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thetownwecallhome · 1 year

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TNBC Shower Thought-cloud #5: Sally the Ragdoll

((OOC:

So the sequel book to Nightmare Before Christmas All Hail the Pumpkin Queen, came out this last year and I just gotta make my stance clear now: if you like that book, cool.

I don't. Like, I really don't. To make a long story short, Shea Anshaw's take on Jack and Sally finally getting married ft the revelations that

Sally wasn't actually made by Dr. Finkelstein

Sally is a princess from another world

Sally wax poetic abt awesome girl-boss royalty ((like, human royalty, the kind that commits genocide and apartheid)) being legit and cool and how you shouldn't question it

This newest girl-bossification of Sally is positing the same question the TNBC-critical sphere has been asking for years: is Sally from Nightmare Before Christmas dependent and therefore can't be a good feminist character?

The hyperbole take on her being " her [Sally's] entire purpose is being supportive of Jack, who isn't supportive of her and who doesn't deserve her as a girlfriend "

This isn't a fringe opinion nor is it held only by people I dislike. Lindsay Ellis jokingly told Sally to "get her bachelor's degree" in one of her vids which I am very obviously not butthurt at all by as you can tell, while Hasani Walker made a webcomic where that functionally happens; Sally and Jack break up to work things out individually before they really try it out as a couple.

Just so we're clear, my disagreeing with these two and other creators is NOT meant to be war on people who don't ship SallyxJack, nor is it a roast on people who are critical of Sally/TNBC as a principle.

BUT, when it comes to Sally ((in the film, not the games or spin offs, the film)) being a doormat of a woman who's too good for her man...I disagree.

---First thing's first, My take on Sally is highly influenced by The Nightmare Before Christmas : The Film, the Art, and the Vision which my sister bought years ago. In that book, Carolyn Thompson said this -

While TNBC is the story of the time Jack did a thing and ruined it for everyone, it's Sally who embodies everything the filmmakers want the audience to feel about Jack.

Set up and seen before Jack is even on screen, Sally is a part of the world of Halloween, but also an outsider in it. This gives her the position to see Jack the way the audience does; Just like Sally, we are awed and enamored with Jack when he first pops up, then saddened and sympathetic for him once we realize his plight. Though she's absent from Jack's finding of Christmas Town, she IS there for the town meeting when we the audience (and her) are gushing over his gushing over Christmas. We sense along with Sally Jack's frustration with the town citizens, are saddened to see him pander to them, and can tell he’s not well when committing to his Xmas experiments. Most important of all, Sally recognizes Jack’s Xmas takeover as wrong and wants to stop it, even if she love him. Even without hearing him sing “I bet I could IMPROVE IT TOO” like we do, Sally knows Jack is wrong. Regardless of her care for Jack, visibly, she’s the only one who sees what’s happening with Santa is wrong. Sally tracks him down in order to help Jack, but she’s none the less Santa’s real ally. From everything we know about her, Sally, like the rest of Halloween Town, is not a mean monster and doesn’t like to spread misery ala Oogie Boogie, and she’s not too hopped up on enthusiasm to forget when she’s hurting people like Jack and the town very much are. Sally is the og critical stan. now join me for a tanget-

Interestingly, any other holiday film ((Year without a Santa Claus, Hocus Pocus, Hop)) would make the voice-of-reason audience-surrogate character a peppy human child who's interacting w the holiday characters, but in TNBC, the writers made the surrogate someone who's also a holiday character- Sally. Sally is kind of to TNBC what Nick Calloway is to The Great Gatsby. Yeah, that's a stretch-Nick is of course the narrator and author-stand in for his story where Sally isn't (although, a TNBC narrated by Sally sounds dope as hell, ngl), tho more importantly, while Nick learns along with the reader how cruel and fruitless the American dream Jay believed in actually was,

---Sally is a character who doesn’t have to learn anything. tanget- again

A lot of people have this opinion on Disney heroines like Belle or Ariel, that good characters, female or otherwise, don't necessarily have to learn anything. I could take or leave Belle and Ariel in as far as if they should learn a lesson in their movies. But in my eyes, that character will always be Sally. Sally is a character you wanna aspire to be like and who doesn’t need to learn the lesson of the story. And yes, Sally is also in-love with Jack. You can be extra cynicalsassy and use this to say "TNBC was made to make you feel like you could make out w Jack Skellington" (( I'd like to point out that Nick is all but canonically in love with Jay in GG)) but that's not the point. More importantly...how/why is that a bad thing that Sally is in love? TNBC doesn’t pass any bectal tests. If women always supporting other women is the only mark of feminism ever then I guess, but I mean, what’s wrong if a woman’s inspo and motivation is a man? What’s especially wrong if she’s self aware and tries to battle that man’s influence within the story. How is that "putting up with" or "enabling/excusing/thinking only of Jack". Sally...really doesn't do that...

---Sally has wants, but within the narrative of Nightmare she's just a bit taken back by needs. At the start of the movie what Sally wants, and the reason she says "I know how you feel" to Jack, is to be active.

“I don’t want to BE patient”

“I’m restless, I can’t help it!”

Sally wants to be anything but Finkelstein's cute assistant because SHE knows she's more than that. She wants to be a part of Halloween Town. What's keeping her back is her reluctance to be free, which she finally throws to the wind after seeing Jack's tower from afar, which is why she's so happy throwing herself out the window - that's her 'let it go' moment of actually taking action in her life. The man she loves is evidently doing it -why shouldn't she? Her actual 'need' is to escape from Dr. Finkelste and it’s really not an obstacle, if we're being honest. The balls are all in her court; Fink's at most an irritation to her. She literally came back to his lab just to be sewn up and smile in his face about poisoning him. She can, and does, so often easily escape because she’s NOT perturbed by him. Sally is, at this point in the film, totally in control of her wants and her needs. But then- the plot kicks in and she has her vision. It's then that her real need in the story, the need she recognizes, outweighs her wants, that need being: "omg I gotta stop this undead himbo from hurting himself and other people!" Sally’s #1 goal in the film is NOT to be Jack's gf, it’s just to save him from himself. Jack inspires her, makes her feel good, but she doesn’t let that stop her from seeing things for how they are ABOUT him. Her words in "Sally Song" never read to me as "notice me senpai I wish I was good ENOUGH" self-loathing. If anything her succumbing to “it’s never to become '' about Jack isn’t some “I love you even though you’ll NEVER luff MEEEEE” devotion, but forlorn frustration. “I think it’s not to be '' = Jack’s never gonna change”. It's Sally's lament about how she doesn't believe Jack will ever want her that way because she just knows what kind of person he is*. But that's not the only thing she sings about in this song. Sally has been apart from the crowd and wants to be a part of it, but any joy she’d have in her new independence is kinda sucked up by knowing Jack is gonna get him and possibly the rest of the town killed. She even wonders in her song if she wants to or ever can be really a part of Halloween Town when she clearly can’t do the hype-Jack-up song and dance like the rest of them. Jack evidently treats her like an equal part of the team, but 1) for Jack that's just another citizen he thinks doesn't understand him, and 2) it's participation in a project she knows she doesn't want to be a part of. Real monkey's paw there, Sally!

If there is anything close enough to a lesson for Sally in the film, arguably, it’d be not to underestimate Jack as unable to change. She’s not only validated by the end of the film, she gets to see Jack really bounce back and be the person she loved at the start- and then is taken aback that he not only does this but finally recognizes her affections, her efforts, and her as a person. final tangent:

((I think the make-or-break-you point with Nightmare is a question of whether or not you think Jack learned his lesson. While I think the filmmakers could have really handled that better, especially in “Poor Jack”, I think what they were going for in their own crunch of an ending is Jack falling in love with Sally is his redemption- he finally came around to seeing her and her way. The Film, the Art, and the Vision makes a point of how Sally is far more than Jack’s romantic interest. ))

Being Mr. Cynical again, you could handwave this as just a throw-in from the writers; "actually she IS REALLY important lookit all the things she do!" but I believe in that statement because they believe in that.

--Sally's MO is centered around Jack. Narratively, yes, she exists in compandum to him. But, within the actual story of the film, Jack isn't her soul purpose in life. The fact that she tries to stop him is proof enough of that.

The argument that Sally is too good and better than the relationship she's in falls apart because Jack and Sally aren't IN a relationship in the film. They hook up at the end -that's not the same as them being together or a couple. The logic of this take is, again, confusing Sally's wants with her needs, and also presuming Jack always loved her and just didn't realize until the end of the story, which is NOT the text of the actual film, that's fan speculation. (( I prefer Jack falling in love with Sally on the spot out of nowhere. It's such a Jack way of doing things...)) I think what convinces people that Sally is “dependent” on Jack or only ever his side-kick is how expanded media treats her as character, as well as her relationship w Jack. In the 2000s, all that mattered for making spin off material of kid’s franchises is keeping the cast recognizable and that means undoing their development if the point of the story is that they change. It happened in every Land Before Time sequel where Cera and Littlefoot have to be the respective team-racist and team-leader, always, ever, all the time; it happened in the Finding Nemo comics set after the movie where writers still made Marlin overprotective of Nemo; it happened to Jack in Kingdom Hearts and Oogie’s Revenge. The writers may want to write an actual story, but it’s easier to just write what the characters are like in the original. SO, Jack HAS to be an oblivious, selfish manchild and can never learn and is also really despondent and prone to abandoning ppl he supposedly cares about. This sucks enough for Jack's character, but I think Sally suffered even worse than him. At that time, media and merch did treat Sally like she was JUST Jack’s love interest. Literally in Oogie’s Revenge's game pamphlet the only disc for her is “she’s sewn her way into Jack’s heart”, like she’s just his side piece and not the woman he ended his movie with who was also a really important character you followed within that movie. We can only repeat what we know from the film so oop!-Jewel’s MIA and Sally has to live with her sexist ex/boss who doesn't even like her.

---While we're here, I'm 100% sure Sally and Dr. Fink’s relationship is not familial. Some fictional mad scientists do love their creations like they were their children (see also: Mad Monster Party, 9, Frankenweenie for animated examples). Not Dr. Fink. While not exactly predatory ((because it's a fricken kids film, ew)) Dr Finkelstein is a sexist old man. He's problematic. Fink made Sally to be his sexy secretary. He's mad because her life doesn’t revolve around him the way he thinks a woman who works for him life should. In the end, he just decided to go and make a copy of himself since he knows now what he wants is to be told how awesome he is. I really don’t vibe some fic authors (and Shea Anshaw's) insistence that they be anything like ‘family’, hence why I made fun of it on this blog.

For all I disagree with between our headcanons, I much prefer Hasani Walker's take on Sally to Long Live the Pumpkin Queen. Hasani went in w good vibes; he made decent takes and criticisms; he made some good art; he did a sweet crossover between stop-motion properties, and MOST importantly, Hasani gave Sally a hat and a cool girl vest. Did Shea Anshaw do that? No!

It feels very at home and on-brand for TNBC that Sally was made from whole cloth as a ragdoll, but is still her own autonomous person by the rest of town and even the leader eventually. Reminds me a lot of the Oz books where the Scarecrow, Jack Pumpkinhead, and Gump are all just possessions but who are seen as people by the heroes, and even made official citizens by the heroes, which they are. What's more Halloweeny than a living-ragdoll-frankenstein woman being co-ruler of everything spoopy, or even just a citizen loved and respected as much as the rest of the town for her own attributes? If that's what you want, and it's what Hasani actually did for her, than give her that. Outside of her purpose within the story that I already mentioned earlier... what about Sally is sexist? So TNBC doesn't pass the bechdel test and Sally's main inspo happens to be her man. Not her soul purpose like in mother!, just her muse, her kin, her dearest friend. Secret of NIMH and Kubo and the Two Strings have female characters whose motives are their men and those characters don't even have first names. I kinda really hate the implication that a woman can't have a male character as a motive ever or else. As a feminist, I agree, women characters should be individuals and not props for the men. The problem to me isn't so much the insistence that a woman be there for support, it's writers crafting a story where certain characters fill more of a role or purpose in cunjunction to another, and when the writer happens to make said character a woman.

Also, since the whole point of LLTPQ was to give Sally her own agency and importance...how is it fair that she HAVE to be a royalty HERSELF in order to be her own person?

Is it because she was made to be a sexy nurse and that's somehow wrong or shameful even though the whole point is it's not her fault? Is it that people would accuse her of “leeching off" Jack just for being in a relationship with him? You know? The thing bad, sexist people do to women and sax workers irl if they have famous boos when they themselves aren't famous? If the only people complaining are those who think Sally is JUST Jack’s sidepiece, why validate those people? Wanting her to have agency within the movie and so giving her different choices as opposed to just INSTANTLY marrying Jack? That's a take I can vibe with because that is true to the nature of what Sally is, which is not just the Mad Scientist's beautiful assistant. By making Sally a "princess all along '', you imply that her even possibly starting from the bottom makes her beneath Jack and she has to rise to be his equal. Sally never had to do this in the original movie. Sally really was the smartest, most in tune person in town.

I talk a big game, of course, but even as my fav character I know I've done Sally wrong too. The "Mothball" comic is one of my biggest regrets from this blog. It's SO badly worded and I think it's a comic that REALLY needed a second opinion. Sally did nothing wrong in that comic, but both it and Jack made her feel like they were both in the wrong. Trying to give Jack and Sally a conflict as a couple was hard and I ended up rehashing some really harmful language, which I didn't want to do for either Sally or Jack. Don't like that comic. My first choice of retype, redraft.

final thoughts?

What people (me, Lindsay, Hasani, Shea, errybody) actually want of Sally is to have her own agency and 'character' apart from Jack. While narratively, yes, Sally functions as being there to endear Jack to the audience, my point is as a character within the narrative-Sally does have her own autonomy apart from him. She is massively independent of him. I know because that's who she is throughout the entire movie. I think it's because we all see she clearly does have her own interests/agency/character beyond that that we're all anxious to get more of that personally from her...which Disney won't do because they're Disney and certain characters can't come as their own especially when they fufilled another character's purpose in the og film.

Anna can't really do anything that isn't tied to Elsa because it's Elsa who's the reason any of Frozen happens at all.

Belle is always only the cheerleader of the Beast because his character arc is what drives the story.

Sally has to always be in toe of Jack because TNBC is Jack's story and she loves Jack.

But, we love Sally.

Give Sally her own limelight. Give her a limelight that isn't compltely making her a different character or demanding she be the same character as Jack.

Let Sally say #$%&

))

#sally the ragdoll #sally the nightmare before christmas #nightmare before christmas #the nightmare before christmas #tnbc analysis #sally skellington #long live the pumpkin queen

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yourlocalsimpsonsandsanriofan · 1 year

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Here's a disturbing theory i have of Dorit man

Honestly, have you ever wondered why Mayor's spider only has six legs instead of having eight legs like the average spider? Well I have a disturbing theory why. As you can see in the movie, when he gets pissed off, it seems he can get pretty aggressive. My evidence: when Lock Shock and Barrel fling things at him when we first see them for the first time in the movie, he growls in anger, and when his spider dosent stay on his chest, he aggressively puts it back on his chest. He also pushes wolf man aside saying, "Move aside." Agressivly, all while trying to get to his hearse. So he's capable of hurting somebody if something dosent go his way. In this case, Jack being missing. My theory here is that one day, the spider didn't do what he wanted, was stay on his chest (or doing anything to piss him off for that matter), so he got so aggressive that he accidentally ripped two of its legs off, wich resulted in it only having six legs now. And maybe thats why it escaped him in the movie, because its scared of him. Or it could be that the spider is a mutant, wich wouldn't be surprising, because we're talking about the world of Tim Burton where things are always twisted, creepy, and weird. But my theory would work, cuz like I said, he gets aggressive when he gets pissed off. And that could be dangerous. That could also tie into his bipolar personality, Where he can change his mood at the drop of a pin. Like I said, this could be dangerous. There is a chance he could go insane by constantly switching emotions (and faces) back and forth. Thats probably why he overreacts (sound familiar?) when Jack is missing. When things don't go his way, he panics. Wich causes him to be hurt, or potentially hurt somebody else. Which obviously isn't good.

I dunno I thought I'd maybe share my thoughts on this. Its a dumb theory, but I think It could work.

Sorry for posting two times today btw

#mayornightmarebeforechristmas #the mayor #thenightmarebeforechristmas #theory #analysis #disturbing #tnbc #tnbctheory

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thewitfire · 3 months

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Immunotherapy in Triple-Negative Breast Cancer (TNBC): An In-Depth Analysis

1Amit Kumar, *Usaman Khan1ResearchScholar, Anand College of Pharmacy*Research Scholar, Anand College of Pharmacy Immunotherapy in Triple-Negative Breast Cancer (TNBC) Article Details Title: Immunotherapy in Triple-Negative Breast Cancer (TNBC): An In-Depth Analysis Authors: Amit Kumar, Usaman Khan Published in: Witfire Volume/Issue: 2(1) Pages: 1-12 Publication Date: 18/01/2024 DOI:…

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#Immunotherapy in Triple-Negative Breast Cancer #Immunotherapy in Triple-Negative Breast Cancer (TNBC): An In-Depth Analysis #Triple-Negative Breast Cancer

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crispywisp · 1 year

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been rewatching a few scenes in tnbc for animation analysis purposes and one detail that i never noticed is how jack's blinking expression is completely different for his snowman outfit. and with the context of knowing how each minor change in expression and/or lipsync is a whole separate jack head that the animators would have to swap out, it makes so much sense for them to just slap on some makeshift eyelids into his eye sockets so that they don't have to take out the green hat and painstakingly pose it on top of his head as close to its original position as possible after a face swap just for a single eye blink in this one shot (if you go frame by frame, you can see tiny positional shifts in the green hat with each new expression/mouth change on jack). stop motion is crazy.

#this is turning me into the joker.#the wisp whispers

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tnbc-thoughtsandheadcanons · 1 year

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I've been thinking about how I want to run this blog, and want to mention some changes that will be coming in 2023.

More below!

2022 was incredibly difficult for me, after losing two of my loved ones. My family heavily relied on my grandmother - and now that she passed, our financial and home situation has been going through hardships. Money is tight, and I am simply not happy living at my home anymore. I can't say I'm happy with my life at *all*.

In the midst of my grieving, I received my copy of Long Live the Pumpkin Queen. I was desperate to find some way to cope, and a way to distract myself while the world around me fell apart. I was unwillingly brought into a pointless online argument about this novel -- and it made me aware of something.

I don’t want to write analysis/discussion posts anymore.

I am still hyperfixated with TNBC, of course, and want to talk about it - but I don’t have the free time and motivation like I used to. When I first ran this blog, I was young and unhealthily obsessed with this movie - I would add long additions to posts I disagreed with. Back then, I would’ve jumped on the hateful bandwagon in response to Shea Ernshaw’s novel, but 2022 numbed me to the point where canonical inaccuracies don’t bother me like they used to. Apparently, this was not expected of me - and I was targeted for not being enraged like other fans were.

I’ve always tried to be thoughtful and open with my opinions, to engage respectful discussions about this movie + its lore. But not all people share this approach, and I’ve learned that the hard way. I’ve been involved in unnecessary Fandom Discourse™. I don’t have the time nor mental capacity for it anymore. I’m tired of being so attached to the TNBC canon that I let myself get genuinely upset when adaptations took different routes. It’s only hampered my mental health, so I’m done with it.

I’ll still post my thoughts/opinions about things, likely when The Battle for Pumpkin King comic releases, but don’t expect me to make long rants about canonical inconsistencies. I also won’t be responding to any venting asks or mentions anymore. They’re not my priority - and I’ll likely be sharing more memes than anything. But I no longer want to be super negative on this blog - I’ve always prioritized civil discussions, and my criticisms were never meant to be anything else. Keep in mind I’ve always been just one fan, who has my own opinions - and you’re never obligated to agree with them. Block me if you must, or just take my posts with a grain of salt. Curate your online experience. I’ll take no personal offense when you do this.

So, expect less analysis / thought posts from me in 2023. You can still send me your thoughts, ideas, headcanons, etc. - but my responses to them may be considerably shorter than they used to. I apologize in advance for this change - but I’m making this decision to look out for my mental health, and engage less in negativity.

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tumimmtxpapers · 4 months

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Single-cell and bulk RNA sequencing analysis of B cell marker genes in TNBC TME landscape and immunotherapy

CONCLUSION: This study has established a robust model based on B-cell marker genes in TNBC, which holds significant potential for predicting prognosis and response to immunotherapy in TNBC patients. http://dlvr.it/T0LDCc

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arrangoiz · 6 months

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Original Molecular Classification of Triple Negative Breast Cancer (TNBC)

Following the description of the main intrinsic breast cancer molecular subtypes based on gene expression analysis: Lehmann et al. demonstrated the complex and heterogeneous nature of TNBCs, and that their definition simply based on interpretation of histopathological features might be of limited efficacy in understanding prognostic behaviour and therapeutic implications They described six…

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blockgeni · 1 year

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The AI biotech company Owkin has for the first time shown that federated learning (FL) can be used to train deep learning models on data from several hospitals on histopathology data without the data leaving hospital firewalls in research. The finding opens the door for AI-driven medical research that makes use of larger multi-centric datasets and frees models from the limitations of single-centric research. The application of safe and privacy-preserving AI may lead to advancements in precision medicine. Owkin developed AI models that can precisely forecast the future response of triple-negative breast cancer (TNBC) patients to neoadjuvant chemotherapy using data stored within four top French institutions. Owkin discovered possible novel biomarkers by extracting data from digital pathology slides using interpretable AI. In the future, this might direct patients toward less harmful or novel experimental treatments, enhancing the personalization of medical care. Through Substra, Owkin's recently open-sourced software that makes every operation traceable using hyperledger technology, the project leveraged federated learning, a collaborative AI framework that protects data privacy and security. For the first time, without the data leaving the hospitals, machine learning models have been developed utilizing histopathology data from various hospitals. Before now, the majority of investigations were limited to mimicking FL using artificial data splitting. It is a significant example of FL in medical research and marks a turning point in the practical application of AI in the field. A total of 650 patients from the Institute Curie in Paris, the Centre Léon Bérard in Lyon, the Gustave Roussy in Villejuif, and the IUCT Oncopole in Toulouse were included in the study, making it one of the largest TNBC cohorts ever gathered for such an analysis. The study expands on Owkin's ground-breaking application of FL for drug discovery research collaboration while protecting privacy, security, and competitive concerns. The MELLODDY project's findings, which were released this year, demonstrated that FL, a first for the sector, makes industrial-scale collaboration in AI for drug development conceivable. Along with resolving privacy and security issues, FL can also make data governance problems simpler by eliminating the need for data transfers and encouraging more collaborative research. "Thanks to our collaborators, we are happy to have completed an original federated analysis on medical data in real-life situations, and the first of its kind on histopathological data," stated Jean du Terrail, the lead author and Senior Machine Learning Scientist at Owkin. They were able to gather enough data on triple-negative breast cancer through federated institution connections for the AI to independently identify histological patterns indicative of treatment response. They anticipate that this proof of concept will encourage medical organizations to cooperate together in federated learning networks to advance research while protecting patient data. Chief Data Officer at the Institute Curie in Paris, France, Julien Guérin, stated, With the implementation of this federated learning infrastructure, which demonstrates a brand-new cutting-edge methodology for constructing AI in cancer research, we have achieved a significant milestone. They are extremely grateful to have been a part of this adventure and are hopeful that it will open up positive possibilities for patient care in the future. Pathologist Dr. Guillaume Bataillon of IUCT Oncopole in Toulouse, France, and formerly of Institut Curie in Paris, France, stated, Through this multidisciplinary collaboration, they are able to confirm the viability of a hospital-to-hospital collaborative federated learning approach on a pertinent biological issue. In order to generate replicable, transferable, and even interpretable models, this made it possible for them to quickly and securely pool diverse datasets.

This demonstration of the concept has the potential to be used as a therapeutic decision-making tool. According to medical oncologist Dr. Pierre Etienne Heudel of Lyon's Center Léon Bérard, the Growing use of digital pathology and the growth of various machine-learning techniques should make medicine more exact and individualized. Furthermore, the federated learning that was achieved in this project by ignoring external data streams streamlines and safeguards the procedure for upcoming routine clinical practice. Pathologist Dr. Magali Lacroix-Triki at Gustave Roussy in Villejuif, France, stated, The third revolution in pathology is represented by digital pathology and AI, and pathologists are eager to lead this paradigm shift in their field. They are getting closer to discovering new oncology biomarkers thanks to federated learning, a leader in AI research in digital pathology that also ensures data security and privacy. Dr. Camille Franchet, a pathologist at IUCT Oncopole in Toulouse, France, stated that "federated learning unlocks one of the major obstacles in machine learning on medical data with no compromise regarding the respect of personal data by enabling AI models to be trained on multicentric data without centralization. Source link

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rnomics · 1 year

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IJMS, Vol. 24, Pages 1799: An Overview of Circulating Cell-Free Nucleic Acids in Diagnosis and Prognosis of Triple-Negative Breast #cancer

Triple-negative breast #cancer (TNBC) is an aggressive subtype of breast #cancer due to its molecular heterogeneity and poor clinical outcomes. Analysis of circulating cell-free tumor nucleic acids (ctNAs) can improve our understanding of TNBC and provide efficient and non-invasive clinical biomarkers that may be representative of tumor heterogeneity. In this review, we summarize the potential of ctNAs to aid TNBC diagnosis and prognosis. For example, tumor fraction of circulating cell-free DNA (TFx) may be useful for molecular prognosis of TNBC: high TFx levels after neoadjuvant chemotherapy have been associated with shorter progression-free survival and relapse-free survival. Mutations and copy number variations of TP53 and PIK3CA/AKT genes in plasma may be important markers of TNBC onset, progression, metastasis, and for clinical follow-up. In contrast, the expression profile of circulating cell-free tumor non-coding #RNAs (ct#ncRNAs) can be predictive of molecular subtypes of breast #cancer and thus aid in the identification of TBNC. Finally, dysregulation of some circulating cell-free tumor #miRNAs (miR17, miR19a, miR19b, miR25, miR93, miR105, miR199a) may have a predictive value for chemotherapy resistance. In conclusion, a growing number of efforts are highlighting the potential of ctNAs for future clinical applications in the diagnosis, prognosis, and follow-up of TNBC. https://www.mdpi.com/1422-0067/24/2/1799?utm_source=dlvr.it&utm_medium=tumblr

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lookchem · 2 years

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1022-45-3 Structure-based drug design: Synthesis and biological evaluation of quinazolin-4-amine derivatives as selective Aurora A kinase inhibitors

Aurora kinases play critical roles in the regulation of the cell cycle and mitotic spindle assembly. Aurora A kinase, a member of the Aurora protein family, is frequently highly expressed in tumors, and selective Aurora A inhibition serves as a significant component of anticancer therapy. However, designing highly selective Aurora A inhibitors is difficult because Aurora A and B share high homology and differ only by three residues in their ATP-binding pockets. Through structure-based drug design, we designed and synthesized a series of novel quinazolin-4-amine derivatives. These derivatives act as selective Aurora A kinase inhibitors by exploiting the structural differences between Aurora A and B. The selectivities of most compounds were improved (the best up to >757-fold) when comparing with the lead compound (3-fold). In vitro biochemical and cellular assays revealed that compound 6 potently inhibited Aurora A kinase and most human tumor cells. Furthermore, compound 6 effectively suppressed carcinoma, such as triple-negative breast cancers (TNBC) in an animal model. Therefore, compound 6 might serve as a promising anticancer drug. Moreover, through molecular dynamic (MD) analysis, we have identified that a salt bridge formed in Aurora B is key contributor for the isoform selectivity of the inhibitor. This salt bridge has not been previously detected in the reported crystal structure of Aurora B. These results might provide a crucial basis for the further development of highly potent inhibitors with high selectivity for Aurora A.

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sophieakatz · 3 years

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Thursday Thoughts: The Jewish Heart of The Nightmare Before Christmas

On a recent episode of the Disney For Scores podcast, Danny Elfman, composer and songwriter for The Nightmare Before Christmas, was asked about his relationship with Halloween and Christmas.

“Since I was a little kid,” Elfman replied, “my least favorite night of the year was Christmas, and my favorite night of the year was Halloween… At Christmas, I was just a lonely Jewish kid in a neighborhood without Jewish friends.”

And I had to pause the podcast and shout, “I KNEW IT!!!”

I love TNBC for a lot of reasons. The music is catchy. The stop-motion animation is amazing. The setting and characters are fascinating, bizarre, lovable, and unforgettable. But the thing I’m happiest to ramble on about when it comes to TNBC is its message.

Last year, I called this film an “Anti-Christmas Movie.” A Christmas movie follows a character who does not value Christmas as they gradually learn to bring Christmas into their life. However, the upshot of TNBC is that despite Jack’s fascination with Christmas, he should NOT bring Christmas into his life. Instead, he should let the Christmas people do their thing, and he should take pride in his own culture, his own people, and his own holiday.

And in my heart, I knew there was no way a movie like this could have been made only by gentiles. Gentiles love Christmas, and they love telling other people that we need Christmas. As a Jewish kid surrounded by non-Jews for most of my life, I know this all too well. When I was in kindergarten, some girls at school told me that if I didn’t believe in Santa (and Jesus and the Easter Bunny), then there would be monsters under my bed forever. That was just the beginning of a long road of well-meaning antisemitism, and at the end of that road, I’m left with a bad taste in my mouth at the very sight of a Christmas tree. To be clear, I don’t care if other people enjoy Christmas – my problem is with people telling me that I should enjoy Christmas.

In my experience, it’s not just religious Christians who were so eager to remind me that I shouldn’t be alone on Christmas. Atheists love Christmas and are very quick to tell me that I should love it, too, even after I politely explain that I don’t need Christmas to be happy. So while I had no idea whether the creators of TNBC were religious Christians, and given that Jesus is not mentioned even once in the film I had a hunch that they were not, I also had a hunch that this movie would not exist without some Jewish person’s contributions.

Now, Tim Burton is not Jewish, despite his clear love for and frequent use of Jewish folklore, imagery, and history. Henry Selick, the often-forgotten director of TNBC, is not Jewish, and I’m pretty sure Caroline Thompson, the screenwriter, is also not Jewish. So that leaves Danny Elfman. The lonely Jewish kid who, to paraphrase him, felt disconnected from the Christian world around him, loved getting to run around in a monster mask at Halloween, and grew gloomy at the sound of Christmas music in the mall. Danny Elfman, who poured his heart and soul into the character of Jack Skellington to the point where his soundtrack demos were often used in the final film instead of the studio recordings.

Sure, you can argue about who really holds the power of storytelling in a film. The characters and basic plot undeniably belong to Tim Burton. But a movie musical truly comes to life in its songs, and in TNBC, the music never stops playing. The music carries us through this world where Christmas isn’t the most important thing, where you don’t need to take on someone else’s culture in order to feel complete, where people love and support you for who you are in all your oddness and uniqueness.

It’s no wonder I love this movie so much, and it’s no wonder that a Jewish man was at the heart of its creation.

#thursday thoughts #nightmare before christmas #the nightmare before christmas #danny elfman #tnbc #jack skellington #Halloween #christmas #christonormativity #judaism #jewish artists #music #musicals #animation #media analysis #disney #disney for scores #tim burton #holidays

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thetownwecallhome · 1 year

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TNBC Shower thought #6: Oog-booge revooge

(( OOC:

If you've followed this blog long enough you probably noticed the distinct lack of a certain gambling boogieman on here despite him being a staple of the franchise. The in-canon explanation is scattered throughout the blog as to why Oogie still be very dead, but I just gotta be honest with you all: I don't dig giving Oogie Boogie 'depth'.

I especially don't dig giving him depth by way of him having a connection with any other (canon) characters. Why?

If we're being totally cynical here, Oogie exists in Nightmare souly to make Jack not look as bad because Jack is the real antagonist of the story, not Oogie.

Oogie is the villain, the one who likes enacting harm, Jack is the heroantagonist all in one, he doesn't mean any harm but all of what happens in TNBC is his fault.

Oogie only plays a part in Jack's Xmas specifically cuz of Jack's lack of oversight and carelessness; even without Jack's specific instructions, Santa and Sally being Oogie's victims are his fault, and it's why Jack has to be the one to save them in the end. Whether or not you think Jack learned his lesson or is a bad person and TNBC is 'bad actually'i s it's own deep dive, but personally I really like followup material that show Jack being his best self (Zero's Journey: peppy, monsterboy pumpkin king doing what he can) as opposed to his worst self (Kingdom Hearts/Oogies Revenge Jack: uber selfabsorbed manchild who never cares about others feelings, despite the movie implying he's learned to do better).

All of this is coming up for me because the newest comic book for Nightmare went into the writer's canon backstory and it delved into one the ideas I absolutely hate: Oogie and Jack were once friends.

Making Jack and Oogie friends in the past or even just amicable to each other is a REALLY big misstep on the part writers, because it makes Jack's murdering Oogie in the film so much worse.

Oogie Boogie's death was the one part of Nightmare that truly disturbed me as a child. Having Jack so passively and aggressively skin Oogie alive and do nothing but scowl as his insides fall out in agony already makes Jack look like a Christian Gray level non-comeuppance-sue but ESPECIALLY if you tack on the idea that Oogie and him were friends once!

Jack's not Optimus Prime or Superman who's all about enacting justice and fighting for what's right tm. He's Jack Skellington. He's still a scary monster Halloween king of nightmares you don't want to mess with. In Henry Selick's words on the 2008 commentary track for Nightmare, the citizens of Halloween Town aren't 'monsters' (bad people) and neither is Jack, really. He's scary because that's his job but he and his town never mean actual harm, it's just that what they ENDS UP doing by way of Jack also being a self absorbed manchild which makes him actually dangerous.

Oogie is the exception to that. I always felt even as a kid, that the implication for why he's locked up by the rest of Halloween Town was always pretty clear: Oogie does mean real harm. Oogie wants to hurt people. He has no delusions of grandeur like Jack, yes, but he wants you dead for his own pleasure and that's really not okay and not 'a good scare'.

"It's much more fun I must confess when life is on the line, not mine of course, but yours old boy, now that would be just fine!" - Oogie, kinning the guy who runs McKanney Manor

Even the demo version of the final fight makes clear Oogie's idea of 'fun' is torture:

"No Jack, messing with MY IDEA OF FUN!"

Jack coming to his own and actually doing something about Oogie should be a moment of "Jack really IS back! 8D! And he's actually finally doing something about the incelcryptobro in his basement that he knows everyone dead! Jack's being responsible! 8D 8D!" for the audience, not "wow. Jack is dirtbag who never faces consequences and murders people for problems he caused 8C. And the movie takes his side because Jack's 'cool' and Oogie just so happened to be causing harm. The movie gives Jack an excuse. 8C 8C"

I'm not saying the latter is what you end up taking away as a viewer. I'm saying that's not the vibe you want and it's why for, in Jack's story, which TNBC is, Oogie really should be just a big bully with no nuance of his own. Or at least, no nuance that means anything TO Jack.

Oogie Boogie is kind of basic. I personally love him for that even though I don't know exactly how to write him and I want to make TNBC stuff without him as a villain. But believe me- as a villain lover I totally get the need to try and make more out of our potato-sack daddy.

If you're rightfully mad that the one BIPOC-voiced character in the cast is the bland ebbul dude, that's beyond valid!!! (no- I don't think think the coding or casting was intentional, but the pro-segregation coding in Lion King also wasn't intentional...doesn't mean it isn't problematic).

If you simply want a more interesting villain-big-bad that exists to make the main hero look better, that's all fine and good too.

Me personally, I'm currently stumped on how to flesh out Oogie and not make him a complete, actual monster by Halloween Town's standards. I'm currently trying to think around this...but we'll have to wait and see...

My biggest issue is how, because he's fun while he kills people, some fans go the opposite route Oogie is made into a harmless hammy bafoon stripped of all his teeth and his real personality. I'm sorry to do this but Oogie is NOT in love with Sally. Oogie is not Sally's sassy best friend who's great at calling Jack out on his bad boyfriend-ness.

That's not Oogie Boogie. That's Angel Dust but that's not Oogie Boogie.

I like my Oogie being a bully. Not a puppy dog, not a tragic character, just an actual unbridled monster in the midst of this town of performance scarers.

But...That's just my take, not yours. If you love Oogie being perfect and flawless to counteract Jack's supposed 'perfectflawlessness', if you wanna see him as a real nuanced character because Oogie is definitely a fun one...right on. I'm not your mom.

But yeah, that's why Oogie doesn't appear too much in my comics except for in prequel stuff. Granted, I do want to do more with him but I'm stumped as for now so Oogie stays double dead.

If he does show up and makes friends, expect his friends to not be Jack and Sally because Sally's got better friends and no way would Oogie trust Jack after all Jack's put him through.

In other news, I'm an annoying boomer now about the comics))

#oogie boogie #nightmare before christmas #the nightmare before christmas #oogie boogie nightmare before christmas #tnbc analysis #halloween town #tim burton

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