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Category: biotech/medical – Page 523

Advancing human leukocyte antigen-based cancer immunotherapy: from personalized to broad-spectrum strategies for genetically heterogeneous populations

Human leukocyte antigen (HLA)-based immunotherapeutics, such as tebentafusp-tebn and afamitresgene autoleucel, have expanded the treatment options for HLA-A*02-positive patients with rare solid tumors such as uveal melanoma, synovial sarcoma, and myxoid liposarcoma. Unfortunately, many patients of European, Latino/Hispanic, African, Asian, and Native American ancestry who carry non-HLA-A*02 alleles remain largely ineligible for most current HLA-based immunotherapies. This comprehensive review introduces HLA allotype-driven cancer health disparities (HACHD) as an emerging research focus, and examines how past and current HLA-targeted immunotherapeutic strategies may have inadvertently contributed to cancer health disparities. We discuss several preclinical and clinical strategies, including the incorporation of artificial intelligence (AI), to address HACHD.

New AI model for drug design brings more physics to bear in predictions

When machine learning is used to suggest new potential scientific insights or directions, algorithms sometimes offer solutions that are not physically sound.

Take, for example, AlphaFold, the AI system that predicts the complex ways in which amino acid chains will fold into 3D protein structures. The system sometimes suggests “unphysical” folds—configurations that are implausible based on the —especially when asked to predict the folds for chains that are significantly different from its .

To limit this type of unphysical result in the realm of drug design, Anima Anandkumar, Bren Professor of Computing and Mathematical Sciences at Caltech, and her colleagues have introduced a new machine learning model called NucleusDiff, which incorporates a simple physical idea into its training, greatly improving the algorithm’s performance.

Grid cells create multiple local maps rather than single global system for spatial navigation, study finds

Grid cells are a class of specialized neurons in a brain region called the entorhinal cortex, which is known to support spatial navigation and some memory processes. Past neuroscience studies have found that as humans and other animals move in their surroundings, these cells fire following a grid-like pattern, creating a sort of internal map of the environment.

Researchers at the Medical Faculty of Heidelberg University, the German Cancer Research Center and EBRI recently carried out a study aimed at shedding new light on the processes via which grid cells encode an animal’s position in space and contribute to spatial navigation. Their findings, published in Nature Neuroscience, suggest that rather than creating and retaining a single global map, these cells produce multiple local maps that can guide the future behavior of animals in their surrounding space.

“Soon after the discovery of grid cells by the group of May-Britt and Edvard Moser, it was proposed that these neurons might support path integration,” Kevin Allen, senior author of the paper, told Medical Xpress. “In this fundamental navigation process, an animal estimates its position by continuously integrating self-motion cues, even in the absence of external landmarks. However, most previous studies of grid cells were conducted in environments rich in external cues, making it difficult to isolate the path-integration processes.”

Spiritual experiences in adolescence linked to adult loneliness and civic engagement

University of North Carolina at Charlotte’s School of Nursing, collaborating with Harvard’s Human Flourishing Program, reports that adolescents who report transformative religious or spiritual experiences show both greater volunteering and voting in early adulthood alongside elevated loneliness and PTSD.

Large national surveys have linked religious or spiritual involvement with health, yet longitudinal evidence on life-changing experiences remains sparse.

Previous research has associated religious or spiritual involvement with positive health indicators and lower stress, while qualitative and clinical literature has described both self-destabilizing elements and intensified and social connectedness.

Brainwave study sheds light on cause of ‘hearing voices’

A new study led by psychologists from UNSW Sydney has provided the strongest evidence yet that auditory verbal hallucinations—or hearing voices—in schizophrenia may stem from a disruption in the brain’s ability to recognize its own inner voice.

In a paper published today in the journal Schizophrenia Bulletin, the researchers say the finding could also be an important step toward finding biological indicators that point to the presence of . This is significant, as there are currently no blood tests, , or lab-based biomarkers—signs in the body that can tell us something about our health—that are uniquely characteristic of schizophrenia.

Professor Thomas Whitford, with the UNSW School of Psychology, has been examining the role of inner speech in the cognition of healthy people and people living with schizophrenia spectrum disorders for some time.

How happy do we need to be to have lower chronic disease mortality risk?

Heart disease, cancer, asthma, and diabetes: All are chronic or non-communicable diseases (NCD), which accounted for about 75% of non-pandemic related deaths in 2021. They may result from genetic, environmental, and behavioral factors, or a combination thereof. But can other factors also influence disease risk?

Now, a new Frontiers in Medicine study has investigated the relationship between and health to find out if happier always means healthier and to determine if happiness and co-occurring health benefits are linear or follow a specific pattern.

“We show that subjective well-being, or happiness, appears to function as a population health asset only once a minimum threshold of approximately 2.7 on the Life Ladder scale is surpassed,” said first author Prof Iulia Iuga, a researcher at 1 Decembrie 1918 University of Alba Iulia. “Above this tipping point, increased happiness is associated with a decrease in NCD mortality.”

A mathematical ‘Rosetta Stone’ translates and predicts the larger effects of molecular systems

Penn Engineers have developed a mathematical “Rosetta Stone” that translates atomic and molecular movements into predictions of larger-scale effects, like proteins unfolding, crystals forming and ice melting, without the need for costly, time-consuming simulations or experiments. That could make it easier to design smarter medicines, semiconductors and more.

In a recent paper in Journal of the Mechanics and Physics of Solids, the Penn researchers used their framework, stochastic thermodynamics with internal variables (STIV), to solve a 40-year problem in phase-field modeling, a widely used tool for studying the shifting frontier between two states of matter, like the boundary between water and ice or where the folded and unfolded parts of a protein join.

“Phase-field modeling is about predicting what happens at the thin frontier between phases of matter, whether it’s proteins folding, crystals forming or ice melting,” says Prashant Purohit, Professor in Mechanical Engineering and Applied Mechanics (MEAM) and one of the paper’s co-authors. “STIV gives us the mathematical machinery to describe how that frontier evolves directly from first principles, without needing to fit data from experiments.”

How a human ‘jumping gene’ targets structured DNA to reshape the genome

Long interspersed nuclear element-1 (LINE-1 or L1) is the only active, self-copying genetic element in the human genome—comprising about 17% of the genome. It is commonly called a “jumping gene” or “retrotransposon” because it can “retrotranspose” (move) from one genomic location to another.

Researchers from the Institute of Biophysics of the Chinese Academy of Sciences have now unveiled the molecular mechanisms that underlie L1’s retrotransposition and integration into genomic DNA. Their study was published in Science on October 9.

L1 is the only autonomously active retrotransposon in the and serves as the primary vehicle for the mobilization of most other retrotransposons. Its retrotransposition process is mediated by the reverse transcriptase ORF2p through a mechanism known as target-primed reverse transcription (TPRT). Until now, the manner in which ORF2p recognizes DNA targets and mediates integration had remained unclear.

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