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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

‘Shameful’ that black boys in London more likely to die than white boys, says Met Police chief

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'Shameful' that black boys in London more likely to die than white boys, says Met Police chief

It is “shameful” that black boys growing up in London are “far more likely” to die than white boys, Metropolitan Police chief Sir Mark Rowley has told Sky News.

The commissioner told Sunday Morning with Trevor Phillips that relations with minority communities “is difficult for us”.

Sir Mark, who came out of retirement to become head of the UK’s largest police force in 2022, said: “We can’t pretend otherwise that we’ve got a history between policing and black communities where policing has got a lot wrong.

“And we get a lot more right today, but we do still make mistakes. That’s not in doubt. I’m being as relentless in that as it can be.”

He said the “vast majority” of the force are “good people”.

However, he added: “But that legacy, combined with the tragedy that some of this crime falls most heavily in black communities, that creates a real problem because the legacy creates concern.”

Sir Mark, who also leads the UK’s counter-terrorism policing, said it is “not right” that black boys growing up in London “are far more likely to be dead by the time they’re 18” than white boys.

“That’s, I think, shameful for the city,” he admitted.

The Met Police chief’s admission comes two years after an official report found the force is institutionally racist, misogynistic and homophobic.

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Police chase suspected phone thief

Baroness Casey was commissioned in 2021 to look into the Met Police after serving police officer Wayne Couzens abducted, raped and murdered Sarah Everard.

She pinned the primary blame for the Met’s culture on its past leadership and found that stop and search and the use of force against black people was excessive.

At the time, Sir Mark, who had been commissioner for six months when the report was published, said he would not use the labels of institutionally racist, institutionally misogynistic and institutionally homophobic, which Casey insisted the Met deserved.

However, London Mayor Sadiq Khan, who helped hire Sir Mark – and could fire him – made it clear the commissioner agreed with Baroness Casey’s verdict.

After the report was released, Sir Mark said “institutional” was political language so he was not going to use it, but he accepted “we have racists, misogynists…systematic failings, management failings, cultural failings”.

A few months after the report, Sir Mark launched a two-year £366m plan to overhaul the Met, including increased emphasis on neighbourhood policing to rebuild public trust and plans to recruit 500 more community support officers and an extra 565 people to work with teams investigating domestic violence, sexual offences and child sexual abuse and exploitation.

Watch the full interview on Sunday Morning with Trevor Phillips from 8.30am on Sunday.

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World

Backlash as Air India crash report points to possible human error – here’s what experts think

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Backlash as Air India crash report points to possible human error - here's what experts think

As investigators continue to piece together the full picture, early findings of the Air India crash are pointing towards a critical area of concern — the aircraft’s fuel control switches.

The flight, bound for London Gatwick, crashed just moments after taking off from Ahmedabad airport on 12 June, killing all but one of the 242 people on board the plane and at least 19 on the ground.

According to the preliminary report by India’s Aircraft Accident Investigation Bureau (AAIB), the two engine fuel control switches on the plane were moved from the “RUN” to “CUTOFF” position.

These switches control fuel flow to the engines and should only be used when the aircraft is on ground, first to start the engines before a flight and later to shut them down at the gate.

They are designed so they’re unlikely to be changed accidentally, pointing to possible human error on the Air India flight.

The findings include the final conversation between the pilots and show there was confusion in the cockpit as well.

When one pilot asked the other why he cut off the fuel, he responded to say he did not do so.

Pic: Takagi
Image:
The Air India plane before the crash. Pic: Takagi

Moments later, a Mayday call was made from the cockpit, but the plane could not regain power quickly enough and plummeted to the ground.

Captain Amit Singh, founder of Safety Matters Foundation, an organisation dedicated to aviation safety, told Sky News: “This exchange indicates that the engine shutdowns were uncommanded.

“However, the report does not identify the cause – whether it was crew error, mechanical malfunction, or electronic failure.”

Previous warning of ‘possible fuel switch issue’

“The Boeing 787 uses spring-loaded locking mechanisms on its fuel control switches to prevent accidental movement,” Mr Singh explained.

But a previous bulletin from the Federal Aviation Administration (FAA) “warned that these switches might be installed with the locking feature disengaged,” he said.

This could “make them susceptible to unintended movement due to vibration, contact, or quadrant flex”, he added.

A tail of an Air India Boeing 787 Dreamliner plane that crashed is seen stuck on a building. Pic: Reuters
Image:
The plane’s tail lodged in a building. Pic: Reuters

Speaking to Sky News, aviation expert Terry Tozner said: “The take-off was normal, the aircraft rotated at the correct speed left the ground and almost immediately, the cut-off switches were selected to off, one then two.

“But nobody has said with any clarity whether or not the latch mechanisms worked okay on this particular aircraft. So we can only assume that they were in normal working order.”

In India, there has been a backlash over the findings, with some saying the report points to pilot error without much information and almost dismisses the possibility of a mechanical or electric failure.

Indian government responds

India’s civil aviation minister Kinjarapu Ram Mohan Naidu has been quick to respond, saying: “We care for the welfare and the wellbeing of pilots so let’s not jump to any conclusions at this stage, let us wait for the final report.

“I believe we have the most wonderful workforce of pilots and crew in the whole world.”

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India plane crash survivor carries brother’s coffin

Both pilots were experienced, with around 19,000 flying hours between them, including more than 9,000 on Boeing 787s.

The report says the aircraft maintenance checks were on schedule and that there are no signs of fuel contamination or a bird strike.

So far, no safety recommendations have been issued to Boeing or General Electric, the engine manufacturers.

Concern over destroyed flight recorder

Mr Singh said “the survivability of the flight recorders also raises concern”.

The plane’s rear flight recorder, designed to withstand impact forces of 3,400 Gs and temperatures of 1,100C for 60 minutes, “was damaged beyond recovery”.

Read more:
Everything you need to know about the crash
Air India’s lone survivor is nothing short of miracle

“The Ram Air Turbine (RAT), which deploys automatically when both engines fail and power drops below a threshold, was observed as deployed in CCTV footage when the aircraft was approximately 60ft above ground level,” Mr Singh said.

“This suggests that the dual engine failure likely occurred before the official timestamp of 08:08:42 UTC, implying a possible discrepancy.”

Prime Minister Narendra Modi/X/AP
Image:
India’s Prime Minister Narendra Modi visiting the crash site. Pic: X/AP

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Mr Singh said it was also “of particular note” that the plane’s emergency locator transmitter (ELT) did not send any signal after the crash.

“Was the ELT damaged, unarmed, mis-wired, or malfunctioning?” he said.

The report has generated more questions than answers on topics including human error, power source failures and mechanical or electrical malfunction.

The final report is expected to take a year. Meanwhile, families grapple with the unimaginable loss of loved ones in one of the worst disasters in India’s aviation history.

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Environment

Tesla launches new software update with Grok, but it doesnt even interface with the car

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Tesla launches new software update with Grok, but it doesnt even interface with the car

Tesla has launched a new software update for its vehicles that includes the anticipated integration of Grok, but it doesnt even interface with the car yet.

Earlier this week, CEO Elon Musk said that Tesla would integrate Grok, the large language model developed by his private company, xAI, into its vehicles.

Today, Tesla started pushing the update to the fleet, but there’s a significant caveat.

The automaker wrote in the release notes (2025.26):

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Grok (Beta) (US, AMD)

Grok now available directly in your Tesla

Requires Premium Connectivity or a WiFi connection

Grok is currently in Beta & does not issue commands to your car – existing voice commands remain unchanged.

First off, it is only available in vehicles in the US equipped with the AMD infotainment computer, which means cars produced since mid-2021.

But more importantly, Tesla says that it doesn’t send commands to the car under the current version. Therefore, it is simply like having Grok on your phone, but on the onboard computer instead.

Tesla showed an example:

There are a few other features in the 2025.26 software update, but they are not major.

For Tesla vehicles equipped with ambient lighting strips inside the car, the light strip can now sync to music:

Accent lights now respond to music & you can also choose to match the lights to the album’s color for a more immersive effect

Toybox > Light Sync

Here’s the new setting:

The audio setting can now be saved under multiple presets to match listening preferences for different people or circumstances:

The software update also includes the capacity to zoom or adjust the playback speed of the Dashcam Viewer.

Cybertruck also gets the updated Dashcam Viewer app with a grid view for easier access and review of recordings:

Tesla also updated the charging info in its navigation system to be able to search which locations require valet service or pay-to-park access.

Upon arrival, drivers will receive a notification with access codes, parking restrictions, level or floor information, and restroom availability:

Finally, there’s a new onboarding guide directly on the center display to help people who are experiencing a Tesla vehicle for the first time.

Electrek’s Take

Tesla is really playing catch-up here. Right now, this update is essentially nothing. If you already have Grok, it’s no more different than having it on your phone or through the vehicle’s browser, since it has no capacity to interact with any function inside the vehicle.

Most other automakers are integrating LLMs inside vehicles with the capacity to interact with the vehicle. In China, this is becoming standard even in entry-level cars.

In the Xiaomi YU7, the vehicle’s AI can not only interact with the car, but it also sees what the car sees through its camera, and it can tell you about what it sees:

Tesla is clearly far behind on that front as many automakers are integrating with other LLMs like ChatGPT and in-house LLMs, like Xiaomi’s.

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