My fifth installment of interesting research papers that I have read over the past few weeks and would like to share with my community.
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New digital cognitive test for diagnosing Alzheimer’s disease
“The unique aspect of our BioCog test is that unlike other digital tests, it has been evaluated in a primary care population, i.e. patients seeking treatment at a health centre because they are experiencing cognitive problems, such as memory problems. Combining the results of the digital test and the blood test increases the accuracy of diagnosing Alzheimer’s disease. The purpose of the test is to make things easier for primary care doctors,” says one of the authors.
The digital test is done by the patient individually on a tablet computer. The test measures:
Alzheimer’s disease is the most common cause of dementia. As new disease-modifying treatments for Alzheimer’s disease are now becoming available, both early and accurate diagnosis in a resource-efficient assessment process are becoming increasingly important, as not everyone responds to the new drugs. Seeking medical care for cognitive impairment is not necessarily the result of Alzheimer’s disease – it can for example be caused by depression, fatigue or other dementias.
“Primary care does not have the resources, time or specialist knowledge to investigate possible Alzheimer’s disease in the same way as specialised memory clinics. And this is where a digital cognitive test can make the biggest difference,” says the senior author.
Unlike pen-and-paper tests, which are generally used to assess cognitive impairment, digital tests provide a more detailed picture. More aspects and new variables that could not previously be measured as easily are included.
Human genome rearrangement with programmable bridge recombinases
Bridge recombinases were discovered from parasitic mobile genetic elements that hijack bacterial genomes for their own survival. Presented last year in the journal Nature, the same team found these elements encode both a new class of structured guide RNA, which they named a “bridge RNA”, and a recombinase enzyme that rearranges DNA. The researchers repurposed this natural system by reprogramming the bridge RNA to target new DNA sequences, creating the foundation for a new type of precise gene editing tool they called bridge recombinases.
Starting with 72 different natural bridge recombinase systems isolated from bacteria, the team found that about 25% showed some activity in human cells, but most were barely detectable. Only one system, called ISCro4, showed enough measurable activity to enable further optimization. They then systematically improved both the protein and its RNA guide components, testing thousands of variations until they achieved 20% efficiency for DNA insertions and 82% specificity for hitting intended targets in the human genome.
While CRISPR uses a single guide RNA to target one DNA location, bridge RNAs are unique because they can simultaneously recognize two different DNA targets through distinct binding loops. This dual recognition enables the system to perform coordinated rearrangements such as bringing together distant chromosomal regions to excise genetic material or flipping existing sequences in reverse orientation. The system acts as molecular scaffolding that holds two DNA sites together while the recombinase enzyme performs the rearrangement reaction.
As a proof-of-concept, the researchers created artificial DNA constructs containing the same toxic repeat sequences that cause progressive neuromuscular decline in Friedreich’s ataxia patients. While healthy individuals carry fewer than 10 sequential copies of a three-letter DNA sequence, people with the disorder can harbor up to 1,700 copies, which interferes with normal gene function. The engineered ISCro4 successfully removed these repeats from the artificial constructs, in some cases eliminating over 80% of the expanded sequences.
The team also demonstrated that bridge recombinases could replicate existing therapeutic approaches by successfully removing the BCL11A enhancer, the same target disrupted in an FDA-approved sickle cell anemia treatment. And because bridge recombinases can move massive amounts of DNA, the technology could also help model the large-scale genomic rearrangements associated with cancers.
For decades, gene-editing science has been limited to making small, precise edits to human DNA, akin to correcting typos in the genetic code. The researchers are changing that paradigm with a universal gene editing system that allows for cutting and pasting of entire genomic paragraphs, rearranging whole chapters, and even restructuring entire passages of the genomic manuscript.
Unlikely Allies? Transhuman Dignity and Catholic Doctrine on Human Flourishing
In this chapter I engage with both the question of whether Creation includes postdigital life and the implications of this potential inclusion for witnessing God’s activity in a transhuman world. To address this twofold inquiry, I investigate whether the Catholic Church can turn out to be, contrary to a received view, a doctrinal ally of transhumanism. To that effect, I dissect various seemingly disparate themes in the transhumanist literature, showing that they can attain coherent articulation once the movement’s theological undercurrent is identified. Subsequently, I show that there is a substantial overlap between this transhumanist theological underpinning and the contemporary epistemology of the Church. This theoretical bridge is possible in virtue of later philosophical developments in Catholic doctrine that are rarely acknowledged.
Phosphatidylcholines Are Biomarkers Of The Omega-3 Index
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Inhaling cannabis may greatly increase your risk of getting asthma
If you’re looking to reduce your chances of developing lung disease, say experts at UC San Francisco, then it may be smart to avoid inhaling cannabis.
A new study in the Journal of General Internal Medicine found that inhaling marijuana every day is associated with a 44% increased chance of developing asthma. It also increased the odds of developing chronic obstructive pulmonary disease (COPD) by 27%.
The COPD risk may be understated, since the disease takes decades to develop, and the researchers did not have detailed information on how long people in the study had been using cannabis.
Galaxies Reveal Hidden Maps of Dark Matter in the Early Universe
Researchers uncover a key protein and a promising strategy to prevent bone damage from steroids.
The rheumatology and orthopedic researchers discovered that a protein called Basigin, which gets activated in stem cells when people take steroids, is a key reason why bones weaken and blood vessels in bone tissue become abnormal. By blocking Basigin, they were able to protect and even restore bone health in mice, suggesting a promising new treatment path.
Their findings were published in Nature Communications.
Graph neural networks learn emergent tissue properties from spatial molecular profiles
Tissue phenotypes arise from molecular states of individual cells and their spatial organisation, so spatial omics assays can help reveal how they emerge. Here, the authors apply graph neural networks to classify tissue phenotypes from spatial omics patterns, and use this approach to understand patterns in cancers and their microenvironments.