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A novel artificial intelligence blood testing technology developed and used by Johns Hopkins Kimmel Cancer Center researchers to successfully detect lung cancer in a 2021 study has now detected more than 80% of liver cancers in a new study of 724 people.
The blood test, called DELFI (DNA evaluation of fragments for early interception) detects fragmentation changes among DNA from cancer cells shed into the bloodstream, known as cell-free DNA (cfDNA). In the most recent study, investigators used the DELFI technology on blood plasma samples obtained from 724 individuals in the U.S., the European Union (E.U.) and Hong Kong to detect hepatocellular cancer (HCC), a type of liver cancer.
The researchers believe this is the first genome-wide fragmentation analysis independently validated in two high-risk populations and across different racial and ethnic groups with different causes associated with their liver cancers.
Their findings were reported Nov. 18 in Cancer Discovery and at the American Association for Cancer Research Special Conference: Precision Prevention, Early Detection, and Interception of Cancer.
It is estimated that 400 million people worldwide are at higher risk of developing HCC because of cirrhosis from chronic liver diseases including chronic viral hepatitis or non-alcoholic fatty liver disease, according to a worldwide analysis of the burden of liver disease (J. Hepatology, 2019).
“Increased early detection of liver cancer could save lives, but currently available screening tests are underutilized and miss many cancers,” says Victor Velculescu, M.D., Ph.D., professor of oncology and co-director of the Cancer Genetics and Epigenetics Program at the Johns Hopkins Kimmel Cancer Center, who co-led the study with Zachariah Foda, M.D., Ph.D., gastroenterology fellow, Akshaya Annapragada, M.D./Ph.D. student, and Amy Kim, M.D., assistant professor of medicine at the Johns Hopkins University School of Medicine.

A team of researchers mapping a molecular atlas for ductal carcinoma in situ (DCIS) has made a major advance toward distinguishing whether the early pre-cancers in the breast will develop into invasive cancers or remain stable.
Analyzing samples from patients who had undergone surgery to remove areas of DCIS, the team identified 812 genes associated with cancer progression. Using this gene classifier, they were then able to predict the risk of cancer cells recurring or progressing.
The study, which published this week in the journal Cancer Cell, was led by E. Shelley Hwang, M.D., of the Duke Cancer Institute, and Rob West, M.D., Ph.D., of the Stanford University Medical Center. Their work is part of the Human Tumor Atlas Network under the Moonshot Initiative funded by the National Cancer Institute.
“There has been a long-standing debate over whether DCIS is cancer or a high-risk condition,” Hwang said. “In the absence of a way to make that determination, we currently treat everyone with surgery, radiation, or both.
“DCIS is diagnosed in more than 50,000 women a year, and about a third of those women have a mastectomy, so we are increasingly concerned that we might be overtreating many women,” Hwang said. “We need to understand the biology of DCIS better, and that’s what our research has been designed to do.”
Hwang, West and colleagues analyzed 774 DCIS samples from 542 patients who were a median of 7.4 years post-treatment. They identified 812 genes associated with recurrence within five years from treatment.
The gene classifier was able to predict both recurrence and invasive progression of cancer, with progression appearing to be dependent on a process that requires interactions between invasive DCIS cells and the unique features of the tumor environment.
Hwang said most of the DCIS cancers analyzed in the study were identified to be at low risk for cancer progression or recurrence — a factor that underscores the need to have an accurate predictive model that can be used during clinical visits to guide care.
“We’ve made great progress in our understanding of DCIS, and this work gives us a real path forward to being able to personalize care by scaling treatments to the risk of cancer progression,” Hwang said. “The real goal is diminishing treatment-related harms without compromising outcomes, and we are excited to be getting closer to achieving this for our patients with DCIS.”
In addition to Hwang and West, study authors include co-principal investigator Carlo Maley, Ph.D., of Arizona State School of Life Sciences, and Graham Colditz, Ph.D., of Washington University at St. Louis, for the Breast Pre-Cancer Atlas Center, as well as collaborators from 12 other institutions as part of the Translational Breast Cancer Consortium.
The study is part of the Human Tumor Atlas Network Consortium of the National Cancer Institute, which is part of the National Institutes of Health (R01 CA185138-01, U2C CA-17-035, UO1 CA214183, R01CA193694). Other funding support was from the Department of Defense (BC132057); The Breast Cancer Research Foundation (19-074, 19-028, 18-006); PRECISION CRUK Grand Challenge (AEI RYC2019- 026576-I); “la Caixa” Foundation (LCF/PR/PR17/51120011); the Lundbeck Foundation (R288-2018-35); the Danish Cancer Society (R229-A13616); and Susan G. Komen.

The wastewater draining from massive pools of sewage sludge has the potential to play a role in more sustainable agriculture, according to environmental engineering researchers at Drexel University. A new study, looking at a process of removing ammonia from wastewater and converting it into fertilizer, suggests that it’s not only technically viable, but also could help to reduce the environmental and energy footprint of fertilizer production — and might even provide a revenue stream for utilities and water treatment facilities.
A Sustainable Nitrogen Source
The production of nitrogen for fertilizer is an energy-intensive process and accounts for nearly 2% of global carbon dioxide emissions. In the last several years researchers have explored alternatives to the Haber-Bosch nitrogen production process, which has been the standard for more than a century. One promising possibility, recently raised by some water utility providers, is gleaning nitrogen from the waste ammonia pulled from water during treatment.
“Recovering nitrogen from wastewater would be a desirable alternative to the Haber-Bosch process because it creates a ‘circular nitrogen economy,'” said Patrick Gurian, PhD, a professor in the College of Engineering who helped lead the research, which was recently published in the journal Science of the Total Environment. “This means we are reusing existing nitrogen rather than expending energy and generating greenhouse gas to harvest nitrogen from the atmosphere, which is a more sustainable practice for agriculture and could become a source of revenue for utilities.”
A Cleaner Way to Clean
Under the Clean Water Act of 1972 municipal water treatment facilities have been challenged to meet water quality standards for water that they discharge into waterways. Increasingly ammonia is seen as both a concern for aquatic environments as elevated levels of ammonia can result in overgrowth of vegetation in streams and rivers which can endanger fish species. The options for removing ammonia are generally time and space consuming and can be energy-intensive undertakings.

An unusual type of antibody that even at miniscule levels neutralizes the Zika virus and renders the virus infection undetectable in preclinical models has been identified by a team led by Weill Cornell Medicine, NewYork-Presbyterian and National Institutes of Health (NIH) investigators.
Because Zika can cause birth defects when passed from a pregnant person to their fetus, this discovery could lead to the development of therapies to protect babies from the potentially devastating effects of this disease.
In research published Nov. 18 in Cell, the investigators isolated an ultrapotent immunoglobulin M (IgM) antibody — a five-armed immune protein that latches onto the virus — using blood cells taken from pregnant people infected with Zika. In experiments with mice, they determined that the antibody not only protected the animals from otherwise lethal infections, but also suppressed the virus to the point that it could not be detected in their blood.
Zika is currently circulating at low levels in many tropical countries, but that will inevitably change, according to co-senior author Dr. Sallie Permar, the Nancy C. Paduano Professor in Pediatrics and chair of pediatrics at Weill Cornell Medicine and pediatrician-in-chief at NewYork-Presbyterian/Weill Cornell Medical Center and NewYork-Presbyterian Komansky Children’s Hospital. Dr. Mattia Bonsignori, chief of the Translational Immunobiology Unit of the Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases (NIAID), part of NIH, is a co-senior author.
“The important thing is that we’ve got to be ready for another outbreak of Zika,” Dr. Permar said.
At this point, doctors have no approved vaccines or treatments to offer patients. With further research, this antibody has the potential to help fill that gap, according to Dr. Permar. “There are two potential ways it could be used: To quickly reduce levels of Zika in the blood of pregnant people who have become infected, or as a preventative measure given to those at risk of contracting the virus during an outbreak.”
Transmitted by infected Aedes aegypti mosquitoes, the Zika virus usually causes a mild illness in adults. However, Zika virus infection in pregnant people can cause severe birth defects, including abnormally small heads and brain damage in their babies.
During a Zika outbreak that began in 2015, researchers in Brazil, led by co-authors Dr. Reynaldo Dietze, of Global Health and Tropical Medicine and the Federal University of Espίrito Santo, and Dr. Camila Giuberti, also of the Federal University of Espίrito Santo, collected blood samples from pregnant people who had infections. The team decided to focus on those who were infected with Zika, but had given birth to babies that appeared healthy, because they suspected these patients might harbor antibodies capable of preventing the congenital infection.
One of these patients gave birth to an apparently healthy baby even after having Zika detectable in their blood for nearly two months, an unusually long period. The laboratory teams, led by first author Dr. Tulika Singh, a former graduate student at Duke University Medical Center where Dr. Permar’s lab was located during part of this study and now a postdoctoral fellow at the University of California, Berkeley, found that their B cells produced an IgM antibody with a potent ability to prevent viral particles from invading cells.
The identity of this antibody, called DH1017.IgM, surprised the investigators because it belongs to a typically weaker, less mature type of antibody that is produced early in an infection. However, in this case, the potent function of this antibody depended on it being an IgM antibody. When the collaborators examined its molecular structure when binding to the virus, they found that multiple arms could latch onto a viral particle simultaneously. The findings suggest that IgM antibodies might be especially effective to protect against Zika virus and possibly other viruses, the authors suggest.
To develop the antibody into a therapy, the researchers plan to begin testing its safety and how effectively it can prevent transmission to a fetus in additional preclinical models. Recalling how pregnant people were left out of COVID-19 vaccine trials, Dr. Permar emphasized that when human studies for new preventive or therapeutic treatments are done for Zika, they must be included. “Pregnant people are the exact population that needs vaccines or immunotherapies for Zika,” she said. “It’s crucial to get anti-Zika vaccines and therapies that are safe in pregnancy rolled out as soon as there is evidence of an outbreak.”
This research was supported by NIAID grant R21-AI123677.

Damages to the central nervous system (CNS), for example in the case of spinal cord injury, can result in permanent loss of sensory and motor function. It is because the severed axons are unable to regenerate. As of today, there are very limited options to help these patients regain their motor abilities. Scientists have been exploring ways to enable the regeneration of severed axons, with a view to developing viable treatments in the long term.
In a study using mice, a research team led by Cheng Associate Professor Kai LIU of the Division of Life Science, the Hong Kong University of Science and Technology (HKUST), untangled some of the complexities in the regeneration of severed axons. They found that the deletion of PTPN2, a phosphatase-coding gene, in neurons can prompt axons to regrow. When combined with the type II interferon IFNγ, it can further accelerate the process and boost the number of axons regenerated. The results have recently been published in the scientific journal Neuron.
The human nervous system is composed of two parts, namely the central and peripheral nervous systems. Unlike the central nervous system, peripheral nerves have stronger ability to regrow and repair by themselves after injury. Scientists have yet to fully understand the relationship between this self-repair and the intrinsic immune mechanism of the nervous system. Two mysteries the team wanted to resolve were how immune-related signaling pathways affected neurons after injury, and whether they could enhance axonal regeneration directly.
This study investigated whether the signaling pathway IFNγ-cGAS-STING had any role in the regeneration process of peripheral nerves. Researchers found that peripheral axons could directly modulate the immune response in their injured environment to promote self-repair after injury.
In previous research, Prof. Liu’s team had already demonstrated that elevating the neuronal activity and regulating the neuronal glycerolipid metabolism pathway could boost axon regenerative capacity. The current study is providing further insights into the search of treatment solutions for challenging conditions such as spinal cord injuries, with one possible option being the joining of several types of different signaling pathways.
The co-first authors of this project are Drs. Xu WANG and Chao YANG of HKUST. The work was done in collaboration with Prof. Zhong-Yin ZHANG of Purdue University alongside Profs. Ruohao WU, and Peiyuan QIAN, Jiguang WANG of HKUST.
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Genetic background has an effect on the metabolism of the essential polyunsaturated fatty acids alpha-linolenic acid and linoleic acid, a recent study from the University of Eastern Finland shows.
Supplementing the diet with camelina oil rich in alpha-linolenic acid, or with sunflower oil rich in linoleic acid altered the concentrations of the metabolites of these fatty acids in the body; however, the changes were dependent on the study participants’ FADS1 genotype. The study was conducted among carriers of two different FADS1 genotypes.
“Camelina oil increased the plasma concentration of eicosapentaenoic acid produced from alpha-linolenic acid in only one of the genotypes studied,” says Researcher and first author Topi Meuronen of the University of Eastern Finland.
Both diet and genes have been found to have an effect on the concentrations of different fatty acids in the body. The FADS1 gene regulates the metabolism of polyunsaturated fatty acids, and the FADS1 genotype has previously been associated with glucose and lipid metabolism disorders, and with the risk of type 2 diabetes.
Linoleic acid and alpha-linolenic acid are essential fatty acids not produced by the human body, i.e., they must be obtained from food. Linoleic acid is the most common dietary fatty acid in the omega-6 family. Alpha-linolenic acid, on the other hand, belongs to the family of omega-3 fatty acids. Varying concentrations of both are found in vegetable oils, seeds and nuts. Of vegetable oils, sunflower oil is particularly rich in linoleic acid. Camelina oil and linseed oils, on the other hand, are rich in alpha-linolenic acid.
High intake and plasma concentration of linoleic acid has been associated with, e.g., a lower risk of type 2 diabetes and cardiovascular disease, but the association of alpha-linolenic acid remains unclear. As metabolites of linoleic acid and alpha-linolenic acid, the body produces lipid mediators which are important, but some of them also pro-inflammatory.

Researchers at UCL Great Ormond Street Institute of Child Health (UCL GOS ICH) have grown ‘mini eyes’, which make it possible to study and better understand the development of blindness in a rare genetic disease called Usher syndromefor the first time.
The 3D ‘mini eyes’, known as organoids, were grown from stem cells generated from skin samples donated by patients at Great Ormond Street Hospital for Children (GOSH). In a healthy eye, rod cells — the cells which detect light — are arranged in the back of the eye in an important region responsible for processing images called the retina. In this research, published in Stem Cell Reports1, the team found that they could get rod cells to organise themselves into layers that mimic their organisation in the retina, producing a ‘mini eye’.
These ‘mini eyes’ are an important step forward because previous research using animal cells couldn’t mimic the same sort of sight loss as that seen in Usher syndrome.
Usher syndrome is the most common genetic cause of combined deafness and blindness, affecting approximately three to ten in 100,000 people worldwide. Children with Type 1 Usher syndrome are often born profoundly deaf, while their sight slowly deteriorates until they are blind by adulthood.
Although cochlear implants can help with hearing loss, there are currently no treatments for retinitis pigmentosa, which causes vision loss in Usher syndrome. While this research is in early stages, these steps towards understanding the condition and how to design a future treatment could give hope to those who are due to lose their sight.
The ‘mini eyes’ developed in this research allow scientists to study light-sensing cells from the human eye at an individual level, and in more detail than ever before. For example, using powerful single cell RNA-sequencing, it is the first time researchers have been able to view the tiny molecular changes in rod cells before they die. Using the ‘mini eyes’, the team discovered that Müller cells, responsible for metabolic and structural support of the retina, are also involved in Usher syndrome. They found that cells from people with Usher syndrome abnormally have genes turned on for stress responses and protein breakdown. Reversing these could be the key to preventing how the disease progresses and worsens.

So far, there no uniform guidelines have existed for the treatment of arthritis of the jaw, a potentially debilitating consequence of juvenile arthritis.
Doctors around the world lack insight into how best to treat arthritis of the jaw, which is a frequent and serious consequence of juvenile arthritis.
Now, a team of researchers from Aarhus University, in collaboration with experts from a wide range of international professional groups, have developed a set of interdisciplinary guidelines to optimise the treatment of patients with the disease.
The guidelines have a special focus on early diagnosis and screening, and they can benefit children all over the world, according to Peter Stoustrup, associate professor at Department of Dentistry and Oral Health at Aarhus University.
“A more timely initiation of treatment will result in a better treatment outcome. Untreated, arthritis of the jaw can cause major problems in adulthood, but treatment of the condition has lagged considerably due to uncertainty among health professionals and health systems, so this study is important for all children with jaw arthritis,” he says.
Complicated joint — complicated treatment
Around 1,500 children in Denmark have a diagnosis of juvenile arthritis, which often results in inflammation of the jaw joint. This leads to pain, reduced joint function, and growth disruption in the face, which in severe cases may give rise to sleep apnoea and a need for surgical treatment of the patient’s jaw.