a little uncharacteristic in terms of things felt a little clunky. Offensive, defensively, we weren't really locked in. But in (other) games, you can tell that we stay on a string. We continue to grind it out, find ways to win, and continue to use all our strengths to our advantages and have a great outside/inside game."

Non-verbal examples have been readily available on the court before the team went its Olympian ways.

Since that loss in Indianapolis, New York (21-4) put up four consecutive wins to wrap up the WNBA's pre-Olympic slate, establishing a formidable 2.5-game lead in the chase for the top seed in the upcoming playoffs. Wins over their closest competition, the Connecticut Sun, sandwiched a home-and-home sweep of the Chicago Sky, who won the first two get-togethers of the campaign (including a 48-point preseason shellacking that unofficially opened the tour).

In its broadest, most-timed honored definition, the Liberty franchise could be described as resilient: two decades of general consistency gave way to extinction nearly brought about by the separation from an NBA brother (which previously befell franchises in Charlotte, Houston, and Sacramento). The light at the end of the tunnel turned out to be star power.

New York continues to boast one of the most electrifying rotations in men's and women's basketball: the additions of Jones, Stewart, and Courtney Vandersloot are now well-known to metropolitan audiences, with that assembly of All-Stars brought together alongside seafoam incumbents Ionescu and Betnijah Laney-Hamilton.

No New Yorker under a certain age needs to be (re)told that with great power comes great responsibility. The Liberty dutifully embraced both last season, which yielded both a Commissioner's Cup title and the franchise's first WNBA Finals appearance in over two decades.

Their definition perhaps had to be rewritten this season through the same basic plot: New York fully retained the top six women (the fateful five plus sixth woman Kayla Thornton) that got them over the semifinal hump and into the Finals ... the latter defined by a heartbreaking four-game defeat at the hands of the Las Vegas Aces, one where shorthanded Sin City earned its second straight ring on Brooklyn hardwood.

With a chanceat redemption brewing, the definition was allowed to be written in relative silence: New York mostly kept to itself in the offseason, quietly re-assembling under the cover of a thrilling NCAA Tournament and wheeling and dealing amongst their WNBA sisters.

General manager Jonathan Kolb took care of some of the dirty work early by getting Laney-Hamilton and Thornton back on multi-year deals before the trek to the Finals started. Jones re-upped, as did Stewart, who rejected an expensive core option to keep the Liberty's assets relatively fresh.

International fan favorites like Marine Johannes and Han Xu stayed overseas to prep for the aforementioned Olympics, leaving replacements like Kennedy Burke and Leonie Fiebich to pick up the slack. The latter duo came up particularly big over the last couple, when each stepped into the starting for an injured Laney-Hamilton and a resting Stewart.

So far, New York's gambit, one that banked on familiarity and a year of working together, has paid off.

The on-court success perhaps pales in comparison to how the Liberty have helped each other off the floor: this season has carried a somber undertone due to some losses in the locker room, as Vandersloot took nearly a month off after the passing of her mother Jan while Jones returned to her native Bahamas shortly after the Commissioner's Cup Final loss to Minnesota to attend the funeral of a youth coach.

Unity is obviously expected in such scenarios, but many other groups dealing with such situations don't have the pressure of a professional basketball title hovering above them. Head coach Sandy Brondello praised the way her team has conducted itself from both a competitive and emotional end.

"I'm proud of the way we respond. When we lose, sometime it's a reality check. (It's about) making them as good as wins because they make you want to refocus and commit back to how we want to play," Brondello said. "We're capable of scoring inside and outside. That's our weapon at the moment."

"To be 21-4 at this stage and have to overcome players having to sit out, not be with the team, it allows other players to step up and see what we have. I think we're a resilient bunch. I think our chemistry continues to grow. We learn more about each other. We're still not where we need to be but we're on the right track."

New Yorkers are keeping busy with the Olympic cauldron set to be lit:: Brondello, Fiebich, Ionescu, Stewart, and Nyara Sabally are off repping their respective nations at the Olympics while the others bide their time at home. A playoff clinch likely awaits upon their return (one more win should likely do it) but the 15-game slate

Liberty basketball, however, has proven to be the solution. The road ahead provides the perfect chance at a definition adjustment ... one that will account for a championship.

Make sure you bookmark All Knicks for the latest news, exclusive interviews, film breakdowns and so much more!

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GEOFF MAGLIOCCHETTI

Editor-In-Chief at All Knicks

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