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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

Can Streeting stop the doctors strikes?

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Can Streeting stop the doctors strikes?

👉Listen to Politics at Sam and Anne’s on your podcast app👈 

After yesterday’s royal welcome from the King, French President Emmanuel Macron will get down to business today, meeting Prime Minister Sir Keir Starmer for lunch, after PMQs.

But, as Sky News’ Sam Coates and Politico’s Anne McElvoy discuss on this episode, away from the pomp, Sir Keir’s in-tray doesn’t look any less challenging.

It includes a headache for Health Secretary Wes Streeting as resident doctors, formerly known as junior doctors, announce a new strike – and there is as a punchy warning from the OBR on making financial promises to the public.

Also today, the welfare bill returns to the House of Commons, with reports of another rebellion brewing.

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World

Why do so many from around the world try to cross the English Channel?

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Why do so many from around the world try to cross the English Channel?

While the politicians talk, so many people come from around the world to try to get across the Channel on small boats. But why?

Why make such a perilous crossing to try to get to a country that seems to be getting increasingly hostile to asylum seekers?

As the British and French leaders meet, with small boats at the forefront of their agenda, we came to northern France to get some answers.

It is not a new question, but it is peppered with fresh relevance.

Over the course of a morning spent around a migrant camp in Dunkirk, we meet migrants from Gaza, Iraq, Eritrea, South Sudan, Sri Lanka and beyond.

Some are fearful, waving us away; some are happy to talk. Very few are comfortable to be filmed.

All but one man – who says he’s come to the wrong place and actually wants to claim asylum in Paris – are intent on reaching Britain.

They see the calm seas, feel the light winds – perfect conditions for small boat crossings.

John has come here from South Sudan. He tells me he’s now 18 years old. He left his war-torn home nation just before his 16th birthday. He feels that reaching Britain is his destiny.

“England is my dream country,” he says. “It has been my dream since I was at school. It’s the country that colonised us and when I get there, I will feel like I am home.

“In England, they can give me an opportunity to succeed or to do whatever I need to do in my life. I feel like I am an English child, who was born in Africa.”

John, a migrant from South Sudan, speaks to Sky News Adam Parsons
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‘England is my dream country,’ John tells Adam Parsons

He says he would like to make a career in England, either as a journalist or in human resources, and, like many others we meet, is at pains to insist he will work hard.

The boat crossing is waved away as little more than an inconvenience – a trifle compared with the previous hardships of his journey towards Britain.

We meet a group of men who have all travelled from Gaza, intent on starting new lives in Britain and then bringing their families over to join them.

One man, who left Gaza two years ago, tells me that his son has since been shot in the leg “but there is no hospital for him to go to”.

Next to him, a man called Abdullah says he entered Europe through Greece and stayed there for months on end, but was told the Greek authorities would never allow him to bring over his family.

Britain, he thinks, will be more accommodating. “Gaza is being destroyed – we need help,” he says.

Abdullah, a migrant from Gaza, speaking to Sky's Adam Parsons
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Abdullah says ‘Gaza is being destroyed – we need help’

A man from Eritrea tells us he is escaping a failing country and has friends in Britain – he plans to become a bicycle courier in either London or Manchester.

He can’t stay in France, he says, because he doesn’t speak French. The English language is presented as a huge draw for many of the people we talk to, just as it had been during similar conversations over the course of many years.

I ask many of these people why they don’t want to stay in France, or another safe European country.

Some repeat that they cannot speak the language and feel ostracised. Another says that he tried, and failed, to get a residency permit in both France and Belgium.

But this is also, clearly, a flawed survey. Last year, five times as many people sought asylum in France as in Britain.

And French critics have long insisted that Britain, a country without a European-style ID card system, makes itself attractive to migrants who can “disappear”.

Read more:
Channel crossings rise 50% in first six months of 2025
French police forced to watch on as migrants attempt crossing

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Migrant Channel crossings hit new record

A young man from Iraq, with absolutely perfect English, comes for a chat. He oozes confidence and a certain amount of mischief.

It has taken him only seven days to get from Iraq to Dunkirk; when I ask how he has made the trip so quickly, he shrugs. “Money talks”.

He looks around him. “Let me tell you – all of these people you see around you will be getting to Britain and the first job they get will be in the black market, so they won’t be paying any tax.

“Back in the day in Britain, they used to welcome immigrants very well, but these days I don’t think they want to, because there’s too many of them coming by boat. Every day it’s about seven or 800 people. That’s too many people.”

“But,” I ask, “if those people are a problem – then what makes you different? Aren’t you a problem too?”

He shakes his head emphatically. “I know that I’m a very good guy. And I won’t be a problem. I’ll only stay in Britain for a few years and then I’ll leave again.”

A young man from Iraq walks away from Sky's Adam Parsons

A man from Sri Lanka says he “will feel safe” when he gets to Britain; a tall, smiling man from Ethiopia echoes the sentiment: “We are not safe in our home country so we have come all this way,” he says. “We want to work, to be part of Britain.”

Emmanuel is another from South Sudan – thoughtful and eloquent. He left his country five years ago – “at the start of COVID” – and has not seen his children in all that time. His aim is to start a new life in Britain, and then to bring his family to join him.

He is a trained electrical engineer, but says he could also work as a lorry driver. He is adamant that Britain has a responsibility to the people of its former colony.

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“The British came to my country – colonising, killing, raping,” he said. “And we didn’t complain. We let it happen.

“I am not the problem. I won’t fight anyone; I want to work. And if I break the laws – if any immigrant breaks the laws – then fine, deport them.

“I know it won’t be easy – some people won’t like me, some people will. But England is my dream.”

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Science

Axiom 4 Mission Crew Settles Down at ISS, Begins Conducting Research

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Axiom 4 Mission Crew Settles Down at ISS, Begins Conducting Research

Axiom 4 mission’s crewmates began conducting biomedical research aboard the International Space Station on Tuesday. Expedition 73 and Ax-4 crews found electrical muscle stimulation and cellular immunity. The Cargo transfers and exercise gear maintenance take a day for orbital residents.

Takuya Onishi, Situation Commander from JAXA( Japan Aerospace Exploration Agency), has begun the shift in continuation of his space biology studies. His blood and saliva samples are being collected for storage and processing. Further, he spun the specimens in a centrifuge and placed the blood samples in the freezer. After that, he stowed the samples in the incubator.

JAXA’s Takuya Onishi Leads Cellular Immunity Study with Blood and Saliva Analysis

According to a report from NASA, the samples will be analysed to determine the effect of microgravity on cellular immunity, observe stress-related immune reactions, and learn about how to treat symptoms of immunity. The flight engineers Johnny Kim, Anne McClain, and Nichole Ayers spent their day on orbital lab maintenance and further support activities of the crew. Kim focused mainly on orbital plumbing as he replaced and drained the Tranquillity module.

Ayers checked cables and power components in the Destiny laboratory module and deactivated and placed the microscope. McClain took the cognition test on the laptop and kept on supporting the Ax-4 crew at a time of a busy schedule.

Ax-4 Crew Explores Muscle Stimulation and Space Suit Fabric Efficiency in Microgravity

Veteran astronaut Peggy Whitson and her Ax-4 crewmates Shubhanshu Shukla, Tibor Kapu and UznaÅ„ski-WiÅ›niewski conducted numerous space investigations throughout the lab. The private scientists in their second full week on the station found out that the electrical muscle simulation escalates the space-related and muscle atrophy in space. Ax-4’s other experiments looked at suit fabrics promote thermal comfort with exercising the weightlessness, crew health and agriculture in space.

Sergey Ryzhikov and Alexey Zubritskiy worked together on the Zvezda service module, repairing and organising components on a treadmill, one of the two inside the space station, which included the COLBERT treadmill. Kirill Peskov started his day by going through the biological samples from the crewmates. At the end of his shift, he transfers water from Progress 92 cargo craft and unloads the stuffs of hardware and crew supplies.

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