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Human Behavior

Delhi HC directs IHBAS to expeditiously fill vacancies of doctors, faculty – Devdiscourse

The Institute of Human Behavior and Allied Sciences (IHBAS) on Wednesday submitted before the Delhi High Court, which was hearing a public interest litigation (PIL) seeking directions to fill the pending vacancies, that it has started the process of recruitment of doctors and faculties. A division bench of Chief Justice DN Patel and Justice Prateek Jalan, however, directed IHBAS to complete the process expeditiously and disposed of the PIL seeking directions to fill the pending vacancies of faculty and medical staff in order to tackle the rise in the Psychiatric and Psychological cases in the country more effectively.

The plea, filed by social activist advocate Amit Sahni, said that the shortage of doctors and medical staff at IHBAS is a matter of serious concern and the responsible respondents have completely failed to tackle the same since long. Advocate Devender Verma, appearing for the Delhi government, apprise the court that the IHBAS has on September 1 already issued a notification regarding the fulfillments of 45 posts of doctors and facilities.

The plea also sought directions to the respondents to redress the promotion related issues and other inconvenience faced by the doctors/faculty of IHBAS to curtail the increasing number of resignations of faculty numbers as it alleged that the respondents have also failed to redress the issue of non-promotion of the faculty posted at IHBAS and the doctors and healthcare professionals working at IHBAS have not been promoted for the last 10 years. Sahni, through the plea, also mentioned that IHBAS at present working with a faculty of 25 faculty against 103 faculty members and added that the shortage of faculty has arisen since several years and the issues of the doctors and faculty members.

It mentioned that India's coronavirus crisis has pushed millions into forced isolation and unemployment, due to which anxiety, depression and suicide are on the rise and that mental health could be the country's next crisis. "There is no health without mental health underlines the fact that mental health is an integral and essential component of health. Mental health, hitherto neglected, is now recognised as a critical requirement and is engaging the attention of policy-makers, professionals and communities in India and across the globe," the plea said. (ANI)

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Human Behavior

Yet Another Article about Information Technology and the Character of War – War on the Rocks

The Maginot Line was arguably the most sophisticated system of fortifications in history. Kilometers thick at points, it had observation posts, anti-tank ditches, fortresses with retractable turrets, flood zones, and thousands of bunkers. Contrary to the way it is often described in history books, it wasnt irrelevant. It blocked an invasion route through northern France, including and especially Alsace-Lorraine, which France had fought for at great cost. It simply wasnt as relevant, or relevant in the way its designers intended, after the character of war changed.

War has an unchanging nature. War is violent, interactive, and fundamentally political. Wars character, by contrast, changes, and reflects how technology, law, ethics, and many other factors influence combatants use of violence to create political outcomes. The character of war is a semi-regular topic of discussion among military theorists, and one that has an unfortunate tendency to descend into esoteric arguments that are fascinating to a small number of people. But debates over the character of war might be more important than they have been in decades. The evolving nature of information technology and its use by militaries may change the character of war. If and when this takes place, competence in and even mastery of some previous ways of war will become less relevant. Failure to lead the next change to the character of war could result in the U.S. militarys advantages in training, resources, and technology quickly diminishing or disappearing altogether.

Changes to the Character of War in History

The French Revolutionary and Napoleonic Wars saw a shift from limited wars of maneuver by professional armies to decisive battles fought, in many cases, by massive armies driven by nationalism. One of the first indications of this shift took place at the Battle of Valmy. The Prussian army fought a mostly cautious battle, then withdrew rather than risk their expensive soldiers. The French army, by contrast, showed the first signs that they would replace the caution of 18th century warfare with the rapid movement, decisive battle, and willingness to absorb casualties that would come to define Revolutionary and Napoleonic warfare. Both sides claimed victory. While the Prussian leaders were not exactly wrong to do so, the changing character of war was already invalidating their perspective and creating defeat out of what seemed to be a victory.

What was foreshadowed at Valmy became reality during Napoleons campaigns. Both the size of armies and the casualties from battle increased quickly. Prior to the French Revolution, battles rarely involved more than 100,000 combatants. By Napoleons final defeat in 1815, the largest battles had more than 500,000 combatants and more than 100,000 casualties. Battle also became far more decisive. By 1805, Napoleons defeat of an Austrian and Russian army at Austerlitz caused the dissolution of the Holy Roman Empire and the end of the Third Coalition against France. A short time later, Prussias crushing losses at Jena and Auerstedt resulted in its subjugation for nearly seven years.

More than 130 years later, the Battle of France served as an abrupt notice of another change to the character of war. French forces rather famously prepared for a repeat of 1918s Western Front, complete with the Maginot Lines massive fortifications, centralized control, and armored support to infantry formations. By 1940, the French army was broadly considered the best in Europe and was prepared to defeat the German forces if they tried to reenact the Schlieffen Plan. Unfortunately for them, their preparations were no longer relevant. German forces employed concentrated and fast-moving armor, aircraft observation, and bombing. They proved able to coordinate operations over the radio to increase their speed and reach, outpacing their opponents both physically and mentally. The German forces swept those of the French aside not because the latter failed to fight well, but because they fought using tactics that had lost much of their relevance since the end of World War I.

Both of the cases above show that a failure to adapt to or even predict a change in the character of war can be catastrophic. Armies that once excelled become far less effective without losing any of their expertise. In both cases, competence in a new way of fighting became more important than expertise in the previous ways of war.

Information Technology and the Character of War

Napoleonic warfare found agrarian societies pitting their armies and, at its pinnacle, most of their resources against one another. Similarly, World War II showed the devastation that industrial nations could produce. The four possibilities below explore how information technology may affect the character of war.

Autonomy

Many conversations about information technology, especially AI, in national defense and national security focus on autonomy. Militaries may be able to digitize and automate key bottlenecks in operations, allowing them to make decisions and act at machine speeds and at greater scale. At slower speeds, staffs and commanders will need less time to process data and generate options, and will have more time to consider their choices. At faster speeds, algorithms will make decisions at a rate humans cannot comprehend. In these cases, a militarys ability to create software that responds effectively and to delegate authority to it appropriately will be as important as any other warfighting skill.

Systems with autonomous components may also change the relationship between humans and machines. Rather than have many humans in charge of one machine, one human may direct many machines, or a small number of humans may direct many machines that will in turn direct even more humans. This would allow militaries to have unprecedented ubiquity of sensors and weapon systems, and extremely fast targeting. While an increase in weapon lethality might shorten war, it might also make it difficult for adversaries with autonomous capabilities to employ tactics that require large formations to maneuver, which are typically a key component of decisive victories.

Autonomy, with all of its potential, is a worthwhile pursuit. Most of its possible benefits, however, are closely tied to the American militarys current advantages in logistics, intelligence collection, and precision strike. While autonomy may change the way in which wars are fought, the U.S. military should not stop with autonomy. It is likely that other applications of information technology will produce more qualitative changes, and an accompanying loss of relevance for militaries that do not change quickly enough.

Softwares Acceleration of Adaptation

Militaries ability to quickly adapt software may soon become a key component of their ability to compete. Modern militaries are reliant on software as much as hardware software helps collect intelligence, creates common operating pictures, and helps service members interact with one another. Software can also play a more active role by guiding weapons, or by actually being a weapon in the case of cyber attacks.

One consequence of softwares increasing importance is that tactical adaptation will include, and in some cases require, software changes. Weapon guidance systems will need to better track adversaries using new camouflage, control systems will need to respond slightly faster to outpace enemies, and electronic warfare platforms will need to better affect enemy systems. This will be especially true as systems with autonomous capabilities begin to play a larger role.

Engineers can develop and implement software updates far more quickly than new hardware is designed, manufactured, and distributed. This is especially true when engineers are enabled by AI. While hardware is constrained by physical limits, such as the speed of shipping, engineers can update or even create new programs as quickly as they can type and verify code. Imagine weapon adaptation taking place at the speed that Silicon Valley can produce software updates instead of in the time required to produce and ship new military hardware. Twenty years ago, a ship departing the United States for a combat zone arrived in theater with the same capabilities as it had when it departed. Soon, a ship that receives updates to its electronic warfare suite and the programs that control its autonomous and automatic systems will have different capabilities when it arrives in theater than when it departed the United States.

The acceleration of adaptation may change the character of warfare in two ways. The first is to increase the importance of learning. While organizational learning is important today, once it takes place at machine speeds, organizations that collect useful data and learn more quickly than their adversaries will be able to overcome significant disadvantages, and those that learn slowly will perform poorly. Phrased differently, militaries build combat power today by building mass and seizing advantageous terrain. As adaptation rates accelerate, militaries will also increase their relative combat power by establishing effective, software-enabled learning systems, collecting data and feeding it into those systems, and denying their adversaries the ability to collect relevant, legitimate data.

Second, rapid adaptation may reduce the role of continuity in warfare. Today, and in previous conflicts, there existed a high probability of continuity from one battle to the next. Adaptation at the rates described above would reduce continuity. If this takes place, militaries that do not develop the technology and processes to adapt at machine speeds will find themselves frequently surprised by their adversaries capabilities even adversaries they have previously fought.

Infrastructure as a Weapon System

The use of infrastructure as a weapon system may also change the character of war. Infrastructure will become increasingly vulnerable to abuse as it becomes more autonomous and more automated. Infrastructure becomes a weapon system when hostile actors deliberately use air and ground traffic systems, electrical grids, water systems, and communications infrastructure to coerce or compel. This differs from attacks on infrastructure, where hostile actors destroy infrastructure to coerce or compel. The use of infrastructure as a weapon system might be as irritating as creating traffic jams, rolling power outages, or interruptions in connectivity. It might also be as damaging as flooding communities, electrical grid fires, or crashing aircraft.

The widespread use of infrastructure as a weapon system would be a qualitative change to warfare. The employment of force for strategic effect is ultimately about forcing an adversarial political group to act in a manner that better aligns with ones interests by threatening or making vulnerable its political base. Traditionally, this has revolved around the direct use of force by one armed group against either another armed group or a civilian population. This has been equally true for forms of warfare that differ as much as the highly conventional battlefields of the Napoleonic Wars and the irregular warfare seen in Iraq and Afghanistan. The use of infrastructure as a weapon system is a new and direct way to attack a governments political base, often without going through its military first. This would bypass battle-centric methods of achieving strategic effects, reducing the importance of battle and therefore the importance of traditional military forces like brigade combat teams, ships, and aircraft.

Individualization of War and Politics

States may also be able to achieve strategic effects by micro-targeting individuals at scale to create a specific outcome by using both lethal and non-lethal effects. Targeting is certainly not new American counterinsurgents in Iraq used social network analysis to map terrorist groups members and relationships, then target key nodes for influence or removal.

Todays technological and social landscape, however, may supercharge individual targeting. Biometric identification combined with genetic databases, facial recognition technology, gait analysis, wireless network sensors such as RF-pose, online behavior, and the growing ubiquity of sensors are making it far easier to find, analyze, and target individuals than it was just a short time ago. As machine learning-enabled analysis becomes even more sophisticated, states may be able to disrupt military operations or even achieve strategic effects in conventional conflicts by individually targeting key political and military actors. This may be much more efficient and much more difficult to counter than operations that rely on destroying part of a military, or threatening an important state resource.

Sentiment attacks are likely to be even more enhanced. The digitization of economic and social interaction increasingly allows those with access to data to map and predict human behavior. Cambridge Analytica used a version of social network analysis powered by much larger databases and machine learning to launch sentiment attacks to shift the behavior of societies. In effect, states can bypass each others militaries and directly target each others populations at the individual level to make courses of action politically unpalatable. This differs qualitatively from historic uses of propaganda that tried to achieve the same effects. Previously, propaganda existed in public, creating the opportunity for public discourse about the relative merit of different ideas. Now, significant portions of a population can be targeted with propaganda individually tailored to their personality, all without their neighbors or even family members knowing.

Discovering the Character of Future Wars

It is difficult to know the character of future wars. After all, its tough to make predictions, especially about the future. Beyond the usual challenges of prophecy, the effects of a new type of technology are only fully revealed when two well-developed forces fight each other, creating emergent effects that cannot be predicted by viewing the forces in isolation. No-one knows the system behavior that will emerge when information age forces fight each other. This is the same condition that faced European militaries in 1914 they understood the effect increasing firepower had on colonial adversaries, but did not understand that firepower and massive armies, combined with western Europes terrain, would give the defense an advantage.

To overcome the unpredictability of changes to the character of war, the United States should attempt to create the next character of war rather than just predicting it or, even worse, being a victim of it. Doing so requires rigorous experimentation at the tactical and strategic levels that produces changes to operational concepts, doctrine, the military education system, and military technology.

Experiments with software adaptation rates should figure out how quickly software can adapt if highly skilled programmers and machine learning experts with the right authorities, system access, and hardware can participate in tactical exercises. Experiments with infrastructure as a weapon system requires a more strategic approach. Wargames should explore what might happen if, during a military operation, electrical grids start mass wildfires, dams flood towns across America, and air traffic control systems begin causing accidents rather than helping avoid them. How might Americans and their political leaders react? How would these disasters affect military resources and planning? Experiments with the individualization of warfare could be the most challenging. What might happen during a training exercise if a well-resourced opposing force was allowed to target key players, unexpectedly removing them from the exercise?

Not Just Technology

The possible qualitative changes listed above focused on technology. It is worth noting that qualitative changes in warfare have rarely, if ever, come from technology changes alone. They have typically been equally or even more driven by social change. While social change is difficult to predict, today the rise of nationalism and urbanization are the most likely to impact the character of war. The extent of that impact and what it might be remains to be seen. The above list is also not an inclusive list of potential technology-based changes to the character of war. Artificial intelligence will almost certainly have impacts not anticipated here, and other types of technology, such as biotechnology or nanotechnology, may have consequences that are even more significant.

Qualitative changes to warfare have always come in the past. There is no reason to suspect this time is unique, that the current way of war is somehow permanent. What would happen if, rather than preparing to fight the war Americans expect and have prepared for, adversaries prepare to fight a type of war that invalidates or reduces American advantages? Could that result in defeat? What might be the consequences of a tactical, operational, or even strategic loss? If they are severe enough, the Department of Defense should go back and see if theres any reason to believe their assumptions about the character of war may in fact be invalid, and that a different type of war may emerge. In this case, as shown above, the potential exists.

While the United States would be foolish to abandon its current advantages, it would be just as foolish to discount possible change. Doing so will allow the American militarys strengths, just like those enjoyed by the Prussian army before the Revolutionary Wars and by the French military before 1939, to suddenly become far less relevant. The Department of Defense and the rest of the national security community need to anticipate, prepare for, and, if possible, create the next qualitative change in warfare. If they do not, someone else surely will.

Justin Lynch served as an active-duty Army officer before transitioning to the Army National Guard. As a civilian, he has served in multiple roles in the national security enterprise, including roles focused on information technology. The opinions expressed in this article are his alone, and do not represent those of any organization with which he is associated.

Image: Imperial War Museum

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Yet Another Article about Information Technology and the Character of War - War on the Rocks

Human Behavior

SIUE takes aim at racism by hiring faculty of color by the handful – Alton Telegraph

Published 12:11pm CDT, Monday, August 31, 2020

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SIUE School of Education, Health and Human Behavior new hires include, top row from left, Candace Hall, EdD, lecturer in the Department of Educational Leadership and co-director of the College Student Personnel Administration (CSPA) program; Nate Williams, PhD, associate professor in the Department of Teaching and Learnings secondary education program and pedagogical, curricular and leadership support at the SIUE East St Louis Charter High School; and Rachel Tenial, PhD, assistant professor in the Department of Psychology; bottom row from left, Cherese Fine, PhD, assistant professor in the Department of Educational Leadership; Cedric Harville, PhD, assistant professor in the Department of Applied Health; and Divah Griffin, SEHHB development officer.

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SIUE School of Education, Health and Human Behavior new hires include, top row from left, Candace Hall, EdD, lecturer in the Department of Educational Leadership and co-director of the College Student

Photo:

SIUE School of Education, Health and Human Behavior new hires include, top row from left, Candace Hall, EdD, lecturer in the Department of Educational Leadership and co-director of the College Student Personnel Administration (CSPA) program; Nate Williams, PhD, associate professor in the Department of Teaching and Learnings secondary education program and pedagogical, curricular and leadership support at the SIUE East St Louis Charter High School; and Rachel Tenial, PhD, assistant professor in the Department of Psychology; bottom row from left, Cherese Fine, PhD, assistant professor in the Department of Educational Leadership; Cedric Harville, PhD, assistant professor in the Department of Applied Health; and Divah Griffin, SEHHB development officer.

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SIUE School of Education, Health and Human Behavior new hires include, top row from left, Candace Hall, EdD, lecturer in the Department of Educational Leadership and co-director of the College Student

SIUE takes aim at racism by hiring faculty of color by the handful

EDWARDSVILLE In one small way to combat a more than 400-year-pandemic of institutionalized racism in the U.S., Southern Illinois University Edwardsville School of Education, Health and Human Behavior (SEHHB) Dean Robin Hughes, PhD, is working in a deliberate and calculated way to make her University better, stronger and more equitable by hiring a group of faculty members of color, known as cluster hires.

I thought about a request for a cluster hire of faculty of color, when I learned about strategic hiring funds during my interview visit, said Hughes. In this case, its a hiring process that recruits and hires a number of faculty of color who are experts in the fields of education, applied health and specifically psychology. We intentionally sought to hire a number of individuals to fill multiple positions in the School of Education, Health and Human Behavior.

Hughes first plans involve hiring four faculty members of color. One position is still in negotiation. The current three SEHHB cluster hires are:

Nate Williams, PhD, associate professor in the Department of Teaching and Learnings secondary education program and pedagogical, curricular and leadership support at the SIUE East St Louis Charter High School

Cherese Fine, PhD, assistant professor in the Department of Educational Leadership

Rachel Tenial, PhD, assistant professor in the Department of Psychology

The University has a commitment and strategic goal to hire faculty of color, noted Hughes. We responded to the Universitys goals.

Hughes also points to research that shows the benefits of hiring faculty of color.

Faculty of color support students growth and social well-being in myriad ways, she continued. They are role models. They increase students sense of belonging. They support student retention overall, and retention of students of color specifically.

For instance, our Department of Psychology was intentional about responding to the needs of students of color. They noted that about 20% of their students were Black, and they had no Black faculty. Psychology faculty believe it is important to hire faculty of color.

The SEHHB cluster hires were achieved through the Universitys Strategic Hiring Funds made available through the Office of the Provost and Vice Chancellor for Academic Affairs and the Office of Institutional Diversity and Inclusion.

The funds include a three-year start-up. The units are responsible for funding after that, explained Hughes. The SEHHB administrative team is well aware of the fiscal responsibility for every hire. This is nothing new to me as a leader. All hires are fiscally strategic. All hires are made to support the expertise of the unit. All hires are made to support the community.

Hughes also named three additional hires:

Cedric Harville, PhD, assistant professor in the Department of Applied Health

Candace Hall, EdD, lecturer in the Department of Educational Leadership and co-director of the College Student Personnel Administration (CSPA) program

Divah Griffin, SEHHB development officer

We deliberately recruit the most brilliant and most qualified in every candidate pool all of the time, added Hughes.

Once hiring faculty of color, a university also has to be calculating about retaining them, according to Hughes.

This means critically reviewing policies that typically drive away faculty of color, she shared. The SEHHB is working to strategically restructure these policies, among other things, to make sure that we keep people once we recruit them. For instance, when a faculty member of color goes up for tenure and has to publish in a top tier journal (which is racist in its subtext and is always ill-defined), we have to make sure that our policies are inclusive of the top tier work that they do. Not top tier according to a few people who made that decision 400 years ago when Harvard first became a university or by the current group of scholars who are affirmed and perpetuate western cannon notions of whats good and top tier.

The SEHHB dean posed a few questions for SIUE and other colleges and universities to consider in seeking to move from an exclusive mindset, practice and environment in higher education to a more inclusive one.

Specifically, in response to questions about how hiring faculty of color advances the goals of any organization, Hughes points to a counternarrative and asked, How has hiring all white or predominantly white staff and faculty improved and advanced a college or university? How has not paying attention to purposely hiring faculty and staff of color impacted your college or university?

Its 2020, and colleges and universities are just now deconstructing racist policies, Hughes. We have some catching up to do.

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SIUE takes aim at racism by hiring faculty of color by the handful - Alton Telegraph

Human Behavior

Unquestioned Trust: How the Financial Industry Can Create Secure (and Seamless) Online Banking Experiences – Banking Exchange

As their investment in digital transformation increases, banking organizations are learning a valuable lesson that all comes down to trust.

In our current pandemic era, customers are dramatically accelerating the demand for this transition. According to the World Retail Banking Report 2020 from Capgemini and Efma, 57 percent of clients surveyed now prefer (and implicitly trust) online to in-person banking (up from 49 percent pre-COVID-19) and as much as 55 percent favor using mobile banking apps (up from 47 percent). As a result of these increases, the global online banking market is expected to reach $20.5 billion by 2026, up from $9.1 billion in 2019, according to a forecast from Valuates.

At the same time, industry executives fully know and trust that hackers are increasing their interest in online banking, too, hoping to cash in on easy-money growth. Four out of five executives cite security/privacy concerns as the primary adoption obstacles to implementing a digital platform model, according to the Capgemini/Efma report. And their reservations are well-founded. Banking trojans such as Dridex, Trickbot and Ramnit are stealing account credentials, gaining remote control of infected systems, intercepting and redirecting users to hacker-controlled servers, and launching spam and malware campaigns.

In June, the FBI issued a warning about the likelihood of cyber criminals targeting mobile banking customers through malicious programs disguised as banking apps. Overall, cyber attacks against the financial sector have grown by 238 percent and ransomware incidents have spiked nine-fold since the outbreak began, according to the VMware Carbon Black, Modern Bank Heists 3.0 research report.

To counter the onslaught, banks are going beyond phishing and social-engineering-vulnerable passwords and are increasing their authentication requirements with device-level authentication. For example, if an account holder types in the right password from an IP address that also matches whats in the file, then the log-in is approved. But this isnt enough in our global, mobile, digital transformation age. Users now connect ubiquitously from multiple devices, making this device-fingerprinting and its continual verifications more cumbersome to users and less reliable for security.

Unfortunately, financial institution leaders often believe that implementing two-factor authentication with challenge questions like, Whats your favorite meal? and What city were you born in? will close the gap. But cyber criminals easily circumvent these controls. Via SIM swapping, for instance, they take control over a victims phone number by convincing the victims mobile carrier to switch their subscriber identity module (SIM) to a new SIM card located in a device under attacker control. With this, the attacker can then hijack the one-time codes sent via SMS, thus exploiting the two-factor authentication. And as for answers to personal security questions that only the legitimate user should know? The same user is literally giving these personally identifiable answers away in their daily social media posts and often within their stolen, personal emails.

Whats worse is that increasing friction into the consumer experience runs counter to the purpose of digital transformation and the goal of both secure and seamless, online banking experiences. These enhanced security measures force users to take multiple, burdensome steps to conduct their business. And when pushed too far, financial institutions start finding their services are more secure as a result of having fewer customers.

Fortunately, there is a better way. Breakthroughs in software and mobile technology are proving the reliability of using behavioral biometrics to deliver stronger, yet more user-friendly, authentication. Behavioral biometrics validates users by tracking how they physically interact with sites, apps and device interfaces whichever device the customer chooses to engage from.

Unique attributes like how an individual presses on touchscreens, moves a mouse, types on a keyboard and holds a smart phone are automatically analyzed to identify suspicious logins and nefarious activities without impacting the authentic customer experience. And because malware and bots are unable to replicate and impersonate both unique and innate human behavior, the technology can rapidly detect and alert on anomalies offering the time to quickly intervene or dramatically reduced effort to resolve fraud investigations. As a result, the interaction is more secure with the process invisible to the banking customer.

There is no turning back in the digital transformation journey. You commit. You invest. You innovate. And then you keep at it, with continuous improvement as a constant driver. And remarkably, it requires a zero-trust approach so that trust, as in human-human interactions, is continuously assessed, built, and evolved with every engagement.

Jordan Blake, BehavioSec

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Unquestioned Trust: How the Financial Industry Can Create Secure (and Seamless) Online Banking Experiences - Banking Exchange

Human Behavior

10 Books to Read About Infectious Disease & Pandemics – One Green Planet

As cases of the coronavirus pandemic continue to rise globally, books on pandemics are in high demand. From historical fiction to nitty-gritty nonfiction, books have the power to reveal important insights regarding the science behind these diseases, how people have coped with them in the past, and what we can do moving forward.

Here is a list of ten books you should read on infectious diseases.

In Spillover: Animal Infections and the Next Human Pandemic, David Quammen chronicles his travels around the world investigating the origins of past infectious disease outbreaks, including Ebola and lesser-known viruses such as Nipah. Quammen tries to show how human behavior can drive destructive zoonotic virus as animals and humans are coming in contact more and morethe spillover of deadly microbes from animals to humans becomes inevitable. Buy Spillover: Animal Infections and the Next Human Pandemic here on Amazon!

People and gorillas, horses and duikers and pigs, monkeys and chimps and bats and viruses, Quammen writes. Were all in this together.

Published in 2018, two people recall their experience on the frontline of the deadly 2014 Ebola outbreak that killed more than 11,300 people in west Africa. Oliver Johnson, a doctor, and Sinead Walsh, then Irish ambassador to Sierra Leone, expose the poor decision-making and failure of local and international leadership in responding to the outbreak. Walsh and Johnson call our attention to the immense courage of those who risked their lives every day to contain the disease. Buy Getting to Zero: A Doctor and a Diplomat on the Ebola Frontlinehere on Amazon!

Written by Laurie Garrett, a Pulitzer Prize-winning reporter, The Coming Plague details how the modern world is full of infectious diseases including HIV, Lassa, Ebola, and others. Garrett explores the conditions that led to recurrent outbreaks of new emerging diseases.

While recent scientific and technological and social developments have greatly helped society ward off disease, Garret also examines how modern science may have led to mutated old viruses, now resistant to all or most treatment, that pose a problem for future generations. Buy The Coming Plague: Newly Emerging Diseases in a World Out of Balance here on Amazon!

This New York Times Bestseller by John M. Barry dives into the 1918 Spanish flu and how it altered the course of history. The Great Influenza highlights the importance of science and truth in combating a pandemic. Buy here on Amazon!

As Barry concludes, The final lesson of 1918, a simple one yet one most difficult to execute, is thatthose in authority must retain the publics trust. The way to do that is to distort nothing, to put the best face on nothing, to try to manipulate no one. Lincoln said that first, and best. A leader must make whatever horror exists concrete. Only then will people be able to break it apart. Buy The Great Influenza: The Story of the Deadliest Pandemic in History here on Amazon!

Combining science and history, Bryn Barnard details how infectious diseases began and dramatically shaped the course of human history. From influenza to smallpox, from tuberculosis to yellow fever, she explores the causes and effects of some of the worlds deadly epidemics. Buy Outbreak! Plagues That Changed Historyhere on Amazon!

How to Survive a Plague follows the story of the grassroots activists who challenged government officials on their lack of scientific research into the AIDS epidemic. Inspired by the 2012 documentary with the same name, How to Survive a Plagueprovides an insiders account of a pivotal moment in the history of American civil rights and medical science. Buy How to Survive a Plague: The Inside Story of How Citizens and Science Tamed AIDS here on Amazon!

InThe Fever: How Malaria Has Ruled Humankind for 500,000 Years,journalist Sonia Shah delivers a riveting overview of the causes, treatments, and effects of malaria which still kills about 1 million people a year. Shah tracks the historical rise of malaria from its birth in Africa through the Industrial Revolution to current global health initiatives. Buy The Fever: How Malaria Has Ruled Humankind for 500,000 Yearshere on Amazon!

Critically acclaimed author Jim Murphy describes the spread of yellow fever and its effects on Philadelphia residents in 1793, drawing connections between 18th-century beliefs and practices to modern-day social and political events. Murphy also highlights the heroic role of Philadelphias free blacks in combating the disease and the effects of yellow fever on the Founding Fathers. Buy An American Plague: The True and Terrifying Story of the Yellow Fever Epidemic of 1793here on Amazon!

In each chapter, science and medical journalist, Madeline Drexler, takes readers through an in-depth account of different emerging diseases. Emerging Epidemics discusses the looming risks of influenza, the potential dangers of bioterrorism, and what scientists on the front-line are doing to stop these threats before its too late.

Drexler warns us that the most ceaselessly creative bioterrorist is still Mother Nature, whose microbial operatives are all around us, ready to pounce whenever conditions are right. BuyEmerging Epidemics: The Menace of New Infections here on Amazon!

Parasite Rex reveals how hidden organisms can infiltrate and control the bodies of their hosts. Through his travels, Carl Zimmer brings the reader into the world of parasites which make of the majority of lifes diversity and have the power to steer the course of evolution. As more and more diseases are transferred through species, Parasite Rex exposes the vectors of disease and teaches us how to survive in a world with these hidden yet powerful creatures. Buy Parasite Rex: Inside the Bizarre World of Natures Most Dangerous Creatureshere on Amazon!

Fictional books can also provide critical insights regarding how people handled previous infectious diseases and how we could prepare for future pandemics. Check out these historical and futuristic works of fiction on deadly diseases:

Read about the top 8 scientific, medical, and culture podcasts to help you stay updated on the coronavirus pandemic.

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10 Books to Read About Infectious Disease & Pandemics - One Green Planet

Human Behavior

Augmented Reality Market to Hit $65.22 Billion by 2027; Speedy Rise in Smartphone Usage around the World to Broaden Market Horizons: Fortune Business…

Pune, Sept. 02, 2020 (GLOBE NEWSWIRE) -- The global augmented reality market size is projected to reach USD 65.22 billion by 2027, exhibiting a CAGR of 48.3% during the forecast period. Growing presence of AR devices and solutions amid COVID-19 pandemic will create new avenue for expansion in the market, finds Fortune Business Insights in its report, titled Augmented Reality Market Size, Share & COVID-19 Impact Analysis, By Component (Hardware, and Software), By Device Type (Head Mounted Display, Heads-Up Display, Handheld Devices, Stationary AR Systems, Smart Glasses, Others), By Industry (Gaming, Media & Entertainment, Automotive, Retail, Healthcare, Education, Manufacturing, and Others), and Regional Forecast, 2020-2027.

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With large swathes of people worldwide confined to their homes to contain the spread of the coronavirus, diverse entities are looking for efficient ways to ensure continuation of work without impediments. AR technology has offered the desired solutions. For instance, first-year medical students at Clevelands Case Western Reserve University have been utilizing HoloAnatomy and HoloLens to study the human body from their homes. In May 2020, Facebook also unveiled its prototype AR and virtual reality (VR) technologies to enable employees to work from home in the long-run, even after the pandemic is over. Thus, AR is proving extremely beneficial for remote working as well as remote learning and as a result, its adoption is all set to surge not just during, but also after the COVID-19 pandemic has abated.

The report states that the global market value in 2019 stood at USD 2.82 billion and offers the following:

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Market Restraint

Potential Negative Effects of AR on Human Behavior May Slow Down Adoption

A study recently conducted by researchers at Stanford University found that after people had experienced augmented reality through computer-generated simulations, their behaviors and interactions changed in the physical world as well. The findings of the study revealed that subjects who were made to wear AR-powered goggles were unable to distinguish between the virtual world and the real world. According to the researchers, excessive usage of AR is likely to have a significant impact on the social-psychological interactions of people in real-world scenarios. Spreading awareness about this drawback of AR may restrict its adoption. In addition to this, many experts fear that overload of information may confuse and overwhelm the wearer, preventing quick decision-making, which will defeat the purpose of deploying augmented reality (AR) tools in organizations. These shortcomings may limit the augmented reality market growth in the upcoming years.

Regional Insights

Robust Investment Culture to Favor Market Growth in North America

With a market size of USD 0.92 billion in 2019, North America is slated to dominate the augmented reality market share during the forecast period. The main reason for the regions leading position is the favorable investment climate, especially in the domain of information & communication technology (ICT). Moreover, companies in the US and Canada are widening the applicability of AR in different fields, which will play a key role in the long-term development of the market.

Promising growth in the automotive, logistics, manufacturing, and gaming industries is expected to be the primary growth driver for the market in Asia Pacific. In Europe, on the other hand, proliferation of companies and start-ups specializing in AR/VR technologies, especially in the UK, is likely to propel the market in the continent.

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Competitive Landscape

Product Diversification to be the Top Growth Strategy for Key Players

Competition in the AR market is characterized by the path-breaking innovations introduced by tech giants such as Microsoft and Qualcomm. These behemoths, with their well-established presence, strong financial health, and loyal customer base, are taking constant efforts to enhance their R&D capacities to develop diversified products and broaden the scope of their proprietary offerings.

Industry Developments:

List of Key Companies Profiled in the Augmented Reality Market Report

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Detailed Table of Content

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Augmented Reality Market to Hit $65.22 Billion by 2027; Speedy Rise in Smartphone Usage around the World to Broaden Market Horizons: Fortune Business...

Cell Biology

Cancer cells reshape spread into the blood, a new study says – News Landed

Johns Hopkins Kimmel Cancer Center and Johns Hopkins University researchers recently conducted some laboratory studies about cancer. They explored how cancer cells may develop from an initial tumor to a remote site within the body, a process known as metastasis.

The scientists usedtissue engineeringto determine how groups of cells migrate to other parts of the body. They also usedtissue engineeringto build up a useful 3-D blood vessel and grewbreast cancer cellsnearby. They recognized the cancer cell falling out to the blood vessel and getting over a stretch of the cell wall. A group of tumor cells is easily released into the bloodstream to migrate to distant places. These are all happening because of the attachment to the blood vessels. Blood vessels also could constrict by the cancer cell, pull on them, or cause them to leak.

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The study was published in the journalCancer Researchpublished on July 14. Senior study author Andrew Ewald, Ph.D., co-director of the Cancer Invasion and Metastasis Program at the Johns Hopkins Kimmel Cancer Center and professor of cell biology at the Johns Hopkins University School of Medicine, said this: We observed that cancer can also rapidly reshape, destroy or integrate into existing blood vessels.

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They also organized the practice in close teamwork with the lab of Peter Searson, Ph.D., Joseph R., and Lynn C. Reynolds, Professor of Materials Science and Engineering, with collective choices in the areas of biomedical engineering, oncology, and physical medicine and rehabilitation.

Ewald says. Just as people going scuba diving versus ice climbing require different tools, cancer brings different equipment depending on the job they also intend to perform. Determining what that equipment is can help us understand how to stop cancer.

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Ewald and associates proposed to see groups of eight to 10 cells, allowing a tumor, moving through a protein wall and crushing between blood vessel walls to travel. We never saw that, What we kept seeing instead was that a piece of an existing tumor would take over a neighboring blood vessel wall, putting cells in direct contact with the circulation, and that the cancer cells could do so in a matter of hours. They didnt have to invade past the blood vessels; they became the blood vessels, and could just release cancer cells there.

The 3-D model changed to study added features of the tumor microenvironment or to examine alternate cancer types, Ewald says.

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Cancer cells reshape spread into the blood, a new study says - News Landed

Cell Biology

New targeted therapy approaches win Rain Therapeutics $63M designed to beat a quick path to approval – Endpoints News

Rain Therapeutics is on a tear.

When the biotech got started in the San Francisco Bay Area, it was singularly focused on tarloxotinib, a small molecule inhibitor named for its design to target low oxygen levels in the tumor and thereby sparing healthy tissues. More than two years later, Rain has tripled its pipeline within days, first licensing a research program from Drexel University, then more recently nabbing a Phase II-ready drug from Daiichi Sankyo.

It also has $63 million in fresh funding to push all three programs, with Boxer Capital, Cormorant Asset Management, Samsara BioCapital, Janus Henderson Investors and Logos Capital now in its corner alongside existing investors BVF Partners and Perceptive Advisors.

Through it all, Rain is retaining its targeted focus, noted CEO Avanish Vellanki.

Starting out with tarloxotinib, for instance, allowed them to tap into the Exon 20 niche within the broader EGFR-positive non-small cell lung cancer as well as NRG1, EGFR, HER2, and HER4 fusions.

Meanwhile RAIN-32, the therapy from Daiichi Sankyo that has superseded tarloxotinib as Rains lead program, targets MDM2 (which inhibits p53, blocking its tumor suppressing effect). The other preclinical program focuses on RAD52, which CSO Robert Doebele calls a critical backup pathway for cancer cells that already have other defects in the DNA damage response pathway.

A veteran trial investigator well-versed in oncogene targets whos continued to practice and research at the University of Colorado after co-founding Rain, Doebele said new approaches are needed to open up new waves of cancer treatment to follow up on the seven oncogenes now covered by FDA-approved treatments.

The number of targets that we can directly inhibit like that like ALK, EGFR, ROS are somewhat thinning a bit, he said. But I think these new strategies where were targeting the p53 pathway and reactivating or using synthetic lethality strategies in a very similar way, basically taking advantage of cancer-specific vulnerabilities, is absolutely of interest.

A general uptick in next-generation sequencing is also speeding up the identification of patients, as Rain has witnessed firsthand with the ongoing Phase II for tarloxotinib.

As with entrectinib and larotrectinib for patients with NTRK fusions, both of which Doebele has helped develop, Rain believes RAIN-32 lends itself to tumor-agnostic or biology-driven as he prefers to call it development.

Thats still a very very young field, he said.

The Series B gives Rain about 2.5 years of runway, fueling its lean team of 8 all the way to the completion of a pivotal trial for RAIN-32 in liposarcoma. Within the subpopulation the company is focusing on, Vellanki said, nearly 100% has an MDM2 gene amplification.

While other companies like Roche and Ascentage have developed MDM2 inhibitors, toxicities remain a big problem for the field, according to Vellanki. Daiichi scientists tried to solve for that with a different dosing schedule that gives patients time to recover from the side effects.

Broadly speaking whenever you have version 2.0 or version 3.0 of any technology, youre able to compensate for the problems of the version 1.0, he said. Advancements of technology always allow you to fine-tune technologies to solve the problems that you didnt know were there in the first place with the initial set of targeted therapies.

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New targeted therapy approaches win Rain Therapeutics $63M designed to beat a quick path to approval - Endpoints News

Cell Biology

Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans – Science Magazine

Immune profiling of COVID-19 patients

Coronavirus disease 2019 (COVID-19) has affected millions of people globally, yet how the human immune system responds to and influences COVID-19 severity remains unclear. Mathew et al. present a comprehensive atlas of immune modulation associated with COVID-19. They performed high-dimensional flow cytometry of hospitalized COVID-19 patients and found three prominent and distinct immunotypes that are related to disease severity and clinical parameters. Arunachalam et al. report a systems biology approach to assess the immune system of COVID-19 patients with mild-to-severe disease. These studies provide a compendium of immune cell information and roadmaps for potential therapeutic interventions.

Science, this issue p. eabc8511, p. 1210

Coronavirus disease 2019 (COVID-19) represents a global crisis, yet major knowledge gaps remain about human immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We analyzed immune responses in 76 COVID-19 patients and 69 healthy individuals from Hong Kong and Atlanta, Georgia, United States. In the peripheral blood mononuclear cells (PBMCs) of COVID-19 patients, we observed reduced expression of human leukocyte antigen class DR (HLA-DR) and proinflammatory cytokines by myeloid cells as well as impaired mammalian target of rapamycin (mTOR) signaling and interferon- (IFN-) production by plasmacytoid dendritic cells. By contrast, we detected enhanced plasma levels of inflammatory mediatorsincluding EN-RAGE, TNFSF14, and oncostatin Mwhich correlated with disease severity and increased bacterial products in plasma. Single-cell transcriptomics revealed a lack of type I IFNs, reduced HLA-DR in the myeloid cells of patients with severe COVID-19, and transient expression of IFN-stimulated genes. This was consistent with bulk PBMC transcriptomics and transient, low IFN- levels in plasma during infection. These results reveal mechanisms and potential therapeutic targets for COVID-19.

The recent emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Wuhan, China, in December 2019 and its rapid international spread caused a global pandemic. Research has moved rapidly in isolating, sequencing, and cloning the virus; developing diagnostic kits; and testing candidate vaccines. However, key questions remain about the dynamic interaction between the human immune system and the SARS-CoV-2 virus.

Coronavirus disease 2019 (COVID-19) presents with a spectrum of clinical phenotypes, with most patients exhibiting mild to moderate symptoms and 15% of patients progressing, typically within a week, to severe or critical disease that requires hospitalization (1). A minority of those who are hospitalized develop acute respiratory disease syndrome (ARDS) and require mechanical ventilation. Epidemiological data so far suggest that COVID-19 has a case fatality rate several times greater than that of seasonal influenza (1). The elderly and individuals with underlying medical comorbidities such as cardiovascular disease, diabetes mellitus, chronic lung disease, chronic kidney disease, obesity, hypertension, or cancer have a much higher mortality rate than healthy young adults (2). The underlying causes of this difference are unknown, but they may be due to an impaired interferon (IFN) response and dysregulated inflammatory responses, as have been observed with other zoonotic coronavirus infections such as severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) (3). Current research is uncovering how the adaptive immune response to SARS-CoV-2 is induced with optimal functional capacities to clear SARS-CoV-2 viral infection (46).

Understanding the immunological mechanisms underlying the diverse clinical presentations of COVID-19 is a crucial step in the design of rational therapeutic strategies. Recent studies have suggested that COVID-19 patients are characterized by lymphopenia and increased numbers of neutrophils (79). Most patients with severe COVID-19 exhibit enhanced levels of proinflammatory cytokines including interleukin-6 (IL-6) and IL-1 as well as MCP-1, IP-10, and granulocyte colony-stimulating factor (G-CSF) in the plasma (10). It has been proposed that high levels of proinflammatory cytokines might lead to shock as well as respiratory failure or multiple organ failure, and several trials to assess inflammatory mediators are under way (11). However, little is known about the immunological mechanisms underlying COVID-19 severity and the extent to which they differ from the immune responses to other respiratory viruses. Furthermore, the question of whether individuals in different parts of the world respond differently to SARS-CoV-2 remains unknown. In this study, we used a systems biological approach [mass cytometry and single-cell transcriptomics of leukocytes, transcriptomics of bulk peripheral blood mononuclear cells (PBMCs), and multiplex analysis of cytokines in plasma] to analyze the immune response in 76 COVID-19 patients and 69 age- and sex-matched controls from two geographically distant cohorts.

COVID-19infected patient samples and samples from age- and sex-matched healthy controls were obtained from two independent cohorts: (i) the Princess Margaret Hospital at Hong Kong University and (ii) the Hope Clinic at Emory University in Atlanta, Georgia, United States. Patient characteristics and the different assays performed are shown in Table 1. We used mass cytometry to assess immune responses to SARS-CoV-2 infection in 52 COVID-19 patients, who were confirmed positive for viral RNA by polymerase chain reaction (PCR), and 62 age- and gender-matched healthy controls distributed between the two cohorts. To characterize immune cell phenotypes in PBMCs, we used a phospho-CyTOF panel that includes 22 cell surface markers and 12 intracellular markers against an assortment of kinases and phospho-specific epitopes of signaling molecules and H3K27aca marker of histone modification that drives epigenetic remodeling (12, 13) (table S1). The experimental strategy is described in Fig. 1A. The phospho-CyTOF identified 12 main subtypes of innate and adaptive immune cells in both cohorts, as represented in the t-distributed stochastic neighbor embedding (t-SNE) plots (Fig. 1B). There was a notable increase in the frequency of plasmablast and effector CD8 T cells in all infected individuals (Fig. 1B) in both cohorts, as has been described recently in other studies (6, 8, 14). Of note, the kinetics of the CD8 effector T cell response were prolonged and continued to increase up to day 40 after onset of the symptoms (fig. S1).

NA, not applicable.

(A) A schematic representation of the experimental strategy. PFA, paraformaldehyde. (B) Representation of mass cytometryidentified cell clusters visualized by t-SNE in two-dimensional space. The box plots on the bottom show frequency of plasmablasts (CD3, CD20, CD56, HLA-DR+, CD14, CD16, CD11c, CD123, CD19lo, CD27hi, and CD38hi) and effector CD8 T cells (CD3+, CD8+, CD38hi, and HLA-DRhi) in both cohorts. (C) Frequencies of pDCs (CD3, CD20, CD56, HLA-DR+, CD14, CD16, CD11c, and CD123+) in healthy and COVID-19infected individuals in both cohorts. (D and E) Box plots showing fold change (FC) of pS6 staining in pDCs (D) and IB staining in mDCs (E) relative to the medians of healthy controls. The histograms on the right depict representative staining of the same. (F) Distinguishing features [false discovery rate (FDR) < 0.01] through linear modeling analysis of the mass cytometry data between healthy and infected subjects. In all box plots, the boxes show median, upper, and lower quartiles. The whiskers show 5th to 95th percentiles. Each dot represents an individual sample (healthy: n = 17 and 45; infected: n = 19 and 54, for Atlanta and Hong Kong cohorts, respectively). For the t-SNE analysis, n = 34 and 60 for Atlanta and Hong Kong cohorts, respectively. The colors of the dots indicate the severity of clinical disease, as shown in the legends. The differences between the groups were measured by Mann-Whitney rank sum test (Wilcoxon, paired = FALSE). The P values depicting significance are shown within the box plots.

We next used manual gating to identify 25 immune cell subsets (fig. S2) and determined whether there were changes in the frequency or signaling molecules of innate immune cell populations consistent between the two cohorts. There were several differences, but notably the frequency of plasmacytoid dendritic cells (pDCs) was significantly reduced in the PBMCs of SARS-CoV-2infected individuals in both cohorts (Fig. 1C). The kinetics of pDC response did not show an association with the time since symptom onset (fig. S1C). Neither did the observed changes correlate with the clinical severity of infection (fig. S1). Additionally, there was reduced expression of pS6 [(phosphorylated ribosomal protein S6), a canonical target of mammalian target of rapamycin (mTOR) activation (15)] in pDCs and decreased IBan inhibitor of the signaling of the NF- transcription factorin myeloid dendritic cells (mDCs) (Fig. 1, D and E). mTOR signaling is known to mediate the production of interferon- (IFN-) in pDCs (16), which suggests that pDCs may be impaired in their capacity to produce IFN- in COVID-19 patients. Finally, we used a linear modeling approach to detect features that distinguish healthy from infected individuals and those that discriminate individuals on the basis of the clinical severity of COVID-19. This analysis was performed with the cohort (Hong Kong or Atlanta) as a covariate to identify only features that were consistent across both cohorts. The distinguishing features between healthy and infected individuals are shown in Fig. 1F. These include frequencies of plasmablast and effector T cells and the changes in innate immune cells described above in addition to STAT1 (signal transducer and activator of transcription 1) and other signaling events in T cells and natural killer (NK) cells. Of note, no features were significantly different between clinical severity groups.

We further examined the effect of various therapeutic interventions on the immune responses using samples from the Hong Kong cohort, in which some patients were treated with IFN-1, corticosteroids, or antivirals. The infected individuals, irrespective of the intervention, showed an increased plasmablast and effector CD8 T cell frequency compared with healthy controls (fig. S3). However, there was an increased frequency of effector CD8 T cells (fig. S3, bottom panel, right column) and decreased pS6 signal in the pDCs of antiviral-treated individuals (fig. S4).

Given the earlier findings that mTOR signaling in pDCs mediates the production of IFN- in response to Toll-like receptor (TLR) stimulation (16), the reduced expression of pS6 in pDCs suggests that such cells may be impaired in their capacity to produce IFN-. To test this, we performed ex vivo stimulation of PBMCs from healthy or COVID-19infected individuals, using a mixture of synthetic TLR7 and TLR 8 (TLR7/8) and TLR3 ligands, which are known to be expressed by viruses, and we performed an intracellular staining assay to detect cytokine responses. The TLR ligands included TLR3 and TLR7/8 ligands, polyIC and R848. Consistent with our hypothesis, there was reduced production of IFN- in response to the TLR stimuli in the pDCs of infected individuals compared with those of healthy controls (Fig. 2A). The TNF- response was also significantly reduced in the pDCs of infected individuals, which demonstrates that the pDCs are functionally impaired in COVID-19 infection. We also determined the ability of mDCs and CD14+ monocytes to respond to TLR stimuli. Notably, the response in mDCs as well as that in monocytes were also significantly lower in response to stimulation with a bacterial ligand cocktail (composed of TLR2, TLR4, and TLR5 ligands) or with the viral TLR cocktail (Fig. 2B and fig. S5). Furthermore, the reduced IB levels did not translate into enhanced NF- subunit p65 phosphorylation as measured by p65 (Ser529) in the same cells (Fig. 2C). These results suggest that the innate immune cells in the periphery of COVID-19infected individuals are suppressed in their response to TLR stimulation, irrespective of the clinical severity.

(A) Box plots showing the fraction of pDCs in PBMCs of healthy or infected donors (CD3, CD20, CD56, HLA-DR+, CD14, CD16, CD11c, and CD123+) producing IFN-, TNF-, or IFN- + TNF- in response to stimulation with the viral cocktail (polyIC + R848). The contour plots on the right show IFN-, TNF-, or IFN- + TNF- staining in pDCs. (B) Box plots showing the fraction of mDCs in PBMCs of healthy or infected donors (CD3, CD20, CD56, HLA-DR+, CD14, CD16, CD123+, and CD11c) producing IL-6, TNF-, or IL-6 + TNF- in response to no stimulation (top), the bacterial cocktail (middle; Pam3CSK4, LPS, and Flagellin), or the viral cocktail (bottom; polyIC + R848). The flow cytometry plots on the right are representative plots gated on mDCs showing IL-6, TNF-, or IL-6 + TNF- response. (C) Fold change of NF- p65 (Ser529) staining in PBMCs stimulated with bacterial cocktail relative to no stimulation in healthy and infected donors to show the reduced induction of p65 phosphorylation in infected individuals. The histograms show representative flow cytometry plots of p65 staining in mDCs. GeoMFI, geometric mean fluorescence intensity. In all box plots, the boxes show median, upper, and lower quartiles. The whiskers show 5th to 95th percentiles. Each dot represents an Atlanta cohort patient (n = 14 and 17 for healthy and infected, respectively). Colors of the dots indicate the severity of clinical disease, as shown in the legends. The differences between the groups were measured by Mann-Whitney rank sum test. The P values depicting significance are shown within the box plots.

The impaired cytokine response of myeloid cells and pDCs in response to TLR stimulation was unexpected and seemingly at odds with the literature describing an enhanced inflammatory response in COVID-19infected individuals. Several studies have described higher plasma levels of cytokines, including but not limited to IL-6, TNF-, and CXCL10 (10, 1719). Therefore, we evaluated cytokines and chemokines in plasma samples from the Atlanta cohort using the Olink multiplex inflammation panel that measures 92 different cytokines and chemokines. Of the 92 analytes measured, 71 proteins were detected within the dynamic range of the assay. Of these 71 proteins, 43 cytokines, including IL-6, MCP-3, and CXCL10, were significantly up-regulated in COVID-19 infection (Fig. 3, top row, and fig. S6). These results demonstrate that plasma levels of inflammatory molecules were significantly up-regulated, despite the impaired cytokine response in blood myeloid cells and pDCs, which suggests a tissue origin of the plasma cytokines.

Cytokine levels in the plasma of healthy or infected individuals. The infected individuals are further classified on the basis of the severity of their clinical COVID-19 disease. The normalized protein expression values plotted on the y axes are arbitrary units defined by Olink Proteomics to represent Olink data. In all box plots, the boxes show median, upper, and lower quartiles. The whiskers show 5th to 95th percentiles. Each dot represents an Atlanta cohort sample (n = 18 healthy, 4 moderate, 18 severe, 12 ICU, 2 convalescent, 8 flu, and 11 RSV). The colors of the dots indicate the severity of clinical disease, as shown in the legends. The differences between the groups were measured by Mann-Whitney rank sum test (Wilcoxon, paired = FALSE; *P < 0.05; **P < 0.01; ***P < 0.001; ns, not significant).

In addition to IL-6 and other cytokines described previously (10), we identified three proteins that were significantly enhanced in COVID-19 infection and strongly correlated with clinical severity (Fig. 3, bottom row). These were TNFSF14 [LIGHT, a ligand of lymphotoxin B receptor that is highly expressed in human lung fibroblasts and implicated in lung tissue fibrosis and remodeling and inflammation (20)], EN-RAGE [S100A12, a biomarker of pulmonary injury that is implicated in pathogenesis of sepsis-induced ARDS (21)], and oncostatin M [(OSM), a regulator of IL-6]. Of note, the TNFSF14 is distinctively enhanced in the plasma of COVID-19infected individuals but not in cases of other related pulmonary infections such as influenza (flu) virus and respiratory syncytial virus (RSV) (Fig. 3). Given the pronounced and unappreciated observations of the enhanced plasma concentrations of TNFSF14, EN-RAGE, and OSM and their correlation to disease severity, we used an enzyme-linked immunosorbent assay (ELISA) to independently validate these results. Consistent with the multiplex Olink analysis, we found a significant increase of these inflammatory mediators in the plasma of severe and intensive care unit (ICU) COVID-19 patients. Furthermore, we found a correlation between multiplex analysis by Olink and the ELISA results (fig. S7). These results suggest that COVID-19 infection induces a distinctive inflammatory program characterized by cytokines released from tissues (most likely the lungs) but suppression of the innate immune system in the periphery. These observations may also represent previously unexplored therapeutic strategies for intervention against severe COVID-19.

To investigate the molecular and cellular processes that lead to the distinctive inflammatory program, we used cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) and profiled the gene and protein expression in PBMC samples of COVID-19infected individuals. Cryopreserved PBMC samples from a total of 12 age-matched subjects in the Atlanta cohort (five healthy controls and seven COVID-19 patients; Table 2) were enriched for DCs, stained using a cocktail of 36 DNA-labeled antibodies (table S2), and analyzed using droplet-based single-cell gene expression profiling approaches (Fig. 4A). We performed the experiment in two batches and obtained transcriptomes for more than 63,000 cells after initial preprocessing. Next, we generated a cell-by-gene matrix and conducted dimensionality reduction through uniform manifold approximation and projection (UMAP) and graph-based clustering. Analysis of cell distribution within the UMAP between experiments revealed no major differences, and we analyzed the datasets from the two experiments together without batch correction (fig. S8). Next, we calculated the per-cell quality control (QC) metrics (fig. S9), differentially expressed genes (DEGs) in each cluster compared with all other cells (fig. S10 and table S4), and the abundance of DNA-labeled antibodies in each cell (fig. S11). Using this information, we filtered low-quality cells and manually annotated the clusters. After QC and cluster annotation, we retained a final dataset with 57,669 high-quality transcriptomes and a median of ~4781 cells per sample and 1803 individual genes per cell that we used to construct the single-cell immune cell landscape of COVID-19 (Fig. 4B).

Dashes indicate that the information is not applicable. dec., deceased; F, female; M, male; B, Black; W, white.

(A) A schematic representation of the DC enrichment strategy used in CITE-seq analysis. (B) UMAP representation of PBMCs from all analyzed samples (n = 12), colored by manually annotated cell type. (C) Pairwise comparison of genes from healthy individuals (n = 5) and COVID-19infected patients (n = 7) was conducted for each cluster. DEGs were analyzed for overrepresentation of BTMs. The ringplot shows overrepresented pathways in up- and down-regulated genes of each cluster. The heatmap on the right shows the average expression levels of 33 ISGs derived from the enriched BTMs in different cell clusters of healthy (n = 5) and COVID-19 subjects (n = 7). (D) UMAP representation of PBMCs from all analyzed samples showing the expression levels of selected IFNs and ISGs. (E) Kinetics of circulating IFN- levels (femtograms per milliliter) in plasma measured using SIMoA technology (n = 18 healthy and 40 COVID-19infected patients). (F) Correlation between circulating IFN- levels in plasma and the average expression of ISGs measured by CITE-seq analysis. (G) Hierarchically clustered heatmap of the expression of the CITE-seq ISG signature (C) in the bulk RNA-seq dataset, performed using an extended group of subjects (n = 17 healthy and 17 COVID-19infected samples). Colors represent gene-wise z scores. (H) Bar chart representing the proportion of variance in CITE-seq ISG signature expression explained by the covariates in the x axis through principal variance component analysis (PVCA). resid, residual. (figure on next page)

We observed several clusters that were primarily identified in COVID-19infected individuals, including a population of plasmablasts, platelets, and red blood cells and several populations of granulocytes. Notably, we detected clusters of T cells and monocytes that were characterized by the expression of interferon-stimulated genes (ISGs) such as IFI27, IFITM3, or ISG15 (see C11-C MONO_IFN and C18-T_IFN in fig. S10). These IFN responseenriched clusters emerged only in samples from COVID-19 patients (fig. S12).

To describe the specific transcriptional state of single cells from COVID-19infected individuals, we determined the DEGs for cells from all COVID-19infected samples in a given cluster compared with the cells from all healthy individuals in the same cluster. We then analyzed these DEGs with overrepresentation analysis using blood transcriptional modules (BTMs) (22) to better understand which immune pathways are differentially regulated in patients with COVID-19 compared with healthy individuals (Fig. 4C and fig. S13). The analysis indicated a marked induction of antiviral BTMs, especially in cell types belonging to the myeloid and dendritic cell lineage. Detailed analysis of the expression pattern of the distinct union of genes driving the enrichment of these antiviral pathways in monocytes and dendritic cells revealed that many ISGs were up-regulated in these cell types (Fig. 4C, heatmap). Given our observations of muted IFN- production in pDCs (Fig. 2A), we investigated the expression of genes encoding various type I and type II IFNs across cell types (Fig. 4D and fig. S14). Notably, with the exception of modest levels of IFN- expression in T and NK cells, we could not detect any expression of IFN- and - genes, which is consistent with the functional data demonstrating impaired type I IFN production by pDCs and myeloid cells (Fig. 2). However, there was an enhanced expression of ISGs in patients with COVID-19 (Fig. 4D) in spite of an impaired capacity of the innate cells in the blood compartment to produce these cytokines.

Despite the lack of type I IFN gene expression, the presence of an ISG signature in the PBMCs of COVID-19infected individuals raised the possibility that low quantities of type I IFNs produced in the lung by SARS-CoV-2 infection (17) might circulate in the plasma and induce the expression of ISGs in PBMCs. We thus measured the concentration of IFN- in plasma using a highly sensitive ELISA enabled by single molecule array (SIMoA) technology. We observed a marked increase in the concentration of IFN-, which peaked around day 8 after onset of symptoms and regressed to baseline levels by day 20 (Fig. 4E). Notably, we observed a strong correlation between the average expression levels of the ISG signature in PBMCs identified by CITE-seq analysis and the IFN- concentration in plasma (Fig. 4F). Additionally, we noticed a strong temporal dependence of the IFN- response.

To investigate this further and to independently validate the observations in the CITE-seq analysis, we performed bulk RNA sequencing (RNA-seq) analysis of PBMCs in an extended group of subjects (17 COVID-19 patients and 17 healthy controls) from the same cohort. We first evaluated whether the ISG signature containing 33 genes identified in the CITE-seq data was also observed in the bulk RNA-seq dataset. We observed a strong induction of the ISGs in COVID-19 subjects compared with healthy donors in this dataset as well (Fig. 4G). Of note, we did not detect expression of genes encoding IFN- or IFN-, consistent with the CITE-seq and flow cytometry experiments (Fig. 4D and Fig. 2, respectively). We also performed an unbiased analysis of an extended set of genes in the IFN transcriptional network (23) and found that these were induced in COVID-19 subjects relative to healthy controls, as observed for the limited ISG signature (fig. S15A). Similar to the observation with CITE-seq data (Fig. 4F), there was a strong correlation between circulating IFN- and the ISG response measured by the bulk transcriptomics (fig. S15B). Additionally, we analyzed the individual impact of major covariatestime, disease severity, sex, and ageon the observed ISG signature. Although time emerged as the primary driver of ISG signature, COVID-19 clinical severity also had an effect (Fig. 4H and fig. S15C). Taken together, these data demonstrate that, early during SARS-CoV-2 infection, there are low levels of circulating IFN- that induce ISGs in the periphery while the innate immune cells in the periphery are impaired in their capacity to produce inflammatory cytokines.

In addition to an enhanced ISG signature, the CITE-seq analysis revealed a significant decrease in the expression of genes involved in the antigen-presentation pathways in myeloid cells (Fig. 4C and fig. S13). Consistent with this, we observed a reduction in the expression of the proteins CD86 and human leukocyte antigen class DR (HLA-DR) on monocytes and mDCs of COVID-19 patients, which was most pronounced in subjects with severe COVID-19 infection (Fig. 5A and fig. S16A). HLA-DR is an important mediator of antigen presentation and is crucial for the induction of T helper cell responses. Using the phospho-CyTOF data from both the Atlanta and Hong Kong cohorts, we confirmed the reduced expression of HLA-DR on monocytes and mDCs in patients with severe COVID-19 disease (Fig. 5B). By contrast, S100A12, the gene encoding EN-RAGE, was substantially increased in the PBMCs of COVID-19 patients, whereas the expression of genes encoding other proinflammatory cytokines was either absent or unchanged compared with healthy controls (Fig. 5C and fig. S16B). Notably, the S100A12 expression was highly restricted to monocyte clusters (Fig. 5D) and showed a significant correlation with EN-RAGE protein levels in plasma measured by Olink (Fig. 5E). Finally, we examined whether there is an association between HLA-DR and S100A12 expression in our dataset, and we found a strong inverse correlation between S100A12 gene expression and the genes encoding the antigen presentation machinery (HLA-DPA1, HLA-DPB1, HLA-DR, and CD74) (Fig. 5F and fig. S17). Notably, the receptor for S100A12, AGER (RAGE), was expressed sparsely in PBMCs (fig. S18), which suggests that the target of EN-RAGE action was likely to be elsewhereperhaps the lung, where RAGE is known to be expressed in type I alveolar epithelial cells and mediate inflammation (24).

(A) Flow cytometry analysis of PBMCs analyzed in parallel to the CITE-seq experiment. The log10 median fluorescence intensity (MFI) of HLA-DR expression is shown. (B) Median intensity of HLA-DR expression in the phospho-CyTOF experiment from Fig. 1. Squares represent individual samples [Hong Kong (HK): healthy = 30, moderate = 15, and severe = 10; and Atlanta: healthy = 17, moderate = 4, and severe = 13]. The boxes indicate median, upper, and lower quartiles. The whisker length equals 1.5 times the interquartile range. (C) Relative (Rel.) expression of genes encoding different cytokines in the bulk RNA-seq dataset. The boxes show median, upper, and lower quartiles, and the whiskers show 5th to 95th percentiles. (D) UMAP representation of S100A12 expression in PBMCs from all samples analyzed by CITE-seq. (E and F) Correlation (Cor) analysis of S100A12 expression in cells from myeloid and dendritic cell clusters (C MONO_1, NC MONO, CDC2, PDC, C MONO_IFN, C MONO_2, and C MONO_3) with EN-RAGE levels in plasma (E) or HLA-DPA1 expression in the same clusters (F) (n = 5 healthy and 7 COVID-19 subjects). The statistical significance between the groups in (B) and (C) was determined by two-sided Mann-Whitney rank-sum test; *P < 0.05; **P < 0.01; ***P < 0.001.

Taken together, CITE-seq analysis of PBMCs in COVID-19 patients revealed the following mechanistic insights: (i) a lack of expression of genes encoding type I IFN and proinflammatory cytokines in PBMCs, which was consistent with the mass cytometry (Fig. 1C) and functional data (Fig. 2); (ii) an early but transient wave of ISG expression, which was entirely consistent with analysis of RNA-seq from bulk PBMCs (Fig. 4G and fig. S15A) and strongly correlated with an early burst of plasma IFN- (Fig. 4F), likely of lung origin (17); and (iii) the impaired expression of HLA-DR and CD86 but enhanced expression of S100A12 in myeloid cells, which was consistent with the mass cytometry (Fig. 5B), Olink (Fig. 3), and ELISA (fig. S7) data, and is a phenotype reminiscent of myeloid-derived suppressor cells described previously (25).

The increased levels of proinflammatory mediators in the plasmaincluding IL-6, TNF, TNFSF14, EN-RAGE, and OSM (Fig. 3)coupled with suppressed innate immune responses in blood monocytes and DCs (Fig. 2 and fig. S5) suggested a sepsis-like clinical condition (26, 27). In this context, it has been previously suggested that proinflammatory cytokines and bacterial products in the plasma may play pathogenic roles in sepsis, and the combination of these factors could be important in determining patient survival (28, 29). Therefore, to determine whether a similar mechanism could be at play in patients with severe COVID-19, we measured bacterial DNA and lipopolysaccharide (LPS) in the plasma. Notably, the plasma of severe and ICU patients had significantly higher levels of bacterial DNA, as measured by PCR quantitation of bacterial 16S ribosomal RNA (rRNA) gene product, and of LPS, as measured by a TLR4-based reporter assay (Fig. 6, A and B). Furthermore, there was a significant correlation between bacterial DNA or LPS and the plasma levels of the inflammatory mediators IL-6, TNF, MCP-3, EN-RAGE, TNFSF14, and OSM (Fig. 6C and fig. S19). These results suggest that the enhanced cytokine release may in part be caused by increased bacterial products in the lung or in other tissues.

(A and B) Box plots showing bacterial 16S rRNA gene (A) and LPS (B) measured in the plasma of healthy or infected individuals. qPCR, quantitative PCR. (C) Spearmans correlation between cytokines and bacterial DNA measured in plasma. Each dot represents a sample (n = 18 and 51 for healthy and infected, respectively). The colors of the dots indicate the severity of clinical disease, as shown in the legends. The boxes show median, upper, and lower quartiles in the box plots. The whiskers show 5th to 95th percentiles. The differences between the groups were measured by Mann-Whitney rank sum test; ***P < 0.001; ****P < 0.0001. NPX, normalized protein expression units; R, correlation coefficient.

We used a systems biology approach to determine host immune responses to COVID-19. Mass cytometry analysis of peripheral blood leukocytes from two independent cohorts revealed several common features of immune responses induced upon SARS-CoV-2 infection. There was a notable and protracted increase in the frequencies of plasmablasts and effector CD8 T cells in the peripheral blood, consistent with recent studies (6, 8, 14). Notably, the effector T cells continued to increase up to day 40 after symptom onset. Studies have shown that SARS-CoV-2 infection induces exhaustion and apoptosis in T cells (30, 31). Whether the continuing effector CD8 T cell response reflects continuous exposure to antigen and whether the cells are exhausted will require further investigation.

In contrast to robust activation of B and T cells, we observed a significant decrease in the frequency of pDCs. Furthermore, mTOR signaling in pDCs was reduced significantly in COVID-19infected individuals, as measured by decreased pS6 signaling by mass cytometry. These results suggest that pDCs, the primary producers of type I IFNs, are impaired in COVID-19 infection, which is consistent with studies in SARS-CoV infection (32). To determine whether the reduced mTOR signaling in pDCs resulted in impairment of type I IFN production, we stimulated cells in vitro with TLR ligands. Our results demonstrate that pDCs from COVID-19infected patients are functionally impaired in their capacity to produce IFN- in response to TLR stimulation. Taken together, these data suggest that COVID-19 causes an impaired type I IFN response in the periphery. Administration of type I IFN has been proposed as a strategy for COVID-19 intervention (33); however, it must be noted that type I IFN signaling has been shown to elevate angiotensin-converting enzyme 2 (ACE2) expression (34) in lung cells, which can potentially lead to enhanced infection.

In addition to the impaired IFN- production by pDCs, there was a marked diminution of the proinflammatory cytokines IL-6, TNF-, and IL-1 produced by monocytes and mDCs upon TLR stimulation (Fig. 2B). This was consistent with the lack of or diminished expression of the genes encoding IL-6 and TNF in the CITE-seq analysis (Fig. 5C). These results suggest an impaired innate response in blood leukocytes of patients with COVID-19. This concept was further supported by the CyTOF and flow cytometry data that showed decreased HLA-DR and CD86 expression, respectively, in myeloid cells (Fig. 5, D and E, and fig. S16). To obtain deeper insight into the mechanisms of host immunity to SARS-CoV-2, we performed CITE-seq single-cell RNA-seq and bulk RNA-seq analysis in COVID-19 patients at various stages of clinical severity. Our data demonstrate that SARS-CoV-2 infection results in an early wave of IFN- in the circulation that induces an ISG signature. Although the ISG signature shows a strong temporal dependence in our datasets, we also find that the ISG signature is strongly induced in patients with moderate COVID-19 infection (Fig. 4G). Consistent with this, Hadjadj et al. (5) have reported an enhanced expression of ISGs in patients with moderate disease compared with those with severe or critical disease. Taken together, these data suggest that SARS-CoV-2 infection induces an early, transient type I IFN production in the lungs that induces ISGs in the peripheral blood, primarily in patients with mild or moderate disease. Additionally, we observed reduced expression of genes encoding proinflammatory cytokines, as well as HLA-DR expression in myeloid cells, which was consistent with the CyTOF and flow cytometry data showing reduced HLA-DR and CD86 expression, respectively, in myeloid cells.

Our multiplex analysis of plasma cytokines revealed enhanced levels of several proinflammatory cytokines, as has been observed previously (35), and revealed a strong association of the inflammatory mediators EN-RAGE, TNFSF14, and OSM with the clinical severity of the disease. Notably, the expression of genes encoding both TNFSF14 and OSM were down-regulated in the PBMCs from COVID-19 patients with severe disease in the analysis of CITE-seq data (Fig. 5C), which suggests a tissue origin for these cytokines. The gene encoding EN-RAGE, however, was expressed at high levels in blood myeloid cells in patients with severe COVID-19 (Fig. 5, C to F) (although it is also possible that EN-RAGE is expressed in the lungs too). Of note, these three cytokines have been associated with lung inflammatory diseases. In particular, EN-RAGE has been shown to be expressed by CD14+ HLA-DRlo cells, the myeloid-derived suppressor cells, and it is a marker of inflammation in severe sepsis (21, 25, 36). Additionally, its receptor, RAGE, is highly expressed in type I alveolar cells in the lung (24). Notably, we observed that the classical monocytes and myeloid cells from severe COVID-19 patients in the single-cell RNA-seq data expressed high levels of S100A12, the gene encoding EN-RAGE, but not the typical inflammatory molecules IL-6 and TNF-. These data suggest that the proinflammatory cytokines observed in plasma likely originate from the cells in lung tissue rather than from peripheral blood cells. Taken together with the mass cytometry data, the plasma cytokine data may be utilized to construct an immunological profile that discriminates between severe versus moderate COVID-19 disease (fig. S20).

These results suggest that SARS-CoV-2 infection results in a spatial dichotomy in the innate immune response, characterized by suppression of peripheral innate immunity in the face of proinflammatory responses that have been reported in the lungs (37). Furthermore, there is a temporal shift in the cytokine response from an early but transient type I IFN response to a proinflammatory response during the later and more severe stages, which is similar to that observed with other diseases such as influenza (38). Notably, there were enhanced levels of bacterial DNA and LPS in the plasma, which were positively correlated with the plasma levels of EN-RAGE, TNFSF14, OSM, and IL-6, which suggests a role for bacterial productsperhaps of lung originin augmenting the production of inflammatory cytokines in severe COVID-19. The biological consequence of the impaired innate response in peripheral blood is unknown but may reflect a homeostatic mechanism to prevent rampant systemic hyperactivation, in the face of tissue inflammation. Finally, these results highlight molecules such as EN-RAGE or TNFSF14, and their receptors, which could represent attractive therapeutic targets against COVID-19.

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Systems biological assessment of immunity to mild versus severe COVID-19 infection in humans - Science Magazine

Cell Biology

Magenta Therapeutics Named Co-Recipient of Grant from the National Institutes of Health to Explore Use of Novel Targeted Conditioning Agents with Gene…

Sept. 2, 2020 16:00 UTC

NIH grant funds an interdisciplinary effort among researchers from University of Southern California; University of Washington and Fred Hutchinson Cancer Research Center; Harvard University and Massachusetts General Hospital; the Ragon Institute; and Magenta Therapeutics

Magenta will utilize its tool CD45 and CD117 antibody-drug conjugate (ADC) conditioning agents, as well as its stem cell biology platform to identify the optimal strategy for curative immune system transplant in patients with HIV

CAMBRIDGE, Mass.--(BUSINESS WIRE)-- Magenta Therapeutics (Nasdaq: MGTA), a clinical-stage biotechnology company developing novel medicines to bring the curative power of immune reset to more patients, today announced it is part of a multi-project, broad-based research effort awarded a five-year, $14.6 million U19 grant from the National Institutes of Health (NIH) to explore gene- and cell-based approaches to advance research into curing HIV.

This cross-institutional research program brings together leaders in the fields of gene editing, HIV and stem cell transplant. The team, which includes researchers from the University of Southern California, the University of Washington, the Fred Hutchinson Cancer Research Center, Harvard University, Massachusetts General Hospital; the Ragon Institute and Magenta Therapeutics, will explore novel hematopoietic stem and progenitor cell (HSPC) engineering and transplantation approaches aimed at achieving complete remission of HIV-1 infection.

We are excited to collaborate with our colleagues in this important multi-institution research team to help advance gene editing approaches with our novel targeted antibody drug conjugate (ADC) conditioning platform to one day be able to cure patients living with HIV, said John Davis Jr., M.D., M.P.H., M.S., Head of Research & Development and Chief Medical Officer, Magenta. These studies leverage our proprietary stem cell biology pipeline and ADC platform to provide important insights into which conditioning strategy is best suited to aim for HIV.

Magenta will utilize its conditioning technology to optimize cell dose in animal models and determine whether targeted conditioning and gene-modified HSPC transplant enables disease control.

About Magenta Therapeutics

Magenta Therapeutics is a clinical-stage biotechnology company developing medicines to bring the curative power of immune system reset through stem cell transplant to more patients with autoimmune diseases, genetic diseases and blood cancers. Magenta is combining leadership in stem cell biology and biotherapeutics development with clinical and regulatory expertise, a unique business model and broad networks in the stem cell transplant world to revolutionize immune reset for more patients.

Magenta is based in Cambridge, Mass. For more information, please visit http://www.magentatx.com.

Follow Magenta on Twitter: @magentatx.

Forward-Looking Statement

This press release may contain forward-looking statements and information within the meaning of The Private Securities Litigation Reform Act of 1995 and other federal securities laws. The use of words such as may, will, could, should, expects, intends, plans, anticipates, believes, estimates, predicts, projects, seeks, endeavor, potential, continue or the negative of such words or other similar expressions can be used to identify forward-looking statements. The express or implied forward-looking statements included in this press release are only predictions and are subject to a number of risks, uncertainties and assumptions, including, without limitation risks set forth under the caption Risk Factors in Magentas Annual Report on Form 10-K filed on March 3, 2020, as updated by Magentas most recent Quarterly Report on Form 10-Q and its other filings with the Securities and Exchange Commission. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this press release may not occur and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as predictions of future events. Although Magenta believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee that the future results, levels of activity, performance or events and circumstances reflected in the forward-looking statements will be achieved or occur. Moreover, except as required by law, neither Magenta nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements included in this press release. Any forward-looking statement included in this press release speaks only as of the date on which it was made. We undertake no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.

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Magenta Therapeutics Named Co-Recipient of Grant from the National Institutes of Health to Explore Use of Novel Targeted Conditioning Agents with Gene...