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jcmarchi · 2 months

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MIT scientists use a new type of nanoparticle to make vaccines more powerful

New Post has been published on https://thedigitalinsider.com/mit-scientists-use-a-new-type-of-nanoparticle-to-make-vaccines-more-powerful/

MIT scientists use a new type of nanoparticle to make vaccines more powerful

Many vaccines, including vaccines for hepatitis B and whooping cough, consist of fragments of viral or bacterial proteins. These vaccines often include other molecules called adjuvants, which help to boost the immune system’s response to the protein.

Most of these adjuvants consist of aluminum salts or other molecules that provoke a nonspecific immune response. A team of MIT researchers has now shown that a type of nanoparticle called a metal organic framework (MOF) can also provoke a strong immune response, by activating the innate immune system — the body’s first line of defense against any pathogen — through cell proteins called toll-like receptors.

In a study of mice, the researchers showed that this MOF could successfully encapsulate and deliver part of the SARS-CoV-2 spike protein, while also acting as an adjuvant once the MOF is broken down inside cells.

While more work would be needed to adapt these particles for use as vaccines, the study demonstrates that this type of structure can be useful for generating a strong immune response, the researchers say.

“Understanding how the drug delivery vehicle can enhance an adjuvant immune response is something that could be very helpful in designing new vaccines,” says Ana Jaklenec, a principal investigator at MIT’s Koch Institute for Integrative Cancer Research and one of the senior authors of the new study.

Robert Langer, an MIT Institute Professor and member of the Koch Institute, and Dan Barouch, director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a professor at Harvard Medical School, are also senior authors of the paper, which appears today in Science Advances. The paper’s lead author is former MIT postdoc and Ibn Khaldun Fellow Shahad Alsaiari.

Immune activation

In this study, the researchers focused on a MOF called ZIF-8, which consists of a lattice of tetrahedral units made up of a zinc ion attached to four molecules of imidazole, an organic compound. Previous work has shown that ZIF-8 can significantly boost immune responses, but it wasn’t known exactly how this particle activates the immune system.

To try to figure that out, the MIT team created an experimental vaccine consisting of the SARS-CoV-2 receptor-binding protein (RBD) embedded within ZIF-8 particles. These particles are between 100 and 200 nanometers in diameter, a size that allows them to get into the body’s lymph nodes directly or through immune cells such as macrophages.

Once the particles enter the cells, the MOFs are broken down, releasing the viral proteins. The researchers found that the imidazole components then activate toll-like receptors (TLRs), which help to stimulate the innate immune response.

“This process is analogous to establishing a covert operative team at the molecular level to transport essential elements of the Covid-19 virus to the body’s immune system, where they can activate specific immune responses to boost vaccine efficacy,” Alsaiari says.

RNA sequencing of cells from the lymph nodes showed that mice vaccinated with ZIF-8 particles carrying the viral protein strongly activated a TLR pathway known as TLR-7, which led to greater production of cytokines and other molecules involved in inflammation.

Mice vaccinated with these particles generated a much stronger response to the viral protein than mice that received the protein on its own.

“Not only are we delivering the protein in a more controlled way through a nanoparticle, but the compositional structure of this particle is also acting as an adjuvant,” Jaklenec says. “We were able to achieve very specific responses to the Covid protein, and with a dose-sparing effect compared to using the protein by itself to vaccinate.”

Vaccine access

While this study and others have demonstrated ZIF-8’s immunogenic ability, more work needs to be done to evaluate the particles’ safety and potential to be scaled up for large-scale manufacturing. If ZIF-8 is not developed as a vaccine carrier, the findings from the study should help to guide researchers in developing similar nanoparticles that could be used to deliver subunit vaccines, Jaklenec says.

“Most subunit vaccines usually have two separate components: an antigen and an adjuvant,” Jaklenec says. “Designing new vaccines that utilize nanoparticles with specific chemical moieties which not only aid in antigen delivery but can also activate particular immune pathways have the potential to enhance vaccine potency.”

One advantage to developing a subunit vaccine for Covid-19 is that such vaccines are usually easier and cheaper to manufacture than mRNA vaccines, which could make it easier to distribute them around the world, the researchers say.

“Subunit vaccines have been around for a long time, and they tend to be cheaper to produce, so that opens up more access to vaccines, especially in times of pandemic,” Jaklenec says.

The research was funded by Ibn Khaldun Fellowships for Saudi Arabian Women and in part by the Koch Institute Support (core) Grant from the U.S. National Cancer Institute.

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thejewishlink · 2 years

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Suspect arrested after setting synagogue sign on fire in Chico, California

Thomas Bona, 36, will be charged with hate crimes, arson and vandalism. (November 7, 2022 / JNS) A 36-year-old man has been arrested in Chico, Calif. for arson and hate crimes after he set a synagogue sign on fire last week and vandalized a mural dedicated to missing and murdered indigenous women. According to the Chico Police Department, they received a call on Nov. 2 “regarding a vandalism…

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#Chico Synagogue Sign Fire #Congregation Beth Israel Vandalized

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autismserenity · 18 days

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A Chabad synagogue in Pomona, New York, burned to the ground on April 17th, along with its three Torah scrolls.

Torah scrolls are hand-written, hand-made, and kept in elaborately decorated cases or wrappings.

Many of them have long histories; my synagogue has two, I think, that were smuggled out of villages being destroyed in pogroms or in Nazi attacks. One of them is the only remaining piece of that village on earth.

Sometimes, the Torah scroll doesn't even belong to the synagogue, but is on loan from a place like the Memorial Scrolls Trust:

There's an entire Jewish holiday just for taking them out and dancing with them: Simchat Torah, "The Joy of Torah."

In fact, that was the holiday on which Hamas's invasion took place.

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So it's a particular tragedy when a Torah is destroyed.

Chabad itself has a page about what goes into making just one Torah scroll:

"An authentic Torah scroll is a mind-boggling masterpiece of labor and skill. Comprising between 62 and 84 sheets of parchment -- cured, tanned, scraped and prepared according to exacting Torah law specifications -- and containing exactly 304,805 letters, the resulting handwritten scroll takes many months to complete.

"An expert pious scribe carefully inks each letter with a feather quill, under the intricate calligraphic guidelines of Ktav Ashurit (Ashurite Script). The sheets of parchment are then sewn together with sinews to form one long scroll. While most Torah scrolls stand around two feet in height and weigh 20-25 pounds, some are huge and quite heavy, while others are doll-sized and lightweight."

I learned all of this on Tumblr.

Once upon time, in people's "punch Nazis" days, I would've been able to find some mention on Tumblr of this synagogue burning.

There is none, so I'm posting about it.

And I'm going to quote Daniel Weiner, Rabbi of Temple de Hirsch Sinai in Bellevue, Washington, when his own synagogue was vandalized last November:

"It’s horrific and heartbreaking.... [Taking out your feelings about] what's going on in the Middle East by defacing a sacred space of a synagogue -- that’s the very definition of antisemitism."

I'm also posting about the Kehillat Shaarei Torah Synagogue in Toronto, whose windows were broken on Friday, April 19th, by someone who also tried to break the front door down.

And the April 15 graffiti outside a Bangor, Maine synagogue that said, "Nazi Israel 30K murdered," next to a crossed-out Star of David. The same synagogue faced pro-Hamas flyers plastered around it in November.

I was going to include all the synagogues vandalized over the past six months. But there are way too many. Several every week. Lots are swastikas.

I'll go back to just doing attacks on and near synagogues.

Someone has to talk about the 1-year-old who was stabbed outside Temple Beth Zion-Beth Israel (BZBI) synagogue, in Philadelphia, on April 13th.

The foiled terrorist attack on a Moscow synagogue on April 11th.

The man who, on April 9th, screamed at the rabbi at Moldova's Great Synagogue, "What are you doing here? How come no one has finished you off for everything you are doing to the Palestinians?" Just one week after people had vandalized a Holocaust memorial in nearby Soroka, and sprayed "Free Palestine" on it.

The Oldenburg, Germany synagogue that was firebombed on April 5th.

The Florida Las Olas Chabad Jewish Center, which on March 16 burned, but not to the ground. The Torah scrolls were safe, and no one was hurt, but the back of the building was severely damaged.

The planned-but-thwarted-on-March-7th ISIS massacre in a Moscow synagogue.

The stabbing of an Orthodox Jew in Switzerland on March 5th. (He was badly injured, but expected to survive.)

A man leaving a synagogue in Paris was beaten on March 3rd.

People set the courtyard of a synagogue in Sfax, Tunisia on fire on February 27th. Firefighters managed to put the fire out before it consumed the inside of the building.

The synagogue is no longer used; there are no Jews left in its area, and fewer than 1,000 Jews left in Tunisia overall.

(Thousands of Tunisian Jews were sent to work camps during the Holocaust. Antisemitism across the Middle East continued to increase rapidly for decades. By the 1970s, 90% of Tunisian Jews had fled to France or Israel.)

On February 18, an Orthodox Jew leaving Synagogue of Inverrary-Chabad in Lauderhill, Florida, was beaten by an attacker yelling racial slurs.

Someone deliberately chose International Holocaust Remembrance Day, January 27, to smash all the windows in the front of Sgoolai Israel Synagogue in downtown Fredericton, New Brunswick.

On December 29, Turkey arrested 32 people linked to ISIS who were planning attacks on synagogues and churches.

On December 17, a man drove a U-Haul truck up onto the sidewalk between a barrier and the front door of the Kesher Israel Congregation in Washington D.C., got out, and started yelling "Gas the Jews." He also sprayed a foul-smelling substance on two people leaving the synagogue.

December 17 also saw 400 synagogues across the United States receive bomb threats.

On December 11, a man attacked an elderly couple on their way into a synagogue in Los Angeles, screaming, "Give me your earrings, Jew!!" and beating one of them bloody with a belt. (Happily, he chased the guy down the street, and caught him when his pants fell down.)

On December 10, a 16-year-old was arrested in Vienna for planning an attack on a synagogue.

On December 8, on the first night of Hanukkah, 15 synagogues in New York State received bomb threats. And someone screamed, "Free Palestine," and fired shots outside of Temple Israel in Albany, NY. Which has a preschool that was in session.

Meanwhile, the five Jews left in Egypt were canceling public Hanukkah candle-lighting at their synagogue out of fear of reprisals. Particularly after two Israelis in Alexandria had been gunned down by terrorists on October 8. (While Israel was still fighting Hamas in Israel.)

On November 15, a terrorist group set the only synagogue in Armenia on fire.

Armenian Secret Army for the Liberation of Armenia (ASALA) has a history of working with the Popular Front for the Liberation of Palestine (PFLP).

(PFLP is part of Hamas's network of groups. Samidoun is their nonprofit arm - which is why Germany banned Samidoun last year, although it's still active in many other countries.

PFLP is also actively supported by the Palestinian Youth Movement (PYM), a diaspora nonprofit group, and Within Our Lifetime (WOL), an SJP spinoff in NYC.)

On November 11, halfway through Shabbat services, police asked Central Shul in Melbourne, Australia to evacuate "as a precaution" due to a "pro-Palestinian" protest that had chosen the neighboring park as its gathering place. Australia has seen some very outspoken antisemitism at protests, including the march shortly after October 7 that chanted "Gas the Jews."

Also on November 11, protesters targeted a synagogue along a march route. They sat in their cars, spraying green smoke and shouting at people leaving the synagogue. The march itself featured a record number of horrifying signs and chants.

On November 7th, Congregation Beth Tikvah in Montreal was firebombed, and the back door of the Jewish organization across the street (Federation CJA) was set on fire.

On November 4, protesters chanted "Bomb Israel," and burned an Israeli flag outside the only synagogue in Malmo, Sweden.

During October, there were 501 antisemitic acts under investigation in France in just three weeks, including groups gathering in front of synagogues shouting threats, and graffiti such as the words “killing Jews is a duty” sprayed outside a stadium.

On October 18, people firebombed a synagogue in Berlin after homes all over the neighborhood were graffitied with stars of David.

And also on October 18, hundreds of "pro-Palestine" rioters attacked the Or Zaruah Synagogue, in the Spanish enclave of Melilla in North Africa, while worshippers were inside.

Based on the video, they seem to have blocked the synagogue entrance completely, while screaming "Murderous Israel" and waving Palestinian flags. (Melilla is an autonomous zone belonging to Spain. It borders Morocco.)

On October 17, during pro-Palestinian protests, hundreds of rioters set fire to Al Hammah synagogue, an abandoned house of prayer in central Tunisia. They hammered down the building’s walls and raised a Palestinian flag on the building. Police did not intervene.

The Facebook page "Tunigate", which has around 88 thousand followers, published a video of the assault. So did "Radio Bousalem”, with 83 thousand users. The vast majority of comments on these videos welcome these acts. The building was severely damaged and almost completely razed to the ground.

On October 15, bomb threats were sent to many East Coast synagogues. Attleboro synagogue Congregation Agudas-Achim received one of the emails, which read, "The bombs will blow up in a few hours. A lot of people will die. You all deserve to die."

On October 8 -- again, while Hamas was still in Israel -- Madrid’s main synagogue was defaced with graffiti that read “Free Palestine” next to a crossed-out Star of David.

And on October 7, an assailant in Rockland, NY fired a BB gun at two women entering a synagogue. Later in the month, a banner at the Stephen Wise Free Synagogue in the area was vandalized with the words, “Fuckin kikes."

#if you have used “Free Palestine” as if it's a sort of verbal assault you can shout in comments or scribble over flyers #if you are unwilling to hear what the Jewish term Zionism means to the people who use it #if you cannot name one Palestinian human rights activist #and most of all if you don't know how Hamas abuses Palestinians and you still think it's The Resistance #then you. are. the. problem.#if you don't know people in gaza have been protesting Hamas and blaming it for deliberately instigating a war they don't want #if you don't know how often they've spoken out about Hamas stealing aid and selling it to them #and especially if you don't want to believe me much less find Palestinians in Gaza to listen to #also if you didn't know about any of the stuff in this post BUT you have taken it upon yourself to tell Jews that “it's not antisemitism”#like seriously everyone deal with your learned distrust of Jews challenge #wall of words #fire tw #guns tw #violence tw #Instagram

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nandovarga · 2 years

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Israel: Doi palestinieni suspectați că plănuiau o "activitate ostilă" au fost arestați la Tel Aviv

Israel: Doi palestinieni suspectați că plănuiau o “activitate ostilă” au fost arestați la Tel Aviv

Reprezentanții forțelor de ordine au declarat că doi palestinieni care au intrat ilegal în Israel au fost arestați la Tel Aviv sub “suspiciunea de activitate ostilă”. Ofițeri ai unității antiteroriste a poliției Yamam și ai agenției de securitate Shin Bet i-au arestat pe cei doi bărbați în sudul Tel Avivului, a precizat poliția israeliană într-un comunicat. Poliția a declarat că “existau temeri…

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#arestare #ISRAEL #palestinieni #shin beth #tel aviv #terorism

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hugheses · 5 months

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Luke, Jack and Timo are at Newark Beth Israel MC

#are they booing or saying luuuuuuke #the giggling…#jack being cozy babygirl #jack hughes #luke hughes #timo meier #hughes brothers

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bookqueenrules · 20 days

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Daryl’s Pilgrimage: Why Daryl Dixson Season 2's Working Title Was Pilgrim

Most of us know that “Pilgrim” was the working title of DD season 2. I believe they changed it to The Book of Carol to throw yet another bone to Carylers because they will not be getting romantic Carly. No matter what the reason, you can’t escape that Season 2 is about Daryl’s pilgrimage. We have gotten some CRAZY hints that this pilgrimage is all about finding Beth.

Exhibit A: Check out the EXACT matching colors between the signage for DD 2 Pilgrim and Emily’s dress in the video for B or C for effort which came out last Fall during the same time DD 2 "Pilgrim" was being filmed.

Meaning of the word pilgrim:

A pilgrim (from the Latin peregrinus) is a traveler (literally one who has come from afar) who is on a journey to a holy place.

So, what is Daryl’s pilgrimage? It’s his journey to a "holy" place that will make him “hole”. A place that has that “something” he first went out looking for. A place that will contain his happy ending.

The Latin form of “peregriuns” is used for a another famous hunter, the The peregrine falcon (Falco peregrinus), also known simply as the peregrine.

Two interesting facts about these birds are that they mate for life and often travel far, usually to a “high place”, to nest. They have been known to even build their nest in skyscrapers. This bird is similar in coloring to the stuffed penguin Daryl finds on the boat in episode one.

Exhibit B: The Camino de Santiago

This is the pilgrimage mentioned in episode 6 of DD season 1. Here is a little background info on the pilgrimage.

Let’s talk about the Hebrew root of the English name, James:

@angelthefirst1 and @frangipanilove have both done wonderful posts about how Daryl=Jacob/Israel right down to being tied to Leah even though he never loved her. Then, Daryl/Israel had to work another 7 years for his “Rachel” or in Daryl’s case, Beth. Another point here is that Jacob leaves his homeland and journeys a long distance, to his mother's people, and there he finds his love, Rachel. It's on this journey that Jacob has the Jacob's ladder dream and names the spot where his head laid during the dream, Beth-el.

So, you could say that this pilgrimage is the Way of Jacob(Daryl). The route starts in various points in France as seen above but ends at the Santiago de Compostela where St. James' remains are said to be.

Compostela means Field of Stars. It comes from the Latin “campus stellae” and is based on the stars of the Milky Way that, according to legend since the Middle Ages, had been outlined by the apostle St. James and followed by pilgrims to reach his tomb.

So, pilgrims follow these stars from France, across the Pyrenees Mountains to find their way to Santiago de Compostela. This ties in perfectly with the Sirius “Dog Star” symbolism we see throughout TWD.

Daryl Dixon season 2 is all about Daryl’s pilgrimage. This spiritual journey will restore Daryl’s faith in God and lead him to his “happy ending” which will be a family with Beth. Just as it was Jacob's children who are the fathers of all of the nation of Israel, I believe it will be Daryl and Beth's children or their descendants who will "save" what is left of humanity.

#team delusional #beth is coming #bethyl #beth greene lives #team defiance #twd daryl and beth #beth is alive #beth greene

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angelthefirst1 · 20 days

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Norman just posted this photo from Paris, which includes a dinosaur 🦕 wearing a beanie and it has love ❤️ heart nostrils.

His post is pointing to Emily's song about a dinosaur 🦕 in the museum of her broken 💔 hearted past.

Read about Emily's broken-hearted dinosaur 🦕 💔 museum here.

Norman's photo also shows symbolism of a bird 🐦 (Emily is marked as the hummingbird or song bird) "nesting" on a diamond 💎

Diamonds are pyramid (Louvre) symbols

You can read more on that here and here.

While the nest symbols are related to where Daryl will find her X.

My personal thoughts are that Daryl will get a clue to her survival at the Louvre and will then have to track her down.

We saw a mini template of this in Consumed (The book of Carol 1.0) when Daryl and Carol entered this office building filled with artwork (representation of the Louvre)

We also see "wing-back" chairs 💺 in this room, significant to Daryl getting his "Angel" or wings back.

Here, Daryl finds a picture 📸 picks it up and looks at it...I personally think this is a shadow of him finding a clue to Beth's survival at the Louvre.

In the next scene, he and Carol look out the window, Carol says, "How did we get here?" A clue to the future and to being in France.

In real time, they do get a clue to where Beth is...the + ambulance 🚑 on the bridge... The bridge symbolism is Jacob's (Israel's) ladder. 🪜

As @bethgreeneprevails has mentioned, the echelon briefing means ladder 🪜

@galadrieljones has done some amazing posts on Jacob and Jacob's ladder. She first clued me into the Leah/Rachel, Jacob (Daryl/Israel) connection.

I talk about how Daryl is Jacob/Israel here and will talk more on it in future posts.

But inside this room, we see a Meridian globe, giving us a hint and pointing to a different time and location.

The Meridian wheels are a representation of the Ferris wheels 🎡 symbolism we see in the show, and Norman recently posted about that too...

Ultimately, these are all symbols of Ezekiel's "wheel within a wheel" vision, which represents a birds eye view (God's view) of everything happening past, present, and future at once - being outside of time.

Interesting Ezekiel 10.10 is where we find this vision.

This Meridian symbolism doesn't just point to France, it points to shifting locations depending on what story they are telling. Which is the biblical end times.

Ezekiel’s Wheel Within a Wheel: What Does It Mean?

Ezekiel, one of the Jews exiled from Israel to Babylon after the fall of Jerusalem, receives this vision as a sign that God has not abandoned him (or the people). The wheels are a sign of God's omnipresence, for he can move anywhere; the height of his throne illustrates that he is always watching from high above us. Another decoration of the wheel chariot was numerous eyes, for God sees everything.

The wheels within wheels allowed the spirits to immediately go in any of four directions where they were told to go (Ezekiel 10:16 - 17).

There is a Ferris wheel in Barcelona, Spain, on the way to the Windsor bridge. It will be interesting to see if they film in a Ferris wheel location at any point when Beth comes back.

I've talked many times before how the "Nest" in France represents Israel, protected by the Archangel Michael, who have a leading role in biblical end time events.

Well, in this room that Daryl and Carol find a Beth clue in, we also get a depiction of Carol's Balaam's donkey symbolism used for DD2 advertising.

Daryl tells Carol that the painting looks like a dog sat in paint and wiped it's ASS 🫏 all over the place...

Dog backwards is god with a little g. This can represent an angel (it can be either holy or fallen depending)

It dipped it's ASS (donkey 🫏) in paint...

Angel donkey painting...numbers 22-Balaam's donkey. I will bless those who bless you and curse those who curse you, a promise made to Abraham's line. X

It wasn't an accident they gave Carol the Balaam's donkey symbolism for DD2. It's so important, and as I've mentioned, it's all related to the biblical end times.

The alcohol symbolism we see around Beth is related to the "spirits." Which I will go into more another time.

Before Daryl spots the ambulance 🚑 on the bridge, we see Daryl and Carol look out the window and see this sign...

This muse sign is pyramid symbolism - as above, so below.

If you read it from top to middle and bottom to middle, you get the word MUSE. Something Emily has written about in her song Jonathan from the album "OH" Jonathan album. Something I have talked about here and here.

Oh Jonathon is about Daryl and Beth.

MUSE is related to art, obviously, so it's just another hint to the Louvre.

One aspect of the dinosaur 🦕 key and the Seahorse key symbolism that I never went into in my previous post on Emily's dinosaur beanie.

Is that it all relates to the rise of the beast as described in Revelation 13.3

🦖🐉🦕🐲

The First Beast

And I saw a beast rising out of the sea, with ten horns and seven heads, with ten diadems on its horns and blasphemous names on its heads. 2 And the beast that I saw was like a leopard; its feet were like a bear’s, and its mouth was like a lion’s mouth. And to it, the dragon gave his power and his throne and great authority. 3 One of its heads seemed to have a mortal wound, but its mortal wound was healed, and the whole earth marvelled as they followed the beast. 4 And they worshipped the dragon, for he had given his authority to the beast, and they worshipped the beast, saying, “Who is like the beast, and who can fight against it?”

Beth's two "clue" cars, have both dinosaur 🦕 and a Seahorse symbolism.

Dinosaur can also mean dragon 🐉 and so can sea dragon, which is a Seahorse. Notice the yellow and blue on the Seahorse key... It's to tell us specifically that it's a sea dragon.

And again, Beth's mortal head wound and her survival, combined with the dragon/beast and sea dragon symbolism, points to her story being linked to the rise of the beast and the biblical end times that revolve around Daryl (Jacob/Israel)

#team delusional #team defiance #bethyl #beth greene #team beth lives #beth is alive #beth x daryl #td #beth is coming #emily kinney #abraham #latter days #king ezekiel #end times #daryl is jacob

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eddieydewr · 4 months

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i hope hamas kills you and then i hope israel turns on you and carpet bombs you to kingdom come. then finally when you think you have reached the afterlife, i will be waiting there with sarin gas to poison you for eternity

whatever helps you get your rocks off, baby.

#ijbol #i don’t think israel plans on attacking my country but i’m definitely shaking 🥺🥺#beth answers

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prolifeproliberty · 5 months

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”But thou, Beth-lehem Ephratah, though thou be little among the thousands of Judah, yet out of thee shall he come forth unto me that is to be ruler in Israel; whose goings forth have been from of old, from everlasting.“

‭‭Micah‬ ‭5‬:‭2‬ ‭KJV‬‬

#Advent #Christmas Eve #Bible

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jcmarchi · 4 months

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New Hope for Early Pancreatic Cancer Intervention via AI-based Risk Prediction - Technology Org

New Post has been published on https://thedigitalinsider.com/new-hope-for-early-pancreatic-cancer-intervention-via-ai-based-risk-prediction-technology-org/

New Hope for Early Pancreatic Cancer Intervention via AI-based Risk Prediction - Technology Org

The first documented case of pancreatic cancer dates back to the 18th century. Since then, researchers have undertaken a protracted and challenging odyssey to understand the elusive and deadly disease. To date, there is no better cancer treatment than early intervention. Unfortunately, the pancreas, nestled deep within the abdomen, is particularly elusive for early detection.

Image credit: MIT CSAIL

MIT Computer Science and Artificial Intelligence Laboratory (CSAIL) scientists, alongside Limor Appelbaum, a staff scientist in the Department of Radiation Oncology at Beth Israel Deaconess Medical Center (BIDMC), were eager to better identify potential high-risk patients. They set out to develop two machine-learning models for early detection of pancreatic ductal adenocarcinoma (PDAC), the most common form of the cancer.

To access a broad and diverse database, the team synced up with a federated network company, using electronic health record data from various institutions across the United States. This vast pool of data helped ensure the models’ reliability and generalizability, making them applicable across a wide range of populations, geographical locations, and demographic groups.

The two models — the “PRISM” neural network, and the logistic regression model (a statistical technique for probability), outperformed current methods. The team’s comparison showed that while standard screening criteria identify about 10 percent of PDAC cases using a five-times higher relative risk threshold, Prism can detect 35 percent of PDAC cases at this same threshold.

Using AI to detect cancer risk is not a new phenomena — algorithms analyze mammograms, CT scans for lung cancer, and assist in the analysis of Pap smear tests and HPV testing, to name a few applications. “The PRISM models stand out for their development and validation on an extensive database of over 5 million patients, surpassing the scale of most prior research in the field,” says Kai Jia, an MIT PhD student in electrical engineering and computer science (EECS), MIT CSAIL affiliate, and first author on an open-access paper in eBioMedicine outlining the new work.

“The model uses routine clinical and lab data to make its predictions, and the diversity of the U.S. population is a significant advancement over other PDAC models, which are usually confined to specific geographic regions, like a few health-care centers in the U.S. Additionally, using a unique regularization technique in the training process enhanced the models’ generalizability and interpretability.”

“This report outlines a powerful approach to use big data and artificial intelligence algorithms to refine our approach to identifying risk profiles for cancer,” says David Avigan, a Harvard Medical School professor and the cancer center director and chief of hematology and hematologic malignancies at BIDMC, who was not involved in the study. “This approach may lead to novel strategies to identify patients with high risk for malignancy that may benefit from focused screening with the potential for early intervention.”

Prismatic perspectives

The journey toward the development of PRISM began over six years ago, fueled by firsthand experiences with the limitations of current diagnostic practices. “Approximately 80-85 percent of pancreatic cancer patients are diagnosed at advanced stages, where cure is no longer an option,” says senior author Appelbaum, who is also a Harvard Medical School instructor as well as radiation oncologist. “This clinical frustration sparked the idea to delve into the wealth of data available in electronic health records (EHRs).”

The CSAIL group’s close collaboration with Appelbaum made it possible to understand the combined medical and machine learning aspects of the problem better, eventually leading to a much more accurate and transparent model. “The hypothesis was that these records contained hidden clues — subtle signs and symptoms that could act as early warning signals of pancreatic cancer,” she adds. “This guided our use of federated EHR networks in developing these models, for a scalable approach for deploying risk prediction tools in health care.”

Both PrismNN and PrismLR models analyze EHR data, including patient demographics, diagnoses, medications, and lab results, to assess PDAC risk. PrismNN uses artificial neural networks to detect intricate patterns in data features like age, medical history, and lab results, yielding a risk score for PDAC likelihood. PrismLR uses logistic regression for a simpler analysis, generating a probability score of PDAC based on these features. Together, the models offer a thorough evaluation of different approaches in predicting PDAC risk from the same EHR data.

One paramount point for gaining the trust of physicians, the team notes, is better understanding how the models work, known in the field as interpretability. The scientists pointed out that while logistic regression models are inherently easier to interpret, recent advancements have made deep neural networks somewhat more transparent. This helped the team to refine the thousands of potentially predictive features derived from EHR of a single patient to approximately 85 critical indicators. These indicators, which include patient age, diabetes diagnosis, and an increased frequency of visits to physicians, are automatically discovered by the model but match physicians’ understanding of risk factors associated with pancreatic cancer.

The path forward

Despite the promise of the PRISM models, as with all research, some parts are still a work in progress. U.S. data alone are the current diet for the models, necessitating testing and adaptation for global use. The path forward, the team notes, includes expanding the model’s applicability to international datasets and integrating additional biomarkers for more refined risk assessment.

“A subsequent aim for us is to facilitate the models’ implementation in routine health care settings. The vision is to have these models function seamlessly in the background of health care systems, automatically analyzing patient data and alerting physicians to high-risk cases without adding to their workload,” says Jia. “A machine-learning model integrated with the EHR system could empower physicians with early alerts for high-risk patients, potentially enabling interventions well before symptoms manifest. We are eager to deploy our techniques in the real world to help all individuals enjoy longer, healthier lives.”

Written by Rachel Gordon

Source: Massachusetts Institute of Technology

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