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Immunology

Cancer Research Institute and Israel Cancer Research Fund Announce Co-Funding of a Translational Immunotherapy Research Grant – Newswise

Newswise NEW YORK, October 11, 2022 The Cancer Research Institute (CRI) and Israel Cancer Research Fund (ICRF) have partnered to award and co-fund, respectively, a Clinic and Laboratory Integration Program (CLIP) grant to support the promising immunotherapy research of Yifat Merbl, PhD, of the Weizmann Institute of Science in Israel. The CLIP grant, providing $200,000 in research funding over two years, was established by CRI to support investigators who are studying critical topics at the intersection of laboratory and clinical research. This collaboration builds on another partnership that supported immunotherapy research conducted in Israel The Immunotherapy Promise betweenCRI, the leading funder of immunotherapy research internationally, and ICRF, North Americas largest nonprofit dedicated to supporting cancer research in Israel and the largest non-governmental funder of Israeli cancer research.

Professor Merbls project, Controlling Proteasomal Degradation for Enhancing Anti-Tumor Immunity, hopes to characterize the proteasome degradation landscape in melanoma, aiming to gain insight into the mechanisms of immune evasion and lack of patient response to immunotherapy. This approach should ultimately lead to a novel system to target proteasome degradation in order to improve cancer treatment. While immunotherapy first emerged as a form of FDA-approved cancer treatment in the late 1980s, it is only within the past decade that this class of therapy has begun to deliver significant survival benefit to more cancer patients, bringing it to the forefront of public attention. New immunotherapeutic approaches have been shown in clinical trials to effectively treat patients with bladder, head and neck, kidney, and lung cancers as well as leukemia, lymphoma, and melanoma, with clinical trials under way for more than 25 other types of cancer.

The Cancer Research Institute and Israel Cancer Research Fund have teamed up again to bring philanthropic support of immunology research to scientists in Israel who are working to harness the immune systems power to fight all types of cancer, and this latest joint initiative furthers our shared goal of finding effective answers to cancer to save more lives and cure as many patients as possible, said Jill ODonnell-Tormey, Ph.D., CEO and director of scientific affairs at the Cancer Research Institute.

Commenting on the partnership, David Abramson, president of ICRF said, We know how crucial immunotherapy is in the area of cancer research and our unique partnership with the Cancer Research Institute has the potential to yield breakthrough discoveries in the field. It is our hope that many more Israeli scientists will benefit from our collaboration with CRI.

About the Cancer Research InstituteThe Cancer Research Institute (CRI), established in 1953, is the worlds leading nonprofit organization dedicated exclusively to transforming cancer patient care by advancing scientific efforts to develop new and effective immune system-based strategies to prevent, diagnose, treat, and eventually cure all cancers. Guided by a world-renowned Scientific Advisory Council that includes four Nobel laureates and 27 members of the National Academy of Sciences, CRI has invested $500 million in support of research conducted by immunologists and tumor immunologists at the worlds leading medical centers and universities and has contributed to many of the key scientific advances that demonstrate the potential for immunotherapy to change the face of cancer treatment. To learn more, go to https://www.cancerresearch.org/.

About Israel Cancer Research FundICRF, a 501(c)(3) organization, is the largest charitable organization outside of Israel solely devoted to supporting cancer research in Israel. Grants issued by ICRF have gone to hundreds of researchers at two dozen leading research institutions, universities, and hospitals across Israel. The efforts of Israeli cancer researchers have resulted in significant cancer breakthroughs which were vital in the development of breakthrough cancer drugs, including Doxil, Gleevec, and Velcade. To learn more, go to https://www.icrfonline.org/.

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Cancer Research Institute and Israel Cancer Research Fund Announce Co-Funding of a Translational Immunotherapy Research Grant - Newswise

Immunology

$2.5 million CDC contract to fund one of the largest SARS-CoV-2 surveillance programs in the U.S. – News-Medical.Net

A team led by Scripps Research scientists has been awarded a contract by the U.S. Centers for Disease Control & Prevention (CDC) in support of one of the largest SARS-CoV-2 surveillance programs in the United States.

The two-year, $2.5 million contract will fund the large-scale, near real-time sequencing of SARS-CoV-2 isolates from hospitals and local public health agencies in San Diego and nearby northwestern Mexico, and the development of software for tracking the evolution and geographical spread of SARS-CoV-2 variants.

The contract, an extension of one originally awarded in 2020, will be carried out by the San Diego Epidemiology and Research for COVID Health (SEARCH) Alliance, which was co-founded by Scripps Research, the University of California San Diego (UC San Diego), and Rady Children's Hospital-San Diego.

CDC's support for SEARCH's genomic surveillance program has already led to significant COVID-19 public health advances as well as new science on SARS-CoV-2, and we expect much more progress in both areas as a result of this new award."

Kristian Andersen, PhD, Principal Investigator, Professor, Department of Immunology and Microbiology at Scripps Research

Since the start of the pandemic, SEARCH has been conducting genomic surveillance of SARS-CoV-2 using clinical samples collected at San Diego hospitals and from sources across the border in Baja California. SEARCH has also developed key protocols and analysis tools to track the emergence and spread of SARS-CoV-2 variants in wastewater. Moreover, SEARCH investigators are actively involved in understanding the emergence of SARS-CoV-2, and in several high-profile publications have found evidence for an initial spread from animals sold at the Huanan Market in Wuhan, China.

SEARCH's efforts involve multiple collaborations, including with the CDC, San Diego County's Health & Human Services Agency, the California Department of Public Health, Sharp Health, Scripps Health, the viral surveillance company Helix, and the Salud Digna healthcare network in Mexico. Since the start of the pandemic, these efforts have yielded publications and analyses of more than 70,000 SARS-CoV-2 sequences.

Under the new contract, SEARCH will accelerate its virus-sequencing workflow to produce more timely and actionable information on local virus spread and evolution-;including the emergence of new variants and subvariants of concern.

"The current process of sampling, sequencing and analyzing a batch of virus samples from local hospital cases and wastewater treatment plants can take several weeks," says Mark Zeller, PhD, project scientist in the Andersen lab. "We're aiming to get that down to a matter of days, which would enable us to monitor the transmission chains in local outbreaks in near real-time."

Working with the County of San Diego, the state of California and Mexican public health labs, the researchers will also continue to analyze the transmission of SARS-CoV-2 across the busy California-Baja border. Additionally, they'll expand their genomic surveillance efforts to additional Mexican border states and popular tourist destinations, including Puerto Vallarta. The team will continue to post their analyses on SEARCH's online dashboards.

The project includes the further development of open-source software tools to support the tracking of local SARS-CoV-2 evolution and transmission.

"The tools we've developed in recent years are already being used widely by the public health community for SARS-CoV-2 sequencing and analysis," says Joshua Levy, PhD, postdoctoral research associate in the Andersen lab. "Under this new contract, we will be developing the technology to permanently transform how genomic surveillance will be used to strengthen our public health response."

These open-source software tools are available at https://andersen-lab.com/secrets/code/. The SEARCH Alliance's SARS-CoV-2 surveillance dashboards are at https://searchcovid.info/Dashboards/.

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$2.5 million CDC contract to fund one of the largest SARS-CoV-2 surveillance programs in the U.S. - News-Medical.Net

Immunology

Evommunes Human Tissue-based Approach Enables Discovery and Development of Safer, Innovative Chronic Inflammation Therapies – BioSpace

Evommune team/courtesy of Evommune

Evommunes novel human tissue-based assay system is proving to be a key differentiator as the company develops therapies to control chronic inflammation in autoimmune diseases.

Working with human tissue puts us closer to the target and yields a model that is much more predictive of outcomes in the human immune system, said Luis Pea, CEO of Evommune, in an interview with BioSpace.

Skin has all of the cell types that are needed to induce specific inflammatory pathways, said Eugene Bauer, M.D., CMO of Evommune. The companys human tissue model is an ex vivo system that uses living skin from human donors, allowing the model to reflect all the immune responses that occur across various tissues in the body that drive inflammation.

Consequently, in this context, it is more robust, predictive and relevant than animal modeling. This most closely mimics a real-time look at immune pathways and how to find the best way to target and modify inflammation. The miniaturized technology enables hundreds of assays to be conducted to study both systemic and topical therapies.

Evolving Immunology

In seeking to evolve immune therapy, Evommune is looking at the following opportunities in treating patients: early intervention in their disease state, improving efficacy, increasing response rates in patients and enhancing safety.

Autoimmune diseases are, in fact, systemic inflammatory conditions that are often associated with serious co-morbidities including infections, cardiovascular events, renal disease and mental health issues, making early intervention and preventing disease progression extremely important, Pea said. The entire body is in an accelerated immune-response mode. So, we are trying to modulate the immune system to dial down some of these responses.

Existing therapeutics have improved our ability to treat inflammatory conditions, but in most diseases, they still only elicit a response in about half the patients treated and achieve a great response rate in only one-third of those, he continued. Creating medicines that have better efficacy and that induce remission is the goal for us.

Improving the safety profile for drugs that treat autoimmune diseases could make a meaningful impact in this space. We want to develop therapies that improve patients quality of life without putting them at risk for other factors, Pea said.

Evommunes senior leadership and scientific teams are primed to do just that. Throughout their careers, they have helped bring more than 25 medicines to patients in need. As Pea noted, the combination of scientific insights, drug development expertise and building companies makes this team a unique group.

Accomplished Team of Experts

A testament to this is that Pea and Bauer were co-founders of Dermira, which Eli Lilly acquired for $1.1 billion to get the rights to lebrikizumab. The two had originally helped acquire this asset from Genentech, despite the drug having failed in prior Phase III trials for a different indication.

We saw that lebrikizumab had promise in atopic dermatitis. We believed lebrikizumab had been under-dosed in previous atopic dermatitis trials, mostly because of a focus on asthma, Pea explained. We adjusted the dose in a Phase II atopic dermatitis program and delivered strong data. Lilly bought us because of that drug and since then, lebrikizumab has had great data from their Phase III studies. We believe lebrikizumab will become a significant therapy for atopic dermatitis and the team at Evommune had the vision to make that happen, he said.

Before Dermira, Bauer was president and CMO of Peplin, Inc. (acquired by LEO Pharma) and shepherded Picato through a global submission, which included the FDA and resulted in an approval for actinic keratosis.

Additionally, the Evommune development team has been responsible for multiple new drug applications or biologics license applications, several investigational new drug applications and numerous other interactions with regulators, including four global clinical development programs.

That combination of intimate knowledge of both immunology and drug development is what separates Evommune from other companies in terms of our ability to move these novel therapies forward, Pea said.

Evommune is committed to this promise with the ongoing expansion of the team, including new management positions across R&D, CMC, legal, strategy and finance who also bring a wealth of diverse drug discovery and development expertise.

A Multifaceted Pipeline

Evommune currently has four programs in the pipeline.

"The goal for all of our programs is to be best in class, Pea said. EVO101 for atopic dermatitis is an IRAK4 inhibitor, which is a very novel target. A randomized, blinded, placebo-controlled Phase IIa clinical trial for patients with mild-to-moderate atopic dermatitis was initiated in Q3 2022.

We define mild-to-moderate atopic dermatitis as affecting between 4 and 12% of an individuals body surface area. For perspective, the palm of your hand is 1%, Bauer elaborated. Study participants will apply a 0.1% cream to the lesions twice daily for eight weeks. Results will be scored using the eczema area severity index (EASI), which measures redness, scaling and thickness of lesions, as well as the extent and severity of the disease.

In EVO101s development work, Evommunes human tissue model enabled researchers to recapitulate disease pathology and inflammatory mediators of atopic dermatitis. Adding low-, mid- and high-potency topical steroids (current standard-of-care therapeutics) to the human tissue model provided a control set of efficacy data a baseline by which we could then compare the performance of EVO101, Bauer explained.

EVO101, at the dosage being used for patients in the clinical trial, lowered inflammation levels to those comparable with doses of ultra-high potency steroids, but with high selectivity.

We believe this could become an alternative to standard-of-care therapies for atopic dermatitis, Bauer said, that may be used to treat both adult and pediatric patients.

In addition, we now have a development stage program that could potentially be a ground-breaking oral therapy for mast cell-mediated diseases, he said.

EVO756 is a completely novel compound that will target the treatment of mast cell-mediated diseases and inflammatory itch, Pea said. EVO756 targets MRGPRX2, a receptor that exists on mast cells and peripheral neurons and regulates mast cell degranulation. EVO756 is targeted for the treatment of mast cell-mediated disorders with highly prevalent populations such as chronic spontaneous urticaria, interstitial cystitis and hereditary alpha-tryptasemia.

In addition, preclinical data have shown that itch can be completely eliminated in mice: knocking out that receptor made it impossible to induce itch. For patients with inflammatory diseases, itch can be severe and have a significant, negative impact on a patients quality of life. We think EVO756 could be a great oral therapy, that can act quickly to relieve itch, Pea continued.

Another program, EVO390, is in development for the treatment of mild-to-moderate psoriasis in the hope of slowing or halting disease progression. This therapeutic agent targets RORt and has the potential to be best-in-class and the agent of choice for these patients. It may also serve as an adjunct therapy in more severe cases. We believe it could be a broadly used therapy for psoriasis, Pea added.

Our fourth program, currently in discovery, targets protein kinase C (PKC) theta, Pea continued. The company has identified several potent molecules that may have broad anti-inflammatory activity, highly targeted to T-effector cell inhibition and T-regulatory cell activation. This may have utility across a number of inflammatory conditions such as rheumatoid arthritis, IBD, atopic dermatitis and psoriasis. In addition, because it is highly targeted, it has the potential to be safer than the JAK inhibitors and other systemic anti-inflammatory agents.

As a company, we understand the importance of working on multiple targets and managing a portfolio of compounds. This approach provides the opportunity to work on different agents, impact many diseases and make a difference in patients lives, Pea said. The companys discovery engine is working to identify new targets so the team can extend its therapeutic impact.

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Evommunes Human Tissue-based Approach Enables Discovery and Development of Safer, Innovative Chronic Inflammation Therapies - BioSpace

Immunology

NexImmune Announces Research Collaboration with National Institute of Neurological Disorders and Stroke (NINDS) of the National Institutes of Health…

GAITHERSBURG, Md., Oct. 06, 2022 (GLOBE NEWSWIRE) -- NexImmune, Inc.(Nasdaq: NEXI), a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to orchestrate a targeted immune response by directing the function of antigen-specific T cells, today announced a collaboration with the National Institute of Neurological Disorders and Stroke(NINDS), a division of the U.S. National Institutes of Health (NIH). The collaboration will focus on enriching and expanding virus-specific T cell populations and determining their activity against infected human cell lines. The goal of this collaboration is to develop adoptive cell therapies that may benefit patients afflicted with immunological disorders related to these viral infections. Initially, we will focus our efforts on studying Epstein-Barr virus (EBV) and Human T-cell Leukemia Virus, type 1 (HTLV-1).

NexImmune is committed to developing novel therapies for the treatment of oncology, infectious disease and autoimmune disorders, said Kristi Jones, Chief Executive Officer of NexImmune. Compelling evidence exists that several autoimmune diseases are mediated by virally-infected cells. Current therapeutic approaches in these diseases broadly target cell populations that may or may not be expressly involved in the disease. NexImmunes AIM platform has the potential to selectively target and eliminate EBV-infected B cells in multiple sclerosis (MS), or HTLV-1-infected cells in HTLV-1 associated myelopathy (HAM), which may offer a unique benefit over current approaches. We will be working with the NINDS to evaluate EBV and HTLV-1 as therapeutic targets in the pathophysiology of neurological immune diseases. This important collaboration will enable us to leverage the AIM platform to develop potentially innovative antigen-specific therapies for these patients.

There is a clear causal relationship between HLTV-1 infection and HTLV-1 Associated Myelopathy and a potential relationship between EBV infection and MS, stated David Hafler, M.D., FANA, and member of NexImmunes Scientific Advisory Board. This work will help advance our understanding of the role immune responses to viral infection play in different neuroimmunological diseases.

AboutNexImmune

NexImmune is a clinical-stage biotechnology company developing a novel approach to immunotherapy designed to employ the bodys own T cells to generate a specific, potent, and durable immune response.

NexImmunes lead programs, NEXI-001, NEXI-002 and NEXI-003, are in Phase 1/2 clinical trials for the treatment of relapsed AML after allogeneic stem cell transplantation, multiple myeloma refractory to 3 or more prior lines of therapy and HPV-related cancers, respectively. NexImmune is also developing AIM nanoparticle constructs and modalities for potential clinical evaluation in oncology and in disease areas outside of oncology, including autoimmune disorders and infectious disease.

The backbone of NexImmunes approach is a proprietary Artificial Immune Modulation (AIM) nanoparticle technology platform. The AIM technology enables NexImmune to construct nanoparticles that function as synthetic dendritic cells capable of directing a specific T cell-mediated immune response. AIM constructed nanoparticles employ natural biology to engage, activate and expand endogenous T cells in ways that combine anti-tumor attributes of antigen-specific precision, potency and long-term persistence with reduced potential for off-target toxicities.

For more information, visit http://www.neximmune.com

AboutThe National Institute of Neurological Disorders and Stroke and its Viral Immunology Section

Created by the U.S. Congress in 1950, the National Institute of Neurological Disorders and Stroke (NINDS) has occupied a central position in the world of neuroscience for over 70 years. The mission of NINDS is to reduce the burden of neurological diseasea burden borne by every age group, every segment of society, and people all over the world.

To accomplish this goal, the Institute supports and conducts basic, translational, and clinical research on the healthy and diseased nervous system; fosters the training of investigators in the basic and clinical neurosciences; and seeks better understanding, diagnosis, treatment, and prevention of neurological disorders.

The Viral Immunology Section studies the role of human viruses in the pathogenesis of chronic progressive neurologic disease. As part of its work, the laboratory is studying virological, immunological, and molecular mechanisms associated with the human T lymphotropic virus type-I associated myelopathy/tropical spastic paraparesis and the association of virus in multiple sclerosis.

Forward Looking Statements

This press release may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 that are based on the beliefs and assumptions and on information currently available to management of NexImmune, Inc. (the Company). All statements other than statements of historical fact contained in this press release are forward-looking statements, including statements concerning our planned and ongoing clinical studies for the Companys product candidates, including NEXI-001 and NEXI-002; the initiation, enrollment, timing, progress, release of data from and results of those planned and ongoing clinical studies; and the utility of prior preclinical and clinical data in determining future clinical results. In some cases, you can identify forward-looking statements by terminology such as may, will, should, expects, plans, anticipates, believes, estimates, predicts, potential or continue or the negative of these terms or other comparable terminology. Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause the Companys actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks and uncertainties include, but are not limited to, the risks and uncertainties set forth in the Risk Factors section of our Annual Report on Form 10-K for the year ended December 31, 2020 filed with the Securities and Exchange Commission (SEC) on March 31, 2021, and subsequent reports that we file with the SEC. Forward-looking statements represent the Companys beliefs and assumptions only as of the date of this press release. Although the Company believes that the expectations reflected in the forward-looking statements are reasonable, it cannot guarantee future results, levels of activity, performance or achievements. Except as required by law, the Company assumes no obligation to publicly update any forward-looking statements for any reason after the date of this press release to conform any of the forward-looking statements to actual results or to changes in its expectations.

Contacts

Investors:Chad Rubin, SVP Corporate AffairsNexImmune, Inc.646.319.3261crubin@neximmune.com

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Anatomy

Anatomy of a Ransomware Attack: 8 Stages of Operation [White Paper] – BlackBerry Blog

Its a dark and rainy night. Thunder rumbles. Lightning flashes. An unexpected crime takes place. Intrigue and deception follow, with a mystery to solve.

When it comes to fiction, you might enjoy reading a good mystery to figure out whodunnit. Not so, when that crime is a ransomware attack with a digital note telling you that threat actors have compromised your organizations network, encrypted all your files, and are demanding immediate payment to restore your operations.

In 2021, the average cost of a ransomware attack hit $1.85 million a 41% increase from the previous year. This includes the ransom, downtime, people time, device cost, network cost, lost opportunity, and more. But beyond the financial and reputational cost, theres another impact few companies talk about: leadership turnover. Recent research reveals that 32% of the time, C-level employees depart the organization after a successful ransomware attack. To add insult to injury, 80% of targeted organizations are hit by a repeat attack.

These are the reasons SANS Institutes Senior InstructorJake Williams, and BlackBerry Principal Incident Response & Forensics ConsultantRyan Chapman, joined forces in a recent SANSwebcastto explain the various stages of a ransomware operation, and steps organizations can take to lessen vulnerability. Their insights are also echoed in the free white paperAnatomy of a Ransomware Operation.

Ransomware is no longer just an executable that drops onto a device and then does bad things on that device, Chapman says in the webcast. Rather, it is an overall operation, and it's carried out by humans with their hands on the keyboard.

Threat actors are doing things human-operated, Chapman concludes. You should too. If you don't have enough security-minded folks, then that's where managed detection and response comes in.

In the webcast, Williams and Chapman list eight distinct stages in a typical ransomware attack:

View thewebcast, or read thefree white paperfor more details on each attack stage, and to understand opportunities to disrupt a ransomware attack as it occurs in your environment. You can also stay up to date on ransomware attack protection and prevention by visitingblackberry.com/ransomware.

TheBlackBerry Incident Response teamcan work with organizations of any size and across any vertical, to evaluate and enhance their endpoint security posture and proactively maintain the security, integrity, and resilience of their network infrastructure.For emergency assistance, please email us atDLIR@blackberry.com, or useourhandraiserform.

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Anatomy of a Ransomware Attack: 8 Stages of Operation [White Paper] - BlackBerry Blog

Anatomy

The Anatomy of the Mets 2022 Collapse – metsmerizedonline.com

Credit: Brett Davis-USA TODAY Sports

When seasons dont end the way you want or expect, people look for a reason or a scapegoat. To wit, the New York Mets announced both Billy Eppler and Buck Showalter were returning next season. On the one hand, it would seem obvious that was the case, but there was a collapse, so it was best to state it outright.

Certainly, both Eppler and Showalter have their fair share of the blame for what happened. However, it is much deeper and much more layered than that.

The seminal moment most Mets fans point to is Starling Martes hand injury in the September 6 game against the Pittsburgh Pirates. Ask a Mets fans, and they staunchly believe the Mets win the division if Marte doesnt get hurt. To a certain extent, there is truth to that.

After all, it meant more Tyler Naquin, who was terrible in September batting .185/.232/.308. He was so poor he was left off the postseason roster despite his terrific numbers against Yu Darvish, a pitcher the Mets never hit.

Looking at Naquin, that should have us revisit the Eppler point. There was a post hoc analysis of the Mets trade deadline moves (which were debated in real time). Prior to the Daniel Vogelbach trade, Mets DHs had a 79 wRC+. From Vogelbachs firsts game with the Mets to the end of the season, that mark improved to a 102 wRC+.

However, that was mostly Vogelbach. Against left-handed pitching. Darin Ruf had a 20 OPS+ with the Mets. Mark Vientos and Francisco lvarez were throw into pennant races and struggled. Notably, Gary Cohen was highly critical of the Mets decision making process noting how the Mets didnt call them up when there was a chance during the season and put too much on them.

To that point, the Atlanta Braves called upMichael Harris and Vaughn Grissom well in advance of September games, and they got much better production. As an aside, the Braves are again extending their young core while the Mets arent, but thats a separate discussion for another day.

All of the above is a worthwhile discussion, however, it is still not getting to the root cause. The Mets collapse began at Citi Field against the Washington Nationals. The Mets would lose two out of three games. It was part of the Mets worst stretch of the season.

From September 3 to September 14, the Mets were 5-6 against the Washington Nationals, Pittsburgh Pirates, Miami Marlins, and Chicago Cubs. During that stretch, the Mets three game lead shrunk to a half game. Over a stretch where the Mets could put the division away, they put the division back in play allowing the Braves to sweep the Mets forcing the Mets to the Wild Card.

Fast-forward for a second to the Atlanta Braves series. There were a number of problems in that series. Chief among them was the starting pitching failed. Figuring out how to prevent this from happening again requires diagnosing how that happened. The answer may be unsatisfying to some, but it is as simple as fatigue.

Wendell Cruz-USA TODAY Sports

Carlos Carrasco, who didnt pitch in the Braves series, pitched a combined 121 2/3 innings over the previous two seasons. He would pitch 152 this season. At the 64 inning mark this season, Carrasco had a 3.52 ERA and was averaging 5 2/3 innings per start. After that, he had a 4.30 ERA averaging under five innings per start.

He had one of the Mets bad losses in September. On September 27, he allowed four runs to the Marlins over three innings. That was one of many games the Mets wanted back.

Taijuan Walker again had a poor second half, but he did salvage it a bit in September. Still, he faltered against the Pirates, and he took the loss against the Milwaukee Brewers. Both were big spots, and he and the Mets wish they had those games back.

Of course, neither Carrasco nor Walker were the biggest culprits, the ultimate blame seems to be directed at Chris Bassitt. Last year, Bassitt pitched 157 1/3 innings, and he had only thrown over 100 innings one other time in his career.

After his September 7 start, he hit the 161 1/3 inning mark. At that point, he had a 3.24 ERA while averaging a little over six innings per start. After that, Bassitt fell apart against the Cubs and Braves. He was very good against bad teams in the Pirates and Oakland Athletics.

Max Scherzer dealt with oblique issues. Jacob deGrom had a blister issue. Neither would ever admit it impacted their performances, but essentially, they were compromised pitchers. When you build a team on starting pitching, you cant have all five starters limping to the finish line. That is exactly what the Mets had.

Unfortunately, they did not have the hitting to overcome this. That was apparent in Atlanta when they scored all of seven runs. Over the final month of the season, in their losses, they averaged 2.5 runs per game. Part of this was the Mets approach at the plate.

Brad Penner-USA TODAY Sports

The Mets hit 171 homers this season ranked 15th in the majors. Pete Alonso and Francisco Lindor accounted for 38.6% of the Mets home run production. The next highest was Eduardo Escobar with 20, and he hit almost half of them in September. Essentially, for most of the season, if Alonso and Lindor werent hitting it out of the park, no one was.

Combine that with very questionable managing from Buck Showalter in Atlanta and the postseason, and you have a 101-win Mets team that fails to win the division. You have a Mets team who gets one hit in an elimination game.

With the Mets, it was no one thing. It was exhausted starting pitching who faltered. It was an offense overly reliant on two players. It was a manager who struggled in bad games making poor decisions in big games. And yes, it was a front office who failed to fully address the teams deeper issues at the trade deadline.

When all was said and done, this was a team built to sustain the rigors of the regular season. However, it was not prepared and built to last deep into the season and go deep into October. We didnt realize it at the time, but it is difficult to overlook now.

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Anatomy

Will Bailey Ever Return to Grey Sloan? Greys Anatomy Boss Explains – TV Insider

After visiting her old workplace to get a glimpse of Grey Sloan Memorials new, bottom of the barrel intern class and getting an earful from the guy who wanted to be the vagina of the surgical program Miranda Bailey (Chandra Wilson) seemed all too happy to let Richard Webber (James Pickens Jr.) handle the situation.

Good luck with that, she said over her shoulder as she sashayed out of the Grey Sloan ER in Greys Anatomys Season 19 premiere on Thursday, October 6,

Bailey got really tired of carrying Grey Sloan on her shoulders last season, Greys showrunner Krista Vernoff explained to TVLine recently. And she made a decision to step away for her sanity and her well-being.

But how long will Baileys fun-employment last? Is she ever coming back to the hospital?

Greys Anatomy spoilers ahead!

Bailey will indeed scrub in again at Grey Sloan, per TVLine, which previously reported that the character will soon team up with Addison, played by returning alum Kate Walsh.Were telling a really powerful story about Addison and Bailey joining forces that is in turns funny and gut-wrenching, and through that story fans will learn a little bit more about Addisons life back in Los Angeles, Vernoff told the site last week.

The Greys boss added that the ABC show will delve into what an ambitious person like Bailey does when they sort of reach the top rung of where they want to go and need to find other areas where that ambition can be useful.

For Bailey, its in so many areas, Vernoff, who also handles the fate of Baileys husband, Ben, as showrunner of spinoff Station 19. It may also be a case of, in some ways, more being less.

Vernoff also teased that the key for Bailey may be finding the joy in taking a lesser title at work in favor of having a richer, happier life.

Nino Muoz/ABC

Actor Chandra Wilson told TheWrap recently that Bailey is too nosy to stay away from Grey Sloan for long. She is actually kind of going through that same transition that most folks in the world are going through right now, where your priorities change as a result of everything that weve been through in the last three years, at this point, she added.

Wilson also said that well see a different side of Bailey in Season 19 as the character redefines her Grey Sloan role. We have seen a person who had goals from Day 1; we got to see her achieve those goals in real time, the SAG Award winner observed. And we also got to see the difference between who she thinks she is and who the audience knows she is. So I think in Baileys mind, shes still the person that you met in the pilot for the most part, but as an audience member, you know better now, right?

Greys Anatomy, Thursdays, 8/7c, ABC

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Will Bailey Ever Return to Grey Sloan? Greys Anatomy Boss Explains - TV Insider

Anatomy

Nine Brains, Three Hearts and Other Octopus Anatomy Facts – Now. Powered by Northrop Grumman.

Octopus anatomy is strikingly different from the human body, unless youre Dr. Otto Gunther Octavius. Eight arms are the most obvious trait, but beneath the mottled skin theres actually an array of brains, one for each tentacle. And just how many hearts does an octopus have? The answer is a surprising three, and each has an important function, so theyre not just spares.

These facts are just the tip of the iceberg for one of the more specialized creatures under the sea.

With such a uniqueness in octopus anatomy, youd expect these cephalopods to live forever. Sadly, no. The usual life span in the wild is only around one to two years for most species, according to National Geographic.

The Nature Conservancy Council of Canada notes that the largest species, the Northern Giant Pacific octopus, is also the longest lived. It reaches up to around five meters in length and between 20 and 50 kilograms in weight (about 16.5 feet and between 44 and 110 pounds), and dies at around five years old, usually after mating or laying and caring for eggs.

Scientific American blogged about the loss of the National Zoos resident octopus, Pandora, who had been entertaining visitors in her tank for 27 months, which is quite a record for an octopus.

An octopus has not one, but three hearts.

Two of them the branchial hearts pump blood to the gills where it picks up oxygen. The third, or systemic heart, pumps the oxygenated blood around the body, fueling up the eight tentacles for whatever they and their suckers plan to do.

Octopuses are quite active as cephalopods, and its thought that the three hearts are necessary to maintain their power. However, when swimming, the octopus does not use its systemic heart and can tire quite easily. It creates water jets with its body mantle instead to power propulsion.

Octopus blood is blue due to the copper-based, oxygen-carrying hemocyanin it contains. Hemocyanin doesnt carry oxygen as well as a humans iron-based hemoglobin, and New Scientist explains this might be why octopuses need more than one heart. Unfortunately, hemocyanin doesnt carry oxygen so well in acidic conditions. Since climate change is gradually lowering the pH of the worlds oceans, the environment here may not be ideal for octopus anatomy in the future.

Another reason for the impressive array of hearts is due to another peculiar feature of octopus anatomy: They have a mini brain in each of the eight tentacles, which helps each arm act independently with speed and sharp reflexes. A ninth brain oversees the entire nervous system and can also somewhat override the mini brain to operate each tentacle.

The brain-to-body ratio for an octopus is the largest for any invertebrate, and they have around the same number of neurons as a dog. They are known to be extremely intelligent, learning to solve puzzles in lab simulations and are also able to recognize people.

Having such a powerful and extensive nervous system takes a lot of energy, hence the three hearts to pump blood around the octopus.

Tentacles, each covered in an array of powerful suckers, are used for locomotion and gathering food. Although octopuses can swim, their preferred locomotion is to crawl along the seabed. Octopuses can also use their tentacles to manipulate objects, unscrewing jars and holding food. Male octopuses use a specialized grooved tentacle called a hectocotylus to pass a spermatophore to the female during mating. The National History Museum describes how some male octopuses also leave the appendage with the female.

Octopus anatomy has inspired robot development; using biomimicry, researchers at Harvard developed a soft tentacle bot that can carefully grasp irregular objects. There have even been attempts to develop climbing robots based on their ability to grasp surfaces such as ladder rungs and rough walls.

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Anatomy

Harry Shum Jr. on Joining Greys Anatomy and New Romances Ahead (VIDEO) – TV Insider

Greys Anatomy is making way for fresh blood in Season 19 and fans got a taste of it in the premiere installment, Everything Has Changed.

Among the newly-introduced lot is Harry Shum Jr.s intern, Benson Kwan, who made quite the impression in the opening episode that aired on October 6. The actor, who is known for his roles on shows like Shadowhunters and Glee, had a surreal experience upon walking onto the set for the first time, as he recalled to TV Insiders Jim Halterman.

(Credit: ABC/Liliane Lathan)

It feels very real, I mean, you feel like youre stepping into a real hospital, Shum Jr. marveled. Theres so many nurses and other doctors walking around, it really doesnt differentiate between reality and the Greys world. So it was nice to step in there.

As for donning the iconic Grey Sloan Memorial scrubs and jacket, Shum Jr. said its like a cape, man, its like a little superhero. Everyones a superhero in this, theyre saving lives but theyre also dealing with a lot of inner turmoil thats happening in their lives and in each others relationships.

Despite the heavier moments that can occur in the medical drama, Shum Jr. teased, Its bringing a lot of the fun back into the interactions with different characters. Shouting out his fellow new interns, Shum Jr. added, Theyve just been wonderful. I think they really chose some great actors to join this new season.

As for fans of the signature doctor-on-doctor romance, Shum Jr. promised, Theres definitely distractions, theres always distractions at Grey Sloan, thats what Ive learned also some distractions that, you know in the Greys world, will lead a lot of shipping to happen. Possibilities that the fans could have fun with and see which ones they like and dont like.

Stay tuned to see how it all unfolds as Greys Anatomy Season 19 continues on ABC, and see Shum Jr.s full interview in the video, above.

Greys Anatomy, Season 19, Thursdays, 9/8c, ABC

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Harry Shum Jr. on Joining Greys Anatomy and New Romances Ahead (VIDEO) - TV Insider