The Friday Five for 26 December 2025
Dec. 26th, 2025 02:37 pm2. What foods would you be sure you got to eat?
3. What landmarks would you be sure you got to see?
4. What airline would you use?
5. Would your knowledge of other languages influence where you went? (i.e., would you be more likely to go to France if you spoke French?)
Copy and paste to your own journal, then reply to this post with a link to your answers. If your journal is private or friends-only, you can post your full answers in the comments below.
If you'd like to suggest questions for a future Friday Five, then do so on DreamWidth or LiveJournal. Old sets that were used have been deleted, so we encourage you to suggest some more!
Interesting Links for 25-12-2025
Dec. 25th, 2025 12:00 pm- 1. The 2025 Headline of the Year Nominees
- (tags:headline funny journalism )
- 2. There's no such thing as a fake feather
- (tags:birds materials video )
- 3. Dutch Tesla Fleet Goes Bankrupt After Betting on Musk's Self-Driving Promises
- (tags:Tesla automation fraud ElonMusk )
- 4. Super Mario Bros. and Yoshi Games' Affordance of Childlike Wonder and Reduced Burnout Risk in Young Adults
- (tags:psychology mentalhealth games Mario )
- 5. Why Britain doesn't have enough dentists
- (tags:teeth UK bureaucracy OhForFucksSake )
A good thread on Terrible Dickens Sequels
Dec. 25th, 2025 09:43 amOver on Bluesky, Ryan Estrada has done a deep dive on the 22 (!) Christmas stories that Dickens wrote in the aftermath of the success of A Christmas Carol.
An old thread is making the rounds again, so here's an updated version. Charles Dickens' A Christmas Carol is one of the most enduring and adapted works of literature in history. But did you know that he wrote 22 sequels? Some are great! Some are trash! Some are bizarrely fascinating.
— Ryan Estrada (@ryanestrada.com) December 24, 2025 at 6:24 PM
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Merry Christmas: Scientists reverse Alzheimer's in mice [sci/bio/med]
Dec. 24th, 2025 07:03 pmBy examining both human Alzheimer's brain tissue and multiple preclinical mouse models, the team identified a key biological failure at the center of the disease. They found that the brain's inability to maintain normal levels of a critical cellular energy molecule called NAD+ plays a major role in driving Alzheimer's. Importantly, maintaining proper NAD+ balance was shown to not only prevent the disease but also reverse it in experimental models.
Why This Approach Differs From Supplements
Dr. Pieper cautioned against confusing this strategy with over the counter NAD+-precursors. He noted that such supplements have been shown in animal studies to raise NAD+ to dangerously high levels that promote cancer. The method used in this research relies instead on P7C3-A20, a pharmacologic agent that helps cells maintain healthy NAD+ balance during extreme stress, without pushing levels beyond their normal range.
NAD+ levels naturally decline throughout the body, including the brain, as people age. When NAD+ drops too low, cells lose the ability to carry out essential processes needed for normal function and survival. The researchers discovered that this decline is far more severe in the brains of people with Alzheimer's. The same pattern was seen in mouse models of the disease.Note, potential conflict of interest: the head of the lab, Dr Pieper, above, has a serious commercial interest in this proving out:
[...]
Amyloid and tau abnormalities are among the earliest and most significant features of Alzheimer's. In both mouse models, these mutations led to widespread brain damage that closely mirrors the human disease. This included breakdown of the blood-brain barrier, damage to nerve fibers, chronic inflammation, reduced formation of new neurons in the hippocampus, weakened communication between brain cells, and extensive oxidative damage. The mice also developed severe memory and cognitive problems similar to those seen in people with Alzheimer's.
[...]
This approach built on the group's earlier work published in Proceeding of the National Academy of Sciences USA, which showed that restoring NAD+ balance led to both structural and functional recovery after severe, long-lasting traumatic brain injury. In the current study, the researchers used a well-characterized pharmacologic compound called P7C3-A20, developed in the Pieper laboratory, to restore NAD+ balance.
The results were striking. Preserving NAD+ balance protected mice from developing Alzheimer's, but even more surprising was what happened when treatment began after the disease was already advanced. In those cases, restoring NAD+ balance allowed the brain to repair the major pathological damage caused by the genetic mutations.
Both mouse models showed complete recovery of cognitive function. This recovery was also reflected in blood tests, which showed normalized levels of phosphorylated tau 217, a recently approved clinical biomarker used to diagnose Alzheimer's in people. These findings provided strong evidence of disease reversal and highlighted a potential biomarker for future human trials.
The technology is currently being commercialized by Glengary Brain Health, a Cleveland-based company co-founded by Dr. Pieper.The actual research article:
2025 Dec 22: Cell Reports Medicine [peer-reviewed scientific journal]: Pharmacologic reversal of advanced Alzheimer's disease in mice and identification of potential therapeutic nodes in human brain by Kalyani Chaubey et al. (+35 other authors!):
Abstract:Full text here: https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00608-1
Alzheimer's disease (AD) is traditionally considered irreversible. Here, however, we provide proof of principle for therapeutic reversibility of advanced AD. In advanced disease amyloid-driven 5xFAD mice, treatment with P7C3-A20, which restores nicotinamide adenine dinucleotide (NAD+) homeostasis, reverses tau phosphorylation, blood-brain barrier deterioration, oxidative stress, DNA damage, and neuroinflammation and enhances hippocampal neurogenesis and synaptic plasticity, resulting in full cognitive recovery and reduction of plasma levels of the clinical AD biomarker p-tau217. P7C3-A20 also reverses advanced disease in tau-driven PS19 mice and protects human brain microvascular endothelial cells from oxidative stress. In humans and mice, pathology severity correlates with disruption of brain NAD+ homeostasis, and the brains of nondemented people with Alzheimer's neuropathology exhibit gene expression patterns suggestive of preserved NAD+ homeostasis. Forty-six proteins aberrantly expressed in advanced 5xFAD mouse brain and normalized by P7C3-A20 show similar alterations in human AD brain, revealing targets with potential for optimizing translation to patient care.
Dossier – Abyssal
Dec. 24th, 2025 11:29 pmOld Gods of Appalachia – all-new through Mon 12 Jan 2026
Dec. 23rd, 2025 06:55 pm
Through Monday, January 12, 2026 we present the all-new Old Gods of Appalachia RPG Bundle featuring the Old Gods of Appalachia Roleplaying Game, the Cypher System RPG of eldritch horror from Monte Cook Games based on the captivating Old Gods of Appalachia anthology podcast created by Steve Shell and Cam Collins. Set in an alternate version of the Appalachian Mountains of the eastern US, Old Gods of Appalachia tells of the Green, the Dark, and things even more ancient. Long before anything human roamed the Earth, the Appalachians towered tall. For eons those peaks entombed beings of malice and unknowable hunger. But now the mountains are mere hills, and the prison walls wear thin. Things that had slumbered, now restless, call to the people in the mountain hollers, whisper to those vulnerable to their temptations, and seek to influence our world.
Funded in a sensational US$2.1M April 2022 Kickstarter campaign, the Old Gods of Appalachia Roleplaying Game is a standalone RPG driven by the Cypher System rules. You play characters who try to protect what matters to them, be that family, community, a place, or something else. You might be a local miner who delved too deep and uncovered something that now stalks your dreaming hours. Perhaps you’re a charismatic preacher who extols the virtuous life, to atone for the dark bargain you made long ago. Or maybe you’re an outsider, a reporter sent here to debunk accounts of monsters from the mountains, but the story you uncovered now lives in your bones. Spin your own tales of ravenous creatures of the Inner Dark, sinister plots of the Hollow Men, unearthed beasts, and angry forces of the Green. Seek to know the unknowable. Every choice requires a sacrifice, and your word is your bond.
Appalachia’s history runs with blood. In the 18th and 19th Centuries, pushing deep into the remote mountains of the eastern United States, European immigrants massacred the original inhabitants from the Atlantic coastline to the far foothills. The settlers formed isolated communities in sheltered valleys called hollers. By necessity these folk had to be self-sufficient to rough out an existence. Though the area is vast and the settlers are diverse, they are united in their shared experience of homesteading, self-reliance, support for neighbors, hardiness, fortitude, and their insular existence.
The region’s “granny magic” and witchcraft include songs, spells, rituals, and charms created to heal or harm, bring good luck or bad, increase fertility or the harvest, dowse for wells, and work with spirits. This magic derives from the Green, an elemental manifestation of life and the natural world. But the long-entombed beings beneath the hills command an ancient magic as old as the land itself, a powerful and wholly unknowable magic that cares nothing for humanity. Characters can tap this Inner Dark to craft powerful objects, call on creatures and ask for favors, and make life-altering bargains with powerful entities. But all magic in this setting comes with a price.
This all-new Old Gods of Appalachia RPG Bundle gives you everything you need to join the Family where the shadows stir in the darkest mountains in the world. Pay just US$7.95 to get all three titles in our Appalachian Starter (retail value $35) as DRM-free .PDF ebooks, including the complete full-color 418-page Old Gods of Appalachia RPG corebook and the Player’s Guide excerpted from it, plus the Railroad Guide prop and play aid.
And if you pay more than the threshold (average) price, which is set at $14.95 to start, you’ll level up and also get our entire Bonus Collection with five more titles worth an additional $38 – a full poke including the recent character rules expansion Dig Your Own Grave, the full-length scenario Best Leave Them Ghosts Alone, the print-and-cut Resource Deck and XP Deck, and the GM Screen.
Get this all-new Old Gods of Appalachia RPG offer before it succumbs to the Black Stag, Lord of the Night and the Forest Day, the Maker of the Poisoned Promise, the Liar Saint, the Uncast Shadow, the Thing Whose Name Sounds Like Horned Head But Is Not, Monday, January 12, 2026.
DIE: The RPG – new through Mon 12 Jan 2026
Dec. 22nd, 2025 06:55 pm
Through Monday, January 12, 2026 we present the new DIE RPG Bundle featuring DIE, the RPG from Rowan, Rook, & Decard based on – rather, created in parallel with – the DIE Image Comics series (20 issues, 2018-21) by Kieron Gillen and Stephanie Hans. In DIE you play a group of flawed and desperate real-world adults (Personas) pulled back into a cursed roleplaying game that, as teenagers years before, you had barely survived. In a realm stitched together from your obsessions, dreams, and nightmares, you’re power players called Paragons. Do you want to return to the real world or to stay here, where you can finally get what you want? Your whole group must agree whether you stay or go; the dead can’t vote; it can get bloody. What will you do to get home safe? What will you do to stay here forever?
Funded in a hugely successful May 2022 Kickstarter campaign, DIE is a pitch-black portal fantasy that gets all too real – a “Goth Jumanji.” As a Neo, Godbinder, Emotion Knight, Dictator, or Fool, you’ll travel the icosahedral planet of Die, visiting pocket dimensions inspired by all the games and settings you’ve ever loved. Each Persona class has ownership of one size of polyhedral die (d4, d6, d8, etc.) and can use its class die to change a particular situation – whether channeling your god’s power, stealing techno-magical Fair Gold, feeding emotion to your arcane weapon, or even manipulating reality itself. Your group will join in the Great Game of diplomacy and intrigue among the realms, and you’ll confront, and maybe succumb to, the personifications of your own strengths and weaknesses. When does the game end? You’ll all decide – those who survive.
In 1991 six British teenagers vanish while playing a tabletop RPG. Two years later, five of them reappear 50 miles away. One is missing an arm. They can’t say what happened to them. Resuming their normal lives, they get jobs, get married, and have kids. Then, in 2018, the thing that happened to them happens again. This is the setup for the 20-issue DIE comic book series. Writer Kieron Gillen, a longtime gamer who co-founded the video game review site Rock Paper Shotgun, designed DIE: The Roleplaying Game while writing the comic, and elements of each influenced the other.
DIE is a meta fantasy that poses the question of why we play games at all. The setting is a d20-shaped world where each face is a distinct region defined as “a certain slice of the elements that metabolized into RPGs. There’s a region inspired by the classic RPG worlds, sure, but there’s also regions inspired by the Brontës’ childhood shared fantasies, the early war-games (called kriegsspiel) of the 19th-Century Prussian military, and the melancholy of Tolkien. However, each region isn’t just playing out the tropes – it’s a hard twist on that genre. The D&D region is a hyper-compressed mashup of a million D&D worlds. The kriegsspiel is Prussian robots driven by pure mechanics. The Tolkien region is about World War I, and brings to the fore all the things in his work shaped by his time in the Somme.” The 20 regions interact with one another – a living argument about what makes up an RPG. Some regions merge into Great Powers – players in the Great Game, with motives and plans of their own.
Each region embodies an aspect of the Personas’ hopes, fears, fantasies, and obsessions. What do you do when the dragon speaks to you in the voice of your angry long-dead father? What happens when the orcs taunt you with the same insults as your childhood bullies, but now you’re armed with a greatsword? When your beloved ex-partner returns to you in the form of an emotion-draining vampire, will you resist?
Jim Rossignol, co-designer of TEETH (in our October 2024 TEETH Bundle) and Gillen’s longtime collaborator on Rock Paper Shotgun, interviewed the designer for a May 2022 Substack newsletter. Rossignol called DIE “a game where you play the once-teenage players of a TTRPG, who were dragged into the game (like in that D&D cartoon) and then forced to return to it as adults in later life, a bit like – wait – a bit like a forty-something writer who has returned to the preoccupations of his youth for reasons of existential examination and cultural-philosophical heartstringing?! Hang on a minute!”
“RPGs are all about the big questions,” Gillen said. “Who are you? Who do you want to be? Who can you imagine yourself being? Do you like that person? And perhaps, can you take this self-knowledge back to the world? Which is what DIE is really about, both in comic and game, and what RPGs are especially good at. […]
“The world wants to make us into consumers. It tries to make us think creativity is something that godly other beings do. RPGs show how easy creativity is. Some friends, some rules, an evening? You can make a world, a story, something personal, something better than what’s being sold to you by the simulacra, because it’s yours. RPGs remind you of your own power. Creativity is infinite and freely available to you. I love that. They’re the most democratic, even anarchistic form.”
DIE continues to tumble vigorously forward. In November the creators started a new Image Comics story, DIE: Loaded. (“They’ve finished with the game. The game isn’t finished with them.”) And Rowan, Rook, & Decard has announced a new DIE RPG campaign supplement, Metadungeon – not “Megadungeon,” but “Meta,” because the dungeon is, itself, a post-modernist commentary on the history of roleplaying. “Every floor is an era of gaming: Paragons will burrow down through the roughly hewn caverns of 1970s classics from the dawn of D&D, through the new factions and foes of the 1980s, the edgy darkness of the 1990s, and on into the schisms and resurrections of the 21st Century.” Metadungeon will be designed by none other than Gareth Hanrahan (Eyes of the Stone Thief). “It’s going to be half dungeon, half psychodrama, half history of the hobby, and yes we’ve done the math on the halves,” Gareth says. “This idea’s been knocking around for a long time – I had ‘What if Planetary but classic RPG campaigns?’ on my list of possible projects years ago, and I’m overjoyed it’s found expression through Kieron’s DIE.” Metadungeon crowdfunds in April.
This new DIE RPG Bundle subjects you to harrowing personal encounters and exposes your most precious buried secrets – for an unbeatable bargain price! Pay just US$14.95 to get all four titles in our DIE Collection (retail value $53.50) as DRM-free .PDF ebooks, including the complete DIE: The Roleplaying Game, previously in last year’s Cornucopia 2024, along with three scenario collections: Vol. 1: Bizarre Love Triangles, Vol 2: Love is a Battlefield, and Vol. 3: Childish Things. The three collections new to the Bundle of Holding have a combined retail value of $28.50.
Rowan, Rook, & Decard has also provided to purchasers of this offer a 15% discount code good through January 26, 2026 for the print versions of all DIE RPG products sold through the RRD webstore.
This DIE RPG offer goes missing in the grim Blubbermarshes of the Vile, where the Deal-Maker traps it in a contract of eternal service, Monday, January 12, 2026.
CMLXXVI ~ The Questmas Spirit (Of Vengeance)
Dec. 24th, 2025 11:03 am
Vengeful Man: All I really want for Questmas is revenge against my enemy - the 6-fingered swordsman!
Masked Man: Oh yeah? All I want for Questmas is revenge against my enemy - the 7-fingered swordsman!
Vengeful Man: Anyway, I got you something.
Masked Man: Thanks! Same here!
The two are overjoyed to find they've each been gifted the severed hand of their enemy
Update on my medical woes
Dec. 23rd, 2025 07:35 pmNo idea why that didn't happen the first time!
A sudden withdrawal
Dec. 23rd, 2025 12:34 pmSo this morning I went in to the local pharmacy. Who can't help me because NHS England and NHS Scotland are two different organisations. But they told me to call NHS 111 and ask them for help.
NHS 111 said "We don't have anyone available who can prescribe, call us back after 6:30PM, or talk to a local GP as "Unregistered or Temporary Residents". So we went in to my dad's GP and they said "We don't help in that situation, go talk to NHS 111, they'll help you." - which would seem to leave me in an endless loop.
Just in case, I called my GP surgery in Scotland, who said that they can't prescribe in England.
At which point, as nobody is considering this very important, I think about the only options are to either call back after 6:30 tonight or to just do without for a week. Which, having checked online, doesn't look like a great idea.
Edit: I called them back at 7:00. Got through to someone helpful who has given me the location of a pharmacy that we're going to visit first thing tomorrow morning, who have been instructed to help us.
No idea why that didn't happen the first time!


