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Archive for the ‘Artificial Intelligence Applications in Health Care’ Category

Live Conference Coverage: International Dialogue in Gynecological Oncology, From Bench to Bedside, Ovarian Cancer

Reporter: Stephen J. Williams, Ph.D.

Join Live on Wednesday May 22, 2024 for an international discussion on the current state of ovarian cancer diagnostics and therapeutics, and potential therapies and biomarkers, and biotargets.  Topics including potential new molecular targets for development of ovarian therapeutics, current changes in ovarian cancer clinical treatment protocols, chemo-resistance, and the use of Artificial Intelligence (AI) in the diagnosis and treatment of cancer will be discussed.

International Dialogue in Gynecological Oncology, From Bench to Bedside, ovarian Cancer meeting flyer

To join by Zoom click the link below

https://temple.zoom.us/j/94458267823 

Agenda:

Introduction

  • 00/15.00 Professor Giordano and Professor Ercoli
  • 10/15.10 We Have Never Been Only Human: a new perspective to defeat ovarian cancer (C. Martinelli)

Molecular Section

  • 20/15.20 DNA Repair mechanisms: understanding their role in cancer development and chemoresistance (L. Alfano)
  • 35/15.35 Progranulins: a new target for oncological treatment (A. Morrione)
  • 50/15.50 Modulation of gene expression and its applications (M. Cuomo)
  • 10.05/16.05 Commanding the cell cycle: the role of CDKs (S.R. Burk
  • 10.20/16.20 Drug development from nature (M. D’Angelo

Clinical Section

  • 05/17.05 Core principles of Radiologic Diagnosis & Staging in Ovarian Cancer(A. Blandino)
  • 20/17.20 Key Indications for Nuclear Medicine in Ovarian Cancer (S. Baldari)
  • 35/17.35 Cutting Edge Decision: Understanding Surgical Indications and Outcomes in Ovarian Cancer (A. Ercoli)
  • 50/17.50 Gold Standard in Oncology for Ovarian Cancer (N. Silvestris)
  • 12.05/18.05 Role of Radiotherapy in Ovarian Cancer (S. Pergolizzi)

Conclusion

12.20/18.20 AI Applied to medical science (V. Carnevale)

Speakers

  • – Professor Alfredo Blandino: Professor Blandino holds the esteemed positions of Head of school of Radiology and director of the department of radiology at the University of Messina. He has made significant contributions to diagnostic imaging with over hundreds of publications to his name, Professor Blandino’s work exemplifies excellence and innovation in radiology.
  • – Professor Alfredo Ercoli, serves as the Director of the Department of Gynecology and Obstetrics at the “G. Martino” University Hospital in Messina. He is also head of school of gynecology and obstetrics at Messina University. Starting his research in France with studies on pelvic anatomy that became a cornerstone in medical literature, He is a pioneer in advanced gynecologic surgery, including laparoscopic and robotic procedures, having performed over thousands of surgical interventions. His research focuses on gynecologic oncology, advanced gynecologic surgery, and endometriosis, urogynecology. Professor Ercoli’s dedication to education and his numerous publications have significantly advanced the field of gynecology.
  • Professor Sergio Baldari, an eminent figure in nuclear medicine. Professor Baldari is the Director of the department of nuclear medicine and head of school of nuclear medicine at the  University of Messina. He has authored or co-authored over 500 publications, with a focus on diagnostic imaging and the use of PET and radiopharmaceuticals in cancer treatment. His leadership and expertise have been recognized through various prestigious positions and awards within the medical community.
  • – Professor Nicola Silvestris is the Director of UOC Oncologia Medica at the University of Messina. His extensive research in cancer, has led to over 360 peer-reviewed publications. Professor Silvestris has made significant contributions to translational research and the development of guidelines for managing complex oncological conditions. His work continues to shape the future of cancer treatment.
  • Professor Stefano Pergolizzi, a leading expert in radiation oncology. Professor Pergolizzi serves as the Director of the department of radiotherapy and head of the school of radiotherapya at the University of Messina. He is also the president of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) His research focuses on advanced radiotherapy techniques for cancer treatment. With a career spanning several decades, Professor Pergolizzi has published numerous papers and has been instrumental in developing innovative therapeutic approaches. His dedication to patient care and education is exemplary.
  • Margherita D’angelo: Graduated in Molecular Biology with honors from the Federico II University of Naples.
    Third year intern in Food Science at the Luigi Vanvitelli University of Naples.
    Research intern in Molecular oncology with the project of developing novel drugs starting from food waste at the Sbarro Institute for Cancer Research and Molecular Medicine at Temple University, Philadelphia (USA), directed by Dr A. Giordano.
  • Vincenzo Carnevale, Ph.D.

Dr. Carnevale is an Associate Professor in the Institute for Computational Molecular Science in the College of Science & Technology, Temple University.  He holds multiple NIH RO1 and NSF grants. Vincenzo Carnevale received B.Sc. and M.Sc. degrees in Physics from the University of Pisa and a PhD from SISSA – Scuola Internazionale Superiore di Studi Avanzati in Trieste, Italy. The Carnevale research group uses statistical physics and machine learning approaches to investigate sequence-structure-function relations in proteins. A central theme of the group’s research is how interactions give rise to collective phenomena and complex emergent behaviors. At the level of genes, the group is interested in epistasis – the complex entanglement phenomenon that causes amino acids to evolve in a concerted fashion – and how this shapes molecular evolution. At the cellular level, the group investigates how intermolecular interactions drive biomolecules toward self-organization and pattern formation. A long-term goal of the group is understanding the molecular underpinnings of electrical signaling in excitable cells. Toward these goals, the group applies and actively develops an extensive arsenal of theoretical and computational approaches including statistical (mean)field theories, Monte Carlo and molecular dynamics simulations, statistical inference of generative models, and deep learning.

  • Professor Andrea Morrione, Ph.D: Research Associate Professor, CST Temple University; After his studies in Biochemistry at Universita’ degli Studi Milano, Milan Italy, Dr. Morrione moved to USA in 1993 and has been working in the field of cancer biology since his postdoctoral training at the Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia, PA in the laboratory of Dr. Renato Baserga, one of the leading experts in IGF-IR oncogenic signaling. In 1997 Dr. Morrione joined the Faculty of Thomas Jefferson University in the Department of Microbiology. In 2002 after receiving an NIH/NIDDK Career Development Award Dr. Morrione joined the Department of Urology at Jefferson where from 2008 to 2018 serves as the Director for Urology Basic Science and Associate Professor. Dr. Morrione joined the Department of Biology and the Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology as Associate Professor of Research, and he is currently professor of Research and Deputy Director of the Sbarro Institute for Cancer Research and Molecular Medicine and Center for Biotechnology. He is a full member of the AACR.

 

  • Canio Martinelli, M.D.: Dr. Marinelli received his MD from Catholic University of the Sacred Heart in Rome, Visiting researcher at SHRO Temple University in Philadelphia, PhD candidate in Translational Molecular Medicine and Surgery & GYN-OB resident at UNIME. He has published numerous clinical papers in gynecologic oncology, risk reduction, and therapy and, most recently investigating clinical utilities of generative AI in gynecologic oncology.
  • Sharon Burk, Sharon Burk is a PhD student with Professor Antonio Giordano at the University of Siena, Italy in the department of Medical Biotechnologies, studying the role of Cyclin Dependent Kinase 10 in Triple Negative Breast Cancer. She received her Bachelor’s of Arts Degree from the University of California, Berkeley with a double major in molecular and cell biology and Italian studies.   She is a member of AACR.

This conference is being sponsored by Sbarro Health Research Organization and the Department of Biology, College of Science & Technology, Temple University.

To join by Zoom click the link below

https://temple.zoom.us/j/94458267823 

A QR code will be supplied at conference start, in addition to Zoom chat, to allow for questions to be submitted.

This conference is free to join on Zoom and will be covered live on @pharmaBI 

and on

 

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Live Notes from JP Morgan Healthcare Conference Virtual Endpoints Preview: January 8-9 2024

Reporter: Stephen J. Williams, Ph.D.

Endpoints at #JPM24 | Primed to unlock biopharma’s next dealmaking wave
Endpoints at JP Morgan Healthcare Conference
January 8-9 | San Francisco, CA80 Mission St, San Francisco, CA

An oasis has emerged in the biopharma money desert as backers look to replenish capital — still, uncertainty remains on whether it’s a mirage or the much needed dealmaking bump the industry needs. Yet spirits run high as JPM24 marks the triumphant return of inking strategic alliances and peering into the industry crystal ball — while keeping an eye out for some major M&A.

We’re back live from San Francisco for JPM Monday and Tuesday — our calendar of can’t-miss panels and fireside chats will feature prominent biopharma leaders to watch. The Endpoints Hub provides the ultimate coworking space with everything you need — 1:1 and group meeting spots plus guest pass capabilities and more. Join us in-person at the Endpoints Hub or watch online to stay plugged into all the action.

8 JAN
Welcome remarks
8:05 AM – 8:25 AM PST
Pfizer vet Mikael Dolsten has some thoughts on Big Pharma R&D

Endpoints News founding editor John Carroll will sit down with longtime Pfizer CSO Mikael Dolsten to talk about Pfizer’s pipeline, what he’s learned on the job about preclinical research and development and what’s ahead for the pharma giant in drug development and deals.

Mikael Dolsten

Chief Scientific Officer, President, Pfizer Research & Development

Pfizer

Pfizer Mikael Dolsten: Pfizer produced a series of AI generated molecules with new properties. Sees rapid adoption of AI in the area of drug discovery and molecular design.

 
 
8:25 AM – 9:05 AM PST
What pharma wants: The industry’s dealmakers look ahead at 2024

The drug industry’s appetite for new assets hasn’t slowed down. Top business development execs will give their outlook on the year, what they’re looking for and how they see the market.

Glenn Hunzinger

Pharmaceutical & Life Sciences Consulting Solutions Leader

PwC US

Rachna Khosla

SVP, Head of Business Development

Amgen

James Sabry

Global Head of Pharma Partnering

Roche

Devang Bhuva

SVP, Corporate Development

Gilead Sciences, Inc.

Endpoints News

Dealmaking panel

Glenn Hunzinger: if you do not have a GLP1 will have a tough time getting a good market price for your company; capital markets are not where they want to be; sees a tough deal making climate like last year.  The problem with many biotech companies are they are coming earlier to the venture capital because of greater funding needs and so it is imperative that they articulate the potential of their company in scientific detail

Rachna Khosla:  Make sure your investors are not just CAPITAL PARTNERS but use their expertise and involve them in development issues you may have, especially ones that a young firm will face.  The problem is most investments assume what the future looks like (for example how antibody drug conjugates, once a field left for dead, has been rejuvenated because of advances in chemistry). 

James Sabry: noted that cardiac and metabolic drugs are now at the focus of many investors, especially with the new anti-obesity drugs on market

Devang Bhuva: Most deals we see start as collaborations or partnerships.  You want to involve an alliance management team early in the deal making process.  This process could take years.

 
9:05 AM – 9:20 AM PST
The IPO: How Apogee Therapeutics went public in the most challenging market in years

Not many biotechs went public in 2023. And of those that did, not many have had a great time of it. Apogee is the exception and our panel will offer a behind-the-scenes look at their decision to enter the market and what life is like as a young public company.

Michael Henderson

CEO

Apogee Therapeutics

Kyle LaHucik

MODERATOR

Senior Reporter

Endpoints News

Michael Henderson:  Not many biotech IPOs deals happened in 2023.  Michael feels it is because too many biotechs focused on building platforms, which was a hard sell in 2023.  He felt not many biotechs had clear milestones and investors wanted a clear primary validated target.  He said many biotech startups are in a funding crunch and most need at least $440M on their balance sheet to get to 2026.

9:50 AM – 10:10 AM PST
Top predictions for biotech in 2024

Catalent CEO Alessandro Maselli will be back at the big JPM healthcare confab to talk with Endpoints News founder John Carroll about their top predictions of what’s coming up for the biotech industry in 2024. The stakes couldn’t be higher as the industry grapples with headwinds and new opportunities in a gale of market forces. Two top observers share their thoughts on the year ahead.

Alessandro Maselli

President & CEO

Catalent

10:15 AM – 10:35 AM PST
Innovation at a crossroads: Keys to unlocking the value of science and technology

The industry has long discussed the promise of technology and the acceleration it provides in scientific advancement and across the industry value chain. However, the promise of its impact has yet to fully be realized. This discussion will outline the keys to unleashing this promise and the implications and actions to be taken by the biopharmaceutical companies across the industry.

Ray Pressburger

North America Life Sciences Industry Lead & Global Life Sciences Strategy Lead

Accenture

SPONSORED BY

10:35 AM – 11:05 AM PST
Activism and Investing: In conversation with Elliott Investment Management’s Marc Steinberg

Elliott has been behind many of 2023’s highest-profile healthcare investments, including multiple activist engagements and taking Syneos Health private. What has made large healthcare companies such interesting investment opportunities for firms like Elliott? What’s Elliott’s investing strategy in healthcare? And what should companies expect when an activist calls?

Marc Steinberg

Senior Portfolio Manager

Elliott Investment Management

Andrew Dunn

MODERATOR

Biopharma Correspondent

Endpoints News

11:05 AM – 11:35 AM PST
Creating ROI from AI

AI is predicted to transform the way drugs are made, from discovery to clinical trials to market. But beyond the initial hype and early adoption, where has AI made meaningful contributions to R&D? How does it help drug developers advance science? Endpoints publisher Arsalan Arif is convening a panel of leading experts to discuss the state of AI in the pharmaceutical landscape and the outlook for 2024. How does AI impact the drug pipeline, from the early steps of discovery to reducing trial failure rate?

Thomas Clozel

Co-Founder & CEO

Owkin

Venkat Sethuraman

SVP, Global Biometrics & Data Sciences

Bristol Myers Squibb

Frank O. Nestle

Global Head of Research & Chief Scientific Officer

Sanofi

Matthias Evers

Chief Business Officer

Evotec

Arsalan Arif

MODERATOR

Founder & Publisher

Endpoints News

SPONSORED BY

11:35 AM – 12:00 PM PST
Biopharma’s dealmaker: Behind the scenes with Centerview Partners co-president Eric Tokat

Almost every major biopharma deal in 2023 had Centerview’s name attached to it. And much of the time, Eric Tokat was the banker making those deals happen. Hear his outlook for 2024, how transactions are getting done and what’s placed his firm at the center of so much action.

E. Eric Tokat

Co-President, Investment Banking

Centerview Partners

CenterView Partners Eric Tokat feels dealmaking will improve in 2024, given the recent flurry of dealmaking at end of last year and right before main JPM Healthcare Conference.  He says Centerview wants to help the biotechs they invest in on their strategic path.  This may translate into buyers more actively involved (more than startups want) and buyers now are in the drivers seat as far as the timeline of deals and development.

Is the megamerger dead for this year?  He says it is very hard to see two major mergers happening but there will be many smaller and mid size biotech deals happening, but these deals will be more speculative in nature..  The focus for large pharma is top line growth.  Most of the buyers have an infrastructure and value is more of buying and dropping it in their business so there is now a huge emphasis on due diligence on whether synergies exist or not

 
12:00 PM – 12:30 PM PST
Founder, legend, leader: In conversation with Nobel laureate Carolyn Bertozzi

Carolyn Bertozzi’s discoveries around bioorthogonal chemistry won the Nobel Prize in Chemistry in 2022 and are at the heart of new therapies being tested in patients. Join us as we discuss what inspires her and where she sees the next big advances.

Carolyn Bertozzi

Prof. of Chemistry, Stanford University and Baker Family Director of Sarafan ChEM-H

Stanford University

Nicole DeFeudis

MODERATOR

Editor

Endpoints News

Bioorthogonal chemistry: class of high yielding chemical reactions that proceed rapidly and selectively in biological environments without side reactions toward endogenous functions.  This is also a type of ‘click chemistry’ in biological system where only specifically alter the biomolecule of interest.

Orthogonal: two chemicals not interacting with each other

Dr. Bertozzi noted she has started a new Antibody-Drug-Conjugate (ADC) company which involves designing with biorthogonal chemistry to make new functional molecules with varying properties

She noted hardly any biologists knew anything about glycobiology when she first started.  However now she feels pharma and academia are working very well with each other

Bioorthogonal and Click Chemistry
Curated by Prof. Carolyn R. Bertozzi, 2022 winner of the Nobel Prize in Chemistry

Source: https://pubs.acs.org/page/vi/bioorthogonal-click-chemistry

The 2022 Nobel Prize in Chemistry has been awarded jointly to ACS Central Science Editor-in-Chief, Carolyn R. Bertozzi of Stanford University, Morten Meldal of the University of Copenhagen, and K. Barry Sharpless of Scripps Research, for the development of click chemistry and bioorthogonal chemistry.

To celebrate this remarkable achievement, 2022 Nobel Prize winner Professor Carolyn R. Bertozzi has curated this Bioorthogonal and Click Chemistry Virtual Issue, highlighting papers published across ACS journals that have built upon the foundational work in this exciting area of chemistry.

From Mechanism to Mouse: A Tale of Two Bioorthogonal Reactions

Ellen M. Sletten and Carolyn R. Bertozzi* Acc. Chem. Res. 2011, 44, 9, 666-676 August 15, 2011

Abstract

Bioorthogonal reactions are chemical reactions that neither interact with nor interfere with a biological system. The participating functional groups must be inert to biological moieties, must selectively reactive with each other under biocompatible conditions, and, for in vivo applications, must be nontoxic to cells and organisms. Additionally, it is helpful if one reactive group is small and therefore minimally perturbing of a biomolecule into which it has been introduced either chemically or biosynthetically. Examples from the past decade suggest that a promising strategy for bioorthogonal reaction development begins with an analysis of functional group and reactivity space outside those defined by nature. Issues such as stability of reactants and products (particularly in water), kinetics, and unwanted side reactivity with biofunctionalities must be addressed, ideally guided by detailed mechanistic studies. Finally, the reaction must be tested in a variety of environments, escalating from aqueous media to biomolecule solutions to cultured cells and, for the most optimized transformations, to live organisms.

9 JAN

9:40 AM – 10:10 AM PST

Biotech downturn survival school

Our panelists have seen the worst, and made it through to the other side. Join us for downturn survival school as our panelists talk about what sets apart the ones who make it through tough times.

These panalists think it will be specialist capital year to shine while the general capital is still sitting on the sidelines

JJ Kang

CEO

Appia Bio

“2023 was a tough year while 2020 was a boon year to start a company.  We will continue to see these cycles; many of these new CEOs have never seen a biotech downturn yet and may not know how to preserve capital for the downturn”.

“Doing a partnership with Kite Pharmaceuticals early in our startp allowed us to get work done without risking a lot of capital, even if it means equity and asset dilution.  That makes sense. However even if you are small insist on being an equal partner.”

“There are many investors we talk to who do not want to invest in cell therapy.  Too risky now”

Carl Gordon

Managing Partner

OrbiMed Advisors

There are many macroeconomic factors affecting investment and capital today which will carry on through 2024.   Not raising money when you do not need money is a bad philosophy.  Always bbe raising captial.  This is especially true when you have to rely on hedge funds.  Parnerships howeve are sometimes the only way for small biotechs to leverage their strengths.

Joshua Boger

Executive Chair

Alkeus Pharmaceuticals, Inc.

Boger: Expect volatility for 2024.  This environment feels very different than past downturns.

Even in downturns there is still lots of capital; remember access to human capital is better in a downturn and is easier to access;  however it has become harder to get drug approvals

The panelists agree that access to capital and funding will be as tricky in 2024 than 2023.  They did

suggest that a new funding avenue, private credit, may be a source of capital.  This is discussed below:

When thinking about a private alternative investment asset class, the first thing that springs to mind is private equity. But there’s one more asset class with the word private in its name that has recently gained much attention. We’re talking about private credit

Indeed, this once little-known investment strategy is now growing rapidly in popularity, offering private investors worldwide an exciting opportunity to diversify their portfolio with, in theory, less risky investments that yield significant returns. 

  • Private credit investments refer to investors lending money to companies who then repay the loan at a given interest rate within the predetermined period.
  • The private credit market has grown significantly over the past years, rising from $875 million in 2020 to $1.4 trillion at the beginning of 2023. 

Please WATCH VIDEO BY GOLDMAN SACHS ON PRIVATE CREDIT

 

 

 

 

10:50 AM – 11:20 AM PST

The New Molecule: How breakthrough technologies are actually changing pharma R&D

Join us for a look at how AI, machine learning and generative technologies are actually being applied inside drugmakers’ labs. We’ll explore how new technologies are being used, their implications, how they intersect with regulatory and IP issues and how this fast-changing field is likely to evolve.

Kailash Swarna

Managing Director & Global Life Sciences Clinical Development Lead

Accenture

Artificial Intelligence is making impact in a grand way on biology in three aspects:

  1. Speeding up target validation: now we can get through 300 molecules a day
  2. Predicition like AlphaFold is doing; molecular simulations
  3. Document submission especially with regulatory and IND submissions

Pamela Carroll

COO

Isomorphic Labs formerly of AlphaFold

We were first with Novartis at last year JPM and was one year old but parnering with them in that initial year was very important for sealing the deal.

They are looking now at neurologic diseases like ALS.  She wondered whether ALS is actually multiple diseases and we need to stratify patients like we do in oncology trials.  Their main competion is the whole tech world like Amazon, Google and other Machine Learning companies so being a tech player in the biotech world means you are not just competing with other biotechs but large tech companies as well.

Jorge Conde

General Partner

Andreessen Horowitz

Need is still great for drug discovery; early adopters show AI tools can be used in big pharma. There are lots of applications of AI in managing care; a lot of back office applications including patient triaging.  He does not see big AI mergers with pharma companies –  this will be mainly partnerships not M&A deals

Alicyn Campbell

Chief Scientific Officer

Evinova, a Healthtech Subsidiary of the AstraZeneca Group

There is a need to turn AI for real world example.  For example AI tools were used in clinical trials to determine patient cohorts with pneumonitis.  At Evinova they are determining how AI can hel[p show clinical benefit with respect to efficacy and safety

Joshua Boger at #JPM24 (Brian Benton Photography)

  January 12, 2024 09:06 AM ESTUpdated 10:00 AM PeopleStartups

Vertex founder Joshua Boger on surviving downturns, ‘painful’ partnerships, and the importance of culture: #JPM24

Andrew Dunn

Biopharma Correspondent

Source: https://endpts.com/jpm24-vertex-founder-joshua-boger-on-surviving-downturns-painful-partnerships-and-the-importance-of-culture/

While the JP Morgan Healthcare Conference was full of voices of measured optimism, rooting for the market to bounce back in 2024, one longtime biotech leader warned against setting any firm expectations.

Instead of predicting when the downturn may end, Vertex Pharmaceuticals founder Joshua Boger said he advises biotech leaders to expect — and plan for — volatility. Speaking Tuesday on an Endpoints News panel alongside OrbiMed’s Carl Gordon and Appia Bio CEO JJ Kang, Boger shared lessons learned on surviving downturns, striking pharma deals, and the importance of keeping a company’s culture based on his two decades of founding and leading Vertex as CEO from 1989 to 2009. The 72-year-old is now serving as executive chairman of Alkeus Pharmaceuticals, a startup developing a rare disease drug.

“I never experienced a straight line up,” Boger said. “Everything had its cycles, and it was how you respond to the cycle, not by predicting when the end is going to be, but just by responding to the present situation.”

At Boger’s first appearance at the JP Morgan conference in 1991, he said the conference’s theme was the end of biotech financing. Just a few months later, Regeneron successfully went public, rapidly changing the outlook for the whole field.

“We had no idea we were ever going to take public money,” he said. “When Regeneron did their IPO, we went, ‘Whoa, there’s something happening here,’ and we pivoted quickly.”

Vertex went public later that year. Throughout his 20-year tenure, Boger said no pharma company ever made an acquisition offer for Vertex, which now commands a market value of $110 billion and recently won the first FDA approval for a CRISPR gene editing therapy.

“We had an uber corporate policy to always make ourselves more expensive than anyone would stomach,” Boger said.

However, Vertex did strike a range of partnerships with Big Pharmas, which Boger described as a painful but necessary part of running a biotech startup.

“It’s impossible for a partnership not to slow you down,” he said. “You can and should try as hard as you can not to do that, but just count on it. They’ll slow you down.”

Boger said startups should insist on being equal partners in pharma deals, at least making sure they have a seat at a partner’s development meetings.

“Realize they’re going to be painful, it’s going to be horrible, and you need to do it,” Boger said.

While Vertex suffered through layoffs, stock price plunges, and trial failures, Boger credited a focus on culture as key to its long-term success.

“It’s the most important ingredient for a successful company,” he said. “Technology is acquirable. Culture is not acquirable. There are 10 companies that will fail because of culture for every one that succeeds, and the successful companies in retrospect will almost always have special cultural aspects that kept them through those downtimes.”

JPM24 opens with ADCs the hottest ticket in San Francisco

By Annalee ArmstrongJan 8, 2024 6:30am

Source: https://www.fiercebiotech.com/biotech/jpm24-opens-adcs-hottest-ticket-san-francisco

The overall deal flow in biopharma tapered off in 2023 but the big companies sure know what they want (what they really, really want), according to a new report from J.P. Morgan.

And that’s antibody-drug conjugates, which drove a fourth-quarter spike in licensing deal proceeds and provided a glimmer of hope to an industry battered by outside forces and grim financing prospects.

J.P. Morgan’s annual 2023 Biopharma Licensing and Venture Report arrived on the eve of the firm’s famous conference, which is set to welcome thousands of attendees in San Francisco today—East Coast weather permitting.

2023 was tough, but clinical biotechs still had a lot of opportunities to wheel and deal, according to J.P. Morgan. While licensing deals, venture investments, M&A and IPOs were down overall in the fourth quarter, deal values stayed fairly high thanks to a flurry of late-stage tie ups.

Follow the Fierce team’s coverage of the 2024 J.P. Morgan Healthcare Conference here

Biopharma licensing partnerships accounted for $63 billion in total value during the fourth quarter from 108 deals. Just one deal—Merck’s ADC partnership with Daiichi Sankyo—accounted for $22 billion of that. Another huge one was another ADC bet, with Bristol Myers Squibb signing on to work with SystImmune for a total value of $8.4 billion. If you exclude the Merck deal, the total value of these partnerships is still higher than the previous quarter, which ended with $32.1 billion.

The total number of licensing deals compares to 149 in the same quarter a year earlier, 195 for Q4 2021 and 223 for Q4 2022.

As for venture investments, the year closed out with $17 billion total across 250 rounds, thanks to $3.5 billion earned through 79 rounds in the last quarter. Aiolos Bio snagged the title of largest venture round of the quarter with $245 million, which also proved to be the largest series A, too.

There was just one IPO in all of the fourth quarter—Cargo Therapeutics making the plunge for $300 million—and 13 overall for the year. It’s a far cry from the heyday of 2021 and experts are still unsure what 2024 will hold. J.P. Morgan reported $2.5 billion raised from 12 completed biopharma IPOs for the year on Nasdaq and NYSE. Nine out of the 12 companies had clinical programs when they took the leap to the public markets. As of December 13, five of the companies were trading above their IPO price.

As for M&A, December saw a rush of Big Pharmas snapping up companies around Christmas. J.P. Morgan tallied the fourth quarter at $37.6 billion and $128.8 billion across 112 total acquisitions for all of 2023.

AbbVie was the top buyer of the quarter with the two largest acquisitions thanks to the $10 billion outlay for ImmunoGen and $8.7 billion buy of Cerevel Therapeutics.

All of this adds up to 270 total deals in the fourth quarter total, which is lower than the third quarter which exceeded 300.

J.P. Morgan sees some big potential for smaller biopharmas looking for licensing partners, as Big Pharmas have been handing out larger upfront payments for the deals they really want.

Cancer was once again the most in-demand therapeutic areas, reaching a new height of $86.1 billion in 2023. Followed by $21.1 billion for neurological disorders.

For More Articles on Real Time Conference Coverage in this Open Access Scientific Journal see:

Part One: The Process of Real Time Coverage using Social Media

Part Two: List of BioTech Conferences 2013 to Present

https://worldmedicalinnovation.org/

https://pharmaceuticalintelligence.com/2022/05/01/2022-world-medical-innovation-forum-gene-cell-therapy-may-2-4-2022-boston-in-person/

 

https://event.technologyreview.com/emtech-digital-2022/agenda-overview

 

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The Continued Impact and Possibilities of AI in Medical and Pharmaceutical Industry Practices

Reporter: Adam P. Tubman, MSc Biotechnology, Research Associate 3, Computer Graphics and AI in Drug Discovery

 

Researchers have been able to discover many ways to incorporate AI into the practices of healthcare, both in terms of medical healthcare and also in pharmaceutical drug development. For example, given the situation where a doctor provides an inaccurate diagnosis to a patient because the doctor had an incomplete or inaccurate medical record/history, AI presents a solution that has the potential to rapidly and correctly account for human error and predict the correct diagnosis based on the patterns identified in other patient’s medical history to disease diagnosis indication. In the pharmaceutical industry, companies are changing and expanding approaches to drug discovery and development given the possibilities that AI can offer. One company, Reverie Labs, located in Cambridge, MA, is a pharmaceutical company utilizing AI for application of machine learning and computational chemistry to discover new possible compounds to be used in the development of cancer treatments.

Today, AI uses have had many other applications in medicine including managing healthcare data and performing robotic surgery, both of which transform the in-person patient and doctor experience. AI has even been used to change in-person cancer patient experiences. For example, Freenome, a company in San Francisco, CA uses AI in initial screenings, blood tests and diagnostic tests when a patient is being initially tested for cancer. The hope is that this technology will aide in speeding up cancer diagnoses and lead to new treatment developments.

The future will continue to bring many possibilities of AI, provided an acceptable level of accuracy is still maintained by AI technologies and that the technology remains beneficial. If research continues to focus on diagnosing diseases at a faster rate given the potential human errors in having an inaccurate or incomplete medical record upon diagnosis, AI could provide an improved experience for patients given the quicker diagnosis and treatment combined with less time spent either treating the wrong underlying condition or not knowing what condition to treat when accounting for an incomplete medical record. If this technology is proven to be successful not just in theory, but in practice, technology would then be available and could be beneficially applied to all diagnoses and treatment plans, across the world.

However, the reality regarding AI development is that its evolution depends on how much human effort is involved in its development. Therefore, the world won’t know or see the full benefits of AI until it is developed and actively applied. Similarly, the impact that AI will have in medical and pharmaceutical practices won’t be known until scientists fully develop and apply the technologies. Many possibilities, including a possible drastic lowering of the cost for pharmaceutical drugs across the board once drugs are much more readily discovered and produced, may carry a profound benefit to patients who currently struggle to afford their own treatment plans. Additionally, unforeseen advances in the medicinal and pharmaceutical fields because of AI development will lead to unforeseen effects on the global economy and many other life changing variables for the entire world.

For more information on this topic, please check out the article below.

SOURCE

Daley, S. (2018). Artificial Intelligence in healthcare: 39 examples Improving the Future of Medicine. Built In. https://builtin.com/artificial-intelligence/artificial-intelligence-healthcare

Read Full Post »

The Use of ChatGPT in the World of BioInformatics and Cancer Research and Development of BioGPT by MIT

Curator: Stephen J. Williams, Ph.D.

Chatbots are being used in multiple interdisciplanary areas in research and medicine and so it was a natural progression to incorporate artificial intelligence (AI), natural language processing (NLP), and chatbot technology like ChatGPT into bioinformatic analysis.

“In domains like informatics, management and marketing, media and communication science, languages and philosophy, psychology and sociology, engineering, design, and human-computer interaction, the fast expanding body of chatbot study is clearly interdisciplinary.

The field of bioinformatics is a natural fit for incorporting this technology.  The curated information below shows some use examples of this technology in bioinformatics related to cancer research.

The text in this reference source was actually generated by ChatGPT (https://chat.openai.com/chat)

Source: https://omicstutorials.com/using-chatgpt-in-bioinformatics-and-biomedical-research/

How ChatGPT can be used in bioinformatics research?
ChatGPT is a variant of the GPT (Generative Pre-trained Transformer) language model that was designed to generate human-like text in a conversational setting. It is not directly related to bioinformatics, which is the field of study that deals with the storage, retrieval, and analysis of biological data, particularly in the context of genetics and genomics. However, ChatGPT could potentially be used in a bioinformatics context as a tool for generating natural language descriptions of genetic or genomic data, or for generating responses to queries about such data.

For example, a researcher could use ChatGPT to generate descriptions of genetic variants or gene expression patterns based on input data. This could be useful for generating summaries of results for reports or papers, or for generating explanations of complex concepts for non-expert audiences. ChatGPT could also be used to generate responses to queries about genetic or genomic data, such as “What is the function of gene X?” or “What are the potential consequences of variant Y?”

It’s worth noting that ChatGPT is just one of many tools and techniques that can be used in bioinformatics, and it is unlikely to be the most suitable or effective option in every situation. There are many specialized tools and resources available for working with biological data, and it is often necessary to use a combination of these tools to fully analyze and understand the data.

Generating descriptions of genetic or genomic data: ChatGPT could be used to generate natural language descriptions of genetic or genomic data based on input data. For example, suppose a researcher has a dataset containing information about gene expression levels in different tissues. The researcher could use ChatGPT to generate a description of the data, such as:
“Gene X is highly expressed in the liver and kidney, with moderate expression in the brain and heart. Gene Y, on the other hand, shows low expression in all tissues except for the lung, where it is highly expressed.”

 

Thereby ChatGPT, at its simplest level, could be used to ask general questions like “What is the function of gene product X?” and a ChatGPT could give a reasonable response without the scientist having to browse through even highly curated databases lie GeneCards or UniProt or GenBank.  Or even “What are potential interactors of Gene X, validated by yeast two hybrid?” without even going to the curated InterActome databases or using expensive software like Genie.

Summarizing results: ChatGPT could be used to generate summaries of results from genetic or genomic studies. For example, a researcher might use ChatGPT to generate a summary of a study that found a association between a particular genetic variant and a particular disease. The summary might look something like this:
“Our study found that individuals with the variant form of gene X are more likely to develop disease Y. Further analysis revealed that this variant is associated with changes in gene expression that may contribute to the development of the disease.”

It’s worth noting that ChatGPT is just one tool that could potentially be used in these types of applications, and it is likely to be most effective when used in combination with other bioinformatics tools and resources. For example, a researcher might use ChatGPT to generate a summary of results, but would also need to use other tools to analyze the data and confirm the findings.

ChatGPT is a variant of the GPT (Generative Pre-training Transformer) language model that is designed for open-domain conversation. It is not specifically designed for generating descriptions of genetic variants or gene expression patterns, but it can potentially be used for this purpose if you provide it with a sufficient amount of relevant training data and fine-tune it appropriately.

To use ChatGPT to generate descriptions of genetic variants or gene expression patterns, you would first need to obtain a large dataset of examples of descriptions of genetic variants or gene expression patterns. You could use this dataset to fine-tune the ChatGPT model on the task of generating descriptions of genetic variants or gene expression patterns.

Here’s an example of how you might use ChatGPT to generate a description of a genetic variant:

First, you would need to pre-process your dataset of descriptions of genetic variants to prepare it for use with ChatGPT. This might involve splitting the descriptions into individual sentences or phrases, and encoding them using a suitable natural language processing (NLP) library or tool.

Next, you would need to fine-tune the ChatGPT model on the task of generating descriptions of genetic variants. This could involve using a tool like Hugging Face’s Transformers library to load the ChatGPT model and your pre-processed dataset, and then training the model on the task of generating descriptions of genetic variants using an appropriate optimization algorithm.

Once the model has been fine-tuned, you can use it to generate descriptions of genetic variants by providing it with a prompt or seed text and asking it to generate a response. For example, you might provide the model with the prompt “Generate a description of a genetic variant associated with increased risk of breast cancer,” and ask it to generate a response. The model should then generate a description of a genetic variant that is associated with increased risk of breast cancer.

It’s worth noting that generating high-quality descriptions of genetic variants or gene expression patterns is a challenging task, and it may be difficult to achieve good results using a language model like ChatGPT without a large amount of relevant training data and careful fine-tuning.

 

To train a language model like chatGPT to extract information about specific genes or diseases from research papers, you would need to follow these steps:

Gather a large dataset of research papers that contain information about the specific genes or diseases you are interested in. This dataset should be diverse and representative of the types of papers you want the model to be able to extract information from.

Preprocess the text data in the research papers by tokenizing the text and creating a vocabulary. You may also want to consider lemmatizing or stemming the text to reduce the dimensionality of the dataset.

Train the language model on the preprocessed text data. You may want to fine-tune a pre-trained model such as chatGPT on your specific dataset, or you can train a new model from scratch.

ChatGPT could also be useful for sequence analysis

A few examples of sequence analysis a ChatGPT could be useful include:

  1. Protein structure
  2. Identifying functional regions of a protein
  3. Predicting protein-protein interactions
  4. Identifying protein homologs
  5. Generating Protein alignments

All this could be done without having access to UNIX servers or proprietary software or knowing GCG coding

ChatGPT in biomedical research
There are several potential ways that ChatGPT or other natural language processing (NLP) models could be applied in biomedical research:

Text summarization: ChatGPT or other NLP models could be used to summarize large amounts of text, such as research papers or clinical notes, in order to extract key information and insights more quickly.

Data extraction: ChatGPT or other NLP models could be used to extract structured data from unstructured text sources, such as research papers or clinical notes. For example, the model could be trained to extract information about specific genes or diseases from research papers, and then used to create a database of this information for further analysis.

Literature review: ChatGPT or other NLP models could be used to assist with literature review tasks, such as identifying relevant papers, extracting key information from papers, or summarizing the main findings of a group of papers.

Predictive modeling: ChatGPT or other NLP models could be used to build predictive models based on large amounts of text data, such as electronic health records or research papers. For example, the model could be trained to predict the likelihood of a patient developing a particular disease based on their medical history and other factors.

It’s worth noting that while NLP models like ChatGPT have the potential to be useful tools in biomedical research, they are only as good as the data they are trained on, and it is important to carefully evaluate the quality and reliability of any results generated by these models.

 

ChatGPT in text mining of biomedical data
ChatGPT could potentially be used for text mining in the biomedical field in a number of ways. Here are a few examples:

Extracting information from scientific papers: ChatGPT could be trained on a large dataset of scientific papers in the biomedical field, and then used to extract specific pieces of information from these papers, such as the names of compounds, their structures, and their potential uses.

Generating summaries of scientific papers: ChatGPT could be used to generate concise summaries of scientific papers in the biomedical field, highlighting the main findings and implications of the research.

Identifying trends and patterns in scientific literature: ChatGPT could be used to analyze large datasets of scientific papers in the biomedical field and identify trends and patterns in the data, such as emerging areas of research or common themes among different papers.

Generating questions for further research: ChatGPT could be used to suggest questions for further research in the biomedical field based on existing scientific literature, by identifying gaps in current knowledge or areas where further investigation is needed.

Generating hypotheses for scientific experiments: ChatGPT could be used to generate hypotheses for scientific experiments in the biomedical field based on existing scientific literature and data, by identifying potential relationships or associations that could be tested in future research.

 

PLEASE WATCH VIDEO

 

In this video, a bioinformatician describes the ways he uses ChatGPT to increase his productivity in writing bioinformatic code and conducting bioinformatic analyses.

He describes a series of uses of ChatGPT in his day to day work as a bioinformatian:

  1. Using ChatGPT as a search engine: He finds more useful and relevant search results than a standard Google or Yahoo search.  This saves time as one does not have to pour through multiple pages to find information.  However, a caveat is ChatGPT does NOT return sources, as highlighted in previous postings on this page.  This feature of ChatGPT is probably why Microsoft bought OpenAI in order to incorporate ChatGPT in their Bing search engine, as well as Office Suite programs

 

  1. ChatGPT to help with coding projects: Bioinformaticians will spend multiple hours searching for and altering open access available code in order to run certain function like determining the G/C content of DNA (although there are many UNIX based code that has already been established for these purposes). One can use ChatGPT to find such a code and then assist in debugging that code for any flaws

 

  1. ChatGPT to document and add coding comments: When writing code it is useful to add comments periodically to assist other users to determine how the code works and also how the program flow works as well, including returned variables.

 

One of the comments was interesting and directed one to use BIOGPT instead of ChatGPT

 

@tzvi7989

1 month ago (edited)

0:54 oh dear. You cannot use chatgpt like that in Bioinformatics as it is rn without double checking the info from it. You should be using biogpt instead for paper summarisation. ChatGPT goes for human-like responses over precise information recal. It is quite good for debugging though and automating boring awkward scripts

So what is BIOGPT?

BioGPT https://github.com/microsoft/BioGPT

 

The BioGPT model was proposed in BioGPT: generative pre-trained transformer for biomedical text generation and mining by Renqian Luo, Liai Sun, Yingce Xia, Tao Qin, Sheng Zhang, Hoifung Poon and Tie-Yan Liu. BioGPT is a domain-specific generative pre-trained Transformer language model for biomedical text generation and mining. BioGPT follows the Transformer language model backbone, and is pre-trained on 15M PubMed abstracts from scratch.

The abstract from the paper is the following:

Pre-trained language models have attracted increasing attention in the biomedical domain, inspired by their great success in the general natural language domain. Among the two main branches of pre-trained language models in the general language domain, i.e. BERT (and its variants) and GPT (and its variants), the first one has been extensively studied in the biomedical domain, such as BioBERT and PubMedBERT. While they have achieved great success on a variety of discriminative downstream biomedical tasks, the lack of generation ability constrains their application scope. In this paper, we propose BioGPT, a domain-specific generative Transformer language model pre-trained on large-scale biomedical literature. We evaluate BioGPT on six biomedical natural language processing tasks and demonstrate that our model outperforms previous models on most tasks. Especially, we get 44.98%, 38.42% and 40.76% F1 score on BC5CDR, KD-DTI and DDI end-to-end relation extraction tasks, respectively, and 78.2% accuracy on PubMedQA, creating a new record. Our case study on text generation further demonstrates the advantage of BioGPT on biomedical literature to generate fluent descriptions for biomedical terms.

Tips:

  • BioGPT is a model with absolute position embeddings so it’s usually advised to pad the inputs on the right rather than the left.
  • BioGPT was trained with a causal language modeling (CLM) objective and is therefore powerful at predicting the next token in a sequence. Leveraging this feature allows BioGPT to generate syntactically coherent text as it can be observed in the run_generation.py example script.
  • The model can take the past_key_values (for PyTorch) as input, which is the previously computed key/value attention pairs. Using this (past_key_values or past) value prevents the model from re-computing pre-computed values in the context of text generation. For PyTorch, see past_key_values argument of the BioGptForCausalLM.forward() method for more information on its usage.

This model was contributed by kamalkraj. The original code can be found here.

 

This repository contains the implementation of BioGPT: Generative Pre-trained Transformer for Biomedical Text Generation and Mining, by Renqian Luo, Liai Sun, Yingce Xia, Tao Qin, Sheng Zhang, Hoifung Poon and Tie-Yan Liu. BioGPT is a github which is being developed by MIT in collaboration with Microsoft. It is based on Python.

License

BioGPT is MIT-licensed. The license applies to the pre-trained models as well.

Contributing

This project welcomes contributions and suggestions. Most contributions require you to agree to a Contributor License Agreement (CLA) declaring that you have the right to, and actually do, grant us the rights to use your contribution. For details, visit https://cla.opensource.microsoft.com.

When you submit a pull request, a CLA bot will automatically determine whether you need to provide a CLA and decorate the PR appropriately (e.g., status check, comment). Simply follow the instructions provided by the bot. You will only need to do this once across all repos using our CLA.

This project has adopted the Microsoft Open Source Code of Conduct. For more information see the Code of Conduct FAQ or contact opencode@microsoft.com with any additional questions or comments.

As of right now this does not seem Open Access, however a sign up is required!

We provide our pre-trained BioGPT model checkpoints along with fine-tuned checkpoints for downstream tasks, available both through URL download as well as through the Hugging Face 🤗 Hub.

Model Description URL 🤗 Hub
BioGPT Pre-trained BioGPT model checkpoint link link
BioGPT-Large Pre-trained BioGPT-Large model checkpoint link link
BioGPT-QA-PubMedQA-BioGPT Fine-tuned BioGPT for question answering task on PubMedQA link
BioGPT-QA-PubMedQA-BioGPT-Large Fine-tuned BioGPT-Large for question answering task on PubMedQA link
BioGPT-RE-BC5CDR Fine-tuned BioGPT for relation extraction task on BC5CDR link
BioGPT-RE-DDI Fine-tuned BioGPT for relation extraction task on DDI link
BioGPT-RE-DTI Fine-tuned BioGPT for relation extraction task on KD-DTI link
BioGPT-DC-HoC Fine-tuned BioGPT for document classification task on HoC link

 

So far as to date (6/12/2023) there are three papers referencing BioGPT on PubMed (abstracts and links below)

 

BioGPT: generative pre-trained transformer for biomedical text generation and mining.

Luo R, Sun L, Xia Y, Qin T, Zhang S, Poon H, Liu TY.Brief Bioinform. 2022 Nov 19;23(6):bbac409. doi: 10.1093/bib/bbac409.PMID: 36156661

We evaluate BioGPT on six biomedical natural language processing tasks and demonstrate that our model outperforms previous models on most tasks. …Our case study on text generation further demonstrates the advantage of BioGPT on biomedical literature to generate fl …

Here they show the advantages of BioGPT over BioBERT and ChatGPT in an example of text extraction and question answer

Table 7. Example of generated text

Input                                           Model                 Text

Bicalutamide                               GPT-2                 Bicalutamide, a synthetic bicalutamide derivative, was found to increase the cellular proliferation

of C. elegans cells. This effect was not observed with the other synthetic bicalutamide derivatives. This is in line with our previous work which showed that bicalutamide increases the proliferation of C. elegans cells but not in the presence of synthetic bicalutamide.

BioGPT             Bicalutamide (Casodex) is an androgen receptor (AR) antagonist approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on or are ineligible for docetaxel chemotherapy, as well as for the treatment of early-stage prostate cancer in men who have not progressed on or are ineligible for docetaxel chemotherapy, as well as for the treatment of metastatic castration-sensitive prostate cancer (mCSPC) in men who have not progressed on or are ineligible for docetaxel chemotherapy.

Janus kinase 3 (JAK-3)                 GPT-2               Janus kinase 3 (JAK-3) mediates the conversion of glucose to glycogen in skeletal muscle. The
increase in glucose uptake by skeletal muscle is believed to be associated with a reduction in muscle protein breakdown and with the release of ketone bodies, which contribute to the metabolism of glucose.

BioGPT             Janus kinase 3 (JAK-3) is a member of the Janus kinase (JAK) family of non-receptor tyrosine kinases and plays an important role in the regulation of cell proliferation, differentiation, survival, migration and angiogenesis.

Apricitabine                                 GPT-2               Apricitabine, duloxetine and citalopram) were investigated in patients with a history of
treatment-resistant depression (n = 10). We found that treatment with the three drugs significantly decreased depressive symptoms, but not depressive symptoms over the next 12 weeks. We conclude that antidepressant drugs that reduce depressive symptoms and reduce depressive symptoms over time may be beneficial in patients with recurrent depression.

BioGPT             Apricitabine is an oral prodrug of 5-aza-2 ’-deoxycytidine (5-aza-CdR), a DNA methyltransferase (DNMT) inhibitor, which has been approved by the US Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) in combination with low-dose cytarabine (Ara-C) and granulocyte colony-stimulating factor (G-CSF) for patients with intermediate-2 or high-risk MDS or AML.

Xylazine                                      GPT-2               Xylazine, the ‘active ingredient’ in ‘bath salts’ (see above) has been linked to numerous deaths,
including those of former University of California, Berkeley, professor Andrew Anglin, who posted

a video of himself having a bath filled with it.

BioGPT             Xylazine is an alpha 2-adrenoceptor agonist which has been used as a sedative and analgesic in veterinary medicine for many years, but its effects on the cardiovascular system have not been extensively studied in the dog, and its effects on the central nervous system (CNS) have not been well characterized in the dog, despite the fact that xylazine has been widely used as a sedative and analgesic in veterinary medicine for more than 30 years.

Psoralen                                      GPT-2               Psoralen, the city of the spiritualist, and had been given to him by God, who wished to show him
the way of salvation, and to draw him back to the true life of Christ, and to bring him into communion with his fellow-man.

BioGPT             Psoralen photochemotherapy (PUVA) is a well-established treatment for psoriasis, but its use is limited by the risk of skin cancer, particularly squamous cell carcinoma (SCC) of the head and neck (H & N), which is the most common site of skin cancer in the United States (US)

CP-673451                                  GPT-2                 CP-673451) and 4-5-6-3-1-2-3-4-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-22-23-24-25-26-27-

28-29-30-31-32-33-34-35-36-37-38-39-40-41-42-43-44-45-46-47-48-49-50…

BioGPT             CP-673451 is a potent, selective, and orally active inhibitor of human neutrophil elastase (HNE) and human cathepsin G (CatG) with in vitro and in vivo anti-inflammatory activity in a variety of animal models of inflammation and in a model of acute lung injury (ALI) in the rat induced by intratracheal instillation of lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha), a model of acute lung injury (ALI) in which neutrophils play an important role.

BIIB-021                                     GPT-2               BIIB-021A-2-1.pdf. Wright, C. (2002). ‘The War on Terror: A Legal Theory of Terrorist Attacks,’ in
L.E.R. Wright, S.R. Warrick and J.H. Rothman (Eds.), The War on Terror: Essays in Honor of Michael T. Klare (New York: Oxford University Press), 143-57.

BioGPT             BIIB-021 is a novel, orally active, non-peptide bradykinin B2 receptor antagonist with potent and long-lasting anti-inflammatory activity in animal models of acute and chronic inflammation and in a rat model of adjuvant-induced arthritis (AIA), an animal model of rheumatoid arthritis (RA) and in a rat model of collagen-induced arthritis (CIA), an animal model of collagen-induced arthritis (CIA), in which arthritis is induced by immunization with bovine type II collagen (CII).

Note how BioGPT is more descriptive and accurate!

EGFI: drug-drug interaction extraction and generation with fusion of enriched entity and sentence information.

Huang L, Lin J, Li X, Song L, Zheng Z, Wong KC.Brief Bioinform. 2022 Jan 17;23(1):bbab451. doi: 10.1093/bib/bbab451.PMID: 34791012

The rapid growth in literature accumulates diverse and yet comprehensive biomedical knowledge hidden to be mined such as drug interactions. However, it is difficult to extract the heterogeneous knowledge to retrieve or even discover the latest and novel knowledge in an efficient manner. To address such a problem, we propose EGFI for extracting and consolidating drug interactions from large-scale medical literature text data. Specifically, EGFI consists of two parts: classification and generation. In the classification part, EGFI encompasses the language model BioBERT which has been comprehensively pretrained on biomedical corpus. In particular, we propose the multihead self-attention mechanism and packed BiGRU to fuse multiple semantic information for rigorous context modeling. In the generation part, EGFI utilizes another pretrained language model BioGPT-2 where the generation sentences are selected based on filtering rules.

Results: We evaluated the classification part on ‘DDIs 2013’ dataset and ‘DTIs’ dataset, achieving the F1 scores of 0.842 and 0.720 respectively. Moreover, we applied the classification part to distinguish high-quality generated sentences and verified with the existing growth truth to confirm the filtered sentences. The generated sentences that are not recorded in DrugBank and DDIs 2013 dataset demonstrated the potential of EGFI to identify novel drug relationships.

Availability: Source code are publicly available at https://github.com/Layne-Huang/EGFI.

 

GeneGPT: Augmenting Large Language Models with Domain Tools for Improved Access to Biomedical Information.

Jin Q, Yang Y, Chen Q, Lu Z.ArXiv. 2023 May 16:arXiv:2304.09667v3. Preprint.PMID: 37131884 Free PMC article.

While large language models (LLMs) have been successfully applied to various tasks, they still face challenges with hallucinations. Augmenting LLMs with domain-specific tools such as database utilities can facilitate easier and more precise access to specialized knowledge. In this paper, we present GeneGPT, a novel method for teaching LLMs to use the Web APIs of the National Center for Biotechnology Information (NCBI) for answering genomics questions. Specifically, we prompt Codex to solve the GeneTuring tests with NCBI Web APIs by in-context learning and an augmented decoding algorithm that can detect and execute API calls. Experimental results show that GeneGPT achieves state-of-the-art performance on eight tasks in the GeneTuring benchmark with an average score of 0.83, largely surpassing retrieval-augmented LLMs such as the new Bing (0.44), biomedical LLMs such as BioMedLM (0.08) and BioGPT (0.04), as well as GPT-3 (0.16) and ChatGPT (0.12). Our further analyses suggest that: (1) API demonstrations have good cross-task generalizability and are more useful than documentations for in-context learning; (2) GeneGPT can generalize to longer chains of API calls and answer multi-hop questions in GeneHop, a novel dataset introduced in this work; (3) Different types of errors are enriched in different tasks, providing valuable insights for future improvements.

PLEASE WATCH THE FOLLOWING VIDEOS ON BIOGPT

This one entitled

Microsoft’s BioGPT Shows Promise as the Best Biomedical NLP

 

gives a good general description of this new MIT/Microsoft project and its usefullness in scanning 15 million articles on PubMed while returning ChatGPT like answers.

 

Please note one of the comments which is VERY IMPORTANT


@rufus9322

2 months ago

bioGPT is difficult for non-developers to use, and Microsoft researchers seem to default that all users are proficient in Python and ML.

 

Much like Microsoft Azure it seems this BioGPT is meant for developers who have advanced programming skill.  Seems odd then to be paying programmers multiK salaries when one or two Key Opinion Leaders from the medical field might suffice but I would be sure Microsoft will figure this out.

 

ALSO VIEW VIDEO

 

 

This is a talk from Microsoft on BioGPT

 

Other Relevant Articles on Natural Language Processing in BioInformatics, Healthcare and ChatGPT for Medicine on this Open Access Scientific Journal Include

Medicine with GPT-4 & ChatGPT
Explanation on “Results of Medical Text Analysis with Natural Language Processing (NLP) presented in LPBI Group’s NEW GENRE Edition: NLP” on Genomics content, standalone volume in Series B and NLP on Cancer content as Part B New Genre Volume 1 in Series C

Proposal for New e-Book Architecture: Bi-Lingual eTOCs, English & Spanish with NLP and Deep Learning results of Medical Text Analysis – Phase 1: six volumes

From High-Throughput Assay to Systems Biology: New Tools for Drug Discovery

Machine Learning (ML) in cancer prognosis prediction helps the researcher to identify multiple known as well as candidate cancer diver genes

 

20 articles in Natural Language Processing

142 articles in BioIT: BioInformatics

111 articles in BioIT: BioInformatics, NGS, Clinical & Translational, Pharmaceutical R&D Informatics, Clinical Genomics, Cancer Informatics

 

Read Full Post »

Artificial Intelligence (AI) Used to Successfully Determine Most Likely Repurposed Antibiotic Against Deadly Superbug Acinetobacter baumanni

Reporter: Stephen J. Williams, Ph.D.

The World Health Organization has identified 3 superbugs, or infective micororganisms displaying resistance to common antibiotics and multidrug resistance, as threats to humanity:

Three bacteria were listed as critical:

  • Acinetobacter baumannii bacteria that are resistant to important antibiotics called carbapenems. Acinetobacter baumannii are highly-drug resistant bacteria that can cause a range of infections for hospitalized patients, including pneumonia, wound, or blood infections.
  • Pseudomonas aeruginosa, which are resistant to carbapenems. Pseudomonas aeruginosa can cause skin rashes and ear infectious in healthy people but also severe blood infections and pneumonia when contracted by sick people in the hospital.
  • Enterobacteriaceae — a family of bacteria that live in the human gut — that are resistant to both carbepenems and another class of antibiotics, cephalosporins.

 

It has been designated critical need for development of  antibiotics to these pathogens.  Now researchers at Mcmaster University and others in the US had used artificial intelligence (AI) to screen libraries of over 7,000 chemicals to find a drug that could be repurposed to kill off the pathogen.

Liu et. Al. (1) published their results of an AI screen to narrow down potential chemicals that could work against Acinetobacter baumanii in Nature Chemical Biology recently.

Abstract

Acinetobacter baumannii is a nosocomial Gram-negative pathogen that often displays multidrug resistance. Discovering new antibiotics against A. baumannii has proven challenging through conventional screening approaches. Fortunately, machine learning methods allow for the rapid exploration of chemical space, increasing the probability of discovering new antibacterial molecules. Here we screened ~7,500 molecules for those that inhibited the growth of A. baumannii in vitro. We trained a neural network with this growth inhibition dataset and performed in silico predictions for structurally new molecules with activity against A. baumannii. Through this approach, we discovered abaucin, an antibacterial compound with narrow-spectrum activity against A. baumannii. Further investigations revealed that abaucin perturbs lipoprotein trafficking through a mechanism involving LolE. Moreover, abaucin could control an A. baumannii infection in a mouse wound model. This work highlights the utility of machine learning in antibiotic discovery and describes a promising lead with targeted activity against a challenging Gram-negative pathogen.

Schematic workflow for incorporation of AI for antibiotic drug discovery for A. baumannii from 1. Liu, G., Catacutan, D.B., Rathod, K. et al. Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii. Nat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01349-8

Figure source: https://www.nature.com/articles/s41589-023-01349-8

Article Source: https://www.nature.com/articles/s41589-023-01349-8

  1. Liu, G., Catacutan, D.B., Rathod, K. et al.Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumanniiNat Chem Biol (2023). https://doi.org/10.1038/s41589-023-01349-8

 

 

For reference to WHO and lists of most pathogenic superbugs see https://www.scientificamerican.com/article/who-releases-list-of-worlds-most-dangerous-superbugs/

The finding was first reported by the BBC.

Source: https://www.bbc.com/news/health-65709834

By James Gallagher

Health and science correspondent

Scientists have used artificial intelligence (AI) to discover a new antibiotic that can kill a deadly species of superbug.

The AI helped narrow down thousands of potential chemicals to a handful that could be tested in the laboratory.

The result was a potent, experimental antibiotic called abaucin, which will need further tests before being used.

The researchers in Canada and the US say AI has the power to massively accelerate the discovery of new drugs.

It is the latest example of how the tools of artificial intelligence can be a revolutionary force in science and medicine.

Stopping the superbugs

Antibiotics kill bacteria. However, there has been a lack of new drugs for decades and bacteria are becoming harder to treat, as they evolve resistance to the ones we have.

More than a million people a year are estimated to die from infections that resist treatment with antibiotics.The researchers focused on one of the most problematic species of bacteria – Acinetobacter baumannii, which can infect wounds and cause pneumonia.

You may not have heard of it, but it is one of the three superbugs the World Health Organization has identified as a “critical” threat.

It is often able to shrug off multiple antibiotics and is a problem in hospitals and care homes, where it can survive on surfaces and medical equipment.

Dr Jonathan Stokes, from McMaster University, describes the bug as “public enemy number one” as it’s “really common” to find cases where it is “resistant to nearly every antibiotic”.

 

Artificial intelligence

To find a new antibiotic, the researchers first had to train the AI. They took thousands of drugs where the precise chemical structure was known, and manually tested them on Acinetobacter baumannii to see which could slow it down or kill it.

This information was fed into the AI so it could learn the chemical features of drugs that could attack the problematic bacterium.

The AI was then unleashed on a list of 6,680 compounds whose effectiveness was unknown. The results – published in Nature Chemical Biology – showed it took the AI an hour and a half to produce a shortlist.

The researchers tested 240 in the laboratory, and found nine potential antibiotics. One of them was the incredibly potent antibiotic abaucin.

Laboratory experiments showed it could treat infected wounds in mice and was able to kill A. baumannii samples from patients.

However, Dr Stokes told me: “This is when the work starts.”

The next step is to perfect the drug in the laboratory and then perform clinical trials. He expects the first AI antibiotics could take until 2030 until they are available to be prescribed.

Curiously, this experimental antibiotic had no effect on other species of bacteria, and works only on A. baumannii.

Many antibiotics kill bacteria indiscriminately. The researchers believe the precision of abaucin will make it harder for drug-resistance to emerge, and could lead to fewer side-effects.

 

In principle, the AI could screen tens of millions of potential compounds – something that would be impractical to do manually.

“AI enhances the rate, and in a perfect world decreases the cost, with which we can discover these new classes of antibiotic that we desperately need,” Dr Stokes told me.

The researchers tested the principles of AI-aided antibiotic discovery in E. coli in 2020, but have now used that knowledge to focus on the big nasties. They plan to look at Staphylococcus aureus and Pseudomonas aeruginosa next.

“This finding further supports the premise that AI can significantly accelerate and expand our search for novel antibiotics,” said Prof James Collins, from the Massachusetts Institute of Technology.

He added: “I’m excited that this work shows that we can use AI to help combat problematic pathogens such as A. baumannii.”

Prof Dame Sally Davies, the former chief medical officer for England and government envoy on anti-microbial resistance, told Radio 4’s The World Tonight: “We’re onto a winner.”

She said the idea of using AI was “a big game-changer, I’m thrilled to see the work he (Dr Stokes) is doing, it will save lives”.

Other related articles and books published in this Online Scientific Journal include the following:

Series D: e-Books on BioMedicine – Metabolomics, Immunology, Infectious Diseases, Reproductive Genomic Endocrinology

(3 book series: Volume 1, 2&3, 4)

https://www.amazon.com/gp/product/B08VVWTNR4?ref_=dbs_p_pwh_rwt_anx_b_lnk&storeType=ebooks

 

 

 

 

 

 

 

 

 

 

  • The Immune System, Stress Signaling, Infectious Diseases and Therapeutic Implications:

 

  • Series D, VOLUME 2

Infectious Diseases and Therapeutics

and

  • Series D, VOLUME 3

The Immune System and Therapeutics

(Series D: BioMedicine & Immunology) Kindle Edition.

On Amazon.com since September 4, 2017

(English Edition) Kindle Edition – as one Book

https://www.amazon.com/dp/B075CXHY1B $115

 

Bacterial multidrug resistance problem solved by a broad-spectrum synthetic antibiotic

The Journey of Antibiotic Discovery

FDA cleared Clever Culture Systems’ artificial intelligence tech for automated imaging, analysis and interpretation of microbiology culture plates speeding up Diagnostics

Artificial Intelligence: Genomics & Cancer

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

The female reproductive lifespan is regulated by the menstrual cycle. Defined as the interval between the menarche and menopause, it is approximately 35 years in length on average. Based on current average human life expectancy figures, and excluding fertility issues, this means that the female body can bear children for almost half of its lifetime. Thus, within this time span many individuals may consider contraception at some point in their reproductive life. A wide variety of contraceptive methods are now available, which are broadly classified into hormonal and non-hormonal approaches. A normal menstrual cycle is controlled by a delicate interplay of hormones, including estrogen, progesterone, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), among others. These molecules are produced by the various glands in the body that make up the endocrine system.

Hormonal contraceptives – including the contraceptive pill, some intrauterine devices (IUDs) and hormonal implants – utilize exogenous (or synthetic) hormones to block or suppress ovulation, the phase of the menstrual cycle where an egg is released into the uterus. Beyond their use as methods to prevent pregnancy, hormonal contraceptives are also being increasingly used to suppress ovulation as a method for treating premenstrual syndromes. Hormonal contraceptives composed of exogenous estrogen and/or progesterone are commonly administered artificial means of birth control. Despite many benefits, adverse side effects associated with high doses such as thrombosis and myocardial infarction, cause hesitation to usage.

Scientists at the University of the Philippines and Roskilde University are exploring methods to optimize the dosage of exogenous hormones in such contraceptives. Their overall aim is the creation of patient-specific minimizing dosing schemes, to prevent adverse side effects that can be associated with hormonal contraceptive use and empower individuals in their contraceptive journey. Their research data showed evidence that the doses of exogenous hormones in certain contraceptive methods could be reduced, while still ensuring ovulation is suppressed. Reducing the total exogenous hormone dose by 92% in estrogen-only contraceptives, or the total dose by 43% in progesterone-only contraceptives, prevented ovulation according to the model. In contraceptives combining estrogen and progesterone, the doses could be reduced further.

References:

https://www.technologynetworks.com/drug-discovery/news/hormone-doses-in-contraceptives-could-be-reduced-by-as-much-as-92-372088?utm_campaign=NEWSLETTER_TN_Breaking%20Science%20News

https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1010073

https://www.medicalnewstoday.com/articles/birth-control-with-up-to-92-lower-hormone-doses-could-still-be-effective

https://www.ncbi.nlm.nih.gov/books/NBK441576/

https://www.sciencedirect.com/science/article/pii/S0277953621005797

Read Full Post »

Verily announced other organizational changes, 1/13/2023

Reporter: Aviva Lev-Ari, PhD, RN

The layoffs come just a few months after Verily raised $1 billion in an investment round led by Alphabet. At the time of the investment round, Verily said the $1 billion would be used to expand its business in precision health. 

In addition to the layoffs, Verily announced other organizational changes.

“We are making changes that refine our strategy, prioritize our product portfolio and simplify our operating model,” Gillett said in his email. “We will advance fewer initiatives with greater resources. In doing so, Verily will move from multiple lines of business to one centralized product organization with increasingly connected healthcare solutions.”

The company will specifically focus on AI and data science to accelerate learning and improving outcomes, with advancing precision health being the top overarching goal. In addition, the company will simplify how it works, “designing complexity out of Verily.” 

Among its product portfolio, Verily plans to “do fewer things” and focus its efforts within research and care. The company is “discontinuing the development of Verily Value Suite and some early-stage products, including our work in remote patient monitoring for heart failure and microneedles for drug delivery,” Gillet said. By eliminating Verily Value Suite, some staff will be redeployed elsewhere, while others will leave the company, Gillet said.

The 15% of eliminated staff include roles within discontinued programs and redundancy within the new, simplified organization. Gillet also announced leadership changes, including expanding the role of Amy Abernethy to become president of product development and chief medical officer. Scott Burke will expand his responsibilities as chief technology officer, adding hardware engineering and devices teams to his responsibilities, as well as serving as the bridge between product development and customer needs. Lisa Greenbaum will expand her responsibilities in a new chief commercial officer role, overseeing sales, marketing and corporate strategy teams.

Related Content

Google Health partners with iCAD in commercial AI imaging push
Former Google company Verily raises $1B
Google Health is no more?
Google’s Verily enters drug trials with big pharma
Google, Verily’s diabetes machine learning algorithm gets clinical testing
Walgreens teams up with Verily to tackle chronic conditions

SOURCE

https://healthexec.com/topics/patient-care/precision-medicine/verily-lays-15-workers-months-after-raising-1b?utm_source=newsletter&utm_medium=he_news

Read Full Post »

Use of Systems Biology for Design of inhibitor of Galectins as Cancer Therapeutic – Strategy and Software

 

 

Curator: Stephen J. Williams, Ph.D.

Below is a slide representation of the overall mission 4 to produce a PROTAC to inhibit Galectins 1, 3, and 9.

 

Using A Priori Knowledge of Galectin Receptor Interaction to Create a BioModel of Galectin 3 Binding

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Now after collecting literature from PubMed on “galectin-3” AND “binding” to determine literature containing kinetic data we generate a WordCloud on the articles.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

This following file contains the articles needed for BioModels generation.

https://pharmaceuticalintelligence.com/wp-content/uploads/2022/12/Curating-Galectin-articles-for-Biomodels.docx

 

From the WordCloud we can see that these corpus of articles describe galectin binding to the CRD (carbohydrate recognition domain).  Interestingly there are many articles which describe van Der Waals interactions as well as electrostatic interactions.  Certain carbohydrate modifictions like Lac NAc and Gal 1,4 may be important.  Many articles describe the bonding as well as surface  interactions.  Many studies have been performed with galectin inhibitors like TDGs (thio-digalactosides) like TAZ TDG (3-deoxy-3-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside).  This led to an interesting article

Dual thio-digalactoside-binding modes of human galectins as the structural basis for the design of potent and selective inhibitors

Affiliations 2016 Jul 15;6:29457.
 doi: 10.1038/srep29457. Free PMC article

Abstract

Human galectins are promising targets for cancer immunotherapeutic and fibrotic disease-related drugs. We report herein the binding interactions of three thio-digalactosides (TDGs) including TDG itself, TD139 (3,3′-deoxy-3,3′-bis-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside, recently approved for the treatment of idiopathic pulmonary fibrosis), and TAZTDG (3-deoxy-3-(4-[m-fluorophenyl]-1H-1,2,3-triazol-1-yl)-thio-digalactoside) with human galectins-1, -3 and -7 as assessed by X-ray crystallography, isothermal titration calorimetry and NMR spectroscopy. Five binding subsites (A-E) make up the carbohydrate-recognition domains of these galectins. We identified novel interactions between an arginine within subsite E of the galectins and an arene group in the ligands. In addition to the interactions contributed by the galactosyl sugar residues bound at subsites C and D, the fluorophenyl group of TAZTDG preferentially bound to subsite B in galectin-3, whereas the same group favored binding at subsite E in galectins-1 and -7. The characterised dual binding modes demonstrate how binding potency, reported as decreased Kd values of the TDG inhibitors from μM to nM, is improved and also offer insights to development of selective inhibitors for individual galectins.

Figures

Figure 1
 
Figure 2
 
Figure 3

 

 

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Genomic data can predict miscarriage and IVF failure

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Infertility is a major reproductive health issue that affects about 12% of women of reproductive age in the United States. Aneuploidy in eggs accounts for a significant proportion of early miscarriage and in vitro fertilization failure. Recent studies have shown that genetic variants in several genes affect chromosome segregation fidelity and predispose women to a higher incidence of egg aneuploidy. However, the exact genetic causes of aneuploid egg production remain unclear, making it difficult to diagnose infertility based on individual genetic variants in mother’s genome. Although, age is a predictive factor for aneuploidy, it is not a highly accurate gauge because aneuploidy rates within individuals of the same age can vary dramatically.

Researchers described a technique combining genomic sequencing with machine-learning methods to predict the possibility a woman will undergo a miscarriage because of egg aneuploidy—a term describing a human egg with an abnormal number of chromosomes. The scientists were able to examine genetic samples of patients using a technique called “whole exome sequencing,” which allowed researchers to home in on the protein coding sections of the vast human genome. Then they created software using machine learning, an aspect of artificial intelligence in which programs can learn and make predictions without following specific instructions. To do so, the researchers developed algorithms and statistical models that analyzed and drew inferences from patterns in the genetic data.

As a result, the scientists were able to create a specific risk score based on a woman’s genome. The scientists also identified three genes—MCM5, FGGY and DDX60L—that when mutated and are highly associated with a risk of producing eggs with aneuploidy. So, the report demonstrated that sequencing data can be mined to predict patients’ aneuploidy risk thus improving clinical diagnosis. The candidate genes and pathways that were identified in the present study are promising targets for future aneuploidy studies. Identifying genetic variations with more predictive power will serve women and their treating clinicians with better information.

References:

https://medicalxpress-com.cdn.ampproject.org/c/s/medicalxpress.com/news/2022-06-miscarriage-failure-vitro-fertilization-genomic.amp

https://pubmed.ncbi.nlm.nih.gov/35347416/

https://pubmed.ncbi.nlm.nih.gov/31552087/

https://pubmed.ncbi.nlm.nih.gov/33193747/

https://pubmed.ncbi.nlm.nih.gov/33197264/

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Will Web 3.0 Do Away With Science 2.0? Is Science Falling Behind?

Curator: Stephen J. Williams, Ph.D.

UPDATED 4/06/2022

A while back (actually many moons ago) I had put on two posts on this site:

Scientific Curation Fostering Expert Networks and Open Innovation: Lessons from Clive Thompson and others

Twitter is Becoming a Powerful Tool in Science and Medicine

Each of these posts were on the importance of scientific curation of findings within the realm of social media and the Web 2.0; a sub-environment known throughout the scientific communities as Science 2.0, in which expert networks collaborated together to produce massive new corpus of knowledge by sharing their views, insights on peer reviewed scientific findings. And through this new media, this process of curation would, in itself generate new ideas and new directions for research and discovery.

The platform sort of looked like the image below:

 

This system lied above a platform of the original Science 1.0, made up of all the scientific journals, books, and traditional literature:

In the old Science 1.0 format, scientific dissemination was in the format of hard print journals, and library subscriptions were mandatory (and eventually expensive). Open Access has tried to ameliorate the expense problem.

Previous image source: PeerJ.com

To index the massive and voluminous research and papers beyond the old Dewey Decimal system, a process of curation was mandatory. The dissemination of this was a natural for the new social media however the cost had to be spread out among numerous players. Journals, faced with the high costs of subscriptions and their only way to access this new media as an outlet was to become Open Access, a movement first sparked by journals like PLOS and PeerJ but then begrudingly adopted throughout the landscape. But with any movement or new adoption one gets the Good the Bad and the Ugly (as described in my cited, above, Clive Thompson article). The bad side of Open Access Journals were

  1. costs are still assumed by the individual researcher not by the journals
  2. the arise of the numerous Predatory Journals

 

Even PeerJ, in their column celebrating an anniversary of a year’s worth of Open Access success stories, lamented the key issues still facing Open Access in practice

  • which included the cost and the rise of predatory journals.

In essence, Open Access and Science 2.0 sprung full force BEFORE anyone thought of a way to defray the costs

 

Can Web 3.0 Finally Offer a Way to Right the Issues Facing High Costs of Scientific Publishing?

What is Web 3.0?

From Wikipedia: https://en.wikipedia.org/wiki/Web3

Web 1.0 and Web 2.0 refer to eras in the history of the Internet as it evolved through various technologies and formats. Web 1.0 refers roughly to the period from 1991 to 2004, where most websites were static webpages, and the vast majority of users were consumers, not producers, of content.[6][7] Web 2.0 is based around the idea of “the web as platform”,[8] and centers on user-created content uploaded to social-networking services, blogs, and wikis, among other services.[9] Web 2.0 is generally considered to have begun around 2004, and continues to the current day.[8][10][4]

Terminology[edit]

The term “Web3”, specifically “Web 3.0”, was coined by Ethereum co-founder Gavin Wood in 2014.[1] In 2020 and 2021, the idea of Web3 gained popularity[citation needed]. Particular interest spiked towards the end of 2021, largely due to interest from cryptocurrency enthusiasts and investments from high-profile technologists and companies.[4][5] Executives from venture capital firm Andreessen Horowitz travelled to Washington, D.C. in October 2021 to lobby for the idea as a potential solution to questions about Internet regulation with which policymakers have been grappling.[11]

Web3 is distinct from Tim Berners-Lee‘s 1999 concept for a semantic web, which has also been called “Web 3.0”.[12] Some writers referring to the decentralized concept usually known as “Web3” have used the terminology “Web 3.0”, leading to some confusion between the two concepts.[2][3] Furthermore, some visions of Web3 also incorporate ideas relating to the semantic web.[13][14]

Concept[edit]

Web3 revolves around the idea of decentralization, which proponents often contrast with Web 2.0, wherein large amounts of the web’s data and content are centralized in the fairly small group of companies often referred to as Big Tech.[4]

Specific visions for Web3 differ, but all are heavily based in blockchain technologies, such as various cryptocurrencies and non-fungible tokens (NFTs).[4] Bloomberg described Web3 as an idea that “would build financial assets, in the form of tokens, into the inner workings of almost anything you do online”.[15] Some visions are based around the concepts of decentralized autonomous organizations (DAOs).[16] Decentralized finance (DeFi) is another key concept; in it, users exchange currency without bank or government involvement.[4] Self-sovereign identity allows users to identify themselves without relying on an authentication system such as OAuth, in which a trusted party has to be reached in order to assess identity.[17]

Reception[edit]

Technologists and journalists have described Web3 as a possible solution to concerns about the over-centralization of the web in a few “Big Tech” companies.[4][11] Some have expressed the notion that Web3 could improve data securityscalability, and privacy beyond what is currently possible with Web 2.0 platforms.[14] Bloomberg states that sceptics say the idea “is a long way from proving its use beyond niche applications, many of them tools aimed at crypto traders”.[15] The New York Times reported that several investors are betting $27 billion that Web3 “is the future of the internet”.[18][19]

Some companies, including Reddit and Discord, have explored incorporating Web3 technologies into their platforms in late 2021.[4][20] After heavy user backlash, Discord later announced they had no plans to integrate such technologies.[21] The company’s CEO, Jason Citron, tweeted a screenshot suggesting it might be exploring integrating Web3 into their platform. This led some to cancel their paid subscriptions over their distaste for NFTs, and others expressed concerns that such a change might increase the amount of scams and spam they had already experienced on crypto-related Discord servers.[20] Two days later, Citron tweeted that the company had no plans to integrate Web3 technologies into their platform, and said that it was an internal-only concept that had been developed in a company-wide hackathon.[21]

Some legal scholars quoted by The Conversation have expressed concerns over the difficulty of regulating a decentralized web, which they reported might make it more difficult to prevent cybercrimeonline harassmenthate speech, and the dissemination of child abuse images.[13] But, the news website also states that, “[decentralized web] represents the cyber-libertarian views and hopes of the past that the internet can empower ordinary people by breaking down existing power structures.” Some other critics of Web3 see the concept as a part of a cryptocurrency bubble, or as an extension of blockchain-based trends that they see as overhyped or harmful, particularly NFTs.[20] Some critics have raised concerns about the environmental impact of cryptocurrencies and NFTs. Others have expressed beliefs that Web3 and the associated technologies are a pyramid scheme.[5]

Kevin Werbach, author of The Blockchain and the New Architecture of Trust,[22] said that “many so-called ‘web3’ solutions are not as decentralized as they seem, while others have yet to show they are scalable, secure and accessible enough for the mass market”, adding that this “may change, but it’s not a given that all these limitations will be overcome”.[23]

David Gerard, author of Attack of the 50 Foot Blockchain,[24] told The Register that “web3 is a marketing buzzword with no technical meaning. It’s a melange of cryptocurrencies, smart contracts with nigh-magical abilities, and NFTs just because they think they can sell some monkeys to morons”.[25]

Below is an article from MarketWatch.com Distributed Ledger series about the different forms and cryptocurrencies involved

From Marketwatch: https://www.marketwatch.com/story/bitcoin-is-so-2021-heres-why-some-institutions-are-set-to-bypass-the-no-1-crypto-and-invest-in-ethereum-other-blockchains-next-year-11639690654?mod=home-page

by Frances Yue, Editor of Distributed Ledger, Marketwatch.com

Clayton Gardner, co-CEO of crypto investment management firm Titan, told Distributed Ledger that as crypto embraces broader adoption, he expects more institutions to bypass bitcoin and invest in other blockchains, such as Ethereum, Avalanche, and Terra in 2022. which all boast smart-contract features.

Bitcoin traditionally did not support complex smart contracts, which are computer programs stored on blockchains, though a major upgrade in November might have unlocked more potential.

“Bitcoin was originally seen as a macro speculative asset by many funds and for many it still is,” Gardner said. “If anything solidifies its use case, it’s a store of value. It’s not really used as originally intended, perhaps from a medium of exchange perspective.”

For institutions that are looking for blockchains that can “produce utility and some intrinsic value over time,” they might consider some other smart contract blockchains that have been driving the growth of decentralized finance and web 3.0, the third generation of the Internet, according to Gardner. 

Bitcoin is still one of the most secure blockchains, but I think layer-one, layer-two blockchains beyond Bitcoin, will handle the majority of transactions and activities from NFT (nonfungible tokens) to DeFi,“ Gardner said. “So I think institutions see that and insofar as they want to put capital to work in the coming months, I think that could be where they just pump the capital.”

Decentralized social media? 

The price of Decentralized Social, or DeSo, a cryptocurrency powering a blockchain that supports decentralized social media applications, surged roughly 74% to about $164 from $94, after Deso was listed at Coinbase Pro on Monday, before it fell to about $95, according to CoinGecko.

In the eyes of Nader Al-Naji, head of the DeSo foundation, decentralized social media has the potential to be “a lot bigger” than decentralized finance.

“Today there are only a few companies that control most of what we see online,” Al-Naji told Distributed Ledger in an interview. But DeSo is “creating a lot of new ways for creators to make money,” Al-Naji said.

“If you find a creator when they’re small, or an influencer, you can invest in that, and then if they become bigger and more popular, you make money and they make and they get capital early on to produce their creative work,” according to AI-Naji.

BitClout, the first application that was created by AI-Naji and his team on the DeSo blockchain, had initially drawn controversy, as some found that they had profiles on the platform without their consent, while the application’s users were buying and selling tokens representing their identities. Such tokens are called “creator coins.”

AI-Naji responded to the controversy saying that DeSo now supports more than 200 social-media applications including Bitclout. “I think that if you don’t like those features, you now have the freedom to use any app you want. Some apps don’t have that functionality at all.”

 

But Before I get to the “selling monkeys to morons” quote,

I want to talk about

THE GOOD, THE BAD, AND THE UGLY

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

THE GOOD

My foray into Science 2.0 and then pondering what the movement into a Science 3.0 led me to an article by Dr. Vladimir Teif, who studies gene regulation and the nucleosome, as well as creating a worldwide group of scientists who discuss matters on chromatin and gene regulation in a journal club type format.

For more information on this Fragile Nucleosome journal club see https://generegulation.org/fragile-nucleosome/.

Fragile Nucleosome is an international community of scientists interested in chromatin and gene regulation. Fragile Nucleosome is active in several spaces: one is the Discord server where several hundred scientists chat informally on scientific matters. You can join the Fragile Nucleosome Discord server. Another activity of the group is the organization of weekly virtual seminars on Zoom. Our webinars are usually conducted on Wednesdays 9am Pacific time (5pm UK, 6pm Central Europe). Most previous seminars have been recorded and can be viewed at our YouTube channel. The schedule of upcoming webinars is shown below. Our third activity is the organization of weekly journal clubs detailed at a separate page (Fragile Nucleosome Journal Club).

 

His lab site is at https://generegulation.org/ but had published a paper describing what he felt what the #science2_0 to #science3_0 transition would look like (see his blog page on this at https://generegulation.org/open-science/).

This concept of science 3.0 he had coined back in 2009.  As Dr Teif had mentioned

So essentially I first introduced this word Science 3.0 in 2009, and since then we did a lot to implement this in practice. The Twitter account @generegulation is also one of examples

 

This is curious as we still have an ill defined concept of what #science3_0 would look like but it is a good read nonetheless.

His paper,  entitled “Science 3.0: Corrections to the Science 2.0 paradigm” is on the Cornell preprint server at https://arxiv.org/abs/1301.2522 

 

Abstract

Science 3.0: Corrections to the Science 2.0 paradigm

The concept of Science 2.0 was introduced almost a decade ago to describe the new generation of online-based tools for researchers allowing easier data sharing, collaboration and publishing. Although technically sound, the concept still does not work as expected. Here we provide a systematic line of arguments to modify the concept of Science 2.0, making it more consistent with the spirit and traditions of science and Internet. Our first correction to the Science 2.0 paradigm concerns the open-access publication models charging fees to the authors. As discussed elsewhere, we show that the monopoly of such publishing models increases biases and inequalities in the representation of scientific ideas based on the author’s income. Our second correction concerns post-publication comments online, which are all essentially non-anonymous in the current Science 2.0 paradigm. We conclude that scientific post-publication discussions require special anonymization systems. We further analyze the reasons of the failure of the current post-publication peer-review models and suggest what needs to be changed in Science 3.0 to convert Internet into a large journal club. [bold face added]
In this paper it is important to note the transition of a science 1.0, which involved hard copy journal publications usually only accessible in libraries to a more digital 2.0 format where data, papers, and ideas could be easily shared among networks of scientists.
As Dr. Teif states, the term “Science 2.0” had been coined back in 2009, and several influential journals including Science, Nature and Scientific American endorsed this term and suggested scientists to move online and their discussions online.  However, even at present there are thousands on this science 2.0 platform, Dr Teif notes the number of scientists subscribed to many Science 2.0 networking groups such as on LinkedIn and ResearchGate have seemingly saturated over the years, with little new members in recent times. 
The consensus is that science 2.0 networking is:
  1. good because it multiplies the efforts of many scientists, including experts and adds to the scientific discourse unavailable on a 1.0 format
  2. that online data sharing is good because it assists in the process of discovery (can see this evident with preprint servers, bio-curated databases, Github projects)
  3. open-access publishing is beneficial because free access to professional articles and open-access will be the only publishing format in the future (although this is highly debatable as many journals are holding on to a type of “hybrid open access format” which is not truly open access
  4. only sharing of unfinished works and critiques or opinions is good because it creates visibility for scientists where they can receive credit for their expert commentary

There are a few concerns on Science 3.0 Dr. Teif articulates:

A.  Science 3.0 Still Needs Peer Review

Peer review of scientific findings will always be an imperative in the dissemination of well-done, properly controlled scientific discovery.  As Science 2.0 relies on an army of scientific volunteers, the peer review process also involves an army of scientific experts who give their time to safeguard the credibility of science, by ensuring that findings are reliable and data is presented fairly and properly.  It has been very evident, in this time of pandemic and the rapid increase of volumes of preprint server papers on Sars-COV2, that peer review is critical.  Many of these papers on such preprint servers were later either retracted or failed a stringent peer review process.

Now many journals of the 1.0 format do not generally reward their peer reviewers other than the self credit that researchers use on their curriculum vitaes.  Some journals, like the MDPI journal family, do issues peer reviewer credits which can be used to defray the high publication costs of open access (one area that many scientists lament about the open access movement; where the burden of publication cost lies on the individual researcher).

An issue which is highlighted is the potential for INFORMATION NOISE regarding the ability to self publish on Science 2.0 platforms.

 

The NEW BREED was born in 4/2012

An ongoing effort on this platform, https://pharmaceuticalintelligence.com/, is to establish a scientific methodology for curating scientific findings where one the goals is to assist to quell the information noise that can result from the massive amounts of new informatics and data occurring in the biomedical literature. 

B.  Open Access Publishing Model leads to biases and inequalities in the idea selection

The open access publishing model has been compared to the model applied by the advertising industry years ago and publishers then considered the journal articles as “advertisements”.  However NOTHING could be further from the truth.  In advertising the publishers claim the companies not the consumer pays for the ads.  However in scientific open access publishing, although the consumer (libraries) do not pay for access the burden of BOTH the cost of doing the research and publishing the findings is now put on the individual researcher.  Some of these publishing costs can be as high as $4000 USD per article, which is very high for most researchers.  However many universities try to refund the publishers if they do open access publishing so it still costs the consumer and the individual researcher, limiting the cost savings to either.  

However, this sets up a situation in which young researchers, who in general are not well funded, are struggling with the publication costs, and this sets up a bias or inequitable system which rewards the well funded older researchers and bigger academic labs.

C. Post publication comments and discussion require online hubs and anonymization systems

Many recent publications stress the importance of a post-publication review process or system yet, although many big journals like Nature and Science have their own blogs and commentary systems, these are rarely used.  In fact they show that there are just 1 comment per 100 views of a journal article on these systems.  In the traditional journals editors are the referees of comments and have the ability to censure comments or discourse.  The article laments that comments should be easy to do on journals, like how easy it is to make comments on other social sites, however scientists are not offering their comments or opinions on the matter. 

In a personal experience, 

a well written commentary goes through editors which usually reject a comment like they were rejecting an original research article.  Thus many scientists, I believe, after fashioning a well researched and referenced reply, do not get the light of day if not in the editor’s interests.  

Therefore the need for anonymity is greatly needed and the lack of this may be the hindrance why scientific discourse is so limited on these types of Science 2.0 platforms.  Platforms that have success in this arena include anonymous platforms like Wikipedia or certain closed LinkedIn professional platforms but more open platforms like Google Knowledge has been a failure.

A great example on this platform was a very spirited conversation on LinkedIn on genomics, tumor heterogeneity and personalized medicine which we curated from the LinkedIn discussion (unfortunately LinkedIn has closed many groups) seen here:

Issues in Personalized Medicine: Discussions of Intratumor Heterogeneity from the Oncology Pharma forum on LinkedIn

 

 

Issues in Personalized Medicine: Discussions of Intratumor Heterogeneity from the Oncology Pharma forum on LinkedIn

 

In this discussion, it was surprising that over a weekend so many scientists from all over the world contributed to a great discussion on the topic of tumor heterogeneity.

But many feel such discussions would be safer if they were anonymized.  However then researchers do not get any credit for their opinions or commentaries.

A Major problem is how to take the intangible and make them into tangible assets which would both promote the discourse as well as reward those who take their time to improve scientific discussion.

This is where something like NFTs or a decentralized network may become important!

See

https://pharmaceuticalintelligence.com/portfolio-of-ip-assets/

 

UPDATED 5/09/2022

Below is an online @TwitterSpace Discussion we had with some young scientists who are just starting out and gave their thoughts on what SCIENCE 3.0 and the future of dissemination of science might look like, in light of this new Meta Verse.  However we have to define each of these terms in light of Science and not just the Internet as merely a decentralized marketplace for commonly held goods.

This online discussion was tweeted out and got a fair amount of impressions (60) as well as interactors (50).

 For the recording on both Twitter as well as on an audio format please see below

<blockquote class=”twitter-tweet”><p lang=”en” dir=”ltr”>Set a reminder for my upcoming Space! <a href=”https://t.co/7mOpScZfGN”>https://t.co/7mOpScZfGN</a&gt; <a href=”https://twitter.com/Pharma_BI?ref_src=twsrc%5Etfw”>@Pharma_BI</a&gt; <a href=”https://twitter.com/PSMTempleU?ref_src=twsrc%5Etfw”>@PSMTempleU</a&gt; <a href=”https://twitter.com/hashtag/science3_0?src=hash&amp;ref_src=twsrc%5Etfw”>#science3_0</a&gt; <a href=”https://twitter.com/science2_0?ref_src=twsrc%5Etfw”>@science2_0</a></p>&mdash; Stephen J Williams (@StephenJWillia2) <a href=”https://twitter.com/StephenJWillia2/status/1519776668176502792?ref_src=twsrc%5Etfw”>April 28, 2022</a></blockquote> <script async src=”https://platform.twitter.com/widgets.js&#8221; charset=”utf-8″></script>

 

 

To introduce this discussion first a few startoff material which will fram this discourse

 






The Intenet and the Web is rapidly adopting a new “Web 3.0” format, with decentralized networks, enhanced virtual experiences, and greater interconnection between people. Here we start the discussion what will the move from Science 2.0, where dissemination of scientific findings was revolutionized and piggybacking on Web 2.0 or social media, to a Science 3.0 format. And what will it involve or what paradigms will be turned upside down?

Old Science 1.0 is still the backbone of all scientific discourse, built on the massive amount of experimental and review literature. However this literature was in analog format, and we moved to a more accesible digital open access format for both publications as well as raw data. However as there was a structure for 1.0, like the Dewey decimal system and indexing, 2.0 made science more accesible and easier to search due to the newer digital formats. Yet both needed an organizing structure; for 1.0 that was the scientific method of data and literature organization with libraries as the indexers. In 2.0 this relied on an army mostly of volunteers who did not have much in the way of incentivization to co-curate and organize the findings and massive literature.

Each version of Science has their caveats: their benefits as well as deficiencies. This curation and the ongoing discussion is meant to solidy the basis for the new format, along with definitions and determination of structure.

We had high hopes for Science 2.0, in particular the smashing of data and knowledge silos. However the digital age along with 2.0 platforms seemed to excaccerbate this somehow. We still are critically short on analysis!

 

We really need people and organizations to get on top of this new Web 3.0 or metaverse so the similar issues do not get in the way: namely we need to create an organizing structure (maybe as knowledgebases), we need INCENTIVIZED co-curators, and we need ANALYSIS… lots of it!!

Are these new technologies the cure or is it just another headache?

 

There were a few overarching themes whether one was talking about AI, NLP, Virtual Reality, or other new technologies with respect to this new meta verse and a concensus of Decentralized, Incentivized, and Integrated was commonly expressed among the attendees

The Following are some slides from representative Presentations

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Other article of note on this topic on this Open Access Scientific Journal Include:

Electronic Scientific AGORA: Comment Exchanges by Global Scientists on Articles published in the Open Access Journal @pharmaceuticalintelligence.com – Four Case Studies

eScientific Publishing a Case in Point: Evolution of Platform Architecture Methodologies and of Intellectual Property Development (Content Creation by Curation) Business Model 

e-Scientific Publishing: The Competitive Advantage of a Powerhouse for Curation of Scientific Findings and Methodology Development for e-Scientific Publishing – LPBI Group, A Case in Point

@PharmaceuticalIntelligence.com –  A Case Study on the LEADER in Curation of Scientific Findings

Real Time Coverage @BIOConvention #BIO2019: Falling in Love with Science: Championing Science for Everyone, Everywhere

Old Industrial Revolution Paradigm of Education Needs to End: How Scientific Curation Can Transform Education

 

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