#Immune system modulation

[cbccindia]

Understanding Immunotherapy for Autoimmune Diseases

Introduction

Immunotherapy, a groundbreaking approach primarily recognized for cancer therapy immunotherapy, is now making significant strides in treating autoimmune diseases. This article delves into how immunotherapy is applied beyond cancer immunology immunotherapy to manage and treat autoimmune conditions.

The Mechanism of Immunotherapy in Autoimmune Diseases

Immunotherapy works by modulating the immune system, enhancing its ability to fight diseases. Unlike in immunotherapy cancer treatment, where the goal is to target and destroy cancer cells, in autoimmune diseases, the therapy aims to recalibrate the immune system to stop attacking the body's tissues.

Types of Immunotherapy for Autoimmune Diseases

There are various types of immunotherapy used to treat autoimmune diseases. These include monoclonal antibodies, cytokine inhibitors, and immune checkpoint inhibitors, each designed to alter specific immune system pathways. While some of these therapies overlap with those used in cancer treatment, their application in autoimmune diseases focuses on immune regulation and suppression of overactive immune responses.

Immunotherapy Medications and Treatments

Immunotherapy medications for autoimmune diseases are tailored to reduce inflammation and curb the immune system's erroneous attacks on healthy cells. The precise medication or combination of therapies depends on the specific autoimmune condition being treated, highlighting the personalized nature of immunotherapy.

The Role of Immunotherapy and Vaccines

Exploring the intersection of immunotherapy and vaccines reveals potential for preventative strategies in autoimmune diseases. Vaccines designed to induce tolerance in the immune system are under research, potentially preventing autoimmune diseases from developing or worsening.

Managing Side Effects and Costs

While immunotherapy offers new hope, it's crucial to consider immunotherapy side effects and immunotherapy cost. Side effects vary widely, from mild to severe, and must be carefully managed under medical supervision. The cost can also be significant, necessitating a discussion about healthcare resources and insurance coverage.

Conclusion

Immunotherapy for autoimmune diseases represents a promising frontier in medical treatment, offering hope for millions suffering from these conditions. As research progresses, it could redefine the therapeutic landscape for autoimmune diseases, much like it has for cancer.

Discovering Excellence in Cancer and Autoimmune Disease Treatment at CBCC India

At the forefront of medical innovation and care, CBCC India stands as one of the leading Cancer Hospital in India, dedicated to eliminating cancer and advancing treatment for autoimmune diseases. Our commitment to innovative research and exceptional care ensures that every patient receives personalized, state-of-the-art treatment. Discover the pinnacle of healthcare excellence at CBCC India, where we strive to conquer cancer and improve the lives of those with autoimmune diseases through cutting-edge immunotherapy and comprehensive care.

[boulevardpharmaceuticalcompoun]

Low-dose naltrexone (LDN) is gaining attention for its potential in treating various medical conditions. Let’s delve into how LDN works and why it’s becoming a popular choice. If you're considering Low-dose Naltrexone (LDN) in Boston, Massachusetts, understanding its mechanisms can help you make an informed decision.

[reasonsforhope]

"People living with diabetes might have a new hope. Scientists have tested a new drug therapy in diabetic mice, and found that it boosted insulin-producing cells by 700% over three months, effectively reversing their disease.

Beta cells in the pancreas have the important job of producing insulin in response to blood sugar levels, but a hallmark of diabetes is that these cells are either destroyed or can’t produce enough insulin. The most common treatment is regular injections of insulin to manage blood sugar levels.

But a recent avenue of research has involved restoring the function of these beta cells. In some cases that’s started with stem cells being coaxed into new beta cells, which are then transplanted into patients with diabetes. Researchers behind this kind of work have described it as a “functional diabetes cure.”

Now, scientists at Mount Sinai and City of Hope have demonstrated a new breakthrough. Previous studies have mostly involved growing new beta cells in a lab dish, then transplanting them into mice or a small device in humans. But this new study has been able to grow the insulin-producing cells right there in the body, in a matter of months.

The therapy involved a combination of two drugs: one is harmine, a natural molecule found in certain plants, which works to inhibit an enzyme called DYRK1A found in beta cells. The second is a GLP1 receptor agonist. The latter is a class of diabetes drug that includes Ozempic, which is gaining attention lately for its side effect of weight loss.

The researchers tested the therapy in mouse models of type 1 and 2 diabetes. First they implanted a small amount of human beta cells into the mice, then treated them with harmine and GLP1 receptor agonists. Sure enough, the beta cells increased in number by 700% within three months of the treatment. The signs of the disease quickly reversed, and stayed that way even a month after stopping the treatment.

“This is the first time scientists have developed a drug treatment that is proven to increase adult human beta cell numbers in vivo,” said Dr. Adolfo Garcia-Ocaña, corresponding author of the study. “This research brings hope for the use of future regenerative therapies to potentially treat the hundreds of millions of people with diabetes.”

The results are intriguing, but of course being an animal study means there’s still much more work to be done before it could find clinical use. So far, harmine alone has recently undergone a phase 1 clinical trial in humans to test its safety and tolerability, while other DYRK1A inhibitors are planned for trials in humans next year.

Perhaps most importantly, the team will soon experiment with combining beta-cell-regenerating drugs with others that modulate the immune system. Ideally this should help overcome a major hurdle: the immune system will continue attacking new beta cells as they’re produced.

The research was published in the journal Science Translational Medicine."

-via New Atlas, July 14, 2024

[thebibliosphere]

Are you familiar with any connection between mast cell issues and type 1 diabetes? I have a family member who developed and got diagnosed with diabetes when he was a kid, and his mother is convinced it was because of his childhood vaccines. Now i'm aware enough that vaccines could cause an immune system reaction like what you were talking about about before, with people who are predisposed to certain conditions that could suddenly self destruct when something like vaccines or a cold just tips the condition over. Unfortunately his mother went full anti-vax after this happened :/ anyways your post made me wonder if there was a connection between diabetes 1 and mast cells

Oh, hey I actually read something about this recently:

Tl;dr:

Mast cells are highly differentiated, widely distributed cells of the innate immune system.

The involvement of mast cells in diabetes is corroborated by findings indicating that these cells are associated with inflamed adipose tissue, the development of certain diabetes complications such as diabetic nephropathy, and reduced wound healing in the case of diabetic foot lesions [70,71,72,73].

In the present review we have discussed the role of mast cells in the diabetic pancreas. Their increased presence in the pancreas of human subjects with type 1 diabetes raises the possibility that these cells could be implicated in the pathophysiology of this form of diabetes, which is due to autoimmune destruction of the insulin-secreting beta cells.

However, it is not clear if and why mast cells could be dangerous or protective in this regard. More studies are needed to determine whether and how manipulation of these cells might impact on the natural history of type 1 diabetes, which could allow the development of a strategic approach targeted to modulate mast cell function

- - -

Basically, damned if we know, but they’re studying it.

As for whether a vaccine caused him to develop type 1 diabetes, personally, my money is on no. It’s primarily (though not always) a genetic autoimmune disorder that’s waiting to go off. The vaccines might have caused an inflammatory response that drew awareness to existing symptoms that resulted in diagnosis, but the pre-disposition was likely always there.

Viruses on the other hand can promote autoimmunity, (though there’s some debate about whether or not the link between viruses and the development of diabetes type 1 is valid. More research is needed) so that’s an even more important reason to vaccinate imo.

Like fuck messing with that. You get rubella AND an autoimmune disease potentially triggering early because of it? Fuck that.

[covid-safer-hotties]

Also preserved in our archive

Hey! Look! A great breakdown of that thing I'm always talking about being a big yet entirely-overlooked deal by 90% of medical professionals in regards to this particular virus!

SARS-CoV-2, the virus behind COVID-19, is not done with us. Over the past four years, it has shown a remarkable ability to adapt, with each new variant outmaneuvering our immune systems in unique ways. The recently published study on the XEC variant (November 22, 2024) provides fresh insights into how this virus is evolving. (1) Combining this with the broader history of immune evasion, we see a troubling pattern: the virus continues to find ways to evade the immune system and in many cases, persist, potentially leaving lasting impacts on our health even for those who experience only mild or asymptomatic infections.

What the Study Found: XEC’s Immune Escape Arsenal The latest study revealed that the XEC variant—an offspring of two previous variants, KS.1.1 and KP.3.3—has developed mechanisms that make it harder for our immune systems to neutralize it. Here’s how it works:

1. Glycosylation Mutations in the N-terminal Domain (NTD):

The XEC variant introduces new glycosylation sites, such as the T22N mutation, which act like a cloak, hiding key parts of the virus from antibodies.

These sugar molecules shield the receptor-binding domain (RBD), a crucial target for vaccines and natural immunity, making it harder for antibodies to bind and neutralize the virus.

2. Allosteric Effects:

Mutations in the NTD don’t just shield the virus—they also alter the behavior of the RBD through a process called allostery. These changes can make the RBD less accessible or alter how it interacts with human cells, further reducing the effectiveness of antibodies.

3. Potential Impact on Membrane Fusion:

The study hints that these mutations may also enhance how efficiently the virus fuses with human cells, potentially increasing its infectivity.

Immune Evasion: A Constant Tug-of-War The ability of SARS-CoV-2 to adapt is not new. Looking back at the history of immune evasion, we see a pattern:

The Early Days: Mutations like D614G made the virus more infectious.

Alpha and Beta Variants: N501Y and E484K mutations increased binding to human cells and evasion of neutralizing antibodies.

Omicron Era: A flurry of spike protein mutations allowed the virus to reinfect people with previous immunity and bypass vaccine-induced protection.

XEC is the next chapter in this story, combining these strategies with new tricks like glycosylation and allosteric modulation to stay ahead of human defenses.

Why This Matters: Beyond Infections Understanding immune evasion isn’t just about tracking infections—it’s about long-term health impacts. Here’s why this evolution is particularly concerning:

1. The Shadow of Long COVID:

Millions of people suffer from Long COVID, characterized by fatigue, brain fog, heart palpitations, and muscle pain. The virus’s ability to persist and evade the immune system might explain why symptoms linger for months or years in some individuals.

Chronic immune activation or hidden reservoirs of the virus could drive these long-term effects.

2. Asymptomatic but Chronic Damage:

Even in people without noticeable symptoms, SARS-CoV-2 has been shown to cause subtle, potentially long-term damage to:

Vascular systems: Leading to inflammation and microclot formation.

Neurological function: Disrupting brain activity and potentially accelerating neurodegenerative conditions. Early onset dementia

Musculoskeletal health: Causing unexplained weakness or pain.

Cognitive performance: Contributing to memory issues and reduced mental clarity. Are you or someone you know having more trouble finding words to use or losing things more often?

3. Vaccines Alone Aren’t Enough:

While vaccines remain essential, their effectiveness is limited by the virus’s rapid evolution. Variants like XEC show how SARS-CoV-2 can sidestep even the most advanced immune defenses, highlighting the need for next-generation vaccines targeting broader parts of the virus. We have know this for a long time now so where are the broader targeting vaccines?

The Future of SARS-CoV-2 Evolution The virus has already demonstrated its ability to adapt to our immune responses in multiple ways, and there’s no reason to believe it will stop. Here are some possibilities for future adaptation:

Further Refinement of Glycosylation: Adding or modifying sugar molecules could make the virus even more difficult to detect.

Enhanced Membrane Fusion: Mutations that improve how the virus merges with human cells could increase its infectivity.

Host Adaptation: Over time, the virus could become better at hiding within human cells, evading both natural immunity and therapeutic interventions.

Increased Chronicity: The virus might evolve to persist at low levels in the body, leading to ongoing inflammation and long-term health consequences.

What We Can Do: Adapting to the Virus’s Adaptations The XEC variant and others like it remind us that SARS-CoV-2 is still a formidable opponent. Here’s what we can do:

1. Invest in Better Vaccines:

Universal or pan-coronavirus vaccines that target conserved regions of the virus are critical.

2. Improve Diagnostics:

Detecting chronic or asymptomatic infections early could help mitigate long-term health effects.

3. Focus on Treatment:

Antiviral drugs that target different parts of the virus, combined with treatments for inflammation and immune dysregulation, could help reduce the impact of Long COVID.

4. Stay Vigilant:

For individuals, maintaining basic preventive measures during high transmission periods can significantly reduce risks.

Conclusion: Learning from the Virus SARS-CoV-2 is teaching us a harsh lesson about evolution. Its ability to adapt and evade our defenses, from antibodies to T-cells, shows no sign of slowing down. Variants like XEC underscore the importance of continued research, innovation, and public health vigilance. By understanding the virus’s strategies and preparing for its next moves, we can better protect ourselves—not just from acute infections but from the long-term consequences.

Reference:

Enhanced immune evasion of SARS-CoV-2 variants KP.3.1.1 and XEC through N-terminal domain mutations (November 22, 2024)

www.thelancet.com/journals/laninf/article/PIIS1473-3099%2824%2900738-2/fulltext

[solas-backpack-mug]

i LOVE godlikes and their weird features. stuff like pallegina's third eyelid, tekēhu's ink squirting, and vatnir's horrible immune system (ouch)

reblog this with weird features of your godlike ocs!!!!

i'll start with my inquisitor asaria (rangi's past life). she's a dawn godlike and as such she continuously glows. that glow gets brighter when she's happy or angry, and dimmer whan she's sad, scared, or sleeping. she can modulate her glow, although it's easier for her to get brighter than to suppress it. she has used her glow to blind people as a part of her inquisitor duties. aside from visible light she also emits infrared and ultraviolet which means that she has an aura of Warmth, Sunburn, and Skin Cancer <3

[theambitiouswoman]

GUT HEALTH: How it Affects Your body 🍽️🤍✨

Having a healthy gut is important because it plays a central role in the overall functioning of your body. The state of a healthy or unhealthy gut affects all of these things:

Digestion and Nutrient Absorption: The gut's main role is to break down food and absorb important nutrients, including vitamins and minerals. When the gut is healthy, it digests food effectively and maximizes nutrient absorption. When it is not, it can result in digestive issues such as bloating, gas, and diarrhea, as well as nutrient deficiencies.

Immune System Support: About 70% of our immune cells are located in the gut. A balanced gut supports a strong immune response, helping the body fend off illnesses and reduce the risk of infections.

Emotions and Mood: The gut and brain are intricately connected through the gut-brain axis. The gut produces many neurotransmitters, including serotonin, which regulates your mood. An imbalanced gut can influence mental health, leading to issues like anxiety, depression, and even cognitive impairments.

Hormonal Balance: The gut plays a role in the production and modulation of certain hormones. This can impact various bodily functions, from stress responses to reproductive health.

Weight Management: The gut microbiome can influence metabolism, appetite, and fat storage. An imbalanced gut can lead to weight gain and metabolic disorders.

Protection Against Chronic Diseases: Poor gut health has been linked to a higher risk of chronic diseases, including type 2 diabetes, cardiovascular disease, and certain types of cancer.

Detoxification: The gut plays a role in eliminating waste products and toxins from the body.

Inflammation Regulation: A healthy gut can help regulate inflammation in the body. Chronic inflammation, often resulting from an imbalanced gut is a root cause of many diseases.

Skin Health: There's a connection between gut health and skin conditions. Issues like acne, eczema, and rosacea can be influenced by the state of the gut. An unhealthy gut can lead to inflammation, which may manifest as skin issues.

Barrier Function: The gut lining acts as a barrier, preventing harmful substances from entering the bloodstream. A compromised gut lining, often referred to as "leaky gut," can allow toxins and pathogens to enter the bloodstream leading to various health issues.

Production of Vital Compounds: Your gut produces essential compounds, like short-chain fatty acids, which has a lot of positive effects on health from reducing inflammation to supporting brain function.

Sleep Function: The gut produces neurotransmitters and hormones that regulate sleep, such as serotonin and melatonin. An unhealthy gut can disrupt sleep patterns.

[thoughtportal]

In eastern Mexico’s underground caverns and streams, a blind fish undergoes a peculiar adolescence: as it approaches maturity, taste buds begin to sprout under its chin and on top of its head, creeping toward its back.

“It’s a pretty wild amplification of the sensory system of taste,” says Josh Gross, an evolutionary geneticist at the University of Cincinnati and a co-author of a recent study on the cave fish in Nature Communications Biology. Gross and his team discovered that the new buds blossom around the time when the fish transition from eating larval crustaceans to gobbling up their adulthood staple: bat guano. Taste buds outside their mouths might be helping the fish detect bat droppings in the utterly dark, “food-starved” caves, Gross says.

Wandering taste buds aren’t unheard of elsewhere, especially in other fish. Some damselfish cultivate taste buds on their fins, and channel catfish have them across their midsections. And as alien as it may seem, many cells throughout the human body can taste, too. They’re just not sharing the flavors with your brain like taste buds do.

Lora Bankova is a Harvard Medical School respiratory biologist who studies tuft cells, a cell type sprinkled within human mucous tissues like those lining your nostrils, throat and gut. These “rapid responder” cells trigger the immune system if they detect an outside threat, and many of them rely on built-in taste receptors (the same kinds found on taste-bud cells) to do so. Bankova notes that many potentially harmful bacteria communicate via signaling chemicals called lactones—which also happen to activate taste receptors attuned to bitter flavors, prompting tuft cells’ immune response. And it turns out that even environmental allergies may be a matter of taste: dust mites and several mold species can also set off a tuft cell’s taste receptors, Bankova says.

“Evolutionarily, taste receptors [have moved around] the body to protect us from the air we inhale and all the attacks we’re getting through the orifices,” Bankova says. “They’re in the inner ear, the urethra, everywhere something can get into your body.”

Such “extra” taste receptors aren’t just bouncers at the door—they taste test for our internal systems, too. Receptors for sweet tastes help to tune insulin production in the pancreas and make sure neurons in the brain have access to enough glucose. Sweet, bitter and umami receptors in the gut modulate digestion.

Gross says it’s still a mystery what taste receptors the bat guano activates in the blind cave fish. “There may be some sugar content if it’s a fruit bat, maybe some protein content if it’s a carnivorous bat,” he says. So far only the cave fish has signed up to sample it.

[deakyjoe]

In Sickness & In Health

Pairing: Din Djarin x Reader (no pronouns used but Din does call Reader “cyar’ika”)

Category: sick fic, fluff

Summary: Din cares for you when you're sick.

Warnings: sickness/illness, Grogu being a menace, Din being awkward, cuddling, hurt/comfort, fluff basically

Word count: 1.2k

A/N: I am recovering from a cold.

Consider buying me a coffee :)

You'd woken up sick, quite possibly in the worst condition of your life. Your limbs ached, your head was pounding, your stomach turned at every tremor of the Crest, your throat was sore and you could barely breathe through your nose. Death felt like it was approaching you at any second.

Din insisted that you were being dramatic.

He was sure that you'd just picked up a minor illness from the last planet you'd stopped on for supplies and would recover in a couple of days. He told you to rest and to stay away from Grogu as much as possible, unsure of the strength of the child's immune system.

Which would have been easy considering all you wanted to do was curl up into a tiny ball in the dark and sleep. Unfortunately, the kid was just a little too curious in nature and wanted to see what was wrong with you. And he wouldn't take no for an answer. This caused Din to lock him away in the cockpit with a shiny ball to occupy him for the majority of the time while you recovered. 

"I feel bad." You told your travelling companion after Grogu had been shut away.

"You'll feel worse if you give him this disease and he dies." The Mandalorian replied, handing you an extra blanket after assuring you that it was fine that you used his bunk to sleep in.

Your eyes widened in fear, heart beating rapidly in your chest suddenly. "I thought you said this was a common illness!"

"Yes, but he is only a child." He sighed, gesturing for you to lie down. "You will be fine. Now go to sleep."

You mumbled to yourself lowly but did as he said anyway, drifting into a dreamless sleep once Din had closed the door.

You awoke some time later, sweat pouring out of you in floods as you burned as hot as a supernova. In your delirious fevered state you got out of the bunk, laid down on the floor of the hull and fell asleep again.

When you woke up again, a few hours later you assumed, you could feel something touching you.

As your eyes cleared, you realised that Din was sat beside you on a crate patting your head.

Your brows raised in surprise. "What are you doing?"

"Soothing you." He mumbled through the modulator.

"By doing this?" You croaked, glancing up to where his wrist hovered above your eyes.

He paused. "Do you... do you not like it?"

"Don't dislike it." You said. "It's just a little strange."

"The kid likes it."

"Do I look like a green baby with large ears to you?"

He hesitated.

"Don't answer that." You grumbled, turning to bury your face in the thin blanket you'd dragged to the floor with you.

"You were talking in your sleep. I thought it might help."

"Oh." You whispered, embarrassed about what you might have said.

"It was mostly incoherent mumbling."

"Oh." Thank the stars.

"Mostly." There was a hint of teasing amusement to his voice which you were terrified to question.

But you did anyway. "What does that mean? What did I say?"

He ignored your questions. "You should get back into bed."

"Too hot."

"Get back into bed, cyar'ika." He insisted, holding a gloved hand out to help you up.

You did as he said, too tired to argue anymore.

"I'll come back to check on you in a while." Din told you before disappearing to the cockpit again.

You faded in and out of sleep before the Mandalorian came back with a bowl of soup and a restless Grogu at his side a little later.

Worry plagued your mind momentarily as you cautiously eyed the kid. "I don't want to get him sick."

"He missed you." Din replied with a small shrug, handing you the bowl and a spoon.

You smiled down at the kid weakly, glad to see him. He was a nice presence to have around, almost always happy about something. The Mandalorian was the opposite in that regard - always unhappy about something, apart from the child, but was still a nice presence to have around. Overall, the combination of the both of them was making you feel better. A lot better. There was no one else you'd rather spend your sick days with.

The three of you ate in silence, just the occassional babble of nonsense from Grogu as he slurped down his dinner. The warm food made your throat hurt less but despite its temperature, you started to get cold.

You wrapped the blanket more tightly around yourself in the hope that it would help but had little success. So you distracted yourself by watching Din and Grogu interact instead. Maybe the warm feeling they created in your heart would extend to the rest of your body.

The dull hum of the ship combined with the quiet mumbled, very much one-sided, conversation between the two other members of the clan caused you to grow sleepy again. Which Din quickly noticed when your eyelids started drooping and your head lolled to the side a couple of times. So he swiftly put the child to bed and sent him back to the cockpit before returning to you.

"You should go back to bed." He stated, noticing your intense grip on the blanket as he sat you down on the end of his bunk. "What's wrong?"

"I'm cold." You confessed, even though it was pretty obvious by your violent shivering and chattering teeth. "Freezing actually."

Din did nothing for a moment, just stared at you and seemingly contemplated something if the way his fingers twitched at his sides was any indication, before hitting a switch and plunging the hull into darkness.

"What are you doing?" You blinked, suddenly feeling more awake as you tried to adjust to the lack of light.

"Sshh." He replied, the clang of metal on metal punctuating the word for him.

Was he... was he undressing?

"Din, stop."

"I said sshh." His voice was clear, no muffling from a modulator or helmet. His face was out in the open.

You stayed silent until you felt hands land on your shoulders, letting out a small gasp at the contact.

"Lie down on your side." Din mumbled, gently pushing you back.

The protest you had prepared died on your tongue as you felt him crawl into the bunk beside you and settle down at your back as the two of you laid down. He got as close to you as possible, arms wrapping around you and legs tangling with yours.

"What're you doing?" You whispered despite relaxing back against him and embracing the heat he was radiating.

"Warming you up." He mumbled into the back of your neck, lips grazing your skin.

"No!" You whined, wriggling a little to attempt getting out of his grasp. "I don't want you to get sick."

"Don't breathe on me then." He answered simply, arms locking around you to hold you in place. "Now go to sleep."

You would've fought more, concerned with his health, if it wasn't for the fact that this position felt good. So good. He was warm and soft and you felt so safe and secure in his hold. Maybe just cuddling for a little while wouldn't be too risky. At least, that's what you told yourself as you fell into a deep slumber.

It only took a couple of days before rattling, shaky coughs could be heard echoing around the ship from a certain bounty hunter's modulator.

[anim-ttrpgs]

The skill point allocation system in Eureka is very elegant.

Is the principle of evening out to 0 something that has often been used in ttrpg design? If so, can you name other games that inspired Eureka in that regard? Or did you come up with it for Eureka?

"All skills can be -n to +n with a cumulative total of 0" seems too usefull, too elegant, as to never been utilized before the year 2024.

I came up with it independently and have literally never seen it anywhere else. I have thought the same way about the Eureka! Point mechanic, though similar things have been done before in other RPGs, just never applied to mystery investigation gameplay. Why hasn't anyone done this yet?

I feel like it must have been used somewhere else at some point in the 50 years of TTRPGs that have been made, I've just never seen it. i agree it feels like too good of an idea to not, like, practically be industry standard, but then again, TTRPGs are not a very innovative industry. It's very stagnant. Most TTRPGs that have come out in the past 50 years have just been D&D clones to some degree or another, and most "innovation" I see has just been "what if we unknowingly reinvented the wheel except this time we made it hexagonal instead of octagonal," total Tesla cybertruck style innovation.

The industry is kind of uniquely set up for that. It's one of the most monopoly-dominated industries/artforms in existence, with one game (of greatly varying quality and thoughtful design between editions) completely dominating it for all 50 years of its existence and being allowed to basically fully define what a "TTRPG" is. The biggest alternative to D&D for the past 20 years has been Pathfinder, which is just like D&D but a little better designed, and before that its biggest competitor was World of Darkness, which, if you actually read their rulebooks, are also designed pretty much like D&D except for some text at the beginning which basically says "you can ignore these extremely dungeon-crawl-y rules to focus more on narrative, don't be like those dumb dungeon crawl players," which if you have been following this blog you know is a load of crap.

Call of Cthuhlu, another big veteran contender for the industry that is still going pretty strong, has been the standard for "investigation" gameplay for nearly 50 years, but it's just a Lovecraft hack of RuneQuest, which was designed for, you guessed it, fantasy dungeon crawling. That's why even though CoC adventure modules do tend to play pretty well with Eureka, most of them are still structured as a short line of like 1 or 2 clues to follow to get the PCs into a spooky scary enclosed dungeon-like monster-filled location as quickly as possible, and you have advice like (uncharitable hyperbole) "if the PCs get stuck, make evidence fall from the sky and land at their feet."

Plus, you have big "actual play" podcasts who really really champion the whole "ignore the rules when they get in the way of your pre-planned three-act-structure plot" and the mega-monopolgy with marketing money making it a selling point that if you ignore the rules enough "D&D5e can do anything."

TTRPGs are also a relatively young artform without a ton of mainstream attention until pretty recently (which, as I mentioned, has been eaten up by D&D5e, Pathfinder, and big "actual plays"), and they are a hard one to participate in because playing a single TTRPG requires a ton of time investment compared to most other popular art forms like books, video games, music, and movies.

All this results in many, many people who play and even design TTRPGs literally never having played anything that wasn't WotC-era D&D, barely one or two degrees of separation from WotC-era D&D, or "it's not important if it's WotC-era D&D or not if you just ignore the rules!" Oh and PbtA and BitD players and designers, you're not immune to this! Those are just the "D&D5e can do anything!" of the indie scene and no they really really are not the best framework/engine for every single game ever!

For all the talent, study, effort, and respect for the artform across the A.N.I.M. team, not even we are immune to this. I haven't played nearly as many TTRPGs as I would like to have before calling myself a "learned" TTRPG designer. There might be some obscure game from 2004 I've never heard of that does some of Eureka's stuff already, that if I had read, I could have made Eureka even better by improving upon and learning from the mistakes of others rather than working in uncharted territory.

So, in conclusion, to use the film industry as an analogy, it's like if, during the past 10 years of every fucking mainstream movie being about superheroes, aspiring film makers, who have watched between 0 and 1 movies that weren't about superheroes, are having the "novel" idea of "what if.. a movie wasn't about superheroes!" and then trying to make a movie not about superheroes with no non-superhero experience or study. And Eureka: The Movie is good and innovative because A.N.I.M. Studios watched a measly 10 different non-superhero movies and studied film theory before making it.

[hummingjay]

New oc for thee: SKUR "Großer Skua”

Under the cut are numerous doodles and SO MUCH YAP it’s very long so be warned.

SKUR

Schwere-Kommando-Ungeheuer-Replika

Heavy-commando-Behemoth-Replica

Großer Skuas, or Schwere-Kampf-ungeheuer-Replikas, “Great Skuas”, often simply referred to as Skuas, are heavy commandos utilized by the nation in dangerous raids. These units are large and bulky, wearing heavy armor and welding weapons that are usually too heavy not to be on a mount. They operate in small groups, usually one to three, commanded by a KLBR, STAR, LSTR, STCR unit, or with an infantry force.

Skuas use a wide variety of heavy weapons, from machine guns and grenade launchers to flamethrowers and shotguns. Whatever the weapon, they’re always hyper-powered and usually too heavy for most units to even carry, much less use. They can unmount vehicle machine guns and use them in a man-portable fashion. Their armor is strong enough to block shotgun rounds at point blank range. Despite their large, heavy appearance, Skuas are deceptively fast. They carry cargos of ammunition and gear, and can be used as workhorses for transport. 

Skuas are the perfect soldier in a way that an angel is the perfect human. They’ve been stripped from their humanity in a barbaric defiance of the natural order of creation, leaving an abomination whose sole purpose is bringing death in the most destructive manner possible. They feature skinless, fleshless, skull-like-heads, and many of their internal organs have been replaced with mechanics. They have no stomach and run instead on pressurized gasolines, and can create improvised fuels from processing and liquidizing organic matter, allowing them to attain fuel in the field and go without supplies for close to years. They can go without fuel for up to a week, and their fuel-processing systems allow them to live on diets of wood and even flesh. Their internal fuel systems and generators are located where their stomach and other organs used to be. Connected to the fuel system and remaining heart and lungs is a sophisticated engine that emits a low whir or hum. With no lips, their voicebox is located directly in the back of the throat, and sounds more mechanical than a normal replika. Their voice tends to be unsettling, like it’s not real or that it cuts through one’s ears. They will often cough the exhaust from their internal engine systems. 

Skuas do not feel pain, and will instead feel a dull pressure when damaged, only so that they’re aware of their wounds. They must be watched closely as they see no difference between a pinprick and decapitation. They feature air filters in the neck and are immune to toxins, and can breathe even through even the thickest smoke and dust. Advanced cooling and ventilation control systems allow them to survive in both extremely hot or cold environments. Their joints are more mechanical, mixing machine pistons with their pseudo-flesh to strengthen them. Their cranial construction and nervous system are organic and interconnected with their machine structures and systems. They lack conventional eidetic modules and utilize instead camera-like lenses that are more immune to flash-grenades and cannot be blinded by debris. A built-in decibel limit also prevents becoming deaf, temporarily or otherwise. Arteries and veins are seamlessly integrated with the other mechanical systems. Though they possess no stomach, intestines, liver, kidneys, and other artificial internal organs that replikas typically have, they still have their heart, blood, and lungs to pump oxygen into the fuel systems. 

Skuas operate well alone and in groups. One can be sent on a near-suicidal operation or can serve as support for a larger infantry. 

Skuas are generally led by a handler, usually an Elster, Kolibri, Storch, or Starling unit. Each handler type fulfills a different role. Elster units lead Skuas far into unsurveyed enemy territory with little information and even less support. Storch-led Skuas operate raids. Starlings lead Skuas among other infantry, and Kolibris will operate a wider variety of roles in-high-stakes operations. Roles may vary, such as Elster units leading a defense campaign or a Starling leading a raid.

The commanding handler of Skua units must be evaluated for loyalty, as Skuas are easy to manipulate due to their unwavering, unquestioning, and extreme obedience. Commanding officers’ sole role is to manage the commandos, dealing with maintenance and orders. While not higher ranking than other officers, having the deadly and intimidating behemoths under their command affords handlers an uncanny authority. Skuas will develop close bonds with their commander, and are extremely protective of them.

Due to their skinless, faceless nature, Skuas are difficult at best to read. It is hard to gauge their emotions by their voice, which itself is monotone and formal, and their demeanor is similarly difficult to gauge. Their commanding handlers are expected to understand the subtle signs that signify their mental state, such as a clenched jaw in anger, and the activation of ventilation systems located in the neck and spine when flustered. Skuas do not possess tear nor mucus ducts, and will emit sporadic growls and hums instead of crying. Similarly, harder, louder, more aggressive growls can be heard if the Skua is particularly angry. When especially happy or content, they will produce deeper, louder humming sounds akin to purrs. Skuas also lack sweat glands, using their internal cooling and ventilation systems to stay at optimal temperature. Oddly, a byproduct of their unorthodox nerve system is that they enjoy being pet. Handlers discover a ‘sweet spot’, usually located on the torso.

Skua personalities appear dull and empty. They speak in monotone voices and tend to be very passive. In combat, they are aggressive and destructive, yet calm, causing maximum damage in minimal time. They fight in an oppressive fashion, fighting in such a manner that enemy combatants hardly have a chance to fire back. Unlike other combat units, they show no affinity nor fondness for violence, it’s simply a task that must be done. Skuas are wholly and entirely obedient to commanding units, utterly unquestioning of the even most appalling orders. While deep down, a sense of morality can theoretically be found, said ethics are completely ignored when an order contradicts what little there is. They will not go out of the way to cause maximum collateral, but have no qualms about it. For these reasons, Skaus can also function as executors. Their obedience makes them easy to manipulate, and are generally under the command of a replika instead of a gestalt. Upon further interaction, Skuas will reveal a calm and soft personality, akin to MNHR type units. When interacting with other units, they will minimize movement, as they do not know their own strength and can cause injury. They tend to not speak, aware of the intrinsic unsettling quality of their voice.

Skuas are physically terrifying to most units. Faceless, monstrous, destructive, and smelling of exhaust, they’re avoided almost entirely. They serve as omens to mass destruction to the enemy. Skuas themselves have no particular fondness for specific units. If any treats them as more than a demonic tool, they will attempt to befriend the person. Showing affection to the unloved units is an effective and easy way to gain their trust. Underneath their corpse-like and violent exterior, Skuas are gentle souls. They are fascinated by gestalts and their lives, as well as other replikas, and display a childlike curiosity with the world. They stabilize their persona by drawing and sketching. They may tattoo each other’s armor so that others can tell them apart, usually drawing little more than numbers. Often, one can find Skaus hidden just off the area where Eules work, as they listen to their singing and music. They enjoy looking for flowers when off duty, and will decorate each other with them.

Naming conventions are random. They have no preference for names and are generally named by their commanding officer, sometimes others, very rarely themselves. More personalized names stem from commanders. More generic names will come from nearby compatriots. 

While technically female, Skuas are often referred to as “it” by others, not afforded the luxury of humanization. They make no movements to correct the notion. They are seen as unmanned combat vehicles rather than replikas, and they know it.  Handlers are to refer to them more humanely, and are to provide names if a unit doesn’t have one.

The gestalt template for the Skua unit was a gunner in an aircraft crew, chosen for their keen eye, unyielding loyalty, and will of steel. Skuas are to be kept on-ground purely as foot soldiers to minimize resurfacing memories. Degraded Skuas are extremely dysphoric and must never look into a mirror. When degraded, Skuas remain mostly obedient but erratic and confused. They become unsteady on their feet and will attempt to board aircraft. Obedience will not decline, but they will question unfamiliar commanders. Late-stage degradation will reveals mania and violence. Decommission degrading Skuas immediately as soon as degradation is confirmed. They can easily be disposed of by having their handler disarm them, though convincing their handler to do so may be difficult. Use anti-armor rounds for a quick operation.

[bumblehoneybee]

Wait can you actually go on about how u think the toys are biologically and such? I noticed how the toys didn’t get tired like the persona but still needed sleep and how dogday didn’t seem to be in too much pain when he was getting sewed together(maybe cuz that’s the fabric part of him and not vitals? idk but please share ur take if u want it sounds really interesting!)

Ok so this may or may not be a long one depending on how heated i get! we'll see as i go

WARNING: talk of gross anatomy and biological functions, body horror, the works

so, starting with dogday and the likes, the bigger bodies. we can see through both catnap and dogday that they retain parts of their original organic body, if somewhat twisted. catnap obviously has a spinal column, and dogday has organs and even blood within him that he loses due to being cut in half. so this implied that the bigger bodies initiative didn't just move a consciousness into the suit, but everything inside that person too

catnap is too big to say that there's simply a body inside the cat body. instead, i see it being something along the lines of the automail in FMA. somehow the scientists have not only transferred over the subject's brain into the toy body, but has also either transferred the nerves or created a delicate wire system that replicates the nervous system. and due to wanting the wires/nerves to be protected as well as the bigger bodies to look relatively normal, they add metal bones.

but the organs, you ask me! the organs are the fun part. why keep a stomach in a mostly artificial body? why keep a circulatory system? why keep lungs, blood, vessels, all that?

a brain can not run on electricity alone! it needs nutrients provided to it by the blood. nutrients gained from eating. and not to mention that the brain is a very delicate thing! it needs to be protected! an immune system is needed

THUSLY, seeing bones in the bigger bodies wouldn't be strange either! blood carries nutrients, bones help with immune system and such, they practically created frankenstein in that thing!

it also goes to show how much worse catnap would've had it if he was made into catnap as a kid as opposed to dogday being an adult when he was changed. kids grow, their systems are all small small small. he'd need lots of restructuring in order to be able to grow while being inside an artificial body. he's mostly stopped by the time the game takes place, if i remember correctly he's about 22 in the events of the game, and luckily so! imagine outgrowing your own body and being unable to do anything about

which is just a lot of blabber to say that catnap no doubt was sympathized by the prototype, even if he was used. y'all saw that radius and ulna. the prototype no doubt knows what that pain is like

so, and i never write it this way, but putting legs or a limb back on dogday, or any one of the bigger bodies is possible due to all the artificial parts of them, but not by the player most likely. artificial nerves, artificial vessels, it can all be fixed! rewiring and putting in new tubes isn't hard to do, when you're a professional scientific team like the ones we see when that guy is turned into that little dinosaur (which it's own thing i won't get into right now)

i can see the vessels too having some sort of shut off valve too, where if they're broken, to preserve blood, they can close themselves off. this would explain why dogday was still alive, and if most of his body is artificial, it can show why he hasn't had to eat as much. he doesn't have as much to support through biological means!

so dogday has eyes that can see without visible eyes. he has a tongue he can move, and a mouth he can open and closed. however, the minute details aren't there, either cause of disrepair, or because the scientists couldn't manage the details in the first place. he can close his mouth, but moving his lips is hard. luckily he has a voice box that modulates his vocal cords, meaning he doesn't need to make the words with his mouth to say them

i dunno if any of this makes sense. when i write, like seriously write the bigger bodies, these are the rules i follow! tho if anyone has other ideas, i'd love to hear them! this stuff is fascinating

[cowgirlgirl2002]

Very tired of hearing how women think their weak and how men are biologically better when is is actually not true at all so here's why women are strong too, I'll put medical and scientific facts about women

1. Women have stronger Immune system

Females have better innate and adaptive immune responses to disease-causing pathogens than males. Females also produce better protective antibodies following vaccination against flu, yellow fever, dengue, and viral infections.

Females typically develop higher innate, humoral and cellular immune responses to viral infections and in response to vaccine

Women see more colors than men

Even when compared to males who have not been diagnosed with color blindness, women seem to be able to distinguish between colors more easily than men. This allows women to more accurately identify the color of an object that may be between two similar hues, like blue and green.

Women have better night vision

However, studies have suggested that there may be slight differences in night vision between men and women. One study published in the journal Ophthalmic and Physiological Optics found that women had better visual acuity in low-light conditions than men.

Women have better muscle endurance

While men usually have the upper-hand when it comes to strength, it may be surprising to many that women may actually have better muscle endurance than men do. Research has shown that in stamina-related exercises, women were able to exercise for about 75% longer than men could. It is suggested that the presence of estrogen in women makes their muscles more resistant to fatigue, and that women have more efficient metabolism within their muscles as compared to men.

Their bodies are structurally made for greater flexibility

When it comes to stretching and flexibility, women have an advantage in several ways.Firstly, their female muscles and tendons contain more elastin, the protein which gives our muscles, organs and skin the ability to stretch, and this gives them greater flexibility on the whole.

Women have higher levels of estrogen in their bodies, leading to wider hips that allow greater movement and flexibility in the pelvic region

Women are way more agile

Women on the other hand have greater agility.This is partly explained by the fact they are smaller and have a lower centre of mass thus are able to change direction and move quicker than their male counterparts. In addition balance is better for the same reason.

Women have stronger legs/lower body

In lower body absolute strength, a woman is 75% as strong as a man. This difference is usually attributed to the similar daily usage of legs between men and women. Both walk and use our lower body muscles about the same. This is not the case in daily activities using upper body strength.

Women have higher survival rate than men

Analysis of three centuries of historical data showed women are more likely than men to survive famines and epidemics. Their advantage is earned early. Female newborns were more likely to survive trying circumstances during the last three centuries. women has fundamental biological underpinnings is supported by the fact that even under these very harsh conditions, women survive better than men, and this starts at a very young age.

Women are more resilient

Several studies show that women score higher on the resilience scale than men. A study found that women outlived men during severe famines and epidemics. This survival advantage was found to be modulated by an interaction of biological, environmental and social factors.

They have better chances of surviving traumatic injuries

Another likely reason for women's longer life expectancy could be the fact that they have higher chances of surviving injury and trauma. Researchers, in studying data on patients who arrived at hospitals with traumatic injuries, found that women in the age range of 13 – 64 were significantly more likely to survive. Again, the key to this advantage may lie in the higher levels of female sex hormones in women, which may have an enhancing effect on the immune system.

Women have better memory

Remembering the faces of people you have just met may be a challenge for many, but it may be apparently less so for women in general. Women have been found to be stronger in memory skills than men, as suggested in studies where they outdid men in memory tests. Their superior memory skills are not just limited to remembering things, like items on a list, but also faces of people as well. Other studies have found that women can remember faces better than men, as they unconsciously spend more time studying features of new faces.

[dragonsdendoodles]

i’m taking a construction course which has a module on waste management, so i now know depending on how old the house is, there are a load of different contaminants which could be floating about and have probably ruined the soil (rip fiona’s plants). according to my revision sheet, some of them could be:

- heavy metals (lead pipes, old plumbing, arsenic-treated wood)

- volatile organic compounds like solvents, alcohols, and formaldehyde, (paint thinners, varnishes, wood + wallpaper chemical treatments)

- asbestos (literally everything that needed to be fireproof or insulating, ie tiles, plaster, pipes, insulation, flooring, etc)

- polychlorinated biphenyls which are pollutive but can also affect your immune and reproductive systems (early elec systems, paints and varnishes)

- technically pesticides but i personally doubt they’d be allowed within a ten mile radius of the house

- creosote + wood preservatives, carcinogenic and also toxic to plants, sorry fiona (railway ties, treated beams and floorboards)

- chlorinated solvents (early cleaning products and degreasing agents)

- i cannot overstate the investment of lead all of those kids have heavy metal poisoning in some way. my notes specifically note ‘neurological damage especially in children’

- coal dust and soot (fireplaces)

in conclusion the reason the ruins were still there when jacob arrived was because nobody was investing to remediate a deeply contaminated brownfield site in the middle of nowhere, and it’s a miracle they didn’t die from the toxicity of everything around them before they made it to london

These children are ticking time bombs in more ways than one and they are so incredibly lucky they did not just immediately die anytime they left the loop oh my god

[tickle-headcanons]

May I request some Metal Sonic tickle headcannons please?

(Of course, anything for more Sonic tickle content :3)

⚙️ Metal Sonic – Tickle Headcanons 🔧💙

General

First was a Switch, but more over time starting going over to Leaning-Ler ➤ Metal Sonic insists he's immune. Cold. Calculating. Not even capable of laughter. ➤ Unfortunately for him, Eggman made his sensory systems very precise. ➤ Why? To detect even the slightest change in wind pressure. The faintest tremor. The most minute touch. ➤ Which means. ➤ He feels EVERYTHING.

🤖 Lee!Metal Sonic

The first time someone snuck up and tickled him (probably Sonic let’s be real), he glitched. ➤ Whole body sparked. Optics scrambled. Nearly rebooted. ➤ Sonic was like, “Oh? OH??? THAT did something???” 😈

Worst spots?? • Under his arms/joints – Sensitive wiring for agility and precision = instant squirming • His neck seam – There’s a connector hidden beneath the metal there, SUPER reactive • Lower back vents – Soft buzzing sounds happen if you get him there • Back of his knees – They twitch!! Like he’s gonna short-circuit!!

Doesn’t technically laugh, but oh boy does he react ➤ Body spasms ➤ Frantic scrambling to get away ➤ Weird warbly sound files play when he gets overwhelmed 🫠 ➤ You’ll catch a brief “Distress signal: c-chk– eee–!!” before he tries to slam-dash outta there

The worst part for him? ➤ His voice modulator occasionally clips and blurts a giggle-like "heh" if pushed too far

🔧 Ler!Metal Sonic

He is CREEPY good at it ➤ No warning. No hesitation. No mercy. ➤ His fingers can vibrate at ultra-high frequencies like a miniature tickle drill 😳 ➤ Activates his invisibility cloaking only to sneak up behind you and give your ribs the BZZZ

Doesn’t say a word. Just stares. ➤ Or plays back your laughter in a distorted remix as psychological warfare 😭 ➤ “Hahahaha~ HAhAha~ hAHa~ Initiating playback.”

Will absolutely hold you down with those hydraulic arms while his chest panels open up and deploy little poking tools 😈 ➤ “Resistance is illogical.” ➤ poke poke poke poke poke

Even though he’s a machine, he’s got this snarky little smugness when he wins ➤ Stands there silently with his glowing red eyes while you curl up into a puddle ➤ Whirring noise of satisfaction™

[l-1-z-a]

Sims 2 and 3 were a big part of my childhood! What were some of the weirdest traits that got proposed or scrapped?

Also, do you know anything about some of the scrapped memories from Sims 2? I’ve documented some of them on TCRF and I’d really like to find out more! - Matt Brown’s Answer from the r/Sims3 AMA (May 11, 2025)

Unfortunately, I don't personally recall how memories worked in Sims 2. Based on their nature, I have a strong feeling they piggy backed off of Wants and Fears which were added very late in development.

Underlying wants and fears was a database of events that a Sim could experience/achieve. Those obviously included much finer grained events than warranted a player visible "memory", but the Sims "remembered" all of them similarly, and I can't see any memories that weren't also want/fear triggers (hidden or visible).

I choose to assume they were *good* parts of your childhood and not traumatic :).

As for traits... for starters, here's the list of traits from the integrated "living world prototype" we created and play tested before production. I have a brief write up on my site, and I'll do a deep dive video sometime in the next couple of weeks. Not all of these are necessarily something we would ever ship and a few are named questionably, but there are a few that I know we didn't. They were often in opposing pairs, but that wasn't required.

*Feel free to follow up comment and I can explain what the intent was behind some of the mystery ones.*

Shy / Outgoing

Mean / Friendly

Sloppy / Neat

Playful / Serious

Lazy / Active

Slow Walker / Fast Walker

Selfless / Greedy

Genius / Airhead

Big Ego / Modest

Good / Evil

Loves Outdoors / Hates Outdoors

Sickly / High Immunity

Good Cook / Horrible Cook

Prefers Baths / Prefers Showers

Hates TV / Loves TV

Overtly Feminine / Overtly Masculine

Clumsy / Dexterous

Conversationalist / Quiet

Placid / Irate

Always Early / Always Late

Curious / Strong

Political

Workaholic

Romantic

Flirty

Artistic

Adventurous

Eccentric

Paranoid

Insane

Whiner

Crybaby

Mooch

Talks to Self

Leaves Toilet Seat Up

Close Talker

Cleptomaniac

Geek

Prankster

Spendthrift

Party Animal

Commitment Issues

Angry Worker

Fast Reader

Fidgety

Childish

Poser

Shallow

Green Thumb

Good Kisser

Funny

Shopaholic / Hates Shopping

And these last few concepts that mostly didn't materilize but which we really loved (these were Ray Mazza Specials iirc :)). They were treated like personality traits but could each have an "object" associated with them (e.g. "Favorite Color is Puce"... "In My Pocket is a yoyo") to make them more unique and special. But the idea was that they could be queried by any system in the game to modulate something interestingly just like regular atomic traits.

Favorite Color

Favorite Food

Favorite Object

Favorite Place

Favorite Music

Favorite Greeting

Favorite Sim Artist

Favorite Kind of TV

Favorite Exclamation

In My Pocket

Source:

https://www.reddit.com/r/Sims3/s/Ics3pVRrfu

https://www.reddit.com/r/Sims3/s/8ZhhUfZ5Ta

https://www.reddit.com/r/Sims3/s/DqNGKhQlEV