The potential for more than one distinct hematolymphoid neoplasm to arise from a common mutated stem or precursor cell has been proposed based on findings in primary human malignancies. Particularly, angioimmunoblastic T-cell lymphoma (AITL), which shares a somatic mutation profile in common with other hematopoietic malignancies, has been reported to occur alongside myeloid neoplasms or clonal B-cell proliferations, with identical mutations occurring in more than one cell lineage. Here we report such a case of an elderly woman who was diagnosed over a period of 8 years with diffuse large B-cell lymphoma, polycythemia vera, and AITL, each harboring identical somatic mutations in multiple genes. Overall, at least five identical nucleotide mutations were shared across multiple specimens, with two identical mutations co-occurring at variable variant allele frequencies in all three specimen types. These findings lend credence to the theory that a common mutated stem cell could give rise to multiple neoplasms through parallel hematopoietic differentiation pathways.

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous group of lymphoid malignancies. Based on gene expression profiling, it has been subdivided into germinal center (GC)-derived and activated B-cell (ABC) types. Advances in molecular methodologies have further refined the subclassification of DLBCL, based on recurrent genetic abnormalities. Here, we describe a distinct case of DLBCL that presented in leukemic form. DNA sequencing targeting 275 genes revealed pathogenically relevant mutations of CD79B, MyD88, TP53, TBL1XR1, and PIM1 genes, indicating that this lymphoma would be best classified as MCD/C5 DLBCL, an ABC subtype. Despite an initial good clinical response to BTK inhibitor ibrutinib, anti-CD20 antibody rituxan, alkylating agent bendamustine, and hematopoietic stem-cell transplant, the lymphoma relapsed, accompanied by morphologic and molecular evidence of disease progression. Specifically, the recurrent tumor developed loss of TP53 heterozygosity (LOH) and additional chromosomal changes central to ABC DLBCL pathogenesis, such as PRDM1 loss. Acquired resistance to ibrutinib and rituxan was indicated by the emergence of BTK and FOXO1 mutations, respectively, as well as apparent activation of alternative cell-activation pathways, through copy-number alterations (CNAs), detected by high-resolution chromosomal microarrays. In vitro, studies of relapsed lymphoma cells confirmed resistance to standard BTK inhibitors but sensitivity to vecabrutinib, a noncovalent inhibitor active against both wild-type as well as mutated BTK. In summary, we provide in-depth molecular characterization of a de novo leukemic DLBCL and discuss mechanisms that may have contributed to the lymphoma establishment, progression, and development of drug resistance.

Over the past decades the zebrafish has emerged as an excellent model organism with which to study the biology of all glial cell types in nervous system development, plasticity, and regeneration. In this review, which builds on the earlier work by Lyons and Talbot in 2015, we will summarize how the relative ease to manipulate the zebrafish genome and its suitability for intravital imaging have helped understand principles of glial cell biology with a focus on oligodendrocytes, microglia, and astrocytes. We will highlight recent findings on the diverse properties and functions of these glial cell types in the central nervous system and discuss open questions and future directions of the field.

Advancements in immunotherapy in the perioperative setting have revolutionised the treatment of resectable nonsmall cell lung cancer (NSCLC). Here we present the methodology and results of the clinical trial CheckMate 816 demonstrating the benefit of neoadjuvant therapy with nivolumab plus chemotherapy compared with chemotherapy alone. Furthermore, this article discusses the implications for future practice in resectable NSCLC and the need for future research.

Lung cancer is one of the leading causes of death worldwide. It can broadly be divided into small cell lung cancer (SCLC) and nonsmall cell lung cancer. There have been many advances over the recent years in both fields. The purpose of this review is to provide a concise summary of SCLC for the general respiratory readership.

HUNDREDS of travellers’ holiday plans are in disarray after all Tigerair flights in and out of Bali were cancelled again today and early tomorrow.

Ministers must follow the UK Government and extend rates relief for businesses in Scotland, Anas Sarwar has said.

Stem cells made in the lab may one day aid cancer treatment by reducing our reliance on donors

They fight invaders, clear debris and tend neural connections, but sometimes microglia go rogue. Preventing this malfunction may offer new treatments for brain conditions including Alzheimer's

A new diet based on research into the body's ageing process suggests you can increase your life expectancy by up to 20 years by changing what, when and how much you eat

A monkey that performed poorly on vision tests did much better after having a stem cell transplant to patch up holes in its retina

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Following its announcement a few weeks ago, the final major update for Dead Cells titled The End is Near, version …

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150 minutes d’activité physique durant le week-end procure des bénéfices similaires à la même durée d’exercice répartie sur sept jours.

A team at Columbia University School of Engineering and Applied Science has developed a technique to enhance chimeric antigen receptor (CAR) T cell therapy in solid tumors. The technique involves engineering E. coli bacteria, that naturally tend to accumulate in the immune privileged core of solid tumors. The bacteria have been engineered to interact with […]

Elemind, a 5-year-old startup based in Cambridge, Mass., today unveiled a US $349 wearable for neuromodulation, the company’s first product. According to cofounder and CEO Meredith Perry, the technology tracks the oscillation of brain waves using electroencephalography (EEG) sensors that detect the electrical activity of the brain and then influence those oscillations using bursts of sound delivered via bone conduction.

Elemind’s first application for this wearable aims to suppress alpha waves to help induce sleep. There are other wearables on the market that monitor brain waves and, through biofeedback, encourage users to actively modify their alpha patterns. Elemind’s headband appears to be the first device to use sound to directly influence the brain waves of a passive user.

In a clinical trial, says Perry [no relation to author], 76 percent of subjects fell asleep more quickly. Those who did see a difference averaged 48 percent less time to progress from awake to asleep. The results were similar to those of comparable trials of pharmaceutical sleep aids, Perry indicated.

“For me,” Perry said, “it cuts through my rumination, quiets my thinking. It’s like noise cancellation for the brain.”

I briefly tested Elemind’s headband in May. I found it comfortable, with a thick cushioned band that sits across the forehead connected to a stretchy elastic loop to keep it in place. In the band are multiple EEG electrodes, a processor, a three-axis accelerometer, a rechargeable lithium-polymer battery, and custom electronics that gather the brain’s electrical signals, estimate their phase, and generate pink noise through a bone-conduction speaker. The whole thing weighs about 60 grams—about as much as a small kiwi fruit.

My test conditions were far from optimal for sleep: early afternoon, a fairly bright conference room, a beanbag chair as bed, and a vent blowing. And my test lasted just 4 minutes. I can say that I didn’t find the little bursts of pink noise (white noise without the higher frequencies) unpleasant. And since I often wear an eye mask, feeling fabric on my face wasn’t disturbing. It wasn’t the time or place to try for sound sleep, but I—and the others in the room—noted that after 2 minutes I was yawning like crazy.

How Elemind tweaks brain waves

What was going on in my brain? Briefly, different brain states are associated with different frequencies of waves. Someone who is relaxed with eyes closed but not asleep produces alpha waves at around 10 hertz. As they drift off to sleep, the alpha waves are supplanted by theta waves, at around 5 Hz. Eventually, the delta waves of deep sleep show up at around 1 Hz.

Ryan Neely, Elemind’s vice president of science and research, explains: “As soon as you put the headband on,” he says, “the EEG system starts running. It uses straightforward signal processing with bandpass filtering to isolate the activity in the 8- to 12-Hz frequency range—the alpha band.”

“Then,” Neely continues, “our algorithm looks at the filtered signal to identify the phase of each oscillation and determines when to generate bursts of pink noise.”

To help a user fall asleep more quickly [top], bursts of pink noise are timed to generate a brain response that is out of phase with alpha waves and so suppresses them. To enhance deep sleep [bottom], the pink noise is timed to generate a brain response that is in phase with delta waves.Source: Elemind

These auditory stimuli, he explains, create ripples in the waves coming from the brain. Elemind’s system tries to align these ripples with a particular phase in the wave. Because there is a gap between the stimulus and the evoked response, Elemind tested its system on 21 people and calculated the average delay, taking that into account when determining when to trigger a sound.

To induce sleep, Elemind’s headband targets the trough in the alpha wave, the point at which the brain is most excitable, Neely says.

“You can think of the alpha rhythm as a gate for communication between different areas of the brain,” he says. “By interfering with that communication, that coordination between different brain areas, you can disrupt patterns, like the ruminations that keep you awake.”

With these alpha waves suppressed, Neely says, the slower oscillations, like the theta waves of light sleep, take over.

Elemind doesn’t plan to stop there. The company plans to add an algorithm that addresses delta waves, the low-frequency 0.5- to 2-Hz waves characteristic of deep sleep. Here, Elemind’s technology will attempt to amplify this pattern with the intent of improving sleep quality.

Is this safe? Yes, Neely says, because auditory stimulation is self-limiting. “Your brain waves have a natural space they can occupy,” he explains, “and this stimulation just moved it within that natural space, unlike deep-brain stimulation, which can move the brain activity outside natural parameters.”

Going beyond sleep to sedation, memory, and mental health

Applications may eventually go beyond inducing and enhancing sleep. Researchers at the University of Washington and McGill University have completed a clinical study to determine if Elemind’s technology can be used to increase the pain threshold of subjects undergoing sedation. The results are being prepared for peer review.

Elemind is also working with a team involving researchers at McGill and the Leuven Brain Institute to determine if the technology can enhance memory consolidation in deep sleep and perhaps have some usefulness for people with mild cognitive impairment and other memory disorders.

Neely would love to see more applications investigated in the future.

“Inverse alpha stimulation [enhancing instead of suppressing the signal] could increase arousal,” he says. “That’s something I’d love to look into. And looking into mental-health treatment would be interesting, because phase coupling between the different brain regions appears to be an important factor in depression and anxiety disorders.”

Perry, who previously founded the wireless power startup UBeam, cofounded Elemind with four university professors with expertise in neuroscience, optogenetics, biomedical engineering, and artificial intelligence. The company has $12 million in funding to date and currently has 13 employees.

Preorders at $349 start today for beta units, and Elemind expects to start general sales later this year. The company will offer customers an optional membership at $7 to $13 monthly that will allow cloud storage of sleep data and access to new apps as they are released.

Autolus Therapeutics’ Aucatzyl is now FDA approved for treating advanced cases of B-cell precursor acute lymphoblastic leukemia. While it goes after the same target as Gilead Sciences’ Tecartus, Autolus engineered its CAR T-therapy with properties that could improve safety, efficacy, and durability.

The post ‘Serial Killing’ Cell Therapy From Autolus Lands FDA Approval in Blood Cancer appeared first on MedCity News.

Dec 5, 2023

David W. Kearn argues that deployment of nuclear weapons cannot rectify a perceived imbalance in conventional forces in the western Pacific.

Stag�s Leap Wine Cellars celebrates the 40th anniversary of The Judgment of Paris, which helped to elevate the esteem of American wine worldwide

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The Hon'ble Delhi High Court in the case of M/s Sanjay Sales India v. Principal Commissioner of Department of Trade and Taxes, Government of NCT, Delhi [Writ Petition (Civil) No. 10234 of 2024 dated July 26, 2024] held that the application for the cancellation of the GST registration cannot be denie

Animals that hibernate need a way to keep their blood flowing as their body temperature drops, and it seems that the mechanical properties of red blood cells may be key

Single-celled organisms called archaea can become multicellular when compressed, highlighting the role of physical forces in evolution

I’m not a fan of phys.org — they summarize interesting articles, but it’s too often clear that their writers don’t have a particularly deep understanding of biology. I wonder sometimes if they’re just as bad with physics articles, and I just don’t notice because I’m not a physicist. Anyway, here’s a summary that raised my […]

Allogeneic hematopoietic cell transplantation (HCT) serves as a widely recognized curative treatment option for patients suffering from inborn errors of immunity (IEI).

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A new research has shed light on how sperm production can go wrong when a certain gene fails to function at the right time. The findings of the study are published in Cell Reports.

Tiny, self-organized three-dimensional (3D) tissue cultures (Organoids) derived from medlinkstem cells/medlink have been developed to produce teeth-protecting

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