Lmst

Interesting new paper in #Nature finds that #ClonalHematopoiesis mutations in the blood can contribute to #ChronicLiverDisease. The authors use a combination of human cohort data and mouse models to show that these mutations lead to more #inflammatory changes in the #liver. https://www.nature.com/articles/s41586-023-05857-4 #science #medicine #genomics #hematology #hepatology #LiverDisease

Forest plots showing odds ratios for association with clonal hematopoiesis status. Odds ratios are about 1.8 for chronic liver disease (in A), 1.8 for alcoholic liver disease and non alcoholic steatohepatitis (NASH) (in B), 4.0 for biopsy-proven NASH (in C), and 2.3 for Mendelian randomization of chronic liver disease (in D).

While #ClonalHematopoiesis mutations in the blood are known to contribute to #IschemicCardiovascularDisease, most studies have focused on the impact on the heart. A new study looks at the prevalence of #CHIP mutations in young #stroke patients and finds high enrichment (>3 times greater than general population studies). Moreover, there was a high prevalence of CHIP even among youngest patients with stroke (age < 40 years old). Link: https://www.ahajournals.org/doi/10.1161/STROKEAHA.122.041416 #medicine #science #genomics #neurology

Panel A shows the prevalence of CHIP among all stroke patients at 20%. Panel B shows prevalence of CHIP by age, increasing from roughly 7% for <40 years old, to 18% for 40-50 years old, to 26% for 50-60 years old. Panel C shows comparisons of CHIP prevalence in stroke to two general population cohorts, adjusted for assay sensitivity; in both cases there is a statistically significant ~3 fold increase.

Rates of #BloodDonation dropped with the arrival of Covid-19 and still haven't recovered to pre-pandemic levels. In the US, that's led to an easing of blood donation rules that had excluded some people from donating. You can read more about blood donation process and the change in rules here: https://wapo.st/3Xlh18s. And if you're thinking about donating blood, you can receive a bonus $10 Amazon giftcard through the end of the month: https://www.redcross.org/give-blood.html

Wanted to share this great work on curating #ClonalHematopoiesis (#CHIP) in biobanks just published in #Blood. This work, led by Dr. Caitlyn Vlasschaert, used known CHIP associations with #aging, #germline variants, and #HealthOutcomes to carefully define variant calling criteria in All of Us and UK Biobank studies (N > 500K). The call sets are in the process of being returned to the biobanks so that they may be used by researchers anywhere! Link: https://doi.org/10.1182/blood.2022018825 #medicine #genomics

Figure 3. Association of CHIP variants defined by minimum allele depth (minAD) strata with age and TERT promoter variant rs7705526. Panels show the associations for strata of CHIP variants defined by minAD 3, 4, 5, and 6 with age (A,C) and the rs7705526 TERT promoter variant (B,D) in UK Biobank and All of Us Cohorts. The right axis plots the results of a simulation experiment wherein the specified proportion of samples in the minAD ≥ 5 CHIP dataset was randomly exchanged for individuals without CHIP in the dataset to estimate misclassification. Each simulation was run 20 times and the average result is shown.

Alex Silver boosted:

More interesting evidence that lithium might extend lifespans?

‘Lithium can extend lifespan in animal models. Lithium in drinking water is correlated with human longevity. We find patients taking lithium have 3.5× lower chances of dying at a given age.’ https://www.aging-us.com/article/204476/text

Recent studies have shown that #AcuteMyeloidLeukemia favors #OxPhos metabolism. This #ASH22 abstract from my colleagues demonstrates with in vitro and in vivo models that the use of #ammocidin, an inhibitor of electron transport chain complex V, works synergistically with low-dose #venetoclax to kill #AML cells. Stop by poster 2652 or read more about it here: https://ashpublications.org/blood/article/140/Supplement%201/5959/492144/Electron-Transport-Chain-Complex-V-Inhibition #leukemia #cancer #oncology #hematology #hemonc #science #medicine

Graph of chimerism of leukemic cells in mouse xenograft model in blood, spleen, and bone marrow. Conditions tested are vehicle, ammocidin, Ven/Aza, and Ven/Aza plus ammocidin. In all compartments, the combination of ammocidin plus Ven/Aza showed significantly less chimerism than Ven/Aza alone

Alex Silver boosted:

So thrilled to welcome @JulieSilverMD@twitter.com IRL to discuss #genderequity at @MacLeanEthics@twitter.com and she starts with this question:

if there was something in medicine that didn’t work for 35 years(!), why should we keep doing it this way?

Alex Silver boosted:

Dear Mastadon hivemind:

The http://www.BiodiversityStripes.info website is highlighting biodiversity loss, globally and regionally using a similar concept to the climate stripes.

We are looking for other sources of biodiversity data which can be turned into stripes to highlight this critical issue.

Any leads for long & coherent time series welcome!

#BiodiversityStripes #COP15

Alex Silver boosted:

Here's my #twittermigration #introduction
Interests include #vascularbiology #cancer #digitaleducation #science #medicine #educationresearch #introduction
I live in #australia
I am a #Professor in Cell Biology

Hoping this platform will be kinder and better supported than twitter

Concise & timely review from my colleague Sarah Reed out in #AACR #ClinicalCancerResearch about #ClonalHematopoiesis in #SolidTumors. See the nice summary figure below and find the full text here: https://aacrjournals.org/clincancerres/article-abstract/doi/10.1158/1078-0432.CCR-22-2598/711363/CHIP-Happens-Clonal-hematopoiesis-of-indeterminate #medicine #science #hematology #oncology #cancer #immunology

Scientific figure. Panel A: schematic of clonal expansion and short lists of common, less common, and uncommon clonal hematopoiesis genes. Panel B: diagram of a tumor in which clonal hematopoiesis immune cells have infiltrated, with arrows pointing to known health associations, specifically decreased survival in patients with solid tumors and in patients treated with immunotherapy. Also, a picture of clonal hematopoiesis cells in the blood vessel, with outcomes listed as increased risk of transformation to leukemia and greater risk for cardiovascular disease. Finally, the figure notes an overall increased risk of all-cause mortality.

Interesting study in #ScientificReports that did #transcriptome profiling of surgically-removed calcified aortic valves from patients with/without #ClonalHematopoiesis. The authors found broad changes to immune cell infiltrates but also to #antibody profiles that correlated with survival. This last point is cool because CH's impact on #myeloid biology is often discussed, but it can obviously have important effects on #lymphoid cells, too: https://www.nature.com/articles/s41598-022-24130-8 #science #medicine #cardiology

Figure from a paper: A) Normalized counts of immunoglobulins in the aortic valves by patient, with several of the clonal hematopoiesis (CH) patients having orders of magnitude higher levels. B) Quantification of IGH, IGHG1, IGKC, all higher in the CH group. C) IGHG1 and IGKC mRNA levels, higher in CH. D) Histology images of the aortic valves with stains showing activated B or plasma cells in the valves of a CH carrier compared to non-CH carrier with calcified valve and a non-CH non-calcified control

Alex Silver boosted:

Ecstatic to share my children's picture book, "The ABC's of Anatomy" is now published @AmazonPub@twitter.com: https://amzn.to/3VwLOi8 for Kindle or paperback.

So grateful for my co-authors Jordan & @LaneMoore28@twitter.com, & mentors in both medical humanities & anatomy. Sharing a sneak peek here!

Alex Silver boosted:

Pleased to have had the opportunity to publish on a groundbreaking benign #hematology clinic staffed by pathologists!

What do you think of this new approach? Will it change patient care - or how #pathology is viewed by other medical professionals (and by students)? Let us know!

https://thepathologist.com/subspecialties/a-space-waiting-to-be-filled

#hematopathology #hemepath #PathMastodon @pathology

Do you use a lot of #genomic data in your research or are you considering getting a direct-to-consumer #WholeGenomeSequencing kit for the holidays? Here's a really great review from #NatureReviewsGenetics that covers the technological and legal protections for genomic data: https://www.nature.com/articles/s41576-022-00455-y #science #medicine #genetics #privacy #genome #WGS

Flow chart of how genetic information is protected by legal and technical safeguards

@freddyeescorcia Yes, indeed! Very exciting time to be in this space in medicine, with lots of cross-pollination. I've already used some gene-therapy related advances to improve the efficiency of our lab's CRISPR knock-in models of leukemia-related mutations. And I'm sure much more to come in the years ahead!

Cool to see another #GeneticMedicine receive approval from the FDA. This new therapy provides the gene for the clotting factor that is missing in #hemophilia, an inherited disease that results in the inability of the blood to form clots and which can lead to life-threatening bleeding. Read more here: https://www.axios.com/2022/11/23/fda-approves-gene-therapy-for-hemophilia #medicine #science #genetics #GeneTherapy

Nice review on the #biology of #ClonalHematopoiesis that covers both acquired point mutations (i.e., CHIP) and large mosaic chromosomal alterations (mCAs). I especially like this figure summarizing known risk factors for each. Full text here: https://www.sciencedirect.com/science/article/abs/pii/S1931524422002511 #hematology #genetics #genomics #science #medicine

Checklist of reported risk factors for CHIP and mCAs, respectively:
Germline predisposition - yes and yes
Age - yes and yes
European ancestry - yes and yes
Smoking - yes and yes
Diet - yes and unknown
Obesity - yes and unknown
Atherogenic lipoproteins - yes and unknown
Environmental pollution - yes and yes
HIV - yes and unknown
Cytotoxic chemotherapy - yes and unknown
Natural premature menopause - yes and unknown

Alex Silver boosted:

EDIT: DO NOT BOOST!

This post is nearly a year old, and boosting will simply spread misinformation. Mastodon now has substantially more funding, and has enough scale to handle its many users.

I would delete this post but my server is not letting me so I'm editing this to reflect that I wish for you to NOT BOOST!

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Be a hero! Donate now! https://www.patreon.com/mastodon

Alex Silver boosted: