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By Pooja Toshniwal Paharia Jun 11 2024 Reviewed by Lily Ramsey, LLM

In a recent study published in Cancer Discovery, researchers developed and validated a blood-based, cell-free deoxyribonucleic acid (cfDNA) fragmentome assay for lung cancer detection, which, if the results were positive, would be followed by low-dose computed tomography (LDCT).

Study:  Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection . Image Credit: MMD Creative/Shutterstock.com Introduction

Lung cancer is a major death cause, and yearly screening is crucial. However, chest LDCT has low adoption due to patient barriers like inadequate awareness, radiation concerns, and limited availability.

Other challenges include poor smoking history recording, a lack of defined practices, and specialist follow-up.

A blood-based lung malignancy screening test, like the fragmentome technique, could increase screening rates by analyzing specific chromatin configurations in peripheral blood. About the study

In the present DELFI-L101 study, researchers developed a hematological test using machine learning to analyze DNA fragmentomes and identify individuals at risk of lung cancer. Individuals testing positive would undergo LDCT.

Beginning March 2021, the researchers enrolled 958 individuals aged 50–80 with ≥20 pack-years of smoking across 47 United States (US) facilities. Eligibility features resembled the LDCT screening criteria of the 2015 National Health Interview Survey (NHIS).

They excluded individuals with cancer therapy within one year, a history of hematologic malignancy or myelodysplasia, organ tissue transplantation, blood product transfusion within 120 days of enrollment, pregnancy, and participation in other trials.

The team divided the study participants into three groups: A (lung cancer), B (non-cancer controls), and C (cancer other than lung cancer). Related StoriesResearch reveals new pathways for treating never-smoker lung cancerCanada's plan to eliminate cervical cancer by 2040: HPV-based screening and vaccination keyLung cancer screening yields early diagnoses and increased cure rates in veterans

The American Joint Committee on Cancer's Cancer Staging Manual (AJCC) criteria ascertained the disease stage. Changes in cfDNA fragmentation patterns (fragmentomes) in blood revealed genomic and chromatin features of lung cancer.

The researchers trained the classifier on 576 cases and controls before validating it on another 382 cases and controls.

They used whole genome sequences from the training dataset to assess fragmentations in 504 non-overlapping-type 5.0 MB sections with strong mappability. Each region included 80,000 pieces and covered a genome size of 2.50 GB.

The team examined genome-wide alterations to Hi-C open-type (A compartment) and closed-type (B compartment) chromatin.

They created the classifier using principal component analysis (PCA) and logistic regressions, incorporating chromosomal arm-level changes, cfDNA fractions derived from the mitochondrial genome, and cfDNA fragment length distributions.

The researchers performed Monte Carlo simulations on 15 million individuals under three scenarios: Base Scenario: Current practices without hematological screening. Low Scenario: 10% uptake of hematological screening for individuals eligible for pulmonary cancer screening but not subjected to low-dose CT in the first year, increasing to 25% in five years. High Scenario: 20% uptake of hematological screening for the same group in the first year, increasing to 50% in five years. Results

The researchers observed 58% test specificity, 84% sensitivity, and 99.8% negative predictive value (NPV). Applying the rest to the screening-eligible group with 0.7% lung cancer prevalence, the number needed to screen (NNS) was 143.

Study validations showed negative and positive results related to NNS with LDCT imaging to detect 414 and 76 cases, respectively, yielding a 5.5 relative risk value. The positive predictive value (PPV) was almost double that of the LDCT qualifying requirements alone.

The cfDNA fragmentomes of lung squamous cell carcinoma (LUSC) patients comprised a component resembling cfDNA profiles from non-cancer individuals and another resembling A/B-type compartments noted in LUSC tissues.

Non-cancer individuals showed cfDNA patterns approximating lymphoblastoid Hi-C findings. Within common locations, fragmentations among samples provided by individuals with cancer presence and absence were similar.

Lung cancer patients had increased cell-free DNA representations fpr 1q, 3q, 5p, 8q, and 12p, as well as lower 1p, 3p, 4q, 5q, 10q, and 17p levels. Their cfDNA fragmentations differed from controls, revealing more closely packed chromatin in cfDNA of closed LUSC spaces, while lymphoblastoid reference regions showed the reverse impact.

At the cut-off of 0.2, ten-fold cross-validation with ten repeats within the training population yielded 50% overall specificity and sensitivities of 75%, 90%, 96%, and 97% for stages I, II, III, and IV, respectively. Sensitivity was constant across ages, with younger people having higher specificity. Using the 2015 NHIS data yielded 80% sensitivity and 58% specificity.

From the ‘base’ scenario (24,489 cases), lung cancer cases identified by screening increased to 63,523 (the ‘low’ scenario) and 100,346 (the ‘high’ scenario). In contrast, stage I cases increased by 4.80% and 9.70%, while stage IV diagnoses decreased by 4.20% and 8.70%, respectively.

In total, 4,720 deaths from lung malignancies could be averted in the ‘base’ scenario, 7,652 in the ‘low’ scenario, and 14,264 deaths in the ‘high’ scenario. LDCT use in screening could reduce the number of tests required to identify lung cancers from 202 (‘base’ scenario) to 150 (‘low’ scenario) and 139 (‘high’ scenario). Conclusion

Based on the study findings, the DNA fragmentome assay provides a novel, accurate, affordable, blood-based tool for initial lung cancer evaluation with LDCT follow-ups.

The assay could contribute to preventing lung cancer-related deaths, with moderate adoption rates possibly lowering late-stage diagnoses and fatalities. Journal reference:

Peter Mazzone et al., (2024) Clinical validation of a cell-free DNA fragmentome assay for augmentation of lung cancer early detection, Cancer Discov (2024), doi: https://doi.org/10.1158/2159-8290.CD-24-0519.https://aacrjournals.org/cancerdiscovery/article/doi/10.1158/2159-8290.CD-24-0519/745696/Clinical-validation-of-a-cell-free-DNA-fragmentome?searchresult=1

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Stars’ Hintz remains game-time call for Game 4

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Stars' Hintz remains game-time call for Game 4

EDMONTON, Alberta — Dallas Stars forward Roope Hintz remains a game-time decision ahead of Game 4 of the Western Conference Final on Tuesday.

The club’s top skater has been sidelined since Game 2 in the series when he took a slash to the left leg from Edmonton Oilers defenseman Darnell Nurse. Hintz took part in warmups before Game 3 on Sunday but exited early and was ruled out. He was back on the ice for Dallas’ optional practice on Monday and told reporters he was “feeling good” and “trying to do everything I can” to get back in for Game 4.

It was early in the third period of Game 2 when Hintz — parked in front of the Oilers’ net — shoved Nurse from behind, and the Oilers’ blueliner responded by swinging his stick at Hintz’s leg. Hintz was down on the ice for several minutes after that before being helped off by Lian Bichsel and Mikael Granlund.

Nurse received a two-minute penalty for the slash on Hintz but no supplementary discipline from the league. The blueliner addressed the incident for the first time Tuesday, explaining it didn’t come with malicious intent.

“I was backing up to net and I got shot in the back. And I think it was just a natural reaction [to respond],” Nurse said. “It’s probably a play that everyone in this room, whether you’re a net-front guy or D man, probably happens a dozen, two dozen times in a year. It’s unfortunate that I must have got [Hintz] in a bad spot. You don’t want to go out there and hurt anyone. But it was just one of those plays that happens so often.”

Having Hintz unavailable hurt the Stars in Game 3, a 6-1 drubbing by the Oilers that put Dallas in a 2-1 hole in the best-of-7 series. Hintz is the Stars’ second-leading scorer in the postseason, with 11 goals and 15 points through 15 games. He was hopeful when taking warmups Sunday that he’d feel good enough to get back in but a quick discussion with the training staff made it clear he wasn’t ready.

Coach Pete DeBoer has since classified Hintz’s status as day-to-day.

“Of course you want to go every night, but sometimes you just can’t,” said Hintz. “I don’t know how close I [was to playing]. But I have played many years [and I] know when it’s good and when it’s not. I should be good to know that [when] it comes to that decision.”

The Oilers will have some lineup changes of their own to sort through in Game 4. Connor Brown is out after he took a hit from Alexander Petrovic in Game 3; he’ll be replaced by the incoming Viktor Arvidsson. Calvin Pickard — injured in Edmonton’s second-round series against Vegas — will return to back up for Stuart Skinner. And Edmonton continues to wait on defenseman Mattias Ekholm, who is getting closer to coming back from a lower-body injury.

Puck drop for Game 4 is 8 p.m. ET on Tuesday.

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‘That’s wonderful’: Canes finally see ECF skid end

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'That's wonderful': Canes finally see ECF skid end

SUNRISE, Fla. — Carolina Hurricanes defenseman Jaccob Slavin is happy to never get another question about his team’s record-setting NHL playoff losing streak.

“Wonderful. That’s wonderful,” he said after Carolina’s 3-0 win over the Florida Panthers in Game 4 of the Eastern Conference finals on Monday night. “The guys in here worked hard tonight and that’s all you can ask for.”

The Hurricanes avoided a sweep by the Panthers, sending the series back to Raleigh, North Carolina, for Game 5 on Wednesday night. In the process, Carolina snapped a 15-game losing streak in the conference finals — the longest losing streak by a team in a playoff round other than the Stanley Cup Final in NHL history.

The Hurricanes’ last win in the Eastern Conference finals was in Game 7 against the Buffalo Sabres in 2006, a game that saw current Carolina coach Rod Brind’Amour score the winning goal.

“It’s been a story. So, yeah, it’s nice to not have to talk about that [anymore],” Brind’Amour said.

When the streak began in 2009, Carolina captain Jordan Staal was helping the Pittsburgh Penguins to a conference finals sweep of the Hurricanes. He said the win over Florida in Game 4 showed how much pride was in the Canes’ locker room, as they refused to allow the Panthers to end their season.

“There’s a lot of guys that didn’t want to go home,” Staal said. “We know we have a huge hill to climb here. We’ve got a great team on the other side that is going to come back with a better effort. It’s a great challenge.”

Florida coach Paul Maurice, whose team had a chance to advance to a third straight Stanley Cup Final with a victory, gave credit to the Hurricanes for a solid and disruptive game while acknowledging that his team could have gotten to its own game better.

“I haven’t been nearly as down on that hockey team as you fine people have been over the last three games, and I won’t be as down on my team tonight,” he said. “[The Hurricanes] were good. They had good sticks. They had good quickness. You see that happen more often when the possessor of the puck’s feet are not moving.”

Three factors changed the vibe for Carolina in Game 4.

Goalie Frederik Andersen had his second shutout of the postseason after being pulled in Game 2 and benched for Game 3. Andersen was 7-2 with a .937 save percentage and a 1.36 goals-against average in nine playoff games before facing Florida. In two games against the Panthers, he gave up nine goals on 36 shots (.750, 5.54). Andersen had given up just 12 goals in his previous nine postseason games.

In Game 4, he was a great last line of defense, stopping all 20 shots.

After the game, Andersen declined to discuss being benched.

“I don’t really want to talk about my feelings. It’s not about that. It’s about the team and trying to put the best lineup on the ice that they feel like gets the job done. So I’m ready for when I’m called upon and glad to be able to play,” he said.

Andersen played a key role in another factor: the Carolina penalty kill. The Panthers were 4-for-5 on the power play in the first two games of the conference finals. The Hurricanes killed off four power plays in each of the past two games.

“Our goalie was great when he needed to be. The penalty kill was phenomenal,” Brind’Amour said. “We gave ourselves a chance, and that’s all we can ask.”

Perhaps most crucially, the Hurricanes scored the first goal. Carolina is now 6-0 when scoring first and 3-5 when it trails first in these playoffs. In the regular season, the Hurricanes were 30-7-2 when scoring first and 17-23-3 when trailing first.

They scored first and then played the type of close, low-scoring game they excel at. As winger Taylor Hall said before Game 4: “We’re thinking about winning the game 1-0. If it’s close, then we’re in a good spot.”

“It’s been a story. So, yeah, it’s nice to not have to talk about that [anymore].”

Rod Brind’Amour on Carolina snapping 15-game losing streak in conference finals

Forward Logan Stankoven opened the scoring at 10:45 of the second period, giving Carolina its first lead of the series. Rookie defenseman Alexander Nikishin made a terrific backhand pass across the neutral zone to spring Stankoven ahead of the Panthers’ defense, and he beat goalie Sergei Bobrovsky for his fifth goal of the playoffs.

Stankoven said he called for the pass from Nikishin, who was playing in his third postseason game.

“The play happened so fast and it was a great feed by him to make that play off the turnover. It all starts with him,” said Stankoven, who was acquired from the Dallas Stars in the Mikko Rantanen deadline trade.

It remained 1-0 until Sebastian Aho and Staal added empty-net goals in the last 2:11 for the 3-0 win.

Slavin said Game 4 was in the Carolina’s comfort zone.

“A thousand percent. It was 1-0 up until the end there. You can’t get any tighter than that,” he said.

With that, the Hurricanes ended their historic losing streak and turned their attention to making more NHL history. Only four teams in the history of the Stanley Cup playoffs have rallied to win a best-of-seven series after trailing 3-0, although two have done it in the past 15 years (Philadelphia Flyers in 2010 and Los Angeles Kings in 2014).

“You watched the way we played tonight. Everyone put their heart on the line,” Slavin said. “We know we’ve got a good group in here. We know we’ve got all the pieces. We just have to bring it every night.”

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ZKPs can prove I’m old enough without telling you my age

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<div>ZKPs can prove I'm old enough without telling you my age</div>

<div>ZKPs can prove I'm old enough without telling you my age</div>

Opinion by: Andre Omietanski, General Counsel, and Amal Ibraymi, Legal Counsel at Aztec Labs

What if you could prove you’re over 18, without revealing your birthday, name, or anything else at all? Zero-knowledge proofs (ZKPs) make this hypothetical a reality and solve one of the key challenges online: verifying age without sacrificing privacy. 

The need for better age verification today

We’re witnessing an uptick in laws being proposed restricting minors’ access to social media and the internet, including in Australia, Florida, and China. To protect minors from inappropriate adult content, platform owners and governments often walk a tightrope between inaction and overreach. 

For example, the state of Louisiana in the US recently enacted a law meant to block minors from viewing porn. Sites required users to upload an ID before viewing content. The Free Speech Coalition challenged the law as unconstitutional, making the case that it infringed on First Amendment rights.

The lawsuit was eventually dismissed on procedural grounds. The reaction, however, highlights the dilemma facing policymakers and platforms: how to block minors without violating adults’ rights or creating new privacy risks.

Traditional age verification fails

Current age verification tools are either ineffective or invasive. Self-declaration is meaningless, since users can simply lie about their age. ID-based verification is overly invasive. No one should be required to upload their most sensitive documents, putting themselves at risk of data breaches and identity theft. 

Biometric solutions like fingerprints and face scans are convenient for users but raise important ethical, privacy, and security concerns. Biometric systems are not always accurate and may generate false positives and negatives. The irreversible nature of the data, which can’t be changed like a regular password can, is also less than ideal. 

Other methods, like behavioral tracking and AI-driven verification of browser patterns, are also problematic, using machine learning to analyze user interactions and identify patterns and anomalies, raising concerns of a surveillance culture.

ZKPs as the privacy-preserving solution

Zero-knowledge proofs present a compelling solution. Like a government ID provider, a trusted entity verifies the user’s age and generates a cryptographic proof confirming they are over the required age.

Websites only need to check the proof, not the excess personal data, ensuring privacy while keeping minors at the gates. No centralized data storage is required, alleviating the burden on platforms such as Google, Meta, and WhatsApp and eliminating the risk of data breaches. 

Recent: How zero-knowledge proofs can make AI fairer

Adopting and enforcing ZKPs at scale

ZKPs aren’t a silver bullet. They can be complex to implement. The notion of “don’t trust, verify,” proven by indisputable mathematics, may cause some regulatory skepticism. Policymakers may hesitate to trust cryptographic proofs over visible ID verification. 

There are occasions when companies may need to disclose personal information to authorities, such as during an investigation into financial crimes or government inquiries. This would challenge ZKPs, whose very intention is for platforms not to hold this data in the first place.

ZKPs also struggle with scalability and performance, being somewhat computationally intensive and tricky to program. Efficient implementation techniques are being explored, and breakthroughs, such as the Noir programming language, are making ZKPs more accessible to developers, driving the adoption of secure, privacy-first solutions. 

A safer, smarter future for age verification

Google’s move to adopt ZKPs for age verification is a promising signal that mainstream platforms are beginning to embrace privacy-preserving technologies. But to fully realize the potential of ZKPs, we need more than isolated solutions locked into proprietary ecosystems. 

Crypto-native wallets can go further. Open-source and permissionless blockchain-based systems offer interoperability, composability, and programmable identity. With a single proof, users can access a range of services across the open web — no need to start from scratch every time, or trust a single provider (Google) with their credentials.

ZKPs flip the script on online identity — proving what matters, without exposing anything else. They protect user privacy, help platforms stay compliant, and block minors from restricted content, all without creating new honeypots of sensitive data.

Google’s adoption of ZKPs shows mainstream momentum is building. But to truly transform digital identity, we must embrace crypto-native, decentralized systems that give users control over what they share and who they are online.

In an era defined by surveillance, ZKPs offer a better path forward — one that’s secure, private, and built for the future.

Opinion by: Andre Omietanski, General Counsel, and Amal Ibraymi, Legal Counsel at Aztec Labs.

This article is for general information purposes and is not intended to be and should not be taken as legal or investment advice. The views, thoughts, and opinions expressed here are the author’s alone and do not necessarily reflect or represent the views and opinions of Cointelegraph.

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