Monthly Archives: February 2024

The Healthiest U.S. Pharma Companies: Ranked by RealRate’s Impressive Artificial Intelligence – Medium

Posted: February 20, 2024 at 6:55 pm

The results for RealRates 2023 ranking for U.S. Pharma are now available and ranked by financial strength!

The Top 10 Pharma companies are as follows:

The top 5 Pharma companies in order are Theravance Biopharma Inc., Chimerix Inc., Ocuphire Pharma Inc., Kiniksa Pharmaceuticals Ltd., and Zomedica Corp.

They had Economic Capital Ratio figures of 587%, 407%, 377%, 331%, and 303%, respectively.

Theravance Biopharma, Chimerix, Ocuphire Pharma, and Kiniksa Pharmaceuticals did well due to the variable Net Income, and Zomedica did well due to its superior Current Liabilities variable.

This increased the companies Economic Capital Ratio scores by 402%, 213%, 168%, 137%, and 60%, respectively.

Theravance Biopharma climbed 191 places since last year to take the top spot. Chimerix climbed 127 places and Kiniksa climbed 98 places. Ocuphire and Zomedica are new to the list this year.

From a total of 446 Pharma companies, 111 received our Top Rated award.

The next 20 Pharma companies are as follows:

The US pharmaceutical industry is a powerhouse, generating billions in revenue annually. With a diverse landscape of companies, including giants like Pfizer, Merck, and Johnson & Johnson, it is a key player in global healthcare.

In 2021, the industrys revenue exceeded $500 billion, illustrating its immense economic significance.

In 2022, an especially profitable year for pharma, the eight biggest US pharmaceutical companies reported profits of $10 billion domestically on revenue of $214 billion.

The impressive thing we do at RealRate is to deliver utterly fair and independent company ratings, bringing together expert knowledge and innovative artificial intelligence in one package.

Our AI model computes the all-important Economic Capital Ratio figure.

Looking at our model in more detail, one can see it is very much unbiased and only uses audited public data. We are not part of any pharmaceutical company.

We are fair, explain ourselves very well and we also avoid any all-important conflicts of interest.

https://realrate.ai The first AI rating agency

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This Is What Vitalik Buterin Thinks About Artificial Intelligence (AI) – BeInCrypto

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Ethereum co-founder Vitalik Buterin has recently highlighted an innovative artificial intelligence (AI) application. This idea, designed for the formal verification of code and bug detection, aims to tackle Ethereums susceptibility to code bugs.

Buterins support for these solutions reflects the growing synergy between AI and blockchain technologies.

Given the increasing complexity of cyber threats, AIs role in bolstering cybersecurity has become crucial. This is especially true for the Decentralized Finance (DeFi) and smart contract ecosystem, which has billions in total value locked (TVL).

Even giants in the tech industry, such as Microsoft and OpenAI, are trying to enhance cybersecurity with AI. They are exploring AIs potential in both identifying and countering cyber threats. Their collaborative efforts are part of a larger initiative to ensure AI is used responsibly and to enhance cybersecurity measures.

Buterins perspective on artificial intelligence extends beyond cybersecurity. Earlier this year, he shared four innovative ideas for integrating AI with cryptocurrency. These concepts suggest a future where AI and blockchain technology work hand in hand.

One application of AI that I am excited about is AI-assisted formal verification of code and bug finding. Right now Ethereums biggest technical risk probably is bugs in code, and anything that could significantly change the game on that would be amazing, Buterin said.

Another notable idea is the inclusion of AI in blockchain systems, particularly in prediction markets. AI could leverage its vast knowledge in these markets for in-depth analysis, enhancing blockchain applications.

Read more: AI for Smart Contract Audits: Quick Solution or Risky Business?

Furthermore, Buterin envisions AI as a user interface that could simplify cryptocurrency transactions for users. This interface could provide guidance, interpret smart contracts, and prevent scams. Despite the potential benefits, Buterin warns against over-reliance on AI. He advocates for a balance with traditional interfaces to ensure user security and clarity.

Vitalik Buterin also proposes using artificial intelligence to set rules for blockchain games or decentralized autonomous organizations (DAOs). In this scenario, AI could act as a judge or a reference for rules. Another innovative idea is the development of AI systems using blockchain technology. This approach aims to create decentralized, impartial, and secure AI systems.

The enthusiasm for AI in the cryptocurrency sector has led to a surge in AI-related tokens, particularly following the announcement of OpenAIs text-to-video AI model, Sora. Tokens associated with AI or claiming to utilize AI technology, such as Worldcoins WLD, have seen significant price increases, with some tokens setting new all-time highs.

Another AI token, The Graph (GRT), saw an almost 60% increase, briefly surpassing $0.27. Despite these gains, GRT remains significantly down from its all-time high.

Render (RNDR) has also made headlines by entering the crypto markets top 50 following a year-on-year gain of 1,100%. Currently trading close to its all-time high, RNDR exemplifies the potential for AI tokens to achieve new milestones.

Read more: 13 Best AI Crypto Trading Bots To Maximize Your Profits

The surge in AI tokens is not limited to the crypto market. It also mirrors the performance of major AI players in traditional finance, such as Nvidia. Nvidias shares have surged by over 45% since the beginning of the year, contributing significantly to the S&P 500s growth and further fueling the AI token rally.

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AI researchers discuss risks and potential regulations suggest putting the brakes on the compute hardware as one … – Tom’s Hardware

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A combination of researchers from OpenAI and various universities have banded together to release a 104-page PDF document to encourage AI compute regulation by regulating the hardware itself, including the potential application of kill switches where an AI is being used for malicious purposes. The original PDF file was released online by University of Cambridge with a Valentine's Day post.

The PDF, titled "Computer Power and the Governance of Artificial Intelligence", discusses how PC compute power (i.e., GPU power) is leveraged for AI workloads. It then goes on to observe that since AI PC hardware has a high degree of supply chain concentration from just a few vendors, applying regulations to that hardware should be a lot easier.

In the "Risks of Compute Governance and Possible Mitigations" section, researchers detail some potential risks of AI before recommending potential solutions. We'll summarize some key points from this section below.

As far as potential solutions to these problems go, the paper proposes a fairly wide variety of different approaches and concerns that come with them. One of these solutions is a global registry of AI chips and unique identifiers for each, which could help limit smuggling and illegitimate use.

"Kill switches," which could be used to remotely deactivate AI hardware being used for malicious purposes, are also discussed as a possible solution within the paper. Though, solutions like this also pose their own risk, since a cybercriminal gaining control of that kill switch could use it to disable legitimate users. Also, it assumes the AI hardware will be accessible to outside entities, which may not be true.

As the technology and policy around artificial intelligence continues to evolve, time will tell just how power over this supposed new frontier will end up consolidating. It seems that quite a few AI experts, including OpenAI researchers, are hoping more of that power ends up in the hands of regulators, considering the dangers of the alternative.

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How AI-generated deepfakes threaten the 2024 election – Journalist’s Resource

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Last month, arobocall impersonating U.S. President Joe Biden went out to New Hampshire voters, advising them not to vote in the states presidential primary election.The voice, generated by artificial intelligence, sounded quite real.

Save your vote for the November election, the voice stated, falsely asserting that a vote in the primary would prevent voters from being able to participate in the November general election.

The robocall incident reflects a growing concern that generative AI will make it cheaper and easier to spread misinformation and run disinformation campaigns. The Federal Communications Commission last week issued a ruling to make AI-generated voices in robocalls illegal.

Deepfakes already have affected other elections around the globe. In recent elections in Slovakia, for example, AI-generated audio recordings circulated on Facebook, impersonating a liberal candidate discussing plans to raise alcohol prices and rig the election. During the February 2023 Nigerian elections, an AI-manipulated audio clip falsely implicated a presidential candidate in plans to manipulate ballots. With elections this year in over 50 countries involving half the globes population, there are fears deepfakes could seriously undermine their integrity.

Media outlets including the BBC and the New York Times sounded the alarm on deepfakes as far back as 2018. However, in past elections, including the 2022 U.S. midterms, the technology did not produce believable fakes and was not accessible enough, in terms of both affordability and ease of use, to be weaponized for political disinformation. Instead, those looking to manipulate media narratives relied on simpler and cheaper ways to spread disinformation, including mislabeling or misrepresenting authentic videos, text-based disinformation campaigns, or just plain old lying on air.

As Henry Ajder, a researcher on AI and synthetic media writes in a 2022 Atlantic piece, Its far more effective to use a cruder form of media manipulation, which can be done quickly and by less sophisticated actors, than to release an expensive, hard-to-create deepfake, which actually isnt going to be as good a quality as you had hoped.

As deepfakes continually improve in sophistication and accessibility, they will increasingly contribute to the deluge of informational detritus. Theyre already convincing. Last month, The New York Times published an online test inviting readers to look at 10 images and try to identify which were real and which were generated by AI, demonstrating first-hand the difficulty of differentiating between real and AI-generated images. This was supported by multiple academic studies, which found that faces of white people created by AI systems were perceived as more realistic than genuine photographs, New York Times reporter Stuart A. Thompson explained.

Listening to the audio clip of the fake robocall that targeted New Hampshire voters, it is difficult to distinguish from Bidens real voice.

The jury is still out on how generative AI will impact this years elections. In a December blog post on GatesNotes, Microsoft co-founder Bill Gates estimates we are still 18-24 months away from significant levels of AI use by the general population in high-income countries. In a December post on her website Anchor Change, Katie Harbath, former head of elections policy at Facebook, predicts that although AI will be used in elections, it will not be at the scale yet that everyone imagines.

It may, therefore, not be deepfakes themselves, but the narrative around them that undermines election integrity. AI and deepfakes will be firmly in the public consciousness as we go to the polls this year, with their increased prevalence supercharged by outsized media coverage on the topic. In her blog post, Harbath adds that its the narrative of what havoc AI could have that will have the bigger impact.

Those engaging in media manipulation can exploit the public perception that deepfakes are everywhere to undermine trust in information. These people use false claims and discredit true ones by exploiting the liars dividend.

The liars dividend, a term coined by legal scholars Robert Chesney and Danielle Keats Citron in a 2018 California Review article, suggests that as the public becomes more aware about the idea that video and audio can be convincingly faked, some will try to escape accountability for their actions by denouncing authentic audio and video as deepfakes.

Fundamentally, it captures the spirit of political strategist Steve Bannons strategy to flood the zone with shit, as he stated in a 2018 meeting with journalist Michael Lewis.

As journalist Sean Illing comments in a 2020 Vox article, this tactic is part of a broader strategy to create widespread cynicism about the truth and the institutions charged with unearthing it, and, in doing so, erode the very foundation of liberal democracy.

There are already notable examples of the liars dividend in political contexts. In recent elections in Turkey, a video tape surfaced showing compromising images of a candidate. In response, the candidate claimed the video was a deepfake when it was, in fact, real.

In April 2023, an Indian politician claimed that audio recordings of him criticizing members of his party were AI-generated. But a forensic analysis suggested at least one of the recordings was authentic.

Kaylyn Jackson Schiff, Daniel Schiff, and Natalia Buen, researchers who study the impacts of AI on politics, carry out experiments to understand the impacts of the liars dividend on audiences. In an article forthcoming in the American Political Science Review, they note that in refuting authentic media as fake, bad actors will either blame their political opposition or an uncertain information environment.

Their findings suggest that the liars dividend becomes more powerful as people become more familiar with deepfakes. In turn, media consumers will be primed to dismiss legitimate campaign messaging. It is therefore imperative for the public to be confident that we can differentiate between real and manipulated media.

Journalists have a crucial role to play in responsible reporting on AI. Widespread news coverage of the Biden robocalls and recent Taylor Swift deepfakes demonstrate that distorted media can be debunked, due to the resources of governments, technology professionals, journalists, and, in the case of Swift, an army of superfans.

This reporting should be balanced with a healthy dose of skepticism on the impact of AI in this years elections. Self-interested technology vendors will be prone to overstate its impact. AI may be a stalking horse for broader dis- and misinformation campaigns exploiting worsening integrity issues on these platforms.

Lawmakers across states have introduced legislation to combat election-related AI-generated dis- and misinformation. These bills would require disclosure of the use of AI for election-related content in Alaska, Florida, Colorado, Hawaii, South Dakota, Massachusetts, Oklahoma, Nebraska, Indiana, Idaho and Wyoming. Most of the bills would require that information to be disclosed within specific time frames before elections. A bill in Nebraska would ban all deepfakes within 60 days of an election.

However, the introduction of these bills does not necessarily mean they will become law. Furthermore, their enforceability could be challenged on the grounds of free speech, based on positioning AI-generated content as satire. Moreover, penalties would only occur after the fact or be evaded by foreign entities.

Social media companies hold the most influence in limiting the spread of false content, being able to detect and remove it from their platforms. However, the policies of major platforms, including Facebook, YouTube, and TikTok state they will only remove manipulated content for cases of egregious harm or if it aims to mislead people about voting processes. This is in line with a general relaxation in moderation standards, including repeals of 17 policies at the former three companies related to hate speech, harassment and misinformation in the last year.

Their primary response to AI-generated content will be to label it as AI-generated. For Facebook, YouTube and TikTok, this will apply to all AI-generated content, whereas for X (formally Twitter), these labels will apply to content identified as misleading media, as noted in recent policy updates.

This puts the onus on users to recognize these labels, which are not yet rolled out and will take time to adjust to. Furthermore, AI-generated content may evade the detection of already overstretched moderation teams and not be removed or labeled, creating false security for users. Moreover, with the exception of X (formerly Twitter)s policy these labels do not specify whether a piece of content is harmful, only that it is AI-generated.

A deepfake made purely for comedic purposes would be labeled, but a manually altered video spreading disinformation might not. Recent recommendations from the oversight board of Meta, the company formerly known as Facebook, advise that instead of focusing on how a distorted image, video or audio clip was created, the companys policy should focus on the harm manipulated posts can cause.

The continued emergence of deepfakes is worrying, but they represent a new weapon in the arsenal of disinformation tactics deployed by bad actors rather than a new frontier. The strategies to mitigate the damage they cause are the same as before developing and enforcing responsible platform design and moderation, underpinned by legal mandates where feasible, coupled with journalists and civic society holding the platforms accountable. These strategies are now more important than ever.

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Pew study paints a picture of the average US atheist – Aleteia

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A new survey measures views of atheists in the US, with data suggesting that not nearly as many "nones" would also consider themselves "atheist."

A survey undertaken by Pew Research Center in the summer of 2023 has shed some light on the portion of US adults who consider themselves atheist. A previous Pew study reported on by Aleteia found that the number of nones, those who do not identify with any particular religion, has surged in recent years. The new survey, however, suggests that not nearly as many of those who fall into the category of none would also fall into the category of atheist.

According to Pew, only 4% of US adults call themselves atheist, a figure that is twice as high as reported in a 2007 Pew study. In the US, men are slightly more likely to call themselves atheist than women, with 6-in-10 self-proclaiming atheists being male. Furthermore, 7-in-10 respondents who said they were atheist reported being aged 49 years or younger.

About three-quarters of self-identified atheists reported having no belief in God or a higher power. This group fits the traditional definition of atheist: as someone who does not believe in the existence of God or gods. There is, however, a considerable portion of self-identified atheists (23%) who say they do believe in some form of higher power, suggesting that there is some discrepancy among atheists as to what constitutes atheism.

Regardless of their beliefs in a higher power, the vast majority of US atheists (98%) responded that religion is not too or not at all important to their daily lives. Still, 79% of US atheists reported a deep sense of wonder about the universe that drives their thoughts at least a few times per year. Of these, however, only 36% reported this line of thought leading to a sense of peace.

US atheists reported high levels of concern with the role religion plays in society. Ninety-four percent of atheist respondents said that religion causes division and intolerance and 91% believe that religion encourages superstition and illogical thinking. Seventy-three percent said that they felt religion does more harm than good to society, but 2-in-5 (41%) said that it helps society by giving life meaning. A further 33% acknowledged the propensity for religion to encourage people to treat others well.

These concerns about religion in society have led many atheists to stay informed about religion. In a 2019 survey on religious knowledge, atheists tended to be among the best-performing groups, on average answering around 18 of 32 questions correctly. For instance, they were most likely to know that there is no religious test required to hold public office, and 8-in-10 also knew that Easter commemorates the Resurrection of Christ.

Read more findings from the 2023 survey at Pew Research Center.

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‘There’s No Science Behind That’: Actor Rob Schneider Passionately Checkmates ‘Bleak’ Worldview Within Atheism – CBN.com

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Comedian Rob Schneider believes having a foundation in God can lead to greater happiness and fulfillment andstudiesconsistently back this assertion.

Listen to them on the latestepisodeof Quick Start

In addition to revealing hope and strength found in faith, Schneider also recently told CBN News he finds the atheistic worldview to be so often devoid of hope.

This idea that things just blew up and the universe is things bumping into things, and expanding, and that we, as human beings, are just this freak accident that happened, he said. [This idea] that this empathy, and compassion, and love that we feel is just this accident that happened, and theres no reason for it, and nothing will come of it,and eventually the universe will just be a series of black holes.

Schneider said he finds such arguments uncompelling and uncorroborated.

I would just go, Well, wait a minute. Theres no science behind that,' he said. And that is a bleak, horrible way to go through life.

Watch Schneider explain:

Schneider said the evidence of love, compassion, and empathy we see in other people exists because it comes from God, the ultimate source of these emotions and expressions.

The actor also said hes spent time of late working on a script about the Shroud of Turin, a famous linen cloth some believe bears the image of Jesus; proponents believe the fascinating apparition was infused on the fabric during his resurrection.

Schneider said his movie about the subject is inching closer to being made, and plans to play a Benedictine monk who helps prove the Shroud is legitimate.

While the films future is still uncertain, one fact is undeniable: the project has built up Schneiders faith.

When you dig into the Shroud of Turin, which is the burial cloth of Jesus Christ, you realize that it could not have possibly been, as they say, a medieval forgery, he said. What the Shroud of Turin ultimately is is the receipt. Thats why its such an important thing. Its the receipt of the price that was paid by Jesus Christ forgiveness for all of humanity.

He continued, I couldnt work on this and couldnt see this without being so moved by it.

Read more about Schneiders faithhere.

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Atheists Find God at the Latin Mass: A Review of Mass of the Ages – CatholicCitizens.org – Catholic Citizens of Illinois

Posted: at 6:53 pm

By Jeremiah Bannister, One Peter Five, August 19, 2024

Mass of the Ages, Episode I: Discover the Traditional Latin Mass Directed by Cameron OHearn Produced by Jonathan Weiss and Cameron OHearn Director of Photography Thomas Shannon Original Score by Mark Nowakowsk

Click here to support the project

If its true (and it is) that the blood of martyrs is the seed of the church, then its fair to say thatthe death of director Cameron OHearns fatheris the seed of the greatest Catholic documentary of the decademaybe even of all time.

Mass of the Agesmay have had humble beginningsafter it wasfunded by a grassroots lay initiativebut I can imagine a moment where the team of young men behind the scenes awoke to the realization that this wasnt an ordinary film. Whether Thomas Shannons awe-inspiring cinematography, Christopher Amodios quintessential color grading, or Mark Nowakowskis sensational score, the movies production had all the mixings of something truly great. And if any doubt remained, it was certainly washed away under wave after wave of priests and bishops, scholars, and laypeople telling the tale of how the Traditional Latin Mass totally transformed their lives.

Of course, much can (and should) be said regarding every jot and tittle of the film, but I was particularly moved bysomething said by Dr. Taylor Marshall. For beyond the saddening statistics concerning the shortage of Catholic priests or the tragic loss of faith among the laity, there was (as Marshall so eloquently said regarding the brilliance of the Blessed Sacrament nestled within the setting of the traditional Roman rite) a kind of diamond in this film. This diamond was cut deep by the Great Lapidary, through which the light of Christ seemed to shine most brightthat being, the Mauss family, the central narrative of the film.

The movie began, symbolically enough, with a well-lit scene proceeding toward the illustrious high altar at the Oratory of St. Francis de Sales in St. Louis, Missouri, followed by a descent through the dimly lit sanctuary of Our Lady of Mt. Carmel in Littleton, Colorado. The optics were captivating, but then, toward the tail end of the departure, the camera gently glides between rows of candlescandles twinkling alongside the black funeral pall of a casket. I shuddered at the sight, and I worried whether this film wasnt what Id expectedor, maybe more accurately, that it was more than I was prepared to handle. The answer came seconds later, witha somber scene at a cemetery, where a family huddled together in prayer.

It was jolting, and tears flooded my eyes, as I saw at this moment a reflection of my own experience. And while I was yet unsure where all of this would lead, one thing was certain: Mass of the Ages wasnt a film I could watch on my own. It was, asthe aftermath of my daughters death with childhood brain cancer, a family affair, something we were destined to experience together. So I rushed to the family room and told them that I had something I wanted them to see and, more importantly, I told them that I needed them, through to the end by my side.

And it was true, for scene after scene struck so many heartstrings, composing a kind of chorus involving the most bittersweet of memories and emotions. Things wed seen, things wed felt, things wed loved and lost many of themso agonizingly beautiful, but all of themthings wehadto do. The comparisons were endless, too! The father,Michael Mauss, was diagnosed with a glioblastoma, given only 12 months to live. My daughter Sami, at only 10-years-old, was diagnosed with anaplastic astrocytoma, which took her life after a mere 16 months.

There was the story of Michael, shortly after learning of his diagnosis, smiling on a hospital bed, assuring everyone hell do his best and that everything will be fine. This fit the exact description of avideo Sami madefor her supporters shortly after learning she had cancer. And there wasthe tear-jerking scene of Michael and Kristine renewing their wedding vows, which reminded us of the time a priest prayed a blessing over my daughter, whom he lovingly referred to as Fire Toes.

Watching this was almost overwhelming, and everyone was in tears, but it was the aftermath of Michaels death that hit me most profoundly. Like Kristine after the loss of her husband, the death of our daughter left my family in limbo, unsure of what the future held in store. By that time, I was a Catholic turned apostate, adrift in the raging seas of secular atheism, lacking what Kristine calls the solid foundation of tradition. But like Fr. Illo points out later in the film, Theres a lot of questions that kids normally have, and if those are not addressed theyll go somewhere else to find the answers. Andmy kids had some serious questions!

Who built the universe,Papa? What is right and wrong, Papa? Why dont you ever pray, Papa?

I addressed them, of course, but I knew I was wrong, and they knew it too, so they continued, even asking to see what church looked like. I did my darnedest to distract and dissuade them, even going so far as to show a series of videos from popular Protestant denominations, banking on the idea that theyd find it all very laughable and they did. But it wasnt enough, as one of them quickly replied,But are we Catholic, Papa?It was specific, and with names like Athanasius, Ambrose Louis, and Teresa Avila Lucille, it was definitely a God thing.

As an Atheist, I finally conceded to our childrens request for God.So like any parent in the 21st century does, we showed them YouTube videos of different religions: Buddhism, Islam, Judaism, as well as the Novus Ordo rite. But when we showed them a video of the Latin Mass, my barely-catechized children understood that that was the only place they sought to find God. Their decision was unanimous: we would go to Christmas Vigil at the local parish where Ambroses godmother attended and where, unbeknownst to us, the priest who blessed my daughter just so happened to preside.

At one point in the film, Crisis Magazines Editor-in-Chief Eric Sammons says, The first impression [of the Latin Mass] for some people isnt always a positive one because its so different from anything they experiencedthey really just dont know what to think. Thats true for some people. For others, that foreign feeling of something timeless and transcendent, something set apart in (and beyond) space and time, is just what theyre looking for and exactly what they need. Kristine knows this all too well, insisting, The idea of eternity, it smacks them in the middle of the eyes every day. For the Mauss family, its where their dad is. For us, its where Sami lives, always smiling, dancing care- and cancer-free for all eternity. And Kristines right: its not to make everything about death, but this life is not what we were created forand to walk my children into heaven however I can is the number one priority of my life.

Conveniently enough, our journey played out in a way that can be summed up by different quotes from the film. Theres Fr. Illos story of the woman who recognized, through the quiet and humbling lens of the Latin Mass, her desire (and complete lack) of control. TheresFr. Joshua Caswell, SJC, detailing how the goal of the liturgy is not to evangelize but to worship God, and yet, how

So many atheists, Satanists, and other people wander into the church, knowing little to nothing about the Catholic faith, and yet are seemingly drawn to it because theres an experience of something bigger than themselves.

And Dr. Peter Kwasniewskis description of how the prayers at the foot of the altar start us slowly and carefully, preparing us for the ascent up the Holy Mountain, granting us a sense of our sinfulness and

A chance to wake up to what we are doing, to catch up with what were doingin a way, to slow us down [serving as] a period of preparation, a period of transition that takes us from secular life to this timeless domain of the sacred.

I was an atheist, but I experienced God at the Latin Mass.And just the married couple recalling their humorous first experience at a Latin MassWhats crazy is that we came back, we kept goingsuddenly we found ourselves returning every Sunday to the traditional Roman rite. For now, like Kristine, my goal and number one priority from that point onward was to walk my children into heaven however I can is the number one priority of my life, and that

The way I have been able to reorder my life [as a parent] has come from traditional Catholicism it has completely, radically transformed every aspect of our livesit is a liturgy and a way of lifethat breeds incredible peace and freedom its a refuge from this crazy scary world, and its the space where I can just place the cross down for a little bit.

Kristine finishes that line of thought with a question: where would we be without this? To which I echo her answer, I dont know, adding only, in a sea of sorrow, a desert of despair anywhere (and everywhere) but Rome sweet home.

And this is the story of countless souls across the world whose lives have been transformed by their encounter with God in the Mass of the Ages. Pope Francis seems to have largely hinged his recentmotu proprioon the claim that the Latin Mass is tied more to the desire and wishes of individual priests than to the real need of the holy People of God (Letter Accompanying Traditionis Custodes). From the grassroots funding for the film, to the stories related therein, to our own experience and those of thousands more, this claim of clericalism could not be further from the truth about the liturgy of our forefathers.

The film elevates the Mauss family brilliantly, set in the cinematic Golden Hour, with Kristine standing with her children along the waters edge of a lakeside shore. Whether dusk or dawn, it doesnt matter, for, as had become evident throughout the film, the Mauss family lives, moves, and has their being in the inextinguishable light of an everlasting fire, one that burns brightly in their hearts, shining forth, mysteriously, through the collective twinkle in their smiling eyes for all the world to see. And behind them, almost prophetically, a skyline of heavenly hills, coruscating clouds, and solace, hidden, yet ever-present, distant, but only for a time. And, as it is with faithful Catholics tethered to the Traditional Latin Mass, its saddled on a circuit, providing warmth and light, as it was in the beginning, is now, and will be forever, world without end, amen.

Mass of the Agesis a MUST-SEE movie fit for people of all ages. As for me and my family, we give it a resounding 5/5 stars. We are eagerly awaiting the premiere of Episode II which hints at addressing the real history of our liturgical chaos and the crisis in the Church.

Photo credit: provided by the author.

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The complete plastome sequences of invasive weed Parthenium hysterophorus: genome organization, evolutionary … – Nature.com

Posted: February 18, 2024 at 10:06 am

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Multi-omic profiling reveals associations between the gut microbiome, host genome and transcriptome in patients with … – Journal of Translational…

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Identification of a set of gut microbes associated with CRC

Most colorectal cancers arise from adenoma to carcinoma as verified by diet, inflammatory processes, gut microbiota, and genetic alterations. Nonetheless, the mechanism by which the microbiota interacts with these etiologic factors to promote CRC is not clear. Therefore, we collected stool samples, tumor and matched normal tissues from 41 CRC individuals, and carried out multi-omics sequencing analyses to evaluate the interplay between cancer cells and gut microbiome (Fig.1 and Additional file 1: Table S1). As shown in Additional file 1: Fig. S1a, the stool samples were subjected to metagenomic sequencing, achieving an average of 7Gb clean data. Additionally, we conducted whole exome sequencing, ensuring a minimum of more than 100X coverage and 20Gb data, respectively (Additional file 1: Table S2).

Metagenomics sequencing of the stool sample and exome and transcriptome sequencing of mucosa tissue in colorectal cancer. We collected stool specimens and matched tumor and normal mucosa tissue from 41 colorectal cancer patients. The former samples were metagenomically shotgun sequenced to yield taxonomic and functional profiles; the latter were processed using exome and transcriptome sequencing technology respectively. Features of the microbiome were correlated with clinic elements somatic mutations, and differentially expressed genes, respectively

We first examined the microbiome dysbiosis by integrating our metagenomic sequencing data with a public Chinese colorectal cancer cohort3 (CRC cohort2 and CON) (Fig.2A). Compared with healthy controls, the CRC patients in our cohort exhibited a significantly decreased alpha diversity (Additional file 1: Fig. S1b), but no obvious difference in the beta diversities (Additional file 1: Fig. S1c). To investigate the alterations in microbiota structure, we conducted the linear discriminant analysis effect size (LEfSe) analysis to compare healthy controls and combined tumor samples. Totally, there were 2 taxa (Viruses_noname and Fusobacteria) at the phylum level and 10 at the genus level significantly altered respectively (Fig.2B and Additional file 1: Table S3). Notably, we figured out 22 species associated with disease status, of which 14 were elevated in CRC group (Fig.2C). Of them, Bacteroides fragilis (LDA=3.897), Parabacteroides spp. (LDA=3.499) and Prevotella intermedia (LDA=3.452) exhibited the highest abundances in CRC patients. In contrast, eight species were enriched in healthy controls, including Faecalibacterium prausnitzii (LDA=4.299), Eubacterium rectale (LDA score=4.255), Eubacterium eligens (LDA=4.002), and so on.

A Microbiome alteration between healthy and CRC subjects. PCoA plot showed the two cohorts used in our project. B Taxonomic profile difference detected with LEfSe. C Differentially abundant species between healthy controls and CRC patients. D Differentially abundant KEGG pathways between healthy controls and CRC patients. E Unsupervised clustering uncovered associations between differentially abundant species and clinic covariates

To further investigate the functions of 22 tumor-associated bacteria, we used HUManN2 to estimate the relative abundance of KEGG ontology (KO) categories. Disease associated KEGG pathway changes were further identified using the method described in Feng Q. et al.4 We observed that bacteria related metabolic pathways were enriched in CRC groups. Especially, one carbon pool by folate metabolic pathway of microbiota was significantly (Reporter score=3.471) higher in CRC patients (Fig.2D). The one carbon pool by folate is a universal cell metabolic process supporting tumorigenesis, obtaining folate (vitamin B9) and cobalamin (vitamin B12) from diet. Furthermore, the cancer enriched species showed positive correlations with the metabolic pathways such as carbon metabolism and oxidative phosphorylation, whereas some well-known beneficial bacteria (including Faecalibacterium prausnitzii), displayed negative correlations (Additional file 1: Fig. S2).

Next, we investigated associations between overall microbiome configuration with CRC clinical covariates. Clinically, of the cohorts 41 individuals (63% male; ages 4679), 26 subjects (63%) belong to COAD and 15 subjects (37%) had carcinomas at rectum. Additionally, 10 subjects were diagnosed at early stage and 31 subjects (76%) at later stage. Among all 41 individuals, we observed that several paraprevotella.ssp were elevated in patients with age<65 (for example, paraprevotella clara, LDA score=3.051; paraprevotella xylaniphila, LDA score=2.478) (Additional file 1: Fig. S3a). Furthermore, Clostridium clostridioforme was predominated found in females (Additional file 1: Fig. S3b, LDA score=3.182). As to Bacteroides genus, the abundance of Bacteroides eggerthii was significantly increased in COAD (LDA score=3.625) whereas Bacteroides massiliensis was enriched in READ (LDA score=4.985) (Additional file 1: Fig. S3c). Bifidobacterium, one of the major probiotics, exhibited a significant increase in the early stage and individuals with age<65 (Bifidobacterium longum, LDA score=3.698; Bifidobacterium dentium, LDA score=2.102) (Additional file 1: Fig. S3a and d).

We also assessed the connections between clinical characteristics and 22 cancer associated bacteria in our subjects through unsupervised clustering (Fig.2E and Additional file 1: Table S4). Of note, we observed significant gender differences (p=0.01) among the C3 community type (Additional file 1: Fig. S4a). Tumor locations (colon or rectum; p=0.01) were linked to the C4 community type, which primarily consisting of the beneficial species (Additional file 1: Fig. S4b).

Previous studies indicated that gut microbes may induce DNA damage, thereby accelerating cancer development [29]. Consequently, we detected somatic mutations using exome sequencing technology from 41 CRC tumors and idntified 4 significantly mutated genes with MutSigCV, including TP53 (Q value=0), APC (Q value=1.26E-11), KRAS (Q value=1.11E-10) and SMAD4 (Q value=7.37E-04) (Fig.3A and Additional file 1: Table S6).

An overview of the associations between cancer genome and microbiome genomes. A Bar plots illustrate the frequently mutated genes in 41 tumor tissues. B The interaction between gut microbial taxa and somatic altered genes

To explore their associations with microbiota composition, we conducted the LEfSe analysis to compare tumors with or without mutated genes (Fig.3B). TP53 is the most prevalent somatic altered genes in our cohort. In TP53 mutated subjects, an enrichment of several disease-associated species, including Alistipes putredinis (LDA score=4.402), Porphyromonas asaccharolytica (LDA score=3.816), and Prevotella intermedia (LDA score=3.795) (Fig.4A). Previous observations uncovered that butyrate treatment could activate the TP53 pathway [30]. Consistently, the abundance of butyrate-producing bacteria, Butyricicoccus pullicaecorum, exhibited a significant reduction in TP53 mutation carriers (LDA score=2.395). Interestingly, Roseburia inulinivorans (LDA score=3.96) and Ruminococcus gnavus (LDA score=3.426), two other butyrate producers, were also significantly depleted in APC mutation carriers (Fig.4B). Besides, the relative abundance of Enterococcus genus was enriched in subjects with KRAS and SMAD4 mutations (Enterococcus faecalis, LDA=2.217; Enterococcus avium, LDA score=3.075) (Fig.4C, D). We also performed similar analysis between gut microbiota and other frequently mutated genes (Additional file 1: Fig. S5). In stool samples, probiotics, including Ruminococcus lactaris(LDA score=3.405), Bifidobacterium bifidum (LDA score=2.425), were dramatically elevated in MUC5B or MUC16 mutated individuals (Additional file 1: Fig. S5e, f). Barnesiella intestinihominis, acting as an enhancer for anticancer therapy, was proven enriched in TNN mutation carriers (LDA score=3.156) (Additional file 1: Fig. S5m).

AD Significantly mutated genes related taxonomic difference. Differentially abundant species between tumors with and without TP53 (A), APC (B), KRAS (C), SMAD4 (D) alterations, respectively

We further characterized the differences of microbial pathways between subjects with specific mutations and control group. Interestingly, the most abundant pathways were generally housekeeping processes encoded by microbes, such as one carbon metabolism, aromatic amino acids, branched chain amino acid and so on (Additional file 1: Fig. S6). One-carbon (1C) metabolism, consistently overexpressed in cancer, supports multiple biological processes, including nucleotides synthesis, methionine recycling pathway and redox defense [31]. An increased level of bacterial purine (reporter score=2.909) and pyrimidine (reporter score=3.188) metabolism were found in TP53 mutation carriers (Additional file 1: Fig. S6a). Similarly, bacterial cysteine-methionine metabolism (reporter score=3.246) and folate biosynthesis (reporter score=1.949) exhibited significant alterations in individuals with APC mutations (Additional file 1: Fig. S6b). Bacteria can synthesize different amino acids. Compared to control group, we found APC (Additional file 1: Fig. S6c) and SMAD4 mutation carriers (Additional file 1: Fig. S6d) were significantly associated with high levels of bacterial tryptophan (Trp) metabolism pathway (reporter score=3.045 and 2.732, respectively). Moreover, we observed an elevated abundance of bacterial phenylalanine metabolism correlated with KRAS mutations (reporter score=4.345) (Additional file 1: Fig. S6c).

We also investigated the relationship between the microbiome composition and the gene expression patterns in CRC. We observed that certain bacterial species were significantly correlated with the gene expression pattern (Additional file 1: Fig. S7 and Table S6). The differentially expressed functional genes were clustered according to their correlation with differentially abundant species, following by annotation with DAVID (Fig.5). We observed that Fusobacterium nucleatum, along with some Clostridium spp. exhibited positive associations nitrogen metabolism and bile secretion pathways, but negatively with cytokine-cytokine receptor interaction pathway.

Correlation of differentially abundant species and deregulated genes. Tumor associated deregulated genes were clustered and annotated with DAVID. The X axis illustrated the DAVID functional annotation and Y axis showed differentially abundant species. Red color represents positive association while green color means negative association

Subsequently, the interaction between 22 bacterial species and up-regulated oncogene expression was explored. As shown in Fig.6A, Fusobacterium nucleatum was positively correlated with PKM (p=0.03), SCD (p=0.0186), FASN (p=0.014), which are key enzymes in glycolysis and fatty acid metabolism. Consistent with the findings, we categorized patients into high and low Fusobacterium nucleatum groups, and found that various metabolism related pathways were significantly enriched in the high groups (pentose and glucuronate interconversions, p=0.026; starch and sucrose metabolism, p=0.007; porphyrin and chlorophyll metabolism, p=0.023; oxidative phosphorylation, p<0.00001) (Fig.6B). Taken together, the intestinal microbiota promotes CRC progression by shaping the expression of host gene expression, especially metabolic pathways.

Gene expression signature and metabolic pathways reprogramming associated with microbial shifts. A The association between up regulated oncogene expression and cancer related species. The X axis represents up regulated cancer genes. Significant associations were highlighted below the heatmap. B Pathway difference between high and low Fusobacterium nucleatum groups

The composition of immune and stromal cell types was identified by XCELL, a gene signature-based method that integrates the advantages of gene set enrichment with deconvolution approaches. Compared with adjacent normal tissues, the overall immune score was significantly lower in tumor tissue (Fig.7A). Especially, the abundance of most B cells and CD8+T cells elevated in tumors while regulatory T cells and T helper cells exhibited a decreasing trend (Additional file 1: Fig. S8), indicating the important role of the immune microenvironment in the progression of CRC. The associations between different microbial species and immune cell types in the CRC were shown in Fig.7B. Fusobacterium nucleatum was negatively associated with dendritic cells and CD8 T cells (Fig.7C). While Faecalibatcerium prausnitzii were significantly positively correlated with dendritic cells and Macrophages M1 (Additional file 1: Fig. S9a).

Fusobacterium nucleatum promoted CRC by modifying the tumor immune environment and TNFSF9 expression. A Comparison of immune cell scores between tumor and adjacent normal tissues. B The heatmap illustrates the correlations between differential abundant species and immune cells. The stars indicate the level of statistical significance. C Significant association of F. nucleatum and aDC and CD8 T cells. D Pathway alteration between normal and tumor tissue. E Significant association between Fusobacterium nucleatum and TNFSF9 gene expression

Interestingly, Gene set enrichment analysis of revealed that the cytokine-cytokine receptor interaction (p<0.001) was significantly altered in CRC (Fig.7D). Correlation analysis of genes related to cytokine-cytokine receptor interaction pathway related genes and 22 species uncovered several significant associations (Additional file 1: Fig. S9b). Among them, Fusobacterium nucleatum exhibited a positive association with TNFSF9, a member of TNF (tumor necrosis factor) family members (r=0.443, p=0.0037) (Fig.7E). Previous study showed that Fusobacterium nucleatum autoinducer-2 (AI-2) enhanced the mobility and M1 polarization of macrophages, possibly through TNFSF9/TRAF1/p-AKT/IL-1 signaling. Our results further suggested that pathogenic bacteria, like Fusobacterium nucleatum, may interact with CRC cells and modify the tumor immune environment by TNFSF9, finally facilitating the tumor development.

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Genomic Time Machine Reveals Secrets of Human DNA – SciTechDaily

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Researchers at EPFL, led by Didier Trono, have developed a novel method to detect previously undetectable transposable elements (TEs) in the human genome, significantly expanding our knowledge of DNA composition. This discovery has profound implications for understanding genetic diseases and the genomes response to various stresses.

The human genome, a complex mosaic of genetic data essential for life, has proven to be a treasure trove of strange features. Among them are segments of DNA that can jump around and move within the genome, known as transposable elements (TEs).

As they change their position within the genome, TEs can potentially cause mutations and alter the cells genetic profile but also are master orchestrators of our genomes organization and expression. For example, TEs contribute to regulatory elements, transcription factor binding sites, and the creation of chimeric transcripts genetic sequences created when segments from two different genes or parts of the genome join together to form a new, hybrid RNA molecule.

Matching their functional importance, TEs have been recognized to account for half of the human DNA. However, as they move and age, TEs pick up changes that mask their original form. Over time, TEs degenerate and become less recognizable, making it difficult for scientists to identify and track them in our genetic blueprint.

In a new study, researchers in the group of Didier Trono at EPFL have found a way to improve the detection of TEs in the human genome by using reconstructed ancestral genomes from various species, which allowed them to identify previously undetectable degenerate TEs in the human genome. The study is published in Cell Genomics.

The scientists used a database of reconstructed ancestral genomes from different kinds of species, like a genomic time machine. By comparing the human genome with the reconstructed ancestral genomes, they could identify TEs in the latter that, over millions of years, have become degenerate (worn out) in humans.

This comparison allowed them to detect (annotate) TEs that might have been missed in previous studies that used data only from the human genome.

Using this approach, the scientists uncovered a larger number of TEs than previously known, adding significantly to the share of our DNA that is contributed by TEs. Furthermore, they could demonstrate that these newly unearthed TE sequences played all the same regulatory roles as their more recent, already-identified relatives.

The potential applications are vast: Better understanding TEs and their regulators could lead to insights into human diseases, many of which are believed to be influenced by genetic factors, says Didier Trono. First and foremost, cancer, but also auto-immune and metabolic disorders, and more generally our bodys response to environmental stresses and aging.

Reference: Ancestral genome reconstruction enhances transposable element annotation by identifying degenerate integrants by Wayo Matsushima, Evarist Planet and Didier Trono, 30 January 2024, Cell Genomics. DOI: 10.1016/j.xgen.2024.100497

The study was funded by the European Research Council, the Swiss National Science Foundation, the EMBO Postdoctoral Fellowship, and the JSPS Overseas Research Fellowship.

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