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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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Politics

‘Big test’ for PM as ex-Labour MP Mike Amesbury steps down to trigger by-election

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'Big test' for PM as ex-Labour MP Mike Amesbury steps down to trigger by-election

Mike Amesbury has officially stepped down as an MP after he was convicted of punching a man in the street.

Amesbury, who was suspended from the Labour Party, was jailed on 24 February.

Politics latest: Welfare reforms ‘imminent’

He was sentenced to 10 weeks behind bars after he pleaded guilty to the assault by beating of 45-year-old Paul Fellows in Frodsham, Cheshire, in the early hours of 26 October.

Following an appeal, his sentence was suspended for two years – so he does not have to serve it in prison.

He announced his resignation as MP for Runcorn and Helsby in a social media post on Monday, describing the assault as a “deeply regrettable incident” for which he had “rightly been punished”.

“I am sincerely sorry to Paul Fellows, my family, colleagues and constituents,” he added.

A by-election will now be triggered in Runcorn and Helsby, where constituents will vote to elect a new MP.

Former Runcorn and Helsby MP Mike Amesbury (centre) leaving Chester Crown Court after he had his 10-week prison sentence for assault suspended for two years following an appeal. Picture date: Thursday February 27, 2025.
Image:
Mike Amesbury leaving Chester Crown Court in February. Pic: PA

By-election a ‘big test’ for PM

It will be the first by-election since Sir Keir Starmer became prime minister, in what Sky News’ political correspondent Liz Bates said would be a “big test” in a seat where Reform UK came second last year.

“Losing it would be an unmitigated disaster given the 14,000 majority achieved last time round,” said Bates.

Amesbury came first in Runcorn and Helsby with 22,358 votes at the 2024 general election – equating to 52.9% of the electorate.

Reform UK came in second with 7,662 votes (18.1%) and the Tories in third with 6,756 votes (16%).

Reform has yet to announce a candidate, but Karen Shore, the deputy leader of Cheshire West and Chester Council, will run for Labour.

The Conservatives have opted for Sean Houlston, a membership services manager for the National Federation of Builders.

Read more:
How is a by-election triggered?
Why Labour MPs are deeply uncomfortable

Sir Keir Starmer speaking to the media follow his 'coalition of the willing' virtual meeting. Pic: PA
Image:
Sir Keir Starmer’s government has been polling very badly indeed. Pic: PA

When will the by-election be?

Under parliamentary procedure, an MP cannot simply resign but must be disqualified from holding their seat.

To do this, they must apply for a role in the paid office of the Crown, meaning they automatically lose their seat because working for the Crown is not seen as impartial.

Titles include the crown steward and bailiff of the Chiltern Hundreds and the Crown Steward and Bailiff of the Manor of Northstead.

Rachel Reeves has now appointed Amesbury to be steward and bailiff of the Three Hundreds of Chiltern, meaning the parliamentary seat is officially vacant.

Once he does, the chief whip will put forward a motion to Lindsay Hoyle, the Commons speaker, to officially begin the process of disqualifying the MP – known as “moving the writ”.

The Speaker then puts the motion to MPs for a vote. If they agree, the writ passes through the Commons and ends up with the returning officer in the local constituency who oversees the by-election.

The writ is typically issued within three months of the MP resigning from their seat and in doing so, the date of the by-election is fixed.

It could potentially coincide with the local elections in May.

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Welfare system will be here ‘for years to come’ amid backlash over impending cuts

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Welfare system will be here 'for years to come' amid backlash over impending cuts

The welfare state will be there for those who need it “now and for years to come”, the work and pensions secretary has said – as the government faces pressure from its own MPs over benefit changes.

Liz Kendall acknowledged there has been “lots of speculation” about the government’s plans to reform welfare, which are due to be announced on Tuesday following a delay because of concerns from Labour backbenchers.

Politics latest: Welfare reforms ‘imminent’

Speaking in the House of Commons, Ms Kendall said she wanted to assure the public the announcements will “ensure there is trust and fairness in the social security system” – and that it will remain in place for those who need it.

Earlier on Monday, Sky News revealed the government has chosen not to freeze the personal independence payment (PIP) next year following pressure from Labour MPs over the past week.

Ministers had wanted to stop PIP (a payment of up to £9,000 a year for people with long-term physical and mental health conditions, and disabilities) rising with inflation as part of a drive to cut the welfare budget.

The proposal had been set to save about £5bn, as Chancellor Rachel Reeves searches for savings.

She has lost £9.9bn of fiscal headroom (the amount she could increase spending or cut taxes without breaking her fiscal rules) since the October budget due to a poor economy and geopolitical events.

Read more:
Which benefits could be cut?

Why Labour MPs are so uncomfortable

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Will there be a backlash over benefits?

What’s the government’s case?

The government is expected to make qualifying for PIP more difficult when Ms Kendall reveals her plans on Tuesday.

Sky News’ deputy political editor Sam Coates, on the Politics At Sam And Anne’s podcast, said the Treasury is also expected to abolish the Work Capability Assessment, which determines whether someone is fit or not to work and to then receive disability payments.

The government has described the system as “dysfunctional”, as those “not fit for work” do not receive employment support or further engagement after the assessment, which could lock them out of future work altogether.

Sir Keir Starmer has made cutting the welfare budget a key project, as spending on sickness benefits soared to £65bn last year – a 25% increase since the year before the pandemic – and is expected to rise to £100bn before the next general election in 2029.

The number of people in England and Wales claiming either sickness or disability benefit has gone from 2.8 million to about four million since 2019.

Ms Kendall also revealed in the Commons the number of young people not working because of mental health conditions has risen by more than 25% in the last year, with the number considered “economically inactive” now reaching 270,000.

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‘1,000 people every day signing on to PIP benefits’

Unhappy Labour MPs

Ms Kendall had been expected to announce welfare cut plans last week.

But due to the scale of the backlash, the government took the unusual step of asking all 404 Labour MPs to attend “welfare roundtables” in Downing Street last week.

Sky News’ political correspondent Amanda Akass said Ms Kendall’s Commons appearance offered no real answers to the “serious concerns” raised by MPs, though social security minister Stephen Timms insisted they would “welcome” many of the changes when they are announced.

Treasury minister Emma Reynolds earlier played down the level of discontent over plans to freeze PIP, telling Sky News the roundtables were nothing more than “everyday business”.

She pointed out Labour created the welfare state in 1945, but said it needs to be “more sustainable”.

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Environment

Toyota the EV battery supplier? Honda will use them to power up its 400,000 hybrids in the US

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Toyota the EV battery supplier? Honda will use them to power up its 400,000 hybrids in the US

Toyota is now a battery supplier? That’s the plan. Honda will use Toyota’s batteries to power up its around 400,000 hybrids sold in the US.

Toyota will supply batteries for Honda hybrids in the US

Toyota’s $14 billion battery plant in North Carolina is ready for business. The facility will begin shipping out batteries next month, and it looks like Toyota already has its first customer.

According to a new Nikkei report, starting in fiscal 2025, Toyota will supply batteries for the roughly 400,000 Honda hybrids sold in the US.

Honda currently uses batteries from China and Japan for vehicles sold in the US, but the company is (like most) preparing for changes under Trump.

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Honda’s electrified vehicles, including EVs and hybrids, accounted for over a quarter of US sales last year. The company sold over 308,500 hybrids and 40,400 electric vehicles in the US in 2024. The batteries will likely be used in the CR-V and other Honda hybrid vehicles.

Honda-Toyota-EV-batteries
Honda Prologue Elite (Source: Honda)

Earlier this month, an extra 10% tariff on imports from China took effect. And that’s on top of the 10% imposed in February.

With more expected, including a 25% increase in vehicles imported from Japan, automakers are tightening up their supply chains.

Toyota-new-bZ4X
Toyota’s new bZ4X AWD model introduced in Europe (Source: Toyota)

A 25% tariff on Japanese vehicles, up from 2.5% currently, is estimated to cost the six major Japanese automakers about $20 billion in the US.

Tariffs on imports from Mexico and Canada could cost Honda roughly $4.7 billion alone. Teaming up with Toyota to use its batteries for its hybrids is part of Japan’s broader global plans to ween off dependence on China and others for batteries and other emerging tech.

Toyota-Honda-EV-batteries
(Source: Toyota)

The new US plant, Toyota Battery Manufacturing North Carolina (TBMC), is over seven million square feet, or about the size of 121 football fields.

As Toyota’s first in-house battery factory outside of Japan, the plant could be a game changer as Trump’s tariffs take effect. Securing Honda as a buyer will already help Toyota cut costs as it ramps up output.

Toyota plans to ramp up electrified vehicle (EV, PHEV, and hybrid) sales in North America from around 40% last year to 80% by 2030.

Electrek’s Take

Trump’s tariffs are already causing havoc, with nearly every automaker warning that they put the US further behind. Overseas automakers are not the only ones feeling the heat, either.

The “Big Three,” GM, Ford, and Jeep maker Stellantis all build vehicles in Canada and Mexico. GM cut output at its plant in Mexico in January, where the electric Chevy Equinox, Blazer, and Honda Prologue are made. Stellantis halted operations at its Brampton Assembly Plant in Canada last month, where it was expected to launch the Jeep Compass EV production. What’s next?

For Toyota, it looks like its $14 billion bet to build batteries in the US is already paying off. Now, we just need it to introduce more EVs.

After unveiling three new electric SUVs in Europe last week, including the updated bZ4X, Toyota hinted more is on the way for the US. Check back soon for updates.

What do you think? Do you want to see more Toyota EVs in the US, like the new C-HR+? Let us know your thoughts in the comments.

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