Oligye

16/04/2022

Objectives: Tumors of the central nervous system (CNS) are the most common pediatric solid tumors, where low grade (LGG) and high grade gliomas (HGG) represent up to 55% of CNS tumors. Current molecular classification of these tumors results in a more accurate diagnosis and risk stratification, which ultimately enables individualized treatment strategies. Identifying known alterations is a suitable approach, particularly in developing countries, where NGS approaches are not easily accessible. We sought to assess molecular alterations in BRAF and histone 3 genes. Study design: FISH, IHC and Sanger sequencing were performed in a series of 102 pediatric glial and glioneuronal tumors. We also correlated these results with clinical and histological findings to evaluate their usefulness as diagnostic and/or prognostic tools. Results: We found that the KIAA1549-BRAF gene fusion was a relevant diagnostic tool for pilocytic astrocytoma, but not related to progression free survival (PFS) and overall survival (OS). BRAFV600E mutation was associated with a decreased OS in LGG, and with decreased PFS and OS among pilocytic astrocytomas. All HGG of the midline were H3K27M mutants, while H3G34R mutant cases were located in brain hemispheres. HGG harboring the H3K27M variant were associated with a decreased PFS and OS. Conclusions: Assessing druggable molecular markers with prognostic value is particularly important in those cases where complete resection or further radiation therapy is not possible. These potential diagnostic/prognostic markers may be suitable as further screening tests to reduce the requirement on NGS, which is not available in all laboratories. Furthermore, these results broaden data on BRAF and Histone 3 alterations in children from geographic regions, other than USA and Europe.
Tumors of the central nervous system (CNS) are the most common solid tumors in pediatric patients; all together they account for more than 20% of all childhood cancers [1]. Within CNS tumors, gliomas represent up to 55% of them. The World Health Organization (WHO) defines these pediatric brain tumors into four stages based on their morphology and histological characteristics, where grades I and II (GI and GII) are considered low grade gliomas (LGG) and grades III and IV (GIII and GIV) are considered high grade gliomas (HGH) [2]. This classification reflects the survival odds and generally speaking, grade I have the highest survival odds and grade IV, the lowest. Pediatric LGG include pilocytic astrocytoma (GI), pleomorphic xanthoastrocytoma (GII), diffuse astrocytoma (GII), those entities related to ganglioglioma (GI/II) and dysembryoplastic neuroepithelial tumor (GI). Pediatric HGG are a heterogeneous group of malignant and poorly delimited tumors which extend both macroscopically and radiologically, beyond apparent margins. The most frequent in pediatrics include anaplastic astrocytoma (GIII), glioblastoma (GIV), diffuse intrinsic pontine glioma (GIV) and diffuse midline glioma H3 K27M-mutant (DMG K27M) (GIV).

According to the Argentine Oncopediatric Hospital Registry (ROHA, Registro Oncopediátrico Hospitalario Argentino), approximately 1400 new cases of cancer are diagnosed annually in our country in children under 15 years of age, where CNS tumors are the most frequent solid tumors [3]. Incidence rates in Argentina are similar to those described in other regions [1]. However, in recent years and given the astonishing advances in molecular biology and its implications in diagnosis, prognostic accuracy and tailored-made treatment strategies of pediatric brain tumors, specific molecular markers for each tumor type have been transferred from the bench to the bed-side [4]. More precisely, DMG K27M was defined by WHO based on the molecular characterization of the H3F3A, HIST1H3B and HIST1H3C genes [2]. This entity harbors a H3K27M hallmark somatic mutations in the histone 3 (H3) isoforms H3.3 (coded by H3F3A gene) or isoform H3.1 (HIST1H3B or HIST1H3C genes) in up to 80% of pediatric diffuse midline gliomas, including thalamic glioma and diffuse intrinsic pontine glioma (DIPG) [5]. A different hallmark mutation, H3G34R/V has been described within the same histone genes in gliomas arising from the cerebral hemispheres [6]. These variants have become the most frequently studied in gliomas; more precisely, H3K27M directly disturbs the target site for lysine specific methyltransferases and prevents methylation of the mutated residues, where the original lysine would have been methylated. Additionally, H3G34R/V interferes with the modification of the nearby K36 residue [7]. Given that H3K27M mutant gliomas have a decreased treatment response and a diminished overall survival, in relation to the non-mutant tumors, H3K27M is now considered a tumor driver mutation and is used as a prognostic marker.

In a similar fashion, the V600E mutation in BRAF (coded by the BRAF gene) highly correlates with a poorer prognosis and overall survival across a broad spectrum of pediatric LGG, while the KIAA1549-BRAF gene fusion aids in the diagnosis of pilocytic astrocytomas (PA) [4]. The MAPK signaling pathway regulates various cellular functions, including cell cycle control, cell proliferation, differentiation and apoptosis, in all of which BRAF acts as a stimulatory factor [8]. Moreover, BRAF V600E mutation has been reported to abnormally up-regulate the MAPK signaling pathway [9, 10]. Even though the BRAF V600E mutation responds unfavorably to conventional treatment, it represents a specific druggable target for personalized therapies with kinase inhibitors [11]. Moreover, CDKN2A has been previously shown to influence the response to treatment and outcome in BRAF V600E pediatric LGG [12–14]. On the other hand, the KIAA1549-BRAF gene fusion is formed by a tandem duplication of a 2 MB region (locus 7q34 in BRAF gene) with the subsequent fusion to KIAA1549 gene, which finally results in the constitutive phosphorylation activity by BRAF and up-regulation of the MAPK pathway [15]. Although several translocation break-points were described, the most common is between exon16 of the KIAA1549 gene and exon 9 of BRAF (16–9 fusion); for a comprehensive review refer to [16]. While the BRAF V600E mutation is found in about 60% of pleomorphic xanthoastrocytoma (PXA), 50% of gangliomas, 9% of PA and 2–12% glioblastoma, the KIAA1549–BRAF fusion is frequently found roughly in 50–80% of PA and pilomyxoid astrocytomas (PMA), which is an aggressive variant of PA [16]. Despite all these facts, BRAF molecular profiling has not yet been included in the latest WHO classification of central nervous system tumors.

The molecular assessment of these markers aids in diagnosis, in identifying risk groups and individualizing treatment strategies, a fact of special importance in pediatrics since it may avoid unnecessary sequelae in a developing child. This approach, assessing known alterations by standard molecular techniques is useful, particularly in developing countries, so as to reduce the requirements for NGS or when the latter approach is not accessible.

In the present study, we evaluated the molecular alterations in BRAF and histone 3 genes in pediatric glial and glioneuronal tumors from our institution. We also correlated the results with clinical and histological findings in our pediatric cohort to evaluate their usefulness as diagnostic or prognostic tools in this age group.

16/04/2022

Under the plan, the rights will become exercisable if anyone acquires ownership of 15% or more of Twitter's outstanding common stock in a transaction not approved by the Board

11/04/2022

We are happy to announce that is opening an office in Warsaw, Poland.

“Capital.com has grown tremendously in the past 18 months. Our success is truly apparent and measurable through the amount of new staff we are hiring to manage and support the different aspects of the business – over the last two years, our headcount has grown almost five-fold. We are very excited to move into our new office in Warsaw’s Skyliner, a state-of-the-art building which is already becoming an iconic landmark in the city,” Jonathan Squires, Group CEO of Capital.com said.

Learn more: capitalcom.info/WarsawOffice

11/04/2022

Due to increasingly stringent fuel consumption and emission regulation, improving thermal efficiency and reducing particulate matter emissions are two main issues for next generation gasoline engine. Lean burn mode could greatly reduce pumping loss and decrease the fuel consumption of gasoline engines, although the burning rate is decreased by higher diluted intake air. In this study, dual injection stratified combustion mode is used to accelerate the burning rate of lean burn by increasing the fuel concentration near the spark plug. The effects of engine control parameters such as the excess air coefficient (Lambda), direct injection (DI) ratio, spark interval with DI, and DI timing on combustion, fuel consumption, gaseous emissions, and particulate emissions of a dual injection gasoline engine are studied. It is shown that the lean burn limit can be extended to Lambda = 1.8 with a low compression ratio of 10, while the fuel consumption can be obviously improved at Lambda = 1.4. There exists a spark window for dual injection stratified lean burn mode, in which the spark timing has a weak effect on combustion. With optimization of the control parameters, the brake specific fuel consumption (BSFC) decreases 9.05% more than that of original stoichiometric combustion with DI as 2 bar brake mean effective pressure (BMEP) at a 2000 r/min engine speed. The NOx emissions before three-way catalyst (TWC) are 71.31% lower than that of the original engine while the particle number (PN) is 81.45% lower than the original engine. The dual injection stratified lean burn has a wide range of applications which can effectively reduce fuel consumption and particulate emissions. The BSFC reduction rate is higher than 5% and the PN reduction rate is more than 50% with the speed lower than 2400 r/min and the load lower than 5 bar.

10/04/2022

Maya Angelou, the great American author and poet, was known for her award-winning autobiographies as well as for her numerous plays, scripts, poems, and essays.

Her most famous work, I Know Why the Caged Bird Sings, has sold millions upon millions of copies. It holds the record for the longest-running nonfiction New York Times best-seller (2 years). And in 2011, Time Magazine named it one of the 100 best and most influential books written in English since 1923.

Angelou is widely known as a voice for women, especially black women, and her works have courageously covered themes of identity, racism, and family. During an interview with USA Today in 1988, Angelou said, “One isn't necessarily born with courage, but one is born with potential. Without courage, we cannot practice any other virtue with consistency. We can't be kind, true, merciful, generous, or honest.”
Maya Angelou’s Writing Routine
As you may expect, Angelou’s creative genius didn’t expose itself without hard work. She was a true master of habits, routines, and consistency.

Here’s how she described her writing habits in 1983 interview with Claudia Tate (as covered in Mason Currey’s book Daily Rituals),

“I usually get up at about 5:30, and I’m ready to have coffee by 6, usually with my husband. He goes off to his work around 6:30, and I go off to mine. I keep a hotel room in which I do my work—a tiny, mean room with just a bed, and sometimes, if I can find it, a face basin. I keep a dictionary, a Bible, a deck of cards and a bottle of sherry in the room. I try to get there around 7, and I work until 2 in the afternoon. If the work is going badly, I stay until 12:30. If it’s going well, I’ll stay as long as it’s going well. It’s lonely, and it’s marvelous. I edit while I’m working. When I come home at 2, I read over what I’ve written that day, and then try to put it out of my mind. I shower, prepare dinner, so that when my husband comes home, I’m not totally absorbed in my work. We have a semblance of a normal life. We have a drink together and have dinner. Maybe after dinner I’ll read to him what I’ve written that day. He doesn’t comment. I don’t invite comments from anyone but my editor, but hearing it aloud is good. Sometimes I hear the dissonance; then I try to straighten it out in the morning.”

Angelou’s routine and her willingness to sit down and do the work for at least five hours each day — even when it was going poorly — is just another indication that great artists don’t wait for inspiration.

Below, you’ll find a range of quotes from Angelou.

Quotes and Thoughts From Maya Angelou
On identity…

“What I represent in fact, what I’m trying like hell to represent every time I go into that hotel room, is myself. That’s what I’m trying to do. And I miss most of the time on that: I do not represent blacks or tall women, or women or Sonomans or Californians or Americans. Or rather I hope I do, because I am all those things. But that is not all that I am. I am all of that and more and less. People often put labels on people so they don’t have to deal with the physical fact of those people. It’s easy to say, oh, that’s a honkie, that’s a Jew, that’s a ju**ie, or that’s a broad, or that’s a stud, or that’s a dude. So you don’t have to think: does this person long for Christmas? Is he afraid that the Easter bunny will become polluted? … I refuse that… I simply refuse to have my life narrowed and proscribed.”

“When I try to describe myself to God I say, “Lord, remember me? Black? Female? Six-foot tall? The writer?” And I almost always get God's attention.”

On dealing with difficulty…

“We may encounter many defeats but we must not be defeated.”

“You may not control all the events that happen to you, but you can decide not to be reduced by them.”

“What you're supposed to do when you don't like a thing is change it. If you can't change it, change the way you think about it. Don't complain.”

On loving yourself…

“I don't trust people who don't love themselves and tell me, ‘I love you.' … There is an African saying which is: Be careful when a naked person offers you a shirt.”

“Success is liking yourself, liking what you do, and liking how you do it.”

“You alone are enough. You have nothing to prove to anybody.”

On finding your calling…

“There is no greater agony than bearing an untold story inside you.”

On courage…

“I love to see a young girl go out and grab the world by the lapels. Life's a bitch. You've got to go out and kick ass.”

On living life…

“I've learned that people will forget what you said, people will forget what you did, but people will never forget how you made them feel.”

“I've learned that you shouldn't go through life with a catcher's mitt on both hands; you need to be able to throw something back.”

“My mission in life is not merely to survive, but to thrive; and to do so with some passion, some compassion, some humor, and some style.”

“I’ve always had the feeling that life loves the liver of it. You must live and life will be good to you, give you experiences. They may not all be that pleasant, but nobody promised you a rose garden. But more than likely if you do dare, what you get are the marvelous returns.”

Masters of Habit is a series of mini-biographies on the rituals, routines, and mindsets of great athletes, artists, and leaders.

If you want more practical ideas for breaking bad habits and creating good habits, check out my book Atomic Habits, which will show you how small changes in habits can lead to remarkable results.

10/04/2022

What goes together like butter and 🍿? and bonus AMC Theatres stock. 🎥

Head to stash.com/party on April 8th at 8 p.m. ET to claim bonus $AMC stock and enter for the chance to win a 12-month AMC A-List Gift Membership.

Offer is subject to Terms and Conditions. This material is not intended as investment advice and is not meant to suggest that any securities are suitable investments for any particular investor. Investment advice is only provided to Stash customers.

All investments are subject to risk and may lose value. All product and company names are trademarks ™ or registered ® trademarks of their respective holders. Use of them does not imply any affiliation with or endorsement by them.

08/04/2022

08/04/2022

Every Day at 8am
Last summer, I was speaking with Todd Henry. Todd is a successful author and does a great job of putting out valuable work on a consistent basis.

I, on the other hand, do a remarkable job of putting out questionable work on an inconsistent basis. I started to explain this to Todd…

“Todd, what do you think about writing only when you feel motivated? I feel like I always do my best work when I get a spark of creativity or inspiration, but that only happens every now and then. I'm pretty much only writing when I feel like it, which means I'm inconsistent. But if I write all the time, then I'm not creating my best work.”

“That's cool,” Todd replied. “I only write when I’m motivated too. I just happened to be motivated every day at 8am.”

The Difference Between Professionals and Amateurs
It doesn't matter what you are trying to become better at, if you only do the work when you’re motivated, then you’ll never be consistent enough to become a professional.

The ability to show up everyday, stick to the schedule, and do the work — especially when you don't feel like it — is so valuable that it is literally all you need to become better 99% of the time.

I've seen this in my own experiences…

When I don't miss workouts, I get in the best shape of my life. When I write every week, I become a better writer. When I travel and take my camera out every day, I take better photos.

It's simple and powerful. But why is it so difficult?

The Pain of Being A Pro
Approaching your goals — whatever they are — with the attitude of a professional isn't easy. In fact, being a pro is painful.

The simple fact of the matter is that most of the time we are inconsistent. We all have goals that we would like to achieve and dreams that we would like to fulfill, but it doesn't matter what you are trying to become better at, if you only do the work when it’s convenient or exciting, then you’ll never be consistent enough to achieve remarkable results.

I can guarantee that if you manage to start a habit and keep sticking to it, there will be days when you feel like quitting. When you start a business, there will be days when you don’t feel like showing up. When you're at the gym, there will be sets that you don’t feel like finishing. When it's time to write, there will be days that you don’t feel like typing. But stepping up when it's annoying or painful or draining to do so, that’s what makes the difference between a professional and an amateur.

Professionals stick to the schedule, amateurs let life get in the way. Professionals know what is important to them and work towards it with purpose, amateurs get pulled off course by the urgencies of life.

07/04/2022

The 5 Stages of the Creative Process
In 1940, an advertising executive named James Webb Young published a short guide titled, A Technique for Producing Ideas. In this guide, he made a simple, but profound statement about generating creative ideas.

According to Young, innovative ideas happen when you develop new combinations of old elements. In other words, creative thinking is not about generating something new from a blank slate, but rather about taking what is already present and combining those bits and pieces in a way that has not been done previously.

Most important, the ability to generate new combinations hinges upon your ability to see the relationships between concepts. If you can form a new link between two old ideas, you have done something creative.

Young believed this process of creative connection always occurred in five steps.

Gather new material. At first, you learn. During this stage you focus on 1) learning specific material directly related to your task and 2) learning general material by becoming fascinated with a wide range of concepts.
Thoroughly work over the materials in your mind. During this stage, you examine what you have learned by looking at the facts from different angles and experimenting with fitting various ideas together.
Step away from the problem. Next, you put the problem completely out of your mind and go do something else that excites you and energizes you.
Let your idea return to you. At some point, but only after you have stopped thinking about it, your idea will come back to you with a flash of insight and renewed energy.
Shape and develop your idea based on feedback. For any idea to succeed, you must release it out into the world, submit it to criticism, and adapt it as needed.
creative-process

The Idea in Practice
The creative process used by Frederic Eugene Ives offers a perfect example of these five steps in action.

First, Ives gathered new material. He spent two years working as a printer's apprentice and then four years running the photographic laboratory at Cornell University. These experiences gave him a lot of material to draw upon and make associations between photography and printing.

Second, Ives began to mentally work over everything he learned. By 1878, Ives was spending nearly all of his time experimenting with new techniques. He was constantly tinkering and experimenting with different ways of putting ideas together.

Third, Ives stepped away from the problem. In this case, he went to sleep for a few hours before his flash of insight. Letting creative challenges sit for longer periods of time can work as well. Regardless of how long you step away, you need to do something that interests you and takes your mind off of the problem.

Fourth, his idea returned to him. Ives awoke with the solution to his problem laid out before him. (On a personal note, I often find creative ideas hit me just as I am lying down for sleep. Once I give my brain permission to stop working for the day, the solution appears easily.)

Finally, Ives continued to revise his idea for years. In fact, he improved so many aspects of the process he filed a second patent. This is a critical point and is often overlooked. It can be easy to fall in love with the initial version of your idea, but great ideas always evolve.

06/04/2022

What to do during the Spring Season?

There are so many things to do to enjoy spring:

Plan a holiday and make a trip. Vacations aren’t just for summer anymore!
Take a walk in a field of flowers.
Meditate: Contemplate and reflect on the beauty of nature. Forget the worries of everyday life and empty the mind. Concentrate on the sounds and the scent of nature.
Spot the things you want to change in your life. Spring is a time for rebirth.

06/04/2022

Hello and welcome