title: Theorem

text: Logically, many theorems are of the form of an indicative conditional: "If A, then B". Such a theorem does not assert "B" — only that "B" is a necessary consequence of "A". In this case, "A" is called the "hypothesis" of the theorem ("hypothesis" here means something very different from a conjecture), and "B" the "conclusion" of the theorem. The two together (without the proof) are called the "proposition" or "statement" of the theorem (e.g. ""If A, then B"" is the "proposition"). Alternatively, "A" and "B" can be also termed the "antecedent" and the "consequent", respectively. The theorem "If "n" is an even natural number, then "n"/2 is a natural number" is a typical example in which the hypothesis is ""n" is an even natural number", and the conclusion is ""n"/2 is also a natural number".


title: Theorem

text: In order for a theorem be proved, it must be in principle expressible as a precise, formal statement. However, theorems are usually expressed in natural language rather than in a completely symbolic form—with the presumption that a formal statement can be derived from the informal one.


title: Theorem

text: It is common in mathematics to choose a number of hypotheses within a given language and declare that the theory consists of all statements provable from these hypotheses. These hypotheses form the foundational basis of the theory and are called axioms or postulates. The field of mathematics known as proof theory studies formal languages, axioms and the structure of proofs.


title: Theorem

text: Some theorems are "trivial", in the sense that they follow from definitions, axioms, and other theorems in obvious ways and do not contain any surprising insights. Some, on the other hand, may be called "deep", because their proofs may be long and difficult, involve areas of mathematics superficially distinct from the statement of the theorem itself, or show surprising connections between disparate areas of mathematics. A theorem might be simple to state and yet be deep. An excellent example is Fermat's Last Theorem, and there are many other examples of simple yet deep theorems in number theory and combinatorics, among other areas.


title: Theorem

text: Other theorems have a known proof that cannot easily be written down. The most prominent examples are the four color theorem and the Kepler conjecture. Both of these theorems are only known to be true by reducing them to a computational search that is then verified by a computer program. Initially, many mathematicians did not accept this form of proof, but it has become more widely accepted. The mathematician Doron Zeilberger has even gone so far as to claim that these are possibly the only nontrivial results that mathematicians have ever proved. Many mathematical theorems can be reduced to more straightforward computation, including polynomial identities, trigonometric identities and hypergeometric identities.


title: Theorem

text: Theorems in mathematics and theories in science are fundamentally different in their epistemology. A scientific theory cannot be proved; its key attribute is that it is falsifiable, that is, it makes predictions about the natural world that are testable by experiments. Any disagreement between prediction and experiment demonstrates the incorrectness of the scientific theory, or at least limits its accuracy or domain of validity. Mathematical theorems, on the other hand, are purely abstract formal statements: the proof of a theorem cannot involve experiments or other empirical evidence in the same way such evidence is used to support scientific theories.


title: Theorem

text: Nonetheless, there is some degree of empiricism and data collection involved in the discovery of mathematical theorems. By establishing a pattern, sometimes with the use of a powerful computer, mathematicians may have an idea of what to prove, and in some cases even a plan for how to set about doing the proof. It is also possible to find a single counter-example and so establish the impossibility of a proof for the proposition as-stated, and possibly suggest restricted forms of the original proposition that might have feasible proofs.


title: Theorem

text: For example, both the Collatz conjecture and the Riemann hypothesis are well-known unsolved problems; they have been extensively studied through empirical checks, but remain unproven. The Collatz conjecture has been verified for start values up to about 2.88 × 10. The Riemann hypothesis has been verified to hold for the first 10 trillion non-trivial zeroes of the zeta function. Although most mathematicians can tolerate supposing that the conjecture and the hypothesis are true, neither of these propositions is considered proved.


title: Theorem

text: Such evidence does not constitute proof. For example, the Mertens conjecture is a statement about natural numbers that is now known to be false, but no explicit counterexample (i.e., a natural number "n" for which the Mertens function "M"("n") equals or exceeds the square root of "n") is known: all numbers less than 10 have the Mertens property, and the smallest number that does not have this property is only known to be less than the exponential of 1.59 × 10, which is approximately 10 to the power 4.3 × 10. Since the number of particles in the universe is generally considered less than 10 to the power 100 (a googol), there is no hope to find an explicit counterexample by exhaustive search.


title: Theorem

text: The word "theory" also exists in mathematics, to denote a body of mathematical axioms, definitions and theorems, as in, for example, group theory (see mathematical theory). There are also "theorems" in science, particularly physics, and in engineering, but they often have statements and proofs in which physical assumptions and intuition play an important role; the physical axioms on which such "theorems" are based are themselves falsifiable.


title: Theorem

text: A number of different terms for mathematical statements exist; these terms indicate the role statements play in a particular subject. The distinction between different terms is sometimes rather arbitrary, and the usage of some terms has evolved over time.


title: Theorem

text: A few well-known theorems have even more idiosyncratic names, for example, the division algorithm, Euler's formula, and the Banach–Tarski paradox.


title: Theorem

text: The end of the proof may be signaled by the letters Q.E.D. ("quod erat demonstrandum") or by one of the tombstone marks, such as "□" or "∎", meaning "end of proof", introduced by Paul Halmos following their use in magazines to mark the end of an article.


title: Theorem

text: The exact style depends on the author or publication. Many publications provide instructions or macros for typesetting in the house style.


title: Theorem

text: It is common for a theorem to be preceded by definitions describing the exact meaning of the terms used in the theorem. It is also common for a theorem to be preceded by a number of propositions or lemmas which are then used in the proof. However, lemmas are sometimes embedded in the proof of a theorem, either with nested proofs, or with their proofs presented after the proof of the theorem.


title: Theorem

text: Corollaries to a theorem are either presented between the theorem and the proof, or directly after the proof. Sometimes, corollaries have proofs of their own that explain why they follow from the theorem.


title: Theorem

text: The well-known aphorism, , is probably due to Alfréd Rényi, although it is often attributed to Rényi's colleague Paul Erdős (and Rényi may have been thinking of Erdős), who was famous for the many theorems he produced, the number of his collaborations, and his coffee drinking.


title: Theorem

text: The classification of finite simple groups is regarded by some to be the longest proof of a theorem. It comprises tens of thousands of pages in 500 journal articles by some 100 authors. These papers are together believed to give a complete proof, and several ongoing projects hope to shorten and simplify this proof. Another theorem of this type is the four color theorem whose computer generated proof is too long for a human to read. It is among the longest known proofs of a theorem whose statement can be easily understood by a layman.


title: Theorem

text: In mathematical logic, a formal theory is a set of sentences within a formal language. A sentence is a well-formed formula with no free variables. A sentence that is a member of a theory is one of its theorems, and the theory is the set of its theorems. Usually a theory is understood to be closed under the relation of logical consequence. Some accounts define a theory to be closed under the semantic consequence relation (formula_1), while others define it to be closed under the syntactic consequence, or derivability relation (formula_2).


title: Theorem

text: For a theory to be closed under a derivability relation, it must be associated with a deductive system that specifies how the theorems are derived. The deductive system may be stated explicitly, or it may be clear from the context. The closure of the empty set under the relation of logical consequence yields the set that contains just those sentences that are the theorems of the deductive system.


title: Theorem

text: In the broad sense in which the term is used within logic, a theorem does not have to be true, since the theory that contains it may be unsound relative to a given semantics, or relative to the standard interpretation of the underlying language. A theory that is inconsistent has all sentences as theorems.


title: Theorem

text: The definition of theorems as sentences of a formal language is useful within proof theory, which is a branch of mathematics that studies the structure of formal proofs and the structure of provable formulas. It is also important in model theory, which is concerned with the relationship between formal theories and structures that are able to provide a semantics for them through interpretation.


title: Theorem

text: Although theorems may be uninterpreted sentences, in practice mathematicians are more interested in the meanings of the sentences, i.e. in the propositions they express. What makes formal theorems useful and interesting is that they may be interpreted as true propositions and their derivations may be interpreted as a proof of their truth. A theorem whose interpretation is a true statement "about" a formal system (as opposed to "within" a formal system) is called a "metatheorem".


title: Theorem

text: The concept of a formal theorem is fundamentally syntactic, in contrast to the notion of a "true proposition," which introduces semantics. Different deductive systems can yield other interpretations, depending on the presumptions of the derivation rules (i.e. belief, justification or other modalities). The soundness of a formal system depends on whether or not all of its theorems are also validities. A validity is a formula that is true under any possible interpretation (for example, in classical propositional logic, validities are tautologies). A formal system is considered semantically complete when all of its theorems are also tautologies.


title: D Smoke

text: Daniel Anthony Farris (born October 17, 1985), known professionally as D Smoke, is an American rapper and songwriter from Inglewood, California. He gained attention after winning the first season of the Netflix music competition show "Rhythm + Flow" in 2019. The following year, he independently released his debut album "Black Habits", which earned him nominations for Best Rap Album and Best New Artist at the 63rd Annual Grammy Awards.


title: D Smoke

text: Farris grew up in a musical family with his mother, brothers, and cousin being gospel singers in Inglewood, California. His mother was backup singer for Tina Turner. His brother SiR is signed to Top Dawg Entertainment. In 2006, he started a songwriting group called WoodWorks with his brothers and his cousin Tiffany Gouché, who wrote songs for Ginuwine and The Pussycat Dolls, and is credited for co-writing "Never" by Jaheim. He was also in a musical trio with his brother called N3D. On May 9, 2006, he released his first album called "Producer of the Year". In 2015, he appeared on SiR's independent album "Seven Sundays" on the song "You Ain't Ready".


title: D Smoke

text: In 2019, Farris was a contestant on the Netflix competition show "Rhythm + Flow", and was named the inaugural winner of the three-week series. On October 24, he released his debut EP "Inglewood High", a 7-track project including a feature from Gouché. "HipHopDX" gave the EP a positive review, saying he could "utilize multiple flows, deliver introspective storytelling, could rap in Spanish incredibly well and had an ear for quality." He performed at the 2019 Soul Train Music Awards with SiR. He also appeared on The Game's album "Born 2 Rap" on the song "Cross on Jesus Back".


title: D Smoke

text: D Smoke later appeared as himself in the Peacock series "Bel-Air", in the episode "PA to LA", based on "The Fresh Prince of Bel-Air.


title: Sohla El-Waylly

text: Sohla El-Waylly (née Muzib) is an American chef, restaurateur, and YouTube personality. She was an assistant food editor at "Bon Appétit", where she appeared in videos produced for the magazine's YouTube channel, and also produced videos with Andrew Rea on the "Babish Culinary Universe" YouTube channel. She currently hosts a food column and video series on other platforms.


title: Sohla El-Waylly

text: Sohla Muzib () was raised in Los Angeles in a Bengali-American family, who owned a Baskin-Robbins store. She continued in the restaurant industry by working for Outback Steakhouse.


title: Sohla El-Waylly

text: She went to University of California, Irvine, where she studied economics and worked at a Cheesecake Factory on the side.


title: Sohla El-Waylly

text: Beginning in 2008, El-Waylly attended The Culinary Institute of America (CIA). She says that while at CIA, she was sexually harassed by a dean, and when she spoke up a female dean told her, "That's what happens in the real world. You better get used to it."


title: Sohla El-Waylly

text: After graduating, El-Waylly worked at restaurants in New York City such as Atera, which has two Michelin stars, and Del Posto, owned by Joe Bastianich.


title: Sohla El-Waylly

text: In March 2016, El-Waylly and her husband opened a diner called Hail Mary in Brooklyn, which attracted favorable reviews. However, an early review from Scott Lynch for "Quick Bites" also stated, "I worry about Hail Mary because it's an ambitious, almost special-occasion restaurant wrapped inside a burger-and-shake joint." The restaurant closed after 11 months, which El-Waylly attributed in part to opening Hail Mary without other investors, and in part to the expectations of white customers. In a 2017 interview with "GQ", El-Waylly explained that she perceived customers as often entering Hail Mary expecting "foreign or exotic ingredients" because of the owners' cultural backgrounds; she stated "There would have been more leeway allowed in the food shrouded by illusion of 'authenticity'...There are white chefs that can pull from different cultures without explanation, but us making white food always needs a thesis behind it." El-Waylly worked at "Serious Eats" as a culinary editor through most of 2018 and joined "Bon Appétit" magazine in August 2019. At "Bon Appétit", she worked as an assistant food editor and appeared regularly on the magazine's popular YouTube channel.


title: Sohla El-Waylly

text: In June 2020, a photo of "Bon Appétit" editor-in-chief Adam Rapoport in brownface resurfaced online and sparked widespread criticism. During an emergency company-wide Zoom meeting, El-Waylly called for Rapoport to step down. She then publicly accused the magazine of discriminating towards employees of color, claiming they were subject to lesser pay than their non-minority counterparts. Rapoport resigned the same day. In August 2020, El-Waylly announced on her Instagram that she would no longer appear in videos on the magazine's YouTube channel due to continued lack of progress by Condé Nast Entertainment in resolving the issues that had arisen, though she would continue to contribute recipes and articles to the magazine and website. Soon after, she announced she had completely severed ties with "Bon Appétit".


title: Sohla El-Waylly

text: On September 23, 2020, a new series titled "Stump Sohla" was announced, which would be hosted on Andrew Rea's "Babish Culinary Universe" YouTube channel. The show premiered the next day. El-Waylly said she decided to work with Rea because she would have more creative control and direct cut of the video revenue. "I just really don't want to be a prop," she said in an interview with "New York" magazine. Rea and El-Waylly ended their collaboration in early 2021. El-Waylly also began a weekly column with Food52 called "Off-Script with Sohla" and is writing a cookbook.


title: Sohla El-Waylly

text: El-Waylly hosts a web series for the American TV network History titled "Ancient Recipes with Sohla". She also hosts a show for the "New York Times" Cooking YouTube channel titled "Mystery Menu." She is also a judge on the HBO Max culinary reality competition "The Big Brunch", along with Dan Levy and Will Guidara.


title: Sohla El-Waylly

text: El-Waylly lives in New York City with her husband, fellow chef Hisham "Ham" El-Waylly. They met while they were both attending the Culinary Institute of America.


title: West Point, New York

text: West Point is the oldest continuously occupied military post in the United States. Located on the Hudson River in New York, West Point was identified by General George Washington as the most important strategic position in America during the American Revolution. Until January 1778, West Point was not occupied by the military. On January 27, 1778, Brigadier General Samuel Holden Parsons and his brigade crossed the ice on the Hudson River and climbed to the plain on West Point and from that day to the present, West Point has been occupied by the United States Army. It comprises approximately including the campus of the United States Military Academy, which is commonly called "West Point".


title: West Point, New York

text: West Point is a census-designated place (CDP) located in the town of Highlands in Orange County, located on the western bank of the Hudson River. The population was 6,763 at the 2010 census. It is part of the New York–Newark–Jersey City, NY–NJ–PA Metropolitan Statistical Area as well as the larger New York–Newark, NY–NJ–CT–PA Combined Statistical Area.


title: West Point, New York

text: West Point (then known as Fort Clinton), was a fortified site during the Revolutionary War. Originally picked because of the abnormal S-curve in the Hudson River at this point, the defenses of West Point were designed by Polish military engineer Tadeusz Kościuszko, who served as a brigadier general in the Continental Army.


title: West Point, New York

text: It was staffed by a small garrison of Continental Army Soldiers from early in 1776 through the end of the war. A great iron chain was laid across the Hudson at this point in 1778 in order to prevent British Navy vessels from sailing further up the Hudson River, which was never tested by the British.


title: West Point, New York

text: The site comprised multiple redoubts, as well as Fort Putnam, situated on a high hill overlooking the river. Named after its builder, Revolutionary War General and engineer Rufus Putnam, the fort is still preserved in its original design.


title: West Point, New York

text: In perhaps the most infamous act of treason in American history, General Benedict Arnold attempted to turn the site over to the British Army in 1780 for a bribe consisting of a commission as a brigadier general in the British Army and a cash reward of £20,000 (about $1.3M in 2009 dollars). Arnold's plot failed when British Major John André was captured as a spy by the Americans. Arnold received a decreased cash reward of £6,000 (roughly $350,000) but was commissioned as a brigadier general in the British Army.


title: West Point, New York

text: After the conclusion of the American Revolution, West Point was used as a storage facility for cannon and other military property used by the Continental Army. For two months in 1784, the United States Army consisted of only about 80 soldiers under the command of Brevet Major John Doughty at West Point.


title: West Point, New York

text: The United States Military Academy was established at West Point in 1802 and is the nation's oldest service academy. West Point has the distinction of being the longest continuously occupied United States military installation.


title: West Point, New York

text: In 1937, the West Point Bullion Depository was constructed; in 1988, it became the West Point Mint, as a branch of the United States Mint.


title: West Point, New York

text: West Point is located at 41° 23′ 42" N 73° 57' 18" W (41.395° N 73.955° W). According to the United States Census Bureau, the CDP has a total area of ; land and water. West Point and the contiguous village of Highland Falls are on the west bank of the Hudson River.


title: West Point, New York

text: West Point has a humid continental climate (Köppen "Dfa"), with four distinct seasons. Summers are hot and humid, while winters are cold with moderate snowfall. The monthly daily average temperature ranges from in January to in July; on average, temperatures reaching or occur on 17 and 1.4 days of the year, respectively. The average annual precipitation is approximately , which is distributed fairly evenly throughout the year; snow averages per season, although this total may vary considerably from year to year. Extremes in temperature range from on July 22, 1926, down to on February 9, 1934.


title: West Point, New York

text: As of the census of 2010 there were 6,763 people, and 685 households residing in the CDP. The population density was 293.4 per square mile (113.3/km). There were 1,044 housing units at an average density of 42.9/sq mi (16.6/km). The racial makeup of the CDP was 82.31% white, 9.09% African American, .5% Native American, 3.35% Asian, .15% Pacific Islander, 1.64% from other races, and 2.96% from two or more races. Hispanic or Latino of any race were 6.56% of the population.


title: West Point, New York

text: There were 685 households, out of which 75.1% had children under the age of 18 living with them, 87.8% were married couples living together, 4.8% had a female householder with no husband present, and 5.7% were non-families. 5.4% of all households were made up of individuals, and none had someone living alone who was 65 years of age or older. The average household size was 3.69.


title: West Point, New York

text: The age distribution is 16.7% under the age of 18, 51.2% from 18 to 24, 23% from 25 to 44, 3.8% from 45 to 64, and .1% who were 65 years of age or older. The median age was 21 years. For every 100 females, there were 207.3 males. For every 100 females age 18 and over, there were 259.7 males. All of these statistics are typical for military bases.


title: West Point, New York

text: The median income for a household in the CDP was $56,516, and the median income for a family was $56,364. About 2.0% of families and 2.0% of the population were below the poverty line, including 2.6% of those under age 18 and none of those age 65 or over.


title: West Point, New York

text: U.S. Route 9W, combined with New York State Route 218 run north-south through West Point. New York Route 293 also runs northeast-southwest through the post. Running through the lower portion of the town is U.S. Route 6, combined with the upper extent of the Palisades Interstate Parkway.


title: West Point, New York

text: The New York Central Railroad well into the 1950s operated several passenger trains a day on the West Shore Railroad through the academy's Gothic style station; both the limited stop trains bound for Albany and the local trains to Newburgh and Kingston made stops at the station. Service finally ended in 1958.


title: West Point, New York

text: Highland Falls-Fort Montgomery Central School District is the local school district. James I. O'Neill High School is its high school.


title: West Point, New York

text: The Department of Defense Education Activity (DoDEA) maintains elementary and middle schools for children of military personnel on-post at USMA, but sends high school aged students who are dependents of on-base military personnel to O'Neill. In March 2022 USMA's contract with O'Neill was renewed.


title: Tembi Locke

text: Tembekile "Tembi" Locke is an American actress who has appeared in television shows and film. She is best known as Dr. Grace Monroe on Syfy's series "Eureka" and as Dr. Diana Davis in "Sliders". Locke is also the author of the bestselling memoir, "From Scratch," which was later adapted into a limited series by Netflix.


title: Tembi Locke

text: Born to civil rights activist parents, she attended Alief Hastings High School in Houston. After high school, Locke lived for a time in Italy on a foreign exchange program. While there, she appeared several times on Italian television, including the "Carnevale Di Venezia". After returning to the United States, she graduated with an art history degree from Wesleyan University, in Connecticut. She speaks fluent Italian.


title: Tembi Locke

text: Locke and her husband, Rosario "Saro" Gullo, a Sicilian chef, lived and worked in Los Angeles, California. Her husband died in 2012. They have one daughter who was 7 at the time of her father's death. She is a vegetarian, and urban homesteader, regularly growing produce on vacant lots in the city. Locke is a gourmet cook, and also enjoys hiking, running and fishing. She is involved in several social activism programs.


title: Tembi Locke

text: While in New York, Locke appeared in several off-Broadway productions, and landed a role on the long-running soap opera "As The World Turns". Afterward, she moved to Los Angeles. Her prime-time television career began by playing one of Will Smith's love interests on "The Fresh Prince of Bel-Air".


title: Tembi Locke

text: Locke has appeared in numerous television dramas, comedies, and films over the course of her career. She played Dr. Grace Monroe, a biotech specialist, on seasons four and five of Syfy's series "EURKA" (2010–2012). She also starred as Dr. Diana Davis on season five of the Fox/Syfy show "Sliders" (1999–2000).


title: Tembi Locke

text: Locke's television work includes shows such as "Castle", "Bones", "The Mentalist", "Windfall", "", and "Beverly Hills, 90210". Her comedic turns include "Friends", "The Jamie Foxx Show", "House of Payne", "Like Family", and "Raising Dad", among others. She has appeared in a number of movies made for television, including "Black Widow, Final Approach" and "Born in the USA". In 2014, Locke appeared as Dr. Walcott in "Dumb and Dumber To".


title: Tembi Locke

text: As of October 2018, her most recent work is in the second installment of Hulu original "Into the Dark" series. She plays the therapist in the episode Flesh & Blood.


title: Tembi Locke

text: Locke's memoir, "From Scratch: A Memoir of Love, Sicily and Finding Home" (published April 30, 2019), is about her romance with her Italian husband and her grief after his untimely death. "From Scratch" was later adapted by producer Reese Witherspoon and writer Marguerite MacIntyre into a limited series starring Zoe Saldana for Hello Sunshine, 3 Arts, Cinestar and Netflix.


title: Worm (web serial)

text: Worm is a self-published web serial by John C. "Wildbow" McCrae and the first installment of the "Parahumans" series, known for subverting and playing with common tropes and themes of superhero fiction. McCrae's first novel, "Worm" features a bullied teenage girl, Taylor Hebert, who develops the superpower to control worms, insects, arachnids and other simple lifeforms. Using a combination of ingenuity, idealism, and brutality, she struggles to do the right thing in a dark world filled with moral ambiguity. It is one of the most popular web serials on the internet, with a readership in the hundreds of thousands. A sequel, titled "Ward", was published from November 2017 to May 2020.


title: Worm (web serial)

text: "Worm" was first published as an online serial with two to three chapters released every week. It began online publishing in June 2011 and continued until November 2013, totaling approximately 1,682,400 words.


title: Worm (web serial)

text: The story was written at a rate comparable to a traditional book being published every month. It followed a strict publication schedule, with new chapters released every Tuesday and Saturday, and bonus chapters on Thursdays as rewards for donations. These chapters were arranged into 31 arcs, each of which covered a specific series of events over six to twelve chapters and concluded with an interlude from the point of view of a side character.


title: Worm (web serial)

text: In contrast to traditional publishing, which follows a short-term model, Worm's readership grew slowly but steadily, beginning with 13 views in June 2011, the month the serial began; 26,844 monthly views a year later; and 207,833 monthly views by June 2013. Views peaked at 1,390,648 in November 2013, when the book ended, and remained steady with 693,675 monthly views even five years later.


title: Worm (web serial)

text: , "Worm" is being edited, and McCrae plans to produce both an eBook version and a physical book via traditional publishing. A fan-made audiobook project was launched in June 2014 and completed in June 2016.


title: Worm (web serial)

text: "Worm" is set in a fictional, alternate universe known as "Earth Bet". The events of Earth Bet closely follow that of our own Earth until a naked, golden man named "Scion" appears over the ocean in 1982. Following his appearance, a fraction of humans gain superpowers if placed in a traumatic and stressful situation, known in-story as a "trigger event".


title: Worm (web serial)

text: The arrival of "parahumans" in 1982 leads to a "Golden Age of Heroism", during which the majority of people with powers work for the public good. In 1989, after a parahuman dies trying to prevent a riot, superpowered serial killers, thieves, cults, and gang members begin to increasingly threaten public safety. Governments worldwide create agencies to counter parahuman criminals, including the Parahuman Response Team (PRT), in Canada and the United States.


title: Worm (web serial)

text: In 1992, a giant monster launches a devastating attack on the Marun Field, Iran. To adequately prepare humanity for future attacks, and to manage the growing villain population, four prominent heroes form the Protectorate, an organization subordinate to the PRT dedicated to cooperation among superheroes. Two more monsters (collectively referred to as "Endbringers") appear and begin attacking cities across the planet, causing the loss of millions of lives, as well as catastrophic and irreversible economic and geographic damage. The PRT and Protectorate are forced to treat villains more leniently in return for assistance in fighting Endbringers. Mired in bureaucracy and politics, the PRT is increasingly unable to cope with the growing frequency and brutality of parahuman crimes.


title: Worm (web serial)

text: The story is set in the fictitious city of Brockton Bay, a formerly wealthy port that has severely declined after Endbringer attacks led to the collapse of the shipping industry. Due to the poverty of the area, it has a higher number of parahumans per capita than any other American city, and a number of superhuman-led gangs vie for control over the city's criminal enterprises.


title: Worm (web serial)

text: Individuals who possess powers in "Worm" are referred to formally as "parahumans" and informally as "capes", a term referencing the general habit of parahumans to establish an alter ego and go out in costume (with or without literal "capes").


title: Worm (web serial)

text: In order to acquire a power in "Worm", one must suffer a trigger event: a moment of severe physical or psychological trauma. The properties of the power are influenced by the nature of the threat the individual faces and the individual's thought process at the time. Some parahumans, when placed under extreme stress reminiscent or beyond that of their initial trigger event may trigger a second time, expanding and refining their powers to increase their odds of survival.


title: Worm (web serial)

text: In rare cases, multiple individuals may suffer a simultaneous trigger event known as a "cluster trigger". Cluster triggers often cause complicated and intense interpersonal relationships within the cluster, often referred to as the Kiss/Kill dynamic.


title: Worm (web serial)

text: Individuals who have spent multiple years around capes will, on occasion, trigger with a similar power. These individuals are generally referred to as "second generation capes" as many are children of previous parahumans, although powers are not, strictly speaking, heritable. The mechanics behind how powers work is gradually explained throughout the story.


title: Worm (web serial)

text: Alternatively, powers can be acquired through Cauldron, a shadowy and secretive group which has discovered a method to artificially induce powers. This process carries a significant risk of deformation or mutilation, with the strength or safety of powers acquired varying greatly. Individuals whose Cauldron-acquired powers result in noticeable or grotesque mutation are referred to as "Case-53s" or "monster capes".


title: Worm (web serial)

text: Powers in "Worm" obey several arbitrary constraints. All powers can be used aggressively, regardless of manifestation. Thus, healers are incredibly rare and often as a byproduct of another power, or have other abilities suited towards combat. Another limitation is the "Manton effect": a parahuman's abilities very rarely affect both organic and inorganic material, and parahumans are instinctively protected from their own power – i.e., a power may affect the landscape, but not the people within it, or vice versa.


title: Worm (web serial)

text: Taylor Hebert is a fifteen-year-old parahuman who has developed the power to sense and control insects following a traumatic event. She lives in the fictional city of Brockton Bay, a hotspot of parahuman activity, and seeks to become a superhero. On her first night out in costume, she defeats a superpowered gang leader and is subsequently mistaken for a villain by a team of teenage parahuman thieves known as the Undersiders who work jobs for a mysterious benefactor. Taylor joins the team, hoping to learn the identity of their boss before turning them into the authorities. However, Taylor grows increasingly close to the Undersiders whilst having repeatedly poor run-ins with the parahuman law enforcement agency known as the Protectorate and finds herself unable to betray them. She commits to the Undersiders, adopting the moniker "Skitter" and abandons her dream of becoming a superhero. After a job, Taylor learns that the Undersiders have unwittingly assisted their patron, the gang lord known as Coil, in the kidnapping of Dinah, a girl with powerful precognitive powers, and is wracked with guilt over her own part.


title: Worm (web serial)

text: In part due to violence initiated by the defeat of various gangs by the Undersiders, Brockton Bay experiences a period of instability. This culminates in an attack by Leviathan, one of three powerful monsters collectively called the Endbringers, which devastates the city. In the aftermath, Coil directs the Undersiders in seizing territory and they begin to operate as makeshift warlords in the ruined city. Privately, Taylor and the Undersiders plot to depose Coil if they cannot secure Dinah's release. When Jack Slash, the theatrical leader of a notorious gang of parahuman serial killers known as the Slaughterhouse Nine, invades Brockton Bay, Dinah predicts he will bring about the end of the world in two years if not stopped. The city weathers the incursion, but its parahumans fail to kill either Jack or his prized protege Bonesaw, a young girl kidnapped and moulded by the gang of serial killers. In the process of escaping the city, Jack learns of Dinah's prophecy and decides to fulfill it and end the world.


title: Worm (web serial)

text: Coil, valuing Dinah's precognitive abilities too highly to consider her release, attempts to assassinate Taylor when she pushes the issue. She survives and the Undersiders kill Coil in retaliation, positioning themselves to take over the remnants of Coil's criminal empire and fully entrenching themselves as the shadowy rulers of Brockton Bay, though it remains ostensibly governed by the United States of America. Together, Taylor and the Undersiders carefully balance staving off attempts by regional criminal organisations to establish footholds in their city with scuffles against the legal authority of the city and assisting the remaining civilian population. At Dinah's counsel, Taylor surrenders herself to the authorities and is forcefully recruited to the Protectorate as the new probationary superhero "Weaver", leaving Brockton Bay for the city of Chicago.


title: Worm (web serial)

text: Over the next two years, Taylor serves out her probation as Weaver with the Chicago Wards, a team of teenage superheroes attached as a youth group to the Chicago Protectorate. When Dinah's deadline passes, Jack returns from hiding at the head of an army of cloned members (and former members) of the Slaughterhouse Nine, forcing Weaver and her allies to go to war against Jack Slash to prevent the apocalypse. They manage to successfully hold off Jack and his army, however, at the last minute, Jack convinces Scion, the most powerful superhero of all, to kill billions in an interdimensional rampage. It is revealed that Scion is the avatar of an unfathomably powerful alien entity referred to as The Warrior, responsible for seeding the planet with superpowers in the first place, as part of his species' reproductive cycle; a cycle that would end in the destruction of the planet and all its alternate-dimension counterparts.


title: Worm (web serial)

text: Taylor, with her power surgically altered to control people as well as insects, seizes complete control over the trans-dimensional array of parahuman defenders and defeats Scion before having her connection to her power removed for good by another powerful precognitive parahuman, Contessa. Contessa is shown to be the final agent and architect of the interdimensional conspiracy known as Cauldron, suggested to be responsible for many of the previous events of the story with the aim of combating the alien Scion. In a series of epilogues, the short-term fate of the remaining Undersiders is addressed and Taylor finds herself living as an unpowered human on the largely untouched Earth-Aleph, the alternate universe which most closely mirrors her own home world.


title: Worm (web serial)

text: If I had to identify a theme running through all of Worm, it’s Taylor wanting to make the world a better place, a safer place, for herself, her family and her friends. If I had to pick a second theme, it would be that those good intentions aren’t enough. Taylor seems to make the best decision at any possible moment, the decision that gets her out of a losing fight, the decision that saves the lives of her friends, the decision that wins a battle. Yet, in doing so, things just get worse.


title: Worm (web serial)

text: Gavin Scott Williams suggested that the story contains an "undercurrent" of the idea that "sometimes you have to go outside the rules to do the right thing". Several authors have compared the story to Alan Moore's "Watchmen", as well as the character of Spider-Man and his themes of responsibility, although McCrae has stated in interviews that no one author has heavily influenced him.


title: Worm (web serial)

text: The title "Worm" has multiple potential meanings. It has been connected to the protagonist's character development, as a "lowly, overlooked" person who is nonetheless useful and dangerous; drawing a parallel with the protagonist's power to control worms and other bugs. The arc titles also generally have double meanings.


title: Worm (web serial)

text: Several reviewers have described the serial as an exercise in repeatedly escalating the stakes of the story.


title: Worm (web serial)

text: A number of reviewers have noted the characters' ingenuity, and the original and creative use of superpowers in the narrative. Author Adam Sherman described one of the recurring themes of the story as "that powers don’t really make the person, it's the person who makes the power". McCrae has described how he would regularly write himself into corners, so that "the desperate gambits we see are echoed by my writerly desperation to figure out a way to keep things going." G.S Williams drew a parallel between the protagonist's power being seemingly underwhelming, and her being overlooked in her civilian life, and the broader theme of things being overlooked.


title: Worm (web serial)

text: "Worm" has received almost entirely favorable reviews. It received substantial attention following a favorable review by author Gavin Scott Williams roughly six months into publication, who praised the story's themes and originality. Readership doubled when it was recommended by author Eliezer Yudkowsky on his website while the story was in its final months.


title: Worm (web serial)

text: Critics favorably compared it to the similar-length book series "A Song of Ice and Fire". Matt Freeman of Doof Media praised the story's originality, noting that it works as a science fiction story to a degree not found in most works of superhero fiction. Media site Toolsandtoys.net published a review by Chris Gonzales, who described it as "one of my favorite stories ever written". However, he also noted that it was "dark", warning "definitely don’t hand this to a kid to read". Chris Ellis of Ergohacks.com noted that the story "managed to hit every single trigger warning we have listed", but called it "among the best books and universes I’ve ever read."


title: Worm (web serial)

text: Reviewers have praised the story's realism and use of consequences, contrasting it favorably with the tendency for characters to miraculously return from the dead in superhero comic books and films. Many praised the story's originality and creative use of superpowers. Several reviewers commended the detail, consistency, and depth of the setting.


title: Worm (web serial)

text: The story also possesses a sizable online fanbase. Fans of the story have collaborated to create a complete audio book, as well as other projects, such as the "We've Got Worm" podcast, a weekly arc-by-arc podcast with a first-time reader and a "Worm" expert. Fan art relating to the novel has been published on DeviantArt, as well as a large amount of fan fiction. There is an IRC chatroom established for readers to comment and discuss the story, which is constantly active, as well as communities of fans on a number of online forums. "Worm", along with McCrae's other completed works "Pact", "Twig", and the Worm sequel "Ward", are consistently among the highest-rated works on ratings site TopWebFiction, and "Worm" is the highest-rated work on several websites that collect serial fiction. "Worm" has an average rating of 4.67 out of 5 stars on Goodreads, with over 3000 user rankings. Of these users, 99% liked the book.


title: Worm (web serial)

text: Several publications have discussed "Worm" within the context of the increasing popularity of web serials, and compared to the work of authors such as Charles Dickens and Mark Twain, who also wrote in the serial format. Authors Olivia Rising and Adam Sherman have credited it as a decisive influence on their work.


title: Worm (web serial)

text: A number of companies have approached McCrae to discuss adapting Worm, as well as another of his serials, "Twig". However, McCrae takes a pessimistic view of whether it will be successfully adapted.


title: Worm (web serial)

text: In October 2017, McCrae announced on his blog that a sequel to Worm would be released. The interim story arc, "Glow-worm", was released beginning October 21, 2017, and the sequel, "Ward", featuring protagonist Victoria Dallon, began serialization on November 11, 2017, and was concluded on May 2, 2020.


title: Super Troopers 2

text: Super Troopers 2 is a 2018 American comedy film directed by Jay Chandrasekhar. A sequel to the 2001 film "Super Troopers", the film was written by and stars the Broken Lizard comedy team, made up of Jay Chandrasekhar, Kevin Heffernan, Steve Lemme, Paul Soter and Erik Stolhanske. The plot follows the Super Troopers being called upon to set up a new Highway Patrol station when an international border dispute arises between the United States and Canada.


title: Super Troopers 2

text: The film had a troubled development period as studios were skeptical that a sequel, produced over a decade after the original, would find an audience. After a successful crowdfunding campaign produced $2 million in seed money in 24 hours (and $4.7 million overall), the film was greenlit and principal photography began in the Central Massachusetts area on October 23, 2015. The film was released in the United States on April 20, 2018, by Fox Searchlight Pictures. A sequel is in development.


title: Super Troopers 2

text: Several years after the first film, the officers have been fired from the Spurbury Police Department after taking Fred Savage on a ride-along that resulted in his death. Farva (Heffernan) is now a construction supervisor, with Mac (Lemme) and Rabbit (Stolhanske) working for him. Thorny (Chandrasekhar) works in logging, and Foster (Soter) is living with his girlfriend and former coworker, Spurbury Police Chief Ursula Hanson (Coughlan). Mac receives a call from his former boss, Captain O'Hagen (Cox), to gather the group and meet for a fishing trip in Canada.


title: Super Troopers 2

text: Once the group arrives, they find that O'Hagen's intention had been for them to have a meeting with Vermont Governor Jessman (Carter). She explains that during a recent land survey, it was discovered that land in Canada was originally designated for the US. Canada has agreed to hand over the land, and Gov. Jessman needs to set up a police department to take over from the Royal Canadian Mounted Police in the region. She invites the group to become state troopers again, with the promise that they will become full-time officers should they succeed at this task.


title: Super Troopers 2

text: At a reception for the police officers, they meet the town mayor, Guy Le Franc (Lowe), the Canadian Mounties they'll be replacing (Labine, MacArthur, and Sasso), and cultural attaché, Genevieve Aubois (Chriqui). The Americans are received poorly by the townspeople, who wish to remain Canadian. The next day, Foster and Mac accompany the Mounties on their patrol to meet the local townspeople, where they are attacked in Le Franc's strip club. Thorny and Rabbit are tasked with replacing metric road signs with their U.S.-equivalent measurements, and Farva is assigned as the dispatcher.


title: Super Troopers 2

text: Thorny and Rabbit encounter several young children under the influence of drugs. They ask the kids to lead them to where they found the drugs, and arrive at an abandoned lake house where they encounter unmarked pills and counterfeit cell phones. The next day, the Canadian Mounties play a prank on the Vermont State Troopers by releasing a bear into their station. In retaliation, the State Troopers kidnap the Mounties and release them in the woods. They then don Mountie uniforms, and attempt to discredit their Canadian counterparts by performing pranks on the people they pull over. However, their pranks are cut short when Le Franc reveals that he will use the serious crime of impersonating an officer to keep the territory from becoming American.


title: Super Troopers 2

text: The State Troopers, realizing that they will not be given their original jobs after failing at this task, intend to return to America. During a botched highway stop, Farva and Mac encounter another cache of drugs and cell phones, as well as AK-48 rifles. The troopers realize that these items are all more valuable in the U.S. than in Canada, and that someone has been planting these items around the town in preparation for the turnover to the U.S, to avoid having to cross the border. Back at the station, Genevieve, who has been flirting with Rabbit, arrives, and the two begin to have sex, only to be attacked and carried-off. The rest of the State Troopers learn about Rabbit's kidnapping by reviewing his dash-cam, and suspect the Canadian Mounties are involved.


title: Super Troopers 2

text: Using a cell-phone triangulator on the counterfeit phones, the State Troopers arrive at a sawmill. They encounter the Mounties, only to realize the Mounties had suspected the State Troopers as the drug smugglers. Guy Le Franc reveals himself as the leader of the smuggling operation, and has captured Genevieve and Rabbit and tied them to a board placed on the saw. Genevieve reveals herself to be a double-agent working for Le Franc, and the groups engage in a shootout. The State Troopers and Mounties are successful, and Rabbit is rescued. Le Franc and his employees are arrested, and Genevieve reveals that she is actually Andrea Spooner, and part of the Ontario Provincial Police and is working undercover.


title: Super Troopers 2

text: Gov. Jessman arrives to congratulate the officers in their success. At a press conference, the Canadian Mounties congratulate their American counterparts, and give praise for their efforts. Gov. Jessman announces that, due to the hidden contraband, the territory will remain in Canadian control for the time being, causing both nations' officers to insult each other and begin brawling once again.


title: Super Troopers 2

text: In a mid-credits scene, body-cam footage is shown from the ill-fated ride along with Fred Savage. The police officers have been called to rescue a cat out of a tree. After Fred Savage learns that their job entails them calling the fire department for the rescue, he begins climbing the tree to rescue the cat himself. He falls out of the tree and manages to land safely, only to be hit and killed by the arriving firetruck.


title: Super Troopers 2

text: In a post-credits scene, Farva blends his pinky toe into a smoothie and drinks it straight out of the blender, the result of losing a bet with Rabbit during the movie.


title: Super Troopers 2

text: Initially as revealed in the 2006 San Diego Comic-Con, the followup to "Super Troopers" was to be a prequel taking place in the 1970s and following the fathers of the main characters in the original film. Jay Chandrasekhar later told Rotten Tomatoes, "The joke is that we'll make it Super Troopers '76, set during the Bicentennial." "We'll have a little shaggier hair and mustaches...We might do it, I don't know. That movie has sort of a special place in a lot of people's hearts, so all we can do is mess it up."


title: Super Troopers 2

text: However, in a January 2009 interview with MovieWeb, Paul Soter and Jay Chandrasekhar revealed that the movie would be a sequel. Chandrasekhar stated "We pick up the story essentially right were we left off. Maybe about three months later. We are all working undercover for the lumber industry. What has happened is that there are all of these eco-terrorists that are trying to blow up the lumber mills. And we are there working as security." Soter added to that: "The big picture is that we are on the Canadian border. And in reality, what has happened is that the government has found places where the markers were off, or wrong. And there are these areas of land that were thought to be Canada, but are actually part of the U.S. We are enlisted to patrol this area that was always thought to be Canadian soil. But no, it is actually the United States. We are enlisted because they have to send someone there to help make it part of the U.S. territory now. We get recruited to be the Highway Patrolmen there. And we are surrounded by all of these Canadian people that aren't happy about this. We essentially have to impose U.S. law on a bunch of Canadians that aren't at all happy about it."


title: Super Troopers 2

text: In November 2009, Broken Lizard revealed that they had finished three drafts of the sequel's screenplay and that independent financiers had agreed to finance the movie. They also revealed that the character of Captain O'Hagan was part of the screenplay and that actor Brian Cox was planning on returning to the role.


title: Super Troopers 2

text: On March 24, 2015, Broken Lizard announced that they had received studio permission to film the sequel, but had to locate production funding themselves. Due to this requirement, Broken Lizard initiated an Indiegogo crowdfunding campaign, asking for $2 million in contributions. For the campaign Broken Lizard teamed up with Fandango to offer tickets to the movie as a potential backer reward. Broken Lizard noted that they made this decision after noticing that many other crowdfunded films left backers feeling "ripped off" as they offered no financial compensation for them to see the movie in a theater.


title: Super Troopers 2

text: Just 14 hours after the funding window opened, Broken Lizard Industries had raised over 73% of necessary funds ($1,459,446). The $2,000,000 funding goal was reached just 26 hours after the window opened but contributions continued to be added in force. Large ticket perks were offered as incentives to get this funding including tickets to a real beerfest in Chicago, a producer title in the credits ($10,000), a "director" listing ($12,500), a speaking actor role ($10,000), a trip to the ballpark with the five main actors ($15,000), and even the patrol car that will be used in the filming of the movie ($35,000) were all sold out within 12 hours of funding. This project is also, as of March 2016, #38 on the list of highest funded crowdfunding projects and is the #7 largest successfully-completed Indiegogo project; its campaign was completed on April 24. The campaign raised $4.7 million for the film, and Fox Searchlight Pictures was scheduled to release the film.


title: Super Troopers 2

text: On top of the raised $4.7 million, Chandrasekhar was able to collect $8 million more in private financing, and received a $2.8 million tax rebate from Massachusetts, bringing the entire production budget of the film to $13.5 million. Principal photography on the film began in the Ware, Massachusetts area on October 23, 2015. On a Funemployment Radio episode May 26, 2016, Jay Chandrasekhar confirmed that a small test segment of the film has been shot. In September 2016, it was announced that Emmanuelle Chriqui, Tyler Labine, Lynda Carter, Rob Lowe, Will Sasso, and Hayes MacArthur joined the cast.


title: Super Troopers 2

text: On August 2, 2017, Broken Lizard announced, via their website, that they had finished post-production on the film.


title: Super Troopers 2

text: "Super Troopers 2" was released by Fox Searchlight Pictures on April 20, 2018, more than 17 years after the original film premiered.


title: Super Troopers 2

text: In the United States and Canada, "Super Troopers 2" was released alongside "I Feel Pretty" and "Traffik", and was originally projected to gross around $6 million from 2,038 theaters in its opening weekend. However, after making $7.9 million on its first day (including $1.35 million from Thursday night previews), weekend estimates were raised to $16 million. It went on to open to $15.2 million, finishing fourth behind "A Quiet Place", "Rampage" and "I Feel Pretty", and nearly matching the $18.5 million the original film made in its entire theatrical run. In its second weekend the film dropped 76% to $3.6 million, finishing 6th.


title: Super Troopers 2

text: On review aggregator website Rotten Tomatoes, the film holds an approval rating of based on reviews, and an average rating of . The website's critical consensus reads, "Meow that the wait for "Super Troopers 2" is finally over, all but the most devoted fans mustache themselves why they waited so long for such cruel and tragic shenanigans." On Metacritic, the film has a weighted average score of 41 out of 100, based on 29 critics, indicating "mixed or average reviews". Audiences polled by CinemaScore gave the film an average grade of "B+" on an A+ to F scale.


title: Super Troopers 2

text: "Variety"s Owen Gleiberman said the jokes in the film felt "even mustier than they did the first time" and wrote, ""Super Troopers 2" is an aggressively lame and slobby comedy full of cardboard characters and in-your-face naughty jokes that feel about as dangerous as old vaudeville routines."


title: Super Troopers 2

text: Conversely, "The New York Times" named the film an NYT Critic's Pick, with reviewer Glenn Kenny calling it "very funny indeed" and adding that "[t]he antics ... almost never fail to amuse."


title: Super Troopers 2

text: "Super Troopers 2" director Jay Chandrasekhar has stated that a second sequel is possible, and on July 21, 2018, Chandrasekhar announced the title, "Super Troopers 3: Winter Soldiers", and that they began writing the script.


title: Diffuse large B-cell lymphoma

text: Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, weight loss, and night sweats.


title: Diffuse large B-cell lymphoma

text: The causes of diffuse large B-cell lymphoma are not well understood. Usually DLBCL arises from normal B cells, but it can also represent a malignant transformation of other types of lymphoma (particularly marginal zone lymphomas) or, in rare cases termed Richter's transformation, chronic lymphocytic leukemia. An underlying immunodeficiency is a significant risk factor for development of the disease. Infections with the Epstein–Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus, human immunodeficiency virus (i.e. HIV), and the "Helicobacter pylori" bacterium are also associated with the development of certain subtypes of diffuse large B-cell lymphoma. However, most cases of this disease are associated with the unexplained step-wise acquisition of increasing numbers of gene mutations and changes in gene expression that occur in, and progressively promote the malignant behavior of, certain B-cell types.


title: Diffuse large B-cell lymphoma

text: Diagnosis of DLBCL is made by removing a portion of the tumor through a biopsy, and then examining this tissue using a microscope. Usually a hematopathologist makes this diagnosis. Numerous subtypes of DLBCL have been identified which differ in their clinical presentations, biopsy findings, aggressive characteristics, prognoses, and recommended treatments. However, the usual treatment for most subtypes of DLBCL is chemotherapy combined with a monoclonal antibody drug that targets the disease's cancerous B-cells, usually rituximab. Through these treatments, more than half of all patients with DLBCL can be cured; the overall cure rate for older adults is less than this but their five-year survival rate has been around 58%.


title: Diffuse large B-cell lymphoma

text: Diffuse large B-cell lymphoma encompasses a biologically and clinically diverse set of disease subtypes, many of which are difficult to separate from one another based on well-defined and widely accepted criteria. The World Health Organization, 2008, classification system defined more than a dozen subtypes, each of which was identified based on the location of the tumor, the presence of other cell types such as T cells in the tumor, and whether the patient had certain other illnesses related to DLBCL. Based on further research, the World Health Organization, 2016, reclassified DLBCL into its most common subtype, diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS). DLBCL, NOS represents 80–85% of all DLBCL. The remaining DLBCL cases consist of relatively rare subtypes that are distinguished by their morphology, (i.e. microscopic appearance), immunophenotype, (i.e. expression of certain marker proteins), clinical findings, and/or association with certain pathogenic viruses. Some cases of DLBCL, NOS, while not included in the 2016 World Health Organization's classification, are clearly associated with, and caused by, chronic infection by the bacterium, "Helicobacter pylori".


title: Diffuse large B-cell lymphoma

text: DLBCL cases that do not fit the distinctive clinical presentation, tissue morphology, neoplastic cell phenotype, and/or pathogen-associated criteria of other DLBCL subtypes are termed Diffuse large B-cell lymphoma, not otherwise specified: DLBCL, NOS, while representing 80–85% of all DLBCL cases, is a diagnosis of exclusion. In general, DLBCL, NOS is an aggressive disease with an overall long-term survival rate in patients treated with standard chemotherapy regimens of ~65%. However, this disease has many variants that differ not only in the just cited parameters but also in their aggressiveness and responsiveness to treatment.


title: Diffuse large B-cell lymphoma

text: About 70% of DLBCL, NOS cases present primarily with lymph node disease. In these cases, the most typical presenting symptom at the time of diagnosis is a mass that is rapidly enlarging and located in a part of the body with multiple lymph nodes such as the groin, arm pits, or neck. In the remaining ~30% of other cases, the disease begins as an extranodal lymphoma, most commonly in the stomach, or, less commonly, in other sites such as the testicles, breasts, uterus, ovaries, kidneys, adrenal glands, thyroid gland, or bone. The presenting signs and symptoms in these cases reflect the presence of a rapidly expanding tumor or infiltrate that produces symptoms specific to the organ of involvement such as increased size, pain, and/or dysfunction. Individuals with nodal or extranodal disease also present with: systemic B symptoms such as weight loss, night sweats, fevers, and/or fatigue in ~33% of cases; unexplained elevations in their blood levels of lactic acid dehydrogenase and beta-2 microglobulin in many cases; malignant cells infiltrating their bone marrow in 10–20% of cases; and/or localized Stage I or II disease in up to 50% of cases and disseminated Stage III or IV disease in the remaining cases. Bone marrow involvement may be due to DLBCL, NOS cells or low grade lymphoma cells; only DLBCL, NOS cell infiltrates indicate a worse prognosis. Uncommonly, DLBCL may arise as a transformation of marginal zone lymphoma (MZL) in individuals who have been diagnosed with this indolent cancer 4–5 years (median times) previously.


title: Diffuse large B-cell lymphoma

text: The International Prognostic Index and more recently, the Index's age-adjusted variant use age >60 years, elevated serum lactate dehydrogenase levels, low performance status, and involvement in more than one extranodal site as contributors to a poor prognosis in patients with DLBCL, NOS. In addition, disease that initially involves the testes, breast, or uterus has a relatively high rate of spreading to the central nervous system while disease initially involving the kidneys, adrenal glands, ovaries, or bone marrow has a high rate of spreading to other organs, including the central nervous system. All of these cases as well as cases initially involving the central nervous system have relatively poor to very poor prognoses. Cases initially involving the stomach, thyroid, or a single bone site have relatively good prognoses.


title: Diffuse large B-cell lymphoma

text: Most cases of DLBCL, NOS appear to result at least in part from the step-wise development of gene changes such as mutations, altered expressions, amplifications (i.e. increases in the number of copies of specific genes), and tranlocations from normal sites to other chromosomal sites. These changes often result in gains or loses in the production or function of the product of these genes and thereby the activity of cell signaling pathways that regulate the maturation, proliferation, survival, spread, evasion of the immune system, and other malignant behaviors of the cells in which they occur. While scores of genes have been reported to be altered in DLBCL, NOS many of these may not contribute to DLBCL, NOS. Changes in the following genes occur frequently in, and are suspected of contributing to, this disease's development and/or progression.


title: Diffuse large B-cell lymphoma

text: As a consequence of these gene changes and possibly other changes that have not yet been identified, the neoplastic cells in DLBCL, NOS exhibit pathologically overactive NF-κB, PI3K/AKT/mTOR, JAK-STAT0, MAPK/ERK, B-cell receptor, toll-like receptor, and NF-κB signaling pathways and thereby uncontrolled pro-malignant behaviors.


title: Diffuse large B-cell lymphoma

text: Microscopic examinations of involved tissues reveal large neoplastic cells that are typically classified as B-cells based on their expression of B-cell marker proteins (e.g. CD20, CD19, CD22, CD79, PAX5, BOB1, OCT2, an immunoglobulin [usually IgM but occasionally IgG or IgA)], CD30, and in ~20–25% of cases PD-L1 or PD-L2 (PD-L1 and PD-L2 are transmembrane proteins that normally function to suppress attack by the immune system). These cells arrange in a diffuse pattern, efface the tissues' architecture, and resemble Centroblast cells (80% of cases), Immunoblast cells (8–10% of cases), or anaplastic cells (9% of cases; anaplastic cells have bizarre nuclei and other features that may mimic the Reed–Sternberg cells of Hodgkin disease or the neoplastic cells of anaplastic large cell lymphoma). Rarely, these neoplastic cells are characterized as having signet ring or spindle shaped nuclei, prominent cytoplasmic granules, multiple microvillus projections, or, when viewed by electron microscopy, tight junctions with other cells. These neoplastic tissue infiltrates are often accompanied by small non-malignant T-cell lymphocytes and histiocytes that have a reactive morphology.


title: Diffuse large B-cell lymphoma

text: The World Health Organization, 2016, requires that the neoplastic cells in DLBCL, NOS be further defined based on whether they are derived from germinal center B-cells (i.e. GBC) or activated B-cells (i.e. ABC) as identified by gene expression profiling (GEP) or are GBC or non-GBC as identified by immunohistochemical (IHC) analyses. As identified by GEP, which measures all cellular messenger RNAs, GBC and ABC represent about 50 and ~35% of DLBCL, NOS cases, respectively, with ~15% of cases being unclassifiable. IHC analyses measure the cellular expression of specific proteins using a panel of fluorescent antibodies that bind to and therefore stain a set of key proteins. For example, one commercially available panel uses three antibodies to detect CD10, BCL6, and MUM1 proteins; GBC express whereas ABC and unidentified cells do not express these proteins; accordingly, this as well as other IHC panels classify ABC and undetermined neoplastic cell types together as non-GBC. Individuals with the ABC, unclassifiable, and non-GBC variants have significantly worse prognoses than individuals with the GBC variant: respective 5 year progression-free and overall survival rates have been reported to be 73–80% for GBC variants and 31–56% for ABC variants. Clinically, however, most DLBCL, NOS cases are analyzed by IHC and therefore classified as either GBC or non-GBC variants with non-GBC variants having progression-free and overall survival rates similar to those of the ABC variants.


title: Diffuse large B-cell lymphoma

text: Gene and protein markers in the neoplastic cells of DLBCL, NOS that have clinical significance include CD5, "MYC", "BCL2", BCL6, CD20, CD19, CD22, CD30, PD-L1, and PD-L2. The 5–10% of DLBCL, NOS cases in which the neoplastic cells express CD5 have a very poor prognosis that is not improved by even aggressive treatment regimens. Cases in which fluorescence in situ hybridization analysis show that the neoplastic cells' in this disease bear translocations in both the "MYC" and "BCL2" genes or "MYC" and "BCL6" genes (termed double hit lymphomas) or in all three genes (termed triple hit lymphomas) are associated with advanced disease that spreads to the central nervous system. These lymphomas, termed high-grade B-cell lymphoma with "MYC, BL2," and/or "BL6" rearrangements or, more simply, DH/THL, are regarded as borderline DLBCL,NOS. They represent 6–14% of all DLBCL, NOS and have had long-term survival rates of only 20–25%. Another variant B-cell lymphoma that is also considered to be a borderline DLBCL, NOS is termed high-grade B-cell lymphoma, not otherwise specified (HGBCL, NOS). These two aggressive borderline B-cell lymphomas were previously grouped together as "B-cell lymphoma, unclassifiable with features intermediate between DLBCL and Burkitt lymphoma" (i.e. BCLU) but were separated into DH/THL and HGBC, NOS by the World Health Organization, 2016. The neoplastic cells in a related variant, double expresser lymphoma (i.e. DEL), express the products of "MYC" and "BCL2" genes, i.e. c-Myc and bcl-2 proteins, respectively, but do not have translocations in either of their genes. DEL, which represents about one-third of all DLBCL, NOS cases, has a poorer prognosis than standard DLBCL, NOS but not as poor as DH/THL cases. Cases in which the neoplastic cells have alterations in the "MYC" gene or its expression without changes in "BLC2" or "BLC6" also have a poor prognosis, particularly in cases where the "MYC" gene translocates (i.e. rearranges) with one of the immunoglobulin gene loci. DLBCL that begin in the testicles are a variant of DLBCL, NOS that some authors suggest should be classified as a distinct DLBCL subtype. This variant, termed Primary testicular diffuse large B-cell lymphoma (PT-DLBCL), is a DLBCL, NOS that in >75% of cases involves activated B-cells, i.e. ABC. These cells, which typically have a centroblast-like morphology, infiltrate one or, in ~6% of cases, both testicles. PT-DLBCL is an aggressive disease that often spreads to the central nervous system and has median overall survival and progression-free survival times of 96 and 49 months, respectively.


title: Diffuse large B-cell lymphoma

text: The neoplastic cells in almost all cases of DLBCL, NOS express CD20. Commercially available anti-CD20 antibody agents such as rituximab or Obinutuzumab (which is sometimes used in place of rituximab) kill cells that express high levels of CD20 by binding to this cell-surface protein and thereby targeting them for attack by the hosts adaptive immune system. The addition of one of these immunotherapy agents to chemotherapy protocols has greatly improved the prognosis of most DLBCL, NOS variants. Neoplastic cell expression of CD30, found in 10–15% of DLBCL, NOS cases is a favorable prognostic indicator. As indicated in the following Treatments and prognoses section, expression of the CD20 and CD30 proteins as well as the CD19, CD20 CD22, CD30, CD79A, CD79B, and D-L1 proteins, expression of the "MYC", "BCL2", "MYD88nd", and "CREBBP" genes, and expression of the PI3K/AKT/mTOR, JAK-STAT, B-cell receptor, toll-like receptor, and NF-κB signaling pathways are being studied as potential therapeutic targets for the individualized treatment of GBC and ABC/non-GBC DLBCL, NOS cases.


title: Diffuse large B-cell lymphoma

text: First-line therapy for patients with the GBC variant of DLBCL, NOS is R-CHOP. R-CHOP consists of rituximab, three chemotherapy drugs (cyclophosphamide, doxorubicin, and vincristine) and a glucocorticoid (either prednisone or prednisolone). The regimen achieves cure, relapse following remission, and unresponsive rates of 60–70%, 30–40% and <10%, respectively, in GBC variant cases. Relapses generally occur within the first 3 years of diagnosis with few cases doing so after 5 years. Patients who are refractory to, relapse within 1 year of diagnosis before starting, relapse within 6 months after completing, or progress within 2 years of starting R-CHOP have poorer prognoses. R-CHOP is less effective and not recommended for patients who have "MYC, BL2," and/or "BL6" rearrangements regardless of their GBC, ABC, or non-GBC type. One recommendation for treating these DH/THL cases is the DA-R-EPOCH regimen (dose-adjusted rituximab, etoposide, prednisolone, oncovin, cyclophosphamide, and hydroxydaunorubicin). S-R-EPOCH achieves 2 year survival rates of 40–67% compared to a ~25% survival rate for R-CHOP in these cases. DA-R-EPOCH has also been recommended for patients with double expresser lymphoma although some experts recommend treating this variant more like a typical DLCBL, NOS. First-line therapy for patients with the ABC, undetermined, or non-GBC variants has been the DA-R-EPOCH regimen. Patients with these variants (including those with double expresser lymphoma) have had a ~40% cure rate when treated with it. A randomized clinical trial conducted in France reported that a R-ACVBP chemotherapy regimen (rituximab, adriamycin, cyclophosphamide, vindesine, bleomycin, and cytarabine followed by sequential consolidation therapy with systemic methotrexate, ifosfamide, and etoposide, and then cytarabine) achieved significantly better response rates than R-CHOP in ABC/NGC variant cases lymphoma. In DLBCL, NOS variants which trend to spread or to the central nervous system, methotrexate has been recommended to be added to regimens not containing it for use as prophylaxis to reduce the incidence of this complication. The role of Autologous stem-cell transplantation as an addition to first-line therapy in the treatment of DLBCL, NOS, including cases with a poor prognosis, is unclear.


title: Diffuse large B-cell lymphoma

text: A phase I clinical research trial found that the addition of lenalidomide to the R-CHOP regimen produce an ~80% complete response rate in GBC as well as non- GBC DLBCL, NOS variants. Two phase III clinical research trials are underway to confirm these results and determine if the R-CHOP + lenalidomide regimen is superior to R-CHOP in the up-front treatment of GBC and/or non-GBC variants.


title: Diffuse large B-cell lymphoma

text: Patients with DLBCL, NOS who relapse or progress following first-line therapy have been treated with "salvage regimens" consisting of high-dose (also termed high-intensity) chemotherapy conditioning drugs followed by autologous stem cell transplantation. This regimen has attained 3-year progression-free survival rates of 21–37%. Relapse following this treatment carries a very poor prognosis with median overall survival times of ~10 months. Patients who have failed or because of health issues are ineligible for autologous stem cell transplantation have been treated with low-dose (i.e. low-intensity) chemotherapy conditioning regimens followed by allogeneic stem cell transplantation. This regimen has achieved 3 year progression-free and overall survival rates of 41% and 52%, respectively. Further studies are underway to determine the best treatment regimens for these cases. Patients refractory to first-line therapy or who relapse within 12 months of receiving "salvage" therapy (including bone marrow transplant) for recurrent disease have had poor prognoses with median overall survival rates of 3.3 and 6.3 months, respectively. The prognosis of these patients appears to be improved by using CAR-T therapy.


title: Diffuse large B-cell lymphoma

text: Chimeric antigen receptor T cell (i.e. CAR-T) adoptive cellular immunotherapy has emerged as a recent advance in treating refractory and relapsed DLBCL, NOS (tisagenlecleucel, axicabtagene ciloleucel, lisocabtagene maraleucel). Chimeric antigen receptor T cells are genetically engineered to express: 1) an artificial T-cell receptor consisting of antigen-recognition and attached hinge domains expressed on their surface membranes; 2) a surface membrane-spanning domain; 3) an intracellular domain which, when the antigen-recognition domain binds its targeted antigen, activates signaling pathways that cause the T-cell to attack and kill cells that bear the recognized antigen on their surface membranes; and 4), in more recently devised second generation CAR-T strategies, an associated intracellular co-stimulating molecule (e.g. CD28 or 4-1BB) which augments activation of the cell-killing signaling pathways. CAR-T therapy, as it pertains to DLBCL, NOS, kills a patient's neoplastic B-cells by isolating this patient's T-cells; genetically engineering these cells to express an artificial T-cell receptor designed to bind an antigen expressed on the surface of their neoplastic B-cells; and infusing these cells back into the donor patient. The targeted antigen has usually been CD19, a surface membrane protein expressed on virtually all B-cells including the neoplastic cells in DLBCL, NOS. However, design of CARs as well as the antigens chosen to be their targets are constantly being changed in order to improve the efficacy of this therapeutic strategy.


title: Diffuse large B-cell lymphoma

text: CAR-T therapy for DLBCL, NOS has been used on patients who are refractory to and/or have progressed on first-line as well as salvage (including autologous stem cell transplantation) treatment regimens. Patients are treated first with a conditioning chemotherapy regimen, usually cyclophosphamide and fludarabine, and then infused with their own T-cells that have been engineered to attack CD19-bearing or, rarely, CD20-bearing cells. A meta-analysis of 17 studies using this or very similar approaches to treat DLBCL, NOS found the treatments gave complete and partial responses rates of 61% and 43%, respectively. While these studies did not have control groups and were too recent for meaningful estimates of remission durations, the remission rates were higher than expected using other treatment approaches. Significant and potentially lethal therapeutic complications of this therapy included development of the cytokine release syndrome (21% of cases), neurotoxicity, i.e. the CAR-T cell-related encephalopathy syndrome (9% of cases), and the hemophagocytic lymphohistiocytosis/macrophage-activation syndrome (i.e. a form of Hemophagocytic lymphohistiocytosis). Individual studies within and outside of this meta-analysis have reported remissions lasting >2 years but also lethal cytokine release syndrome and neurotoxicity responses to this therapy. As a consequence of these studies, the Committee for Advanced Therapies and the Committee for Medicinal Products for Human Use of the European Medicines Agency recommend granting marketing authorization for tisagenlecleucel (i.e. chimeric antigen receptor T cells directed against CD19) in adult patients with DLBCL, NOS who have relapsed after or are refractory to two or more lines of systemic therapy. The Committee for Orphan Medicinal Products of the European Medicines Agency recommends tisagenlecleucel retain its orphan drug designation. The USA Food and Drug Administration (FDA) has also approved the use of this drug for relapsed or refractory DLBCL of the large B-cell lymphoma subtype in patients who have failed after two or more lines of systemic therapy. Monoclonal antibodies directed against CD19, CD22, CD30, and PD-L1 have been developed for use as immunotherapeutic agents in other hematological malignancies and are being or plan to be tested for their usefulness in DLBCL, NOS. In August 2020, the FDA approved the humanized Fc-modified cytolytic CD19 targeting monoclonal antibody tafasitamab in combination with lenalidomide as a treatment for adult patients with relapsed or refractory DLBCL. In April 2021, the FDA approved the CD19-directed antibody-drug conjugate loncastuximab tesirine as a treatment for adult patients with relapsed or refractory DLBCL after systemic therapy.


title: Diffuse large B-cell lymphoma

text: Neoplastic cell expression of CD30 in DLBCL, NOS is a favorable prognostic indicator; in these cases, brentuximab vedotin may be a useful addition to chemotherapy treatment protocols. This agent is a CD30-targeting antibody that delivers a toxin, monomethyl auristatin E, to CD30-expressing cells, has therapeutic efficacy against other CD30-expressing lymphomas, and may prove useful in treating the 10–15% of DLBCL, NOS cases expressing this protein. The neoplastic cells in the GBC variant of DLBCL, NOS often have mutations in the "EZH2, BCL2" and "CREBBP" genes and overactive PI3K/AKT/mTOR and JAK-STAT signaling pathways while neoplastic cells in the ABC variant often have mutations in the "MYD88, CD79A" and "CD79B" (polatuzumab vedotin) genes and overactive B-cell receptor, toll-like receptor, and NF-κB signaling pathways. These different gene mutations and dysregulated signaling pathways are also being studied as potential therapeutic targets for the individualized treatment of GBC and ABC/non-GBC cases. CUDC-907, an inhibitor of PI3K and histone deacetylases, is being evaluated in two separate clinical trials for the treatment of refractory and/or relapsed DLBCL, NOS including cases with alterations in the "MYC gene". GSK525762, an inhibitor of the BET family of proteins, suppresses expression of the "MYC" gene and is undergoing a phase I clinical trial for the treatment of high-grade B-cell lymphoma with "MYC, BL2," and/or "BL6" rearrangements (i.e. DH/THL). RO6870810, another BET inhibitor, in combination with Venetoclax, an inhibitor of the Bcl-2 protein, is likewise in a phase I clinical trial for the treatment of DH/THL. Pharmacological inhibition of BCL-2 is effective in most B cell lymphomas, but often leads to acquired resistance due to the expression of other major anti-apoptotic BCL-2 family proteins like BCL-XL and MCL-1. Combined therapy using MCL-1 inhibitor (S63845) or BCL-XL inhibitor (A-1331852) in addition to Venetoclax can be a solution to overcome this issue.


title: Diffuse large B-cell lymphoma

text: DLBCL subtypes have been sorted into groups based on their distinctive morphology or immunophenotype, distinctive clinical issues, and distinctive virus-driven etiology. The prognoses and treatment of these subtypes varies with their severity. Most subtypes are aggressive diseases and consequently treated in a manner similar to DLBCL,NOS. Further details on these subtypes, including their treatments, can be found in their respective main article linkages.


title: Diffuse large B-cell lymphoma

text: T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a DLBCL in which tumors containing small numbers of usually large neoplastic B-cells embedded in a background of reactive T-cells and histiocytes develop in the liver, spleen, bone marrow and/or, rarely other sites. Patients usually present with advanced disease; their overall 3 year survival rates in different studies range between 46% and 72%.


title: Diffuse large B-cell lymphoma

text: ALK+ large B-cell lymphoma (ALK+ LBCL) is a DLBCL in which neoplastic lymphocytes that express the ALK tyrosine kinase receptor protein infiltrate lymph nodes as well as extranodal sites, e.g. the mediastinum, bones, bone marrow, nasopharynx, tongue, stomach, liver, spleen, and skin. About 60% of these individuals present with advanced disease. ALK+ LBCL has an overall 5 year survival rate of ~34%.


title: Diffuse large B-cell lymphoma

text: Plasmablastic lymphoma (PBL) is a DLBCL in which neoplastic immunoblastic or plasmablastic cells embedded in a background of other cell types infiltrate the oral/nasal cavity or much less often the gastrointestinal tract. Some 70% of individuals with PBL are infected with EBV and/or (particularly those with oral/nasal cavity disease) human immunodeficiency virus (HIV). PBL is an aggressive disease with a median survival time of ~15 months.


title: Diffuse large B-cell lymphoma

text: Intravascular large B-cell lymphoma (IVLBCL) is a DLBCL in which medium- to large-sized neoplastic B-cells infiltrate small- to medium-sized blood vessels and sinusoids in the liver, spleen, and/or bone marrow. IVLBCL may be associated with the hemophagic syndrome (i.e. excessive cytokine secretion and systemic inflammation). Patients with the latter syndrome have very short survival times. The poor prognosis of this disease has been significantly improved by rituximab or similar immunochemotherapy drugs but significant proportions of these responding cases relapse, often with central nervous system involvement.


title: Diffuse large B-cell lymphoma

text: Large B-cell lymphoma with IRF4 rearrangement (LBCL with IRF4 rearrangement) is a DLBCL in which tissue infiltrates containing intermediate- or large-sized neoplastic B-cells strongly express a chromosomal translocation involving the "IRF4" gene on the short arm of chromosome 6. These cells form follicular, follicular and diffuse, or entirely diffuse infiltrates in Waldeyer's tonsillar ring or other regions of the head and neck. The disease, which represents ~0.05% of all DLBCL, occurs primarily in children and young adults and typically has a good prognoses. Cases with a follicular pattern of tissue infiltrates often have indolent disease and an excellent prognosis following excision and may not need chemotherapy. Cases with a purely diffuse tissue infiltrate pattern, in contrast, often do require chemotherapy.


title: Diffuse large B-cell lymphoma

text: Primary mediastinal large B-cell lymphoma (PMBL), also termed primary mediastinal (thymic) large B-cell lymphoma, is a DLBCL in which neoplastic B-cells infiltrates are commonly located in sclerotic/fibrous tissues of the thymus and mediastinal lymph nodes. The disease represents 6–10% of all DLBCL cases, presents with early stage disease in ~80% of cases, and has an overall survival rate at 5 years of 75–85%.


title: Diffuse large B-cell lymphoma

text: Primary cutaneous diffuse large B-cell lymphoma, leg type (PCDLBCL-LT) is a DLBCL in which diffuse patterns of immunoblastic and/or centroblastic B-cells infiltrate the dermis and/or subcutaneous tissue principally, but not exclusively, of the legs. This disease's 5-year overall survival rate is 50–60%.


title: Diffuse large B-cell lymphoma

text: Primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS, also termed primary central nervous system lymphoma [PCNSL]) is a DLBCL in which diffuse patterns of neoplastic B-cells with centroblastic, immunoblastic, or poorly differentiated features infiltrate the brain, spinal cord, leptomeninges, or eye. The disease usually presents as a single lesion with a predilection for the supratentorial region of the brain but may involve the eye in 15–25% of cases, the cerebrospinal fluid in 7–42% of cases, and the spinal cord in ~1% of cases. The disease has a 5-year overall survival rate of ~30%.


title: Diffuse large B-cell lymphoma

text: Diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) is an Epstein–Barr virus-associated lymphoproliferative disease arising in persons with a long and persistent history of chronic inflammation. The disease's lesions consist of large, mature-appearing B-cells infiltrating the lung's pleura and nearby tissues. Most cases have occurred in patients who were given a pneumothorax (i.e. therapeutic introduction of air into the chest cavity in order to collapse and thereby "rest" the lung) to treat pulmonary tuberculosis that had progressed to a pyothorax (i.e. pus in the pleural cavity). Fibrin-associated large B-cell lymphoma (FA-DLBCL), often considered a sub-type of DLBCL-CI, is an infiltration of large neoplastic B-cells and fibrin affix to a prosthesis (e.g., cardiac valve, orthopaedic device) or accumulate within a hydrocele, pseudocyst, cardiac myxoma, or chronic subdural hematoma. The B-cells in these lesions are often but not always infected with the Epstein–Barr virus. DLBCL-CI occurring in cases of pleural empyema (sometimes termed pyothorax-associated lymphoma, i.e. PAL) is an aggressive lymphoma with a five-year overall survival rate of 20–35%; FA-DLBCL, when involving the heart (e.g. occurring on myxommas or prosthetic valves) or vasculature structures (e.g. on thrombus-laden vascular grafts), may involve life-threatening cardiovascular complications, particularly strokes. Outside of these complications, however, DLBCL-CI usually has a highly favorable outcome.


title: Diffuse large B-cell lymphoma

text: Lymphomatoid granulomatosis (LYG) is a DLBCL in which large, atypical B-cells with immunoblastic or Hodgkin disease-like features that are infected by the Epstein-Barr virus center around and destroy the microvasculature. Lymphomatoid granulomatosis almost always involves the lung but may concurrently involve the brain, peripheral nervous system, skin, kidneys, liver, gastrointestinal tract, and/or upper respiratory tract; LYG has an increased incidence in persons with Wiskott–Aldrich syndrome or HIV or who are immunosuppression due to chemotherapy or organ transplantation. The disease's prognosis is highly variable: patients with low grade disease often require no therapy except watchful waiting while patients with high grade disease usually require chemotherapy.


title: Diffuse large B-cell lymphoma

text: Primary effusion lymphoma (PEL) is a DLBCL in which neoplastic B cells that resemble immunoblasts, plasmablasts, or Reed–Sternberg cells infiltrate the pleural, pericardial, or peritoneal membranes that surround the lungs, heart, and abdominal organs, respectively. This infiltration leads to the seeping of fluid into the cavities which are encased by these membranes, i.e. it leads to pleural effusions, pericardial effusions, and abdominal ascites. Some cases of PEL also involve the gastrointestinal tract and lymph nodes. The disease occurs primarily in people who are immunosuppressed or test positive for HIV and are also latently infected with Kaposi's sarcoma-associated herpesvirus; PEL is an aggressive disease with an overall 1 year survival rate of ~30%.


title: Diffuse large B-cell lymphoma

text: Epstein–Barr virus-positive diffuse large B cell lymphoma, not otherwise specified (EBV+ DLBCL, NOS) is a B-cell lymphoma in which neoplastic B-cells that are infected with the Epstein-Barr virus cause a disease that does not fit into other subtypes of DLBCL. In EBV+ DLBCL, small neoplastic B-cells, other lymphocyte typess, plasma cells, histiocytes and epithelioid cells interspersed with Reed–Sternberg-like cells infiltrate, almost exclusively, lymph nodes. Elderly patients with the disease have median survival times of ~2 years while young patients have long-term treatment-related remissions in >80% of cases.


title: Diffuse large B-cell lymphoma

text: HHV8-positive diffuse large B-cell lymphoma, NOS (HHV8+ DLBCL, NOS; also termed HHV8-positive diffuse large B-cell lymphoma [HHV8+ DLBCL]) is a DLBCL in which Kaposi's sarcoma-associated herpesvirus-infected, medium- to large-size neoplastic B-cells that resemble lymphocytes or immunoblasts infiltrate lymph nodes (~80% of cases) and, when disseminated (20% of cases), the liver and spleen. This infiltration usually disrupts the normal architecture of the involved tissues. HHV8+ DLBCL develops in HIV-infected individuals in ~50% of cases, in individuals with multicentric Castleman disease, plasma cell variant in uncommon cases, and in individuals with Kaposi sarcoma in rare cases. HHV8+ DLBCL commonly takes an aggressive course and has a poor prognosis.


title: Diffuse large B-cell lymphoma

text: Rare cases of DLBCL are associated with the presence of the bacterium, "Helicobacter pylori", in the neoplastic B-cells. While the histology of "Helicobactor pylori"-associated diffuse large B-cell lymphoma ("H. pylori"+ DLBCL) is typical of DLBCL, the disease is sometimes a progression of mantle cell lymphoma, is often restricted to the stomach, is less aggressive that most DLBCL cases, and may respond to a drug regimen consisting of antibiotics and proton pump inhibitors directed at killing the bacterium. Perhaps because of these features of the disease, "H. pylori"+ DLBCL has not been classified as a DLBCL by the World Health Organization, 2016.


title: Diffuse large B-cell lymphoma

text: Recent studies suggest that localized, early-stage "H. pylori"+ DLBCL, when limited to the stomach, is successfully treated with "H. pylori eradication protocols" consisting of two or more antibiotics plus a proton pump inhibitor. However, these studies also agree that patients treated with one of these "H. pylori" eradication regimes need to be carefully followed: those unresponsive to, or worsening on, these regimens should be switched to a chemotherapy regimen (e.g. R-CHOP) and/or, for complicated bulky disease, surgery and/or local radiotherapy.


title: Diffuse large B-cell lymphoma

text: Epstein-Barr virus-positive mucocutaneous ulcer (EBVMCU) was first described as a lymphoproliferative disorder in which Epstein–Barr virus-infected B-cells proliferate and cause ulcerations in the mucous membranes and skin of immunosuppressed individuals. Its lesions consist of Epstein–Barr virus-positive, variable-sized, atypical B-cells that by conventional histopathologic criteria indicate the lesions are a form of DLBCL. Since these lesions regress spontaneously without anti-cancer treatment, EBVMCU is now considered a pseudo-malignant disorder. Elderly individuals that evidence the disease but have no other cause for immunosuppression may exhibit a relapsing and remitting course with their ulcers worsening but then regressing spontaneously. Persistent and/or severely symptomatic cases have had excellent responses to rituximab. Individuals developing these ulcers as a consequence of immunosuppressive therapy generally have a remission after the dosage of the drugs used in their immunosuppressive treatments are reduced. Most of these patients do not relapse.


title: Simon Webbe

text: Simon Solomon Webbe (born 30 March 1979) is a British singer. He is best known as a member of the boy band Blue, forming in 2000 before splitting in 2005 and reforming in 2009, selling over 15 million records. Webbe released three solo studio albums in 2005, 2006 and 2017, sold over 700,000 records worldwide and had five UK Top 40 singles.


title: Simon Webbe

text: The band released their debut single "All Rise" in May 2001 and it reached number 4 in the UK Singles Chart. Blue's second single was released in August with the chart-topping "Too Close", a cover version of Next's US number 1 hit produced by Ray Ruffin. Their second number one came in November with "If You Come Back" also produced by Ray Ruffin and co-written by Nicole Anderson aka Nicole Formescu, Lee Brennan, Ian Hope and Ray Ruffin off the album "All Rise", which was released in time for Christmas and reached number one, eventually selling in excess of about 1.8 million albums sold in the UK. Blue reached number six in March 2002 with their fourth single, "Fly By II" – a remix of album track "Fly By", which also went to number 30 in Portugal.


title: Simon Webbe

text: Their second studio album "One Love" was released in 2002. The album entered at UK number 1, where it stayed for one week. Three singles were released from the album: "One Love" (UK number 3), "Sorry Seems to Be the Hardest Word" featuring Elton John (UK number 1), and "U Make Me Wanna" (UK number 4). The group also performed the song "Flexin'" at the 2003 MTV Asia Awards with the Philippines' singer Kyla.


title: Simon Webbe

text: "Guilty" (the album and the single [UK number 2]) was released in late 2003. The next singles were "Signed, Sealed, Delivered, I'm Yours" (sung with Stevie Wonder and Angie Stone) (UK number 11), "Breathe Easy" (UK number 4), and "Bubblin'" (UK number 9). The album "Guilty" sold more than one million copies in the UK.


title: Simon Webbe

text: The band decided to split after Elton John suggested that their popularity was decreasing and that they should concentrate on their solo careers. "Best of Blue" greatest hits compilation was released in 2004, which contained all-time hits including new tracks such as "Curtain Falls", "Get Down on It" and "Only Words I Know". The album was No.2 on charts in Portugal with a double platinum certification.


title: Simon Webbe

text: Webbe launched his post-Blue career on 22 August 2005 with his first solo single "Lay Your Hands" which peaked at number 4 on the UK Singles Chart. His follow-up single "No Worries" reached No.4 in the UK, making him the only Blue member to have multiple Top 10 singles. After the release of two singles, Webbe released his debut solo album "Sanctuary" which debuted at number 28 on the UK Albums Chart. Despite its relatively low debut it eventually reached number 7 on the chart and has now gone double platinum. The third single from "Sanctuary", "After All This Time" was released in February 2006, but it failed to do as well as his previous releases and peaked at number 16.


title: Simon Webbe

text: On 30 October 2006, came the first single from Webbe's new album "Coming Around Again". When released it reached number 12 in the UK Singles Chart. His second album "Grace" was released on 13 November 2006, and peaked at number 11 in the UK Albums Chart. The second single "My Soul Pleads for You" was released on 19 February 2007, and reached 45 on the singles chart. On 21 May 2007, Webbe launched his first tour to support his second album "Grace". The tour consisted of 18 dates through May and June, starting in Cambridge and culminating in London. In early June, it was announced that Webbe would be releasing the title track from his second studio album with the theme song from the upcoming film "". The single was a double A-side release of "Grace"/"Ride the Storm". It reached number 36 in the UK. In Europe, "Seventeen" was released instead of "Grace".


title: Simon Webbe

text: During his 2007 UK Tour, Webbe previewed some songs from his third studio album, including "Run", which he claimed had been announced as the first single. He also claimed that 'Run' could possibly be the title of the album. It is thought that the album was postponed from its 2009 release date due to the reunion of Blue, and that it will be released at some point in the future.