#clinical trials journal

[symbiosis-online-publishing]

Preventive Strategies and Public Health

Welcome to the Journal of Clinical Trials in Cardiology, a leading publication dedicated to advancing knowledge and innovation in cardiovascular clinical trials. Our journal serves as a distinguished platform for researchers, clinicians, and healthcare professionals to contribute and access the latest advancements in cardiology research. At the heart of our mission is the commitment to fostering evidence-based practice and enhancing patient care through the dissemination of high-quality clinical trial findings. The Journal of Clinical Trials in Cardiology strives to promote rigorous research methodologies, ethical conduct, and transparency in cardiovascular clinical trials.

Key Features:

Rigorous Peer Review: All submitted manuscripts undergo a thorough and unbiased peer-review process by experts in the field to ensure the highest scientific standards.

Comprehensive Scope: The journal covers a wide range of topics within cardiovascular clinical trials, including but not limited to novel therapies, diagnostic tools, and prevention strategies.

Global Collaboration: We encourage international collaboration and welcome contributions from researchers around the world to facilitate a diverse and impactful exchange of ideas.

Our primary audience includes cardiologists, researchers, clinical trial specialists, and healthcare professionals dedicated to advancing cardiovascular medicine. We aim to provide a valuable resource for staying informed about the latest developments in the field.

[savannah-xox]

According to a University of Plymouth Study, board games are extremely popular with people who have autism (17/07/2024)

INTRODUCTION

Hi there, and welcome to my very first post of Science With Savannah, where I discuss latest developments in the scientific world and make it bite-sized.

(Kinda. This article ran away from me.)

Today, we're delving into this rather intriguing study that I found online, called: Game Changer: Exploring the Role of Board Games in the Lives of Autistic People.

I chose this article because there are many people close to my heart who have autism, yet one of them absolutely hates board games. Hence, I wanted to understand this research and this take and so here we are. :)

IMPORTANT THINGS TO NOTE

Source: University of Plymouth. "Why are board games so popular among many people with autism? New research explains. Science Daily Article

Original Scientific Journal: Cross, L., Belshaw, F., Piovesan, A. et al. Game Changer: Exploring the Role of Board Games in the Lives of Autistic People. J Autism Dev Disord (2024). https://doi.org/10.1007/s10803-024-06408-0

NB: When I cite the 'source' this means that this is the link where I originally learned about the study. When I cite the 'original scientific journal,' I cite the actual scientific article which goes into depth about the research methods.

Disclaimer:

I am neurotypical, and so if my language comes off as tone deaf at any point, please feel free to correct me. I'm always wanting to improve and learn more.

Furthermore, I will not be delving into what autism is, as it is not the point of my post. If you want to learn more about autism, please note the Abstract Section of the original source, and do your own research.

Finally, please remember that I am not a medical professional, but rather a teenager who wants to share new things that she has learned.

Key Takeaways

Essentially, the study suggests that board games are especially well suited for autistic people by comparing and analysing data from various sources and reaching a conclusion.

The article suggests that playing board games can be beneficial for those who are autistic. The main reasoning this study gives for this suitability is because variety of board games can be specifically well suited for an autistic person's passion (or special interest) as well as their cognitive ability, because board games focus less on people, and focuses more on the actual game at hand, which removes difficulties such as trying to read implicit body language, that some people with autism find difficult.

Furthermore, autistic individuals who play in a group are suggested to feel accepted and able to express their true selves because everyone enjoys the game, and it helps to develop close relationships.

The article suggests that board games can lead to better social relationships and mental health and that this should be studied more to see if board games can be used as a therapy for people with autism.

After explaining this, the scientific journal goes on to describe several studies that were used to reach this conclusion, the sample sizes that helped reach each conclusion, and ultimately an accumulation of all the information that was presented, ending with the sentiment that more research should be done in this specific subject area because of its positive potential.

Should we be wary of this article?

It should be acknowledged that there has not been a lot of specific research in this area and is instead based on 'anecdotal evidence of a total of three studies. In this post, I'd like to highlight the key issues with the first study only, as the sample sizes for the other studies were small, with less than fifty people.

The first piece of research that the article gives us is based upon the mental health conditions and other demographics of board gamers online, and is based on a study of over 1,600 adults. Of those who answered positively for autism, this percentage of those found to have autism was higher than the world average of people with autism, suggesting that they were overrepresented amongst board gamers in comparison to the general population. The large sample size suggests the reliability of this study, including the breakdown with several questions, was effective, but as with all studies, it may not be showing the whole picture. For example, the majority of participants were Male and White and the sample was carried out in the Western. This may imply that even though this study spanned 63 countries the experiences of women and women of colour who have autism may have not come into light. Furthermore, the majority of participants proved to be university educated, which may lessen credibility of this study and conclusion of this article because it leaves out many, many people with autism who may not have gone into tertiary level education.

However, this does not mean we should discredit this article completely. This article was clearly peer reviewed and was written by two Professors of Psychology at leading UK universities, meaning that there is valid truth to these findings, and although there are some discrepancies, this is normal in the world of scientific research.

Thanks for reading, and I hope that you have learned something new :)

[afeelgoodblog]

The Best News of Last Week

1. ‘We are just getting started’: the plastic-eating bacteria that could change the world

In 2016, Japanese scientists Oda and Hiraga published their discovery of Ideonella sakaiensis, a bacterium capable of breaking down PET plastic into basic nutrients. This finding marked a shift in microbiology's perception, recognizing the potential of microbes to solve pressing environmental issues.

France's Carbios has successfully applied bacterial enzyme technology to recycle PET plastic waste into new plastic products, aligning with the French government's goal of fully recycling plastic packaging by 2025.

2. HIV cases in Amsterdam drop to almost zero after PrEP scheme

According to Dutch AIDS Fund, there were only nine new cases of the virus in Amsterdam in 2022, down from 66 people diagnosed in 2021. The organisation claimed that 128 people were diagnosed with HIV in Amsterdam in 2019, and since 2010, the number of new infections in the Dutch capital has fallen by 95 per cent.

3. Cheap and drinkable water from desalination is finally a reality

In a groundbreaking endeavor, engineers from MIT and China have designed a passive solar desalination system aimed at converting seawater into drinkable water.

The concept, articulated in a study published in the journal Joule, harnesses the dual powers of the sun and the inherent properties of seawater, emulating the ocean’s “thermohaline” circulation on a smaller scale, to evaporate water and leave salt behind.

4. World’s 1st drug to regrow teeth enters clinical trials

The ability to regrow your own teeth could be just around the corner. A team of scientists, led by a Japanese pharmaceutical startup, are getting set to start human trials on a new drug that has successfully grown new teeth in animal test subjects.

Toregem Biopharma is slated to begin clinical trials in July of next year after it succeeded growing new teeth in mice five years ago, the Japan Times reports.

5. After Decades of Pressure, US Drugmaker J&J Gives Up Patent on Life-Saving TB Drug

In what can be termed a huge development for drug-resistant TB (DR-TB) patients across large parts of the world, bedaquiline maker Johnson and Johnson said on September 30 (Saturday) that it would drop its patent over the drug in 134 low- and middle-income countries (LMICs).

6. Stranded dolphins rescued from shallow river in Massachusetts

7. ‘Staggering’ green growth gives hope for 1.5C, says global energy chief

The prospects of the world staying within the 1.5C limit on global heating have brightened owing to the “staggering” growth of renewable energy and green investment in the past two years, the chief of the world’s energy watchdog has said.

Fatih Birol, the executive director of the International Energy Agency, and the world’s foremost energy economist, said much more needed to be done but that the rapid uptake of solar power and electric vehicles were encouraging.

---

That's it for this week :)

This newsletter will always be free. If you liked this post you can support me with a small kofi donation here:

Buy me a coffee ❤️

Also don’t forget to reblog this post with your friends.

[reasonsforhope]

"People living with diabetes might have a new hope. Scientists have tested a new drug therapy in diabetic mice, and found that it boosted insulin-producing cells by 700% over three months, effectively reversing their disease.

Beta cells in the pancreas have the important job of producing insulin in response to blood sugar levels, but a hallmark of diabetes is that these cells are either destroyed or can’t produce enough insulin. The most common treatment is regular injections of insulin to manage blood sugar levels.

But a recent avenue of research has involved restoring the function of these beta cells. In some cases that’s started with stem cells being coaxed into new beta cells, which are then transplanted into patients with diabetes. Researchers behind this kind of work have described it as a “functional diabetes cure.”

Now, scientists at Mount Sinai and City of Hope have demonstrated a new breakthrough. Previous studies have mostly involved growing new beta cells in a lab dish, then transplanting them into mice or a small device in humans. But this new study has been able to grow the insulin-producing cells right there in the body, in a matter of months.

The therapy involved a combination of two drugs: one is harmine, a natural molecule found in certain plants, which works to inhibit an enzyme called DYRK1A found in beta cells. The second is a GLP1 receptor agonist. The latter is a class of diabetes drug that includes Ozempic, which is gaining attention lately for its side effect of weight loss.

The researchers tested the therapy in mouse models of type 1 and 2 diabetes. First they implanted a small amount of human beta cells into the mice, then treated them with harmine and GLP1 receptor agonists. Sure enough, the beta cells increased in number by 700% within three months of the treatment. The signs of the disease quickly reversed, and stayed that way even a month after stopping the treatment.

“This is the first time scientists have developed a drug treatment that is proven to increase adult human beta cell numbers in vivo,” said Dr. Adolfo Garcia-Ocaña, corresponding author of the study. “This research brings hope for the use of future regenerative therapies to potentially treat the hundreds of millions of people with diabetes.”

The results are intriguing, but of course being an animal study means there’s still much more work to be done before it could find clinical use. So far, harmine alone has recently undergone a phase 1 clinical trial in humans to test its safety and tolerability, while other DYRK1A inhibitors are planned for trials in humans next year.

Perhaps most importantly, the team will soon experiment with combining beta-cell-regenerating drugs with others that modulate the immune system. Ideally this should help overcome a major hurdle: the immune system will continue attacking new beta cells as they’re produced.

The research was published in the journal Science Translational Medicine."

-via New Atlas, July 14, 2024

[symbiosisonlinepublishing]

Symbiosis Online Publishing invites practicing experts, researchers, and students to submit original articles on clinical trials in cardiology. Now, read about the casual argument between treatment and the control of the disease.

Visit: https://symbiosisonlinepublishing.com/cardiology/

[lifewithchronicpain]

Medical research has shortchanged women for decades. This is particularly true of older women, leaving physicians without critically important information about how to best manage their health.

Late last year, the Biden administration promised to address this problem with a new effort called the White House Initiative on Women’s Health Research. That inspires a compelling question: What priorities should be on the initiative’s list when it comes to older women?

Stephanie Faubion, director of the Mayo Clinic’s Center for Women’s Health, launched into a critique when I asked about the current state of research on older women’s health. “It’s completely inadequate,” she told me.

One example: Many drugs widely prescribed to older adults, including statins for high cholesterol, were studied mostly in men, with results extrapolated to women.

“It’s assumed that women’s biology doesn’t matter and that women who are premenopausal and those who are postmenopausal respond similarly,” Faubion said.

“This has got to stop: The FDA has to require that clinical trial data be reported by sex and age for us to tell if drugs work the same, better, or not as well in women,” Faubion insisted.

Consider the Alzheimer’s drug Leqembi, approved by the FDA last year after the manufacturer reported a 27% slower rate of cognitive decline in people who took the medication. A supplementary appendix to a Leqembi study published in the New England Journal of Medicine revealed that sex differences were substantial — a 12% slowdown for women, compared with a 43% slowdown for men — raising questions about the drug’s effectiveness for women.

This is especially important because nearly two-thirds of older adults with Alzheimer’s disease are women. Older women are also more likely than older men to have multiple medical conditions, disabilities, difficulties with daily activities, autoimmune illness, depression and anxiety, uncontrolled high blood pressure, and osteoarthritis, among other issues, according to scores of research studies. (Read more at link)

While it certainly isn’t a panacea, for certain things I will only see a female doctor. No one is immune to bias and I’ve had bad experiences with some women, overall I feel more listened to and more at ease at appointments. Medical sexism is way too real, and we should use any tool we can to minimize it.

[covid-safer-hotties]

Yes, there's hope in the fight against Long Covid.

Hope doesn't come in the form of natural immunity or subpar vaccines rolled out after waves of illness have already peaked. It comes in the form of clean indoor air, widespread masking, and better treatments. In that vein, the NIH is finally launching a new batch of clinical trials focused on Long Covid, five total, dedicated to different aspects of the condition. Institutes like Mount Sinai are running clinical trials on repurposed HIV drugs. So is HealthBio, a startup working on immune diseases. (They're testing maraviroc and atorvastatin.) Post-Viral Trials News is sharing updates as they roll in. Of course, the NIH and FDA need steady pressure to make sure they're funding trials that focus on a range of options. Given the urgency of the crisis, we should be doing far more. As Harvard economist David Cutler has said on developing treatments for Long Covid, "There is no amount that's overdoing it." We're talking about a $16 trillion crisis.

We're talking about an urgent need for dozens of expedited clinical trials for drugs that already exist, which have shown effectiveness in preventing and treating Long Covid in its various incarnations. We're talking about making those drugs accessible right now for off-label use, so that Covid survivors can finally get the help they need.

Long Covid is an emergency.

We're going to talk about prescription treatments first, and then supplements and extracts you can find yourself. Up front, you can try services like RTHM and CURE ID that aim to connect patients with treatments without endless waits. (I'm not endorsing them. I'm just telling you they exist.)

Let's dig in.

Healthcare largely abandoned monoclonal antibodies during the first Omicron wave, but some of them remain effective in higher doses as postviral therapies. We've also found new ones. For example: A study in Nature offers 5B8 as a therapy for fibrinogen, a protein in your body that binds to the Covid spike protein during infection. Afterward, that protein starts to behave differently, "forming pro-inflammatory blood clots" that lead to cardiac and brain dysfunction, especially in young patients with mild infections. It also suppresses your natural killer cells, weakening your immune system. So, damaged fibrinogen is the culprit behind a lot of the "mysterious" health problems we're seeing.

As the authors show, "fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute Covid-19 and Long Covid." The monoclonal antibody 5B8 "provides protection...without adverse effects." The sooner you get it, the better it works.

A 2024 study in the American Journal of Emergency Medicine also found that the monoclonal antibody regeneron helped Long Covid survivors recover. Researchers "expressed surprise at the swift and comprehensive improvements observed in the patients," adding that "regardless of the duration of their Long Covid experience, significant progress was noted within a mere 5 days of receiving the Regeneron treatment." It might work because it helps your immune system eliminate residual amounts of virus or viral fragments, or it might replace damaged antibodies that attack your cells.

A 2022 study found that another monoclonal antibody, Sotrovimab, helped survivors with persistent viral loads after initial infection who were still reporting fatigue, chest pain, and trouble breathing months after infection. As the researchers note, the patients showed "rapid improvement of symptoms and inflammation markers as well as negative swabs."

Yet another 2022 study in Clinical Infectious Diseases found that a monoclonal antibody treatment called Leronlimab could help Long Covid patients recover by boosting their immune system in cases where Covid downregulated it, causing a drop in their CCR5 levels, a receptor found on a range of cells that fight pathogens, including your CD4 lymphocytes.

The Long Covid Action Project is also developing a list of drugs that desperately need clinical trials and faster deployment. They stress the need for monoclonal antibodies and antivirals like pemivibart, azvudine, ensitrelvir (Xocova), and sofosbuvir. They'll be releasing a full list later this year.

So while these monoclonal antibodies might not save your life during early infection, they can help your recovery.

There should be more clinical trials and off-label use.

Interferon treatments, specifically Interferon-Lambda, have shown the potential to help with immune system problems and cognitive deficits (caused by brain inflammation) after Covid infections.

Also:

A 2022 study in Frontiers in Immunology found that high doses of immunoglobulin have shown "a significant to remarkable clinical benefit" in treating a full range of brain, heart, and lung problems in Long Covid patients. A major 2023 study in Frontiers in Neuroscience confirmed that immunoglobulin lead to significant improvement in neurological problems. As researchers in a third study on immunoglobulins and Long Covid state, we already use this therapy to treat a variety of chronic inflammatory diseases, as well as flu, HIV, and measles. (The NIH has included immunoglobulins in their new clinical trials.)

HIV drugs have also shown promise for helping Long Covid patients. A 2023 study in Clinical Infectious Diseases found that Tenofovir reduced someone's Covid risk regardless of whether they had HIV. A range of studies have supported the use of Tenofovir, Darunavir Ethanolate, and Azvudine for Covid. As we noted earlier, clinical trials are currently testing HIV drugs for Long Covid.

Another study in Antiviral Research found that cobicistat, used to boost HIV antivirals, also fights Covid and leads to a significant reduction in overall risk. The researchers found that higher doses work better. They also found that higher doses work better for ritonavir, one of the key components of Paxlovid. By the way, ritonavir has been used in HIV treatments since the mid-1990s.

The research on repurposed HIV drugs points to the potential of many antiretroviral therapy (ART) medications for Long Covid, given that viral persistence plays a large role in most cases.

When you consider that Paxlovid itself contains an HIV antiviral, it sounds a little less extreme to compare Covid to HIV and discuss repurposing existing drugs.

Finally, studies have shown that molnupiravir and metformin have shown effectiveness against Covid. In particular, a 2024 study in Clinical Infectious Diseases found that metformin prescribed in the early stages of a Covid infection led to a 41 percent drop in Long Covid risk.

Other research has revealed that sometimes it takes a combination of these drugs to help patients recover. In a 2022 study in Clinical Infectious Diseases, researchers used nanopore technology to identify the specific variants patients were infected with and select the most effective treatments for that variant. In one case, a Long Covid patient with severe Paxlovid rebound only got better after doctors prescribed Paxlovid again and added remdesivir. Nobody had thought to try that yet.

It worked.

These are the drugs that demand renewed attention and clinical trials, given that most research on Long Covid points to ongoing infection, viral persistence, and the disruption of your immune system, which could mean a downregulated or weakened immune system or an overactive one. We especially need clinical trials that match drugs with specific conditions.

Specialists are going to decide the right dose for prescription drugs. Generally, the research indicates that if a standard dose doesn't work, a higher dose might as long as it doesn't trigger side effects. A combination of drugs can work when a single drug fails.

What can you do if you don't have access to these drugs?

This:

A major 2023 study in Cells found that eriodictyol, a flavonoid extracted from yerba santa, can help with the brain inflammation caused by Covid infections that leads to cognitive deficits and fatigue. Researchers have found that at least part of the "brain fog" from Long Covid happens when the virus triggers immune cells to attack the brain. Eriodictyol can also be derived from citrus fruits, tomatoes, and grapes. As the authors explain, a range of flavonoids "have been reported to prevent neuroinflammation, provide neuroprotection, and reduce cognitive dysfunction, especially brain fog."

The authors of the Cell study list flavanoids liposomal luteolin, oleuropein, and sulforaphane as all beneficial for recovering brain function. They identify formulas called BrainGain and FibroProtek containing flavonoids that helped Long Covid patients with severe brain fog in previous studies. Those contain luteolin. They ultimately recommend ViralProtek, which combines several flavonoids, "alone or together" with eriodictyol.

These formulas aren't just managing symptoms. According to the studies, they're helping you clear viral remnants and rehabilitate your immune system. They inhibit your microglia and mast cells, immune cells that often drive the brain inflammation behind Long Covid cognitive problems.

What else?

A 2022 study in Molecules found promise in nattokinase, "a popular traditional Japanese food made from soybeans fermented by Bacillus subtilis var." Not so coincidentally, nattokinase also "decreases the plasma levels of fibrinogen," the same protein that drives thrombosis in Long Covid patients and indeed "has drawn central attention in thrombolytic drug studies," as well as tumor treatment. It also inhibits the replication of bovine herpes virus. Clinical trials have found no adverse effects from eating natto. In this particular study, the researchers found that nattokinase degrades the Covid spike protein, inhibiting infection. As they conclude, "nattokinase and natto extracts have potential effects on the inhibition of SAS-cOv-2 host cell entry."

Martha Eckey describes natto extracts in more detail here, along with benefits, recommended dosage, and possible side effects. Respondents to her survey reported the best results when they took Solaray's natto extract along with serrapeptase, an enzyme and commonly used drug in Japan and Europe that helps your body break down proteins. A large number of patients reported improvement after taking the natto-serra combination, often within a week or two. Many of them also benefited from adding lumbrokinase, an enzyme shown to facilitate healing.

Like natto, lumbrokinase breaks down fibrin. We're seeing a theme here. Any kind of treatment that breaks down fibrin, whether it's a monoclonal antibody or an enzyme, helps after a Covid infection.

Take a look for yourself:

Eckey discusses cromolyn for brain inflammation and neurological issues, and some people have said it helps with other problems. She also wrote this great post about protecting kids from Long Covid.

A lot of it also applies to adults.

Another surprising study in Viruses from 2021 found that grapeseed extract (V. vinifera) contained dozens of flavonoid compounds that inhibited viral replication, including for Covid. The researchers used concentrations from 500 μg/ml down to 10 μg/ml.

Studies have even found that taurine supplements can do a lot to reduce your Covid risks, including Long Covid. A 2024 study in PLoS One found that the amino acid can serve as both a biomarker and a target for treatment in Long Covid. As they write, taurine has already "shown benefits such as reducing depressive behavior, improving memory, and mitigating age-related issues by addressing cellular senescence, chronic inflammation, DNA damage, and mitochondrial dysfunction." It can play "a potential protective role" in "alleviating the burdens of PCC." If that weren't enough, "taurine supplementation has demonstrated diverse therapeutic properties, including anti-oxidation, anti-aging, antiepileptic, cytoprotective, and cardioprotective effects in many diseases." Yes, even taurine from energy drinks. (And I guess it's a good thing I drink them.)

A standard diet contains about 40-400 mg of taurine per day. Medical use often starts at 6 grams a day.

There's a reason why many of these treatments don't get the attention they deserve, and Timothy Ferriss of all people describes it very well in the opening to The 4-Hour Body. As he learns from talking with a wide range of doctors and medical researchers, the industry frowns on any kind of treatment that doesn't look or feel "elite" enough. There's not a lot of incentive for major research on supplements or cheap, widely available drugs because they're just not cool enough, even if they work. For drug makers, it can't just work. It also has to generate enough profit.

That's what happens when you privatize medicine.

As a society, we have to overcome that. This shortcoming isn't going to help us address the myriad public health challenges of the future.

It's a little ironic that the catchphrase "do your own research," once levied against anti-vaxxers, is now used to insult Long Covid survivors and advocates who are trying desperately to find treatments. The difference is that we're not rejecting medicines.

We're simply not getting them.

This article can't replace a doctor or a nutritionist, but it offers a comprehensive starting point for anyone who needs it. You can do more digging and confirm what's here. You could also just make a list of all the things discussed here and take them to someone you trust, and go from there.

It's crucial for us to develop a range of treatments and therapies for Covid that go beyond the mainstream reliance on Paxlovid and vaccines, conveniently dominated by a single pharmaceutical company.

It won't last forever.

In fact, research has shown that Paxlovid leads increasingly to rebound infections in which "the virus can return unimpeded by the drug, bringing the risk of disease and even death."

That's the part left out by corporate media. Rebound doesn't simply mean another round of Paxlovid. It means decreased effectiveness.

It means evasion.

Just like our mediocre vaccines, Covid is developing resistance to Paxlovid. According to an article in Nature, researchers around the world are now quietly racing to develop alternatives. No doubt, viral evolution offers one of the unspoken reasons why many of us find it so hard to access the drug now. The elites are terrified of losing the thing that enables their denial and wishful thinking.

Here's what one researcher said:

“This type of approach helped to improve HIV drugs, and we think it’s a good way to improve antivirals against SARS-CoV-2,” says Sho Iketani, PhD, assistant professor of medical sciences at Columbia University’s Vagelos College of Physicians and Surgeons and Aaron Diamond AIDS Research Center, who co-led the research..."

Western countries are well behind the curve on these fronts. Japan now offers a drug called Xocova (ensitrelvir), arguably more effective than Paxlovid, and it's been sitting in the FDA approval queue for about a year. China approved HIV antivirals for Long Covid back in 2022. While some healthcare workers in Europe and North America know about combining and repurposing drugs, many of them are still busy pretending Covid is over.

It's time for government agencies to pull their heads out of the sand and do their jobs. If there had been more urgency over the last four years, and less favoritism toward one or two drug giants, we would already have these treatments deployed. As things stand, we need leaders to not only run these long overdue clinical trials but also prepare to scale up production considerably, while making sure that everyone has access, not just those with platinum insurance plans. We could already be doing that for emergency off-label use now. Why aren't we?

Although it's infuriating and demoralizing it took us so long to get here, it's encouraging to know that teams of scientists around the world have been working on this crisis and producing results. We just need the gates unlocked.

There's no time to waste.

Let's get moving.

[australianwomensnews]

Medical research has a major problem: an alarmingly high number of trials are based on fake, fraudulent or misinterpreted data.

Research misconduct sleuths call them “zombie” studies. They look like real research papers but they’re rotten to the core. And when these studies go on to influence clinical guidelines, that is, how patients are treated in hospitals and doctors’ rooms, they can be dangerous.

Professor Ben Mol, head of the Evidence-based Women’s Health Care Research Group at Monash University, is a professional zombie hunter. For years, he has warned that between 20 and 30 per cent of medical trials that inform clinical guidelines aren’t trustworthy.

“I’m surprised by the limited response from people in my field on this issue,” he says. “It’s a topic people don’t want to talk about.”

The peer review process is designed to ensure the validity and quality of findings, but it’s built on the assumption that data is legitimate.

Science relies on an honour system whereby researchers trust that colleagues have actually carried out the trials they describe in papers, and that the resulting data was collected with rigorous attention to detail.

But too often, once findings are queried, researchers can’t defend their conclusions. Figures such as former BMJ editor Richard Smith and Anaesthesia editor John Carlise argue it’s time to assume all papers are flawed or fraudulent until proven otherwise. The trust has run out.

“I think we have been naive for many years on this,” Mol says. “We are the Olympic Games without any doping checks.”

How bad science gets into the clinic

Untrustworthy papers may be the result of scientists misinterpreting their data or deliberately faking or plagiarising their numbers. Many of these “zombie” papers emerge from Egypt, Iran, India and China and usually crop up in lower-quality journals.

The problem gets bad when these poor-quality papers are laundered by systematic reviews or meta-analyses in prestigious journals. These studies aggregate hundreds of papers to produce gold-standard scientific evidence for whether a particular treatment works.

Often papers with dodgy data are excluded from systematic reviews. But many slip through and go on to inform clinical guidelines.

My colleague Liam Mannix has written about an example of this with the hormone progesterone. Official guidelines held that the hormone could reduce the risk of pre-term birth in women with a shortened cervix.

But those guidelines were based on a meta-analysis largely informed by a paper from Egypt that was eventually retracted due to concerns about the underlying data. When this paper was struck from the meta-analysis, the results reversed to suggest progesterone had no preventative effect.

There’s a litany of other examples where discounting dodgy data can fundamentally alter the evidence that shapes clinical guidelines. That’s why, in The Lancet’s clinical journal eClinical Medicine, Mol and his colleagues have reported a new way to weed out bad science before it makes it to the clinic.

Holding back the horde

The new tool is called the Research Integrity in Guidelines and evIDence synthesis (RIGID) framework. It mightn’t sound sexy, but it’s like a barbed-wire fence that can hold back the zombie horde.

The world-first framework lays out a series of steps researchers can take when conducting a meta analysis or writing medical guidelines to exclude dodgy data and untrustworthy findings. It involves two researchers screening articles for red flags.

“You can look at biologically implausible findings like very high success rates of treatments, very big differences between treatments, unfeasible birth weights. You can look at statistical errors,” says Mol.

“You can look at strange features in the data, only using rounded numbers, only using even numbers. There are studies where out of dozens of pairs of numbers, everything is even. That doesn’t happen by chance.”

A panel decides if a paper has a medium to high risk of being untrustworthy. If that’s the case, the RIGID reviewers put their concerns to the paper’s authors. They’re often met with stony silence. If authors cannot address the concerns or provide their raw data, the paper is scrapped from informing guidelines.

The RIGID framework has already been put to use, and the results are shocking.

In 2023, researchers applied RIGID to the International Evidence-based Guidelines for Polycystic Ovary Syndrome (PCOS), a long misunderstood and misdiagnosed syndrome that affects more than 1 in 10 women. As a much maligned condition, it was critical the guidelines were based on the best possible evidence.

In that case, RIGID discounted 45 per cent of papers used to inform the health guidelines.

That’s a shockingly high number. Those potentially untrustworthy papers might have completely skewed the guidelines.

Imagine, Mol says, if it emerged that almost half of the maintenance reports of a major airline were faked? No one would be sitting around waiting for a plane to crash. There would be swift action and the leadership of the airline sacked.

[brightlotusmoon]

Lesser-Known Cannabis Component CBG Linked To Improved Memory And Reduced Anxiety, First-Ever Human Trial Finds

https://weedmaps.com/news/2024/08/lesser-known-cannabis-component-cbg-linked-to-improved-memory-and-reduced-anxiety-first-ever-human-trial-finds/?lid=o479kqour5qo&utm_medium=email&utm_source=braze&utm_campaign=newsletter&utm_content=news&utm_term=USA_CAN

A lesser-known cannabinoid known as CBG has surprised scientists after a first-ever human clinical trial found that it appears to improve memory while also “significantly” reducing anxiety and stress.

The non-intoxicating cannabinoid might not be as well-known as THC and CBD, for example, but as it's grown in popularity, researchers at Washington State University (WSU) and the University of California at Los Angeles (UCLA) set out to investigate its therapeutic potential amid anecdotal, survey-based reports about its therapeutic potential.

The study, published in the journal Scientific Reports this month, found that cannabigerol, or CBG, caused “significant overall reductions in anxiety as well as reductions in stress” among study participants compared to the placebo. “CBG also enhanced verbal memory relative to placebo,” with “no evidence of subjective drug effects or impairment.”

That finding about CBG's effects on memory took the research team by surprise.

[symbiosis-online-publishing]

"International Journal of Cardiology: Advancing Global Cardiovascular Health"

The "International Journal of Cardiology" is a renowned publication dedicated to advancing the field of cardiology and promoting cardiovascular health on a global scale. Our journal serves as a dynamic platform for exploring the intricacies of the cardiovascular system, fostering international collaborations, and addressing the challenges and opportunities within the realm of cardiology and cardiovascular science. Within the pages of the "International Journal of Cardiology," you will embark on an enlightening journey through the multifaceted world of cardiovascular health. Key highlights of the "International Journal of Cardiology" encompass:

Global Insights: It offers a platform for healthcare professionals and researchers worldwide to share their clinical expertise, experiences, and innovative techniques for managing cardiovascular conditions.

Global Impact: Recognizing the worldwide significance of cardiovascular health, the journal covers cardiovascular issues from various regions, addressing cultural, economic, and geographic diversity.

Education and Collaboration: "International Journal of Cardiology" promotes knowledge exchange, international collaboration, and interdisciplinary engagement within the global cardiology community, fostering continuous learning and improvement.

Our publication is an invaluable resource for cardiologists, cardiovascular researchers, nurses, allied healthcare professionals, educators, and individuals passionate about heart health across borders. Join us in advancing global cardiovascular health, navigating the complexities of cardiovascular science, and ultimately contributing to a healthier and brighter future for individuals affected by cardiovascular diseases worldwide.

[mariacallous]

Since it was first identified in 1983, HIV has infected more than 85 million people and caused some 40 million deaths worldwide.

While medication known as pre-exposure prophylaxis, or PrEP, can significantly reduce the risk of getting HIV, it has to be taken every day to be effective. A vaccine to provide lasting protection has eluded researchers for decades. Now, there may finally be a viable strategy for making one.

An experimental vaccine developed at Duke University triggered an elusive type of broadly neutralizing antibody in a small group of people enrolled in a 2019 clinical trial. The findings were published today in the scientific journal Cell.

“This is one of the most pivotal studies in the HIV vaccine field to date,” says Glenda Gray, an HIV expert and the president and CEO of the South African Medical Research Council, who was not involved in the study.

A few years ago, a team from Scripps Research and the International AIDS Vaccine Initiative (IAVI) showed that it was possible to stimulate the precursor cells needed to make these rare antibodies in people. The Duke study goes a step further to generate these antibodies, albeit at low levels.

“This is a scientific feat and gives the field great hope that one can construct an HIV vaccine regimen that directs the immune response along a path that is required for protection,” Gray says.

Vaccines work by training the immune system to recognize a virus or other pathogen. They introduce something that looks like the virus—a piece of it, for example, or a weakened version of it—and by doing so, spur the body’s B cells into producing protective antibodies against it. Those antibodies stick around so that when a person later encounters the real virus, the immune system remembers and is poised to attack.

While researchers were able to produce Covid-19 vaccines in a matter of months, creating a vaccine against HIV has proven much more challenging. The problem is the unique nature of the virus. HIV mutates rapidly, meaning it can quickly outmaneuver immune defenses. It also integrates into the human genome within a few days of exposure, hiding out from the immune system.

“Parts of the virus look like our own cells, and we don’t like to make antibodies against our own selves,” says Barton Haynes, director of the Duke Human Vaccine Institute and one of the authors on the paper.

The particular antibodies that researchers are interested in are known as broadly neutralizing antibodies, which can recognize and block different versions of the virus. Because of HIV’s shape-shifting nature, there are two main types of HIV and each has several strains. An effective vaccine will need to target many of them.

Some HIV-infected individuals generate broadly neutralizing antibodies, although it often takes years of living with HIV to do so, Haynes says. Even then, people don’t make enough of them to fight off the virus. These special antibodies are made by unusual B cells that are loaded with mutations they’ve acquired over time in reaction to the virus changing inside the body. “These are weird antibodies,” Haynes says. “The body doesn’t make them easily.”

Haynes and his colleagues aimed to speed up that process in healthy, HIV-negative people. Their vaccine uses synthetic molecules that mimic a part of HIV’s outer coat, or envelope, called the membrane proximal external region. This area remains stable even as the virus mutates. Antibodies against this region can block many circulating strains of HIV.

The trial enrolled 20 healthy participants who were HIV-negative. Of those, 15 people received two of four planned doses of the investigational vaccine, and five received three doses. The trial was halted when one participant experienced an allergic reaction that was not life-threatening. The team found that the reaction was likely due to an additive in the vaccine, which they plan to remove in future testing.

Still, they found that two doses of the vaccine were enough to induce low levels of broadly neutralizing antibodies within a few weeks. Notably, B cells seemed to remain in a state of development to allow them to continue acquiring mutations, so they could evolve along with the virus. Researchers tested the antibodies on HIV samples in the lab and found that they were able to neutralize between 15 and 35 percent of them.

Jeffrey Laurence, a scientific consultant at the Foundation for AIDS Research (amfAR) and a professor of medicine at Weill Cornell Medical College, says the findings represent a step forward, but that challenges remain. “It outlines a path for vaccine development, but there’s a lot of work that needs to be done,” he says.

For one, he says, a vaccine would need to generate antibody levels that are significantly higher and able to neutralize with greater efficacy. He also says a one-dose vaccine would be ideal. “If you’re ever going to have a vaccine that’s helpful to the world, you’re going to need one dose,” he says.

Targeting more regions of the virus envelope could produce a more robust response. Haynes says the next step is designing a vaccine with at least three components, all aimed at distinct regions of the virus. The goal is to guide the B cells to become much stronger neutralizers, Haynes says. “We’re going to move forward and build on what we have learned.”

[afeelgoodblog]

The Best News of Last Week

🦾 - High-Five for Bionic Hand

1. Houston-area school district announces free breakfast and lunch for students

Pasadena ISD students will be getting free breakfast and lunch for the 2023-24 school year, per an announcement on the district's social media pages.

The 2023-24 free lunch program is thanks to a Community Eligibility Provision grant the district applied for last year. The CEP, which is distributed by the Department of Agriculture, is specially geared toward providing free meals for low-income students.

2. Dolphin and her baby rescued after being trapped in pond for 2 years

A pair of dolphins that spent nearly two years stuck in a Louisiana pond system are back at sea thanks to the help of several agencies and volunteers.

According to the Audubon Nature Institute, wildlife observers believe the mother dolphin and her baby were pushed into the pond system near Grand Isle, Louisiana, during Hurricane Ida in late August 2021.

3. Studies show that putting solar panels over waterways could boost clean energy and conserve water. The first U.S. pilot project is getting underway in California.

Some 8,000 miles of federally owned canals snake across the United States, channeling water to replenish crops, fuel hydropower plants and supply drinking water to rural communities. In the future, these narrow waterways could serve an additional role: as hubs of solar energy generation.

4. Gene therapy eyedrops restored a boy's sight. Similar treatments could help millions

Antonio was born with dystrophic epidermolysis bullosa, a rare genetic condition that causes blisters all over his body and in his eyes. But his skin improved when he joined a clinical trial to test the world’s first topical gene therapy.

The same therapy was applied to his eyes. Antonio, who’s been legally blind for much of his 14 years, can see again.

5. Scientists develop game-changing vaccine against Lyme disease ticks!

A major step in battling Lyme disease and other dangerous tick-borne viruses may have been taken as researchers announced they have developed a vaccine against the ticks themselves.

Rather than combatting the effects of the bacteria or microbe that causes Lyme disease, the vaccine targets the microbiota of the tick, according to a paper published in the journal Microbiota on Monday.

6. HIV Transmission Virtually Eliminated in Inner Sydney, Australia

Sydney may be the first city in the world to end AIDS as a public health threat by 2030. Inner Sydney has reduced new HIV acquisitions by 88%, meaning it may be the first locality in the world to reach the UN target to end AIDS as a public health threat by 2030

7. New bionic hand allows amputees to control each finger with unprecedented accuracy

In a world first, surgeons and engineers have developed a new bionic hand that allows users with arm amputations to effortlessly control each finger as though it was their own body.

Successful testing of the bionic hand has already been conducted on a patient who lost his arm above the elbow.

----

That's it for this week :)

This newsletter will always be free. If you liked this post you can support me with a small kofi donation:

Support this newsletter ❤️

Also don’t forget to reblog.

[reportwire]

AI used to predict future flares of ulcerative colitis activity

Newswise — Ulcerative colitis assessment could be improved after new research shows that an artificial intelligence model could predict flare-ups and complications after reading biopsies. In a new paper published in Gastroenterology today (Friday 3 March), researchers supported by the National Institute for Health and Care Research Birmingham Biomedical Research Centre have trialled an AI…

[reasonsforhope]

"Since it was first identified in 1983, HIV has infected more than 85 million people and caused some 40 million deaths worldwide.

While medication known as pre-exposure prophylaxis, or PrEP, can significantly reduce the risk of getting HIV, it has to be taken every day to be effective. A vaccine to provide lasting protection has eluded researchers for decades. Now, there may finally be a viable strategy for making one.

An experimental vaccine developed at Duke University triggered an elusive type of broadly neutralizing antibody in a small group of people enrolled in a 2019 clinical trial. The findings were published today [May 17, 2024] in the scientific journal Cell.

“This is one of the most pivotal studies in the HIV vaccine field to date,” says Glenda Gray, an HIV expert and the president and CEO of the South African Medical Research Council, who was not involved in the study.

A few years ago, a team from Scripps Research and the International AIDS Vaccine Initiative (IAVI) showed that it was possible to stimulate the precursor cells needed to make these rare antibodies in people. The Duke study goes a step further to generate these antibodies, albeit at low levels.

“This is a scientific feat and gives the field great hope that one can construct an HIV vaccine regimen that directs the immune response along a path that is required for protection,” Gray says.

-via WIRED, May 17, 2024. Article continues below.

Vaccines work by training the immune system to recognize a virus or other pathogen. They introduce something that looks like the virus—a piece of it, for example, or a weakened version of it—and by doing so, spur the body’s B cells into producing protective antibodies against it. Those antibodies stick around so that when a person later encounters the real virus, the immune system remembers and is poised to attack.

While researchers were able to produce Covid-19 vaccines in a matter of months, creating a vaccine against HIV has proven much more challenging. The problem is the unique nature of the virus. HIV mutates rapidly, meaning it can quickly outmaneuver immune defenses. It also integrates into the human genome within a few days of exposure, hiding out from the immune system.

“Parts of the virus look like our own cells, and we don’t like to make antibodies against our own selves,” says Barton Haynes, director of the Duke Human Vaccine Institute and one of the authors on the paper.

The particular antibodies that researchers are interested in are known as broadly neutralizing antibodies, which can recognize and block different versions of the virus. Because of HIV’s shape-shifting nature, there are two main types of HIV and each has several strains. An effective vaccine will need to target many of them.

Some HIV-infected individuals generate broadly neutralizing antibodies, although it often takes years of living with HIV to do so, Haynes says. Even then, people don’t make enough of them to fight off the virus. These special antibodies are made by unusual B cells that are loaded with mutations they’ve acquired over time in reaction to the virus changing inside the body. “These are weird antibodies,” Haynes says. “The body doesn’t make them easily.”

Haynes and his colleagues aimed to speed up that process in healthy, HIV-negative people. Their vaccine uses synthetic molecules that mimic a part of HIV’s outer coat, or envelope, called the membrane proximal external region. This area remains stable even as the virus mutates. Antibodies against this region can block many circulating strains of HIV.

The trial enrolled 20 healthy participants who were HIV-negative. Of those, 15 people received two of four planned doses of the investigational vaccine, and five received three doses. The trial was halted when one participant experienced an allergic reaction that was not life-threatening. The team found that the reaction was likely due to an additive in the vaccine, which they plan to remove in future testing.

Still, they found that two doses of the vaccine were enough to induce low levels of broadly neutralizing antibodies within a few weeks. Notably, B cells seemed to remain in a state of development to allow them to continue acquiring mutations, so they could evolve along with the virus. Researchers tested the antibodies on HIV samples in the lab and found that they were able to neutralize between 15 and 35 percent of them.

Jeffrey Laurence, a scientific consultant at the Foundation for AIDS Research (amfAR) and a professor of medicine at Weill Cornell Medical College, says the findings represent a step forward, but that challenges remain. “It outlines a path for vaccine development, but there’s a lot of work that needs to be done,” he says.

For one, he says, a vaccine would need to generate antibody levels that are significantly higher and able to neutralize with greater efficacy. He also says a one-dose vaccine would be ideal. “If you’re ever going to have a vaccine that’s helpful to the world, you’re going to need one dose,” he says.

Targeting more regions of the virus envelope could produce a more robust response. Haynes says the next step is designing a vaccine with at least three components, all aimed at distinct regions of the virus. The goal is to guide the B cells to become much stronger neutralizers, Haynes says. “We’re going to move forward and build on what we have learned.”

-via WIRED, May 17, 2024

[ellesthots]

Fateful Beginnings

XVI. “sweetener”

parts: previous / next

plot: after months of rejections, a certain offer crops up with such sweetener you can’t possibly resist… though you wish it was under better circumstance.

pairing: battinson!bruce wayne x fem!reader

cw: 18+, talk of death, grief, cancer, angst, unintentional weight loss

words: 3.9k

The next two months were a blur. Your days melted together, only distinguishable by doctor's visits and which job rejected you that day. The economy was in shambles; going on Indeed you were seeing hundreds of applications to a single Dunkin' barista job. You tried your best to forget about Bruce Wayne, and kept replaying the conversation over and over in the week following. His promise not to hurt you, the vague sense of safety and danger you got when you were around him... but it was soothing knowing that he was all the way on the other side of the US. This relief went away when it was deep into the night and you remembered he had all the money, all the tech, all the opportunity to hunt you down if he wanted to, but you did your best to trust the humanity he fronted with. You kicked yourself for forgetting to bring up the loan thing, adrenaline having been coursing through your veins blocking out any real coherent thought outside of the direct moment. It couldn't have been him, it could've been another donor. Maybe it was even Alfred checking my texts when I’d gone to the bathroom or some shit.

The days still blurred together however, and secretly you relished not knowing what day it was; not knowing meant you didn't know how close the draw was. Your mother's clinical trial started beginning of August, and would be a biweekly shot... if she was accepted. At each and every appointment leading up to that fateful day the staff engaged in tempering assurances, albeit assuring hardly anyone would make it into that trial. For a split second whenever a doctor or nurse mentioned it at the end of her appointments you felt a white-hot rod in your throat that froze you in your tracks. The doctors said this was her only hope. And only if she avoids placebo.

Walter was growing increasingly anxious as well. Walter refused to leave her side to the point you had called the office to see if they would ever make an exception to bring a cat inside. No. Allergies. Your dad had taken to staying home with him, otherwise he would go on a food strike. It would take hours of petting and cooing to him to make him comfortable enough to eat again if your mom ever got out of his sight. It was better with your dad there, though. Instead of three hours of cuddling, it might take two for him to eat again. You tried not to think about what would ever happen if your mom's battle ended... poorly.

Your dad started going back to work, only part time. You made sure to spend all the time possible out in the living room with your mother and Walter while she knit and pulled pieces of yarn from Walter's teeth, and watched some sort of romcom. When your dad came back you would all start cooking dinner, then eat, engage in some sort of discussion (your dad had taken to downloading an 'icebreaker' app and would pull one question each day from it) and then you'd spend the rest of the night submitting job apps. It was monotonous, a bit draining, but also sweet. It was such a far cry from Gotham that at just over a month gone from the city, you'd started to wonder if you'd dreamt it and you'd actually been here with them all along... until the day before the clinical trial announcement when you'd woken up to a particular email.

Dear Miss Y/L/N,

It is at the referral of Gotham City University President Dr. Janay Vry that we extend to you an offer of employment in the position of JOURNALISM DEPARTMENT ASSISTANT for the academic year of 2024-25. This is a part-time position requiring 20 hours of on-site time per week including outreach of no more than 5 hours per week. Duties include management of a public column in the Gotham Gazette and various office responsibilities as-needed. Compensation includes a housing stipend of fifteen-hundred dollars per month and an hourly rate of forty-three dollars and forty-five cents.

Please respond before Friday, August 2nd at 5pm. There is a mandatory meeting on Monday, August 5th at 12 noon in Challey Hall, Room 245. Flight and one-week hotel stay will be provided upon acceptance.

We look forward to hearing from you.

Gotham City University Faculty Administrator

You stared at the screen as if you'd seen a ghost. For weeks you hadn't had to worry about Gotham; the crime, the sleazes, Bruce Wayne. I'm balls deep in rejections and now Gotham sweetens the deal. You kicked the sheets off of you then paused, horrified, before remembering Walter didn't sleep in your bed anymore.

Breakfast was as usual. Your dad made omelets and the three of you made small talk about the happenings of the day ahead. Today your mother was getting a visit from Debra, her old friend from the Y back when she volunteered there on weekends. Your dad was working the same shift—10am to 3pm—and would put steak on the grill when he got back. "Looks like it might hit a hundred if we get lucky."

"Y/N," She asked after taking a sip of coffee. "Can you make sure Walter's water is filled? I think I might go to Debra's to get out of the house." You looked under the table to see Walter slurping up the last puddles of his water and rose to fill it. You grabbed a few ice cubes so it could stay cold just the way he liked it; a sobering thought of leaving this for Gotham threatened to sever your spine. After pouring a few cups into his bowl and giving him a proper pet, your dad followed up on your job search. "Any luck on those applications?"

More than anything you didn't want to tell them about Gotham. But as your parents had talked, the more you began to mull over the money in your mind. Free housing. 1500 would be enough for a good studio. 800 a week. A plane ticket's 200 round trip. I could visit, easy. I would visit. It would only be temporary, I wouldn't probably last the whole year before I got offered a position at home. What if Mom doesn't get into the trial? What if she does and she gets placebo? How long does she have? Will it be painful? Do I need to think about a job right now? It would look fucking great on a resumé, which would increase odds of getting ahead of the job seekers in WA quite significantly...

"Hun? Any offers?" Your dad turned to look at you and you blurted out the contents of the email. A second of silent surprise then an uproar of celebration. "Thank heavens, that sounds wonderful! Did you already accept?"

You looked back at them with shock, your mouth hanging slightly open. What? Walter finished his food and brushed against your legs as he wandered to your mom, looking pitifully up at her slices of bacon. "Well, no. It's Gotham. I thought it was too dangerous." You guys nearly prohibited me from even going to Gotham in the first place...

"That was before we visited!" Your mom was ecstatic; she rose to come and give you a big hug, and your dad tried to swat Walter away from jumping on the chair to sneak a bite. You wanted to think it was cute, but your mind raced. How could they be so supportive? Unquestionably? "It's Gotham, Mom," You took her hug not in celebration, but in an effort to commit the feeling to memory.

"How much is the pay?" Your dad pulled in the chair so he couldn't jump and walked over to the sink to put his plate away. You shut your eyes and hid a sigh. Once they know how good the pay is they won't let me stay. "Good, I guess."

"What, 15, 16 an hour?" Your parents eyed you expectantly and you shrugged. "A little more. Than that." You followed the linoleum's vertical lines to where it met the carpet. "And a housing stipend." You cringed. They weren't going to let this opportunity go.

"Wowza, honeybee!" Your dad called you that when he was particularly pleased, which only served to coil your stomach lining. Gotham? Gotham. This was over Gotham. The place we got into screaming matches over me going to only a handful of years ago. "I don't know,"

"Why not? It sounds perfect." Your mom was a foot away from you boring her eyes into your soul. Does she really have no idea why I wouldn't want to leave? "Mom,"

"If this is anything about my cancer," So she did.

"Don't say that," You tried to play it off and stuttered something about how you didn't particularly like Gotham anyway, you could keep looking for jobs here, but she wasn't having it.

"No no. I want you to live your life, sweetie. This is a spectacular opportunity!" Her singsong tone was back and you suddenly wanted to throw up. You wanted to blurt HOW MUCH TIME IS LEFT WITH YOU?? I CAN'T MISS IT! But, you didn't say anything and walked out of the kitchen back to your room. You didn't quite slam the door, but didn't make it silent. While your mother's selflessness was admirable, it was also frustrating. I only get one mom. You sat on the edge of your bed with your head in your hands. Whispers wafted from the kitchen but you couldn't make them out. The sound of footsteps, a pause, and then knocking on your door. "Hun, let's talk." It was your father.

"Dad, no, I'm tired,"

"You just woke up honeybun, I'm not buying that." He sat beside you on the end of your bed. It sagged a bit, not used to the extra company. He placed a hand on your shoulder. "What you're feeling about your mother, I've felt it too. I had the same conversation with her before going back to work.”

"I'm sure she was receptive." You rolled your eyes. He squinted at you. "Now, where is this attitude coming from?"

"I don't want to tell her because it'll make her sad. But. I. I have no idea how much longer she has left. And working would just take time away from her."

"Have you thought about how that might make your mother feel? Her life has changed enough. She's already reminded enough about her... illness."

"Cancer, Dad. Cancer." He never said the words. He shuddered but continued on.

"Her life has been turned upside, over, and back around. She does not need more reminders of how sick she might be."

"How sick she is." You shot a glare at your father, just then realizing how much contempt you felt toward him. It came rushing out of you. "You didn't even think to tell me her mobility changed. I had to see her frail and in a fucking wheelchair,"

"Now, calm yourself!" He snapped at you and took his hand off your shoulder. You scooted a little further from him, annoyed. Your voice was softer but the rock in your chest remained. "You didn't even tell me. She's lost so much weight. Her hair changed. You didn't even tell me. You won't even say the word 'cancer'." Your voice was starting to raise and he stood up. "Talk to your mother."

"Why? Didn't you say that'd just add extra stress? Remind her of her 'illness'?" You stood up and watched him walk to the door. "You weren't in the room with the doctor when he told me. He said it's this trial or fucking nothing."

"Don't use that language in my house!"

"It's my house too." By this point your mind was racing and your palms were sweaty and clammy and head hot, hands shaking. "If she doesn't get into this trial and this medicine doesn't work she's fucked."

He paused with his hand on the doorknob. "If you brought it up to her... maybe you'd see she's come to more peace than you have about it." With that, he left.

At 1:13pm the next day the phone rang. You hadn't talked to your mom about it as she was already headed out the door to see Debra, and didn't come back until late in the evening when she was visibly exhausted. Your dad helped tuck her into bed and she fell asleep quickly. Breakfast the next morning was fine, but tense; you were all anxiously awaiting this phone call. Your dad had stayed home from work just in case, and now your mom picked up the phone. "Yes, that's she. Yes. Yes, that's correct." And just by some small miracle, she'd gotten in.

Debra joined the party that evening. After a tearful raucous she was the first one your family called. Not ten minutes later she had arrived with a pie. "I baked it this morning. I figured we'd want something sweet no matter what."

The logistics were as-follows: your mom was going to be receiving her first shot of the drug (or, terrifyingly, a placebo) the following Friday. She would keep a diligent record of any side effects, even if they didn't seem related. Two weeks later she would receive her second dose and turn in the side-effect sheet, and that would continue for the following month until switching to once a month injections for the rest of the year. The first week of the new year your mother would get another scan, and that would be the first check-in. "They told me if everything goes how it should with the medication, I could not only see growth stunted, but be on the road to remission." Seeing how happy your parents were the rest of the evening only made the offer in Gotham more inviting; she'd been accepted, and if the results were, god forbid, horrendous in the new year, you would come home and help with the money you'd saved.

Clutching the laptop with white knuckles, you sent the acceptance email at 4:50pm the next day, ten minutes before the deadline. Half an hour later you were booked for your flight that Sunday at noon. Saturday was filled with laundry and packing bags; now Walter didn't want to leave your side. That night you hardly slept, staying up to pet him on the couch while your parents nodded off to a TV movie. The phrase mutually assured destruction came back to haunt you—you hadn't meant that to be a threat, but what if it was? You'd planned on never having to see him again... but the city was big. You could avoid him. And if you were going to trust him, he had said that even if you had written the exposé he wouldn't have hurt you.

You planned to come back once a month, leaving Thursday night and returning Sunday night. It fit well with your mom's trial schedule for the latter portion of the year, and you'd be able to come with her to her appointments. When you got on the plane and tucked your carryon under the seat it didn't feel so terrible. It felt less like leaving and more like a weird vacation. But as soon as you woke up in Gotham a rock hit the pit of your stomach. Fuck. I'm back.

The W was the hotel Dr. Vry had set up for you, only a floor below where you'd stayed with your parents the last time. You had one week to find an apartment, and Dr. Vry said to list her on any applications to 'speed up the process'. While waiting on the Uber to pick you up in the airport you'd sent one application to a place in North Gotham, a gorgeous gem of a spot with a full-size tub and in-unit washer dryer. Just as you pushed the key into your room at the hotel, you received a confirmation email with the date to retrieve your keys. Fuck, they made it too easy.

With a lot of time on your hands and a new neighborhood to explore, you abandoned your room and wandered around the blocks surrounding. You went more north this time, to avoid any fleeting memory of Bruce and whatever the hell he'd been up to.

Northern Gotham was certainly more family-friendly. You saw couples taking their babies out on walks instead of throngs of people clustering around the various clubs on every block. There was only one club you'd seen so far, and that one allowed minors until seven pm. You'd lived more downtown, central city, and never had reason to go further north until now. The apartment you'd been in was less than a thousand a month, which made sense how riddled it was with crime. It wasn't even close to Washington, but this didn't quite feel like the Gotham you knew close to campus.

You noticed a cute themed coffee shop on the corner ahead and went in. There were a few people and a couple sitting around the small room, working on their laptops or reading a book. It really felt like it wasn't Gotham, like you'd been transported back home for a quick moment. You went on Maps and saw that your new apartment was only three blocks east of the cafe. Safety. Serenity. Never thought I'd find a crumb of it here. You resigned to coming here as often as possible. You ordered a macchiato and sat on a leather loveseat as you waited. Your jeans bit into your stomach and you adjusted uncomfortably, the leather loud as you wiggled. I guess this is why this seat was empty. You were called up for your drink quickly and thanked them as you walked out back from whence you came. Though you hadn't been in the store for five minutes, it was already raining. Even Washington didn't rain in August, but you couldn't be too pressed. The rain was nice when it wasn't forcing you to be locked in the city mansion with the... no.

Bruce doesn't own this city. There's millions of people here. With your coffee in hand you made the trek back to the hotel, and after hopping into the giant bed you sat with your thoughts for a moment. Challey Hall... that wasn't the journalism department. The term started three Mondays later, and alongside the fifteen-hundred stipend for rent and utilities, Dr. Vry had emailed you with an extra thousand in the form of a digital check. In her words it was a 'settle-in fee'. Monday would be the meeting and then Dr. Vry would give you a tour of the places you'd be frequenting. You'd receive your schedule, and Tuesday through Sunday would be reserved for settling into the apartment and getting items for it so it wasn't an empty box. Why are they being so generous with the money? It didn't feel right, not when there was so much inequality in the city. You'd make sure to cut some costs and offer whatever was left after your first paycheck to the houseless people around campus.

As you walked back you couldn't help but think about how gigantic the city was. When considering whether or not to accept the position, you had vastly underrepresented the impact of the sheer size of the city on your psyche. It made you feel completely unimportant and equally as lost. It only served your insecurities, making you feel like even more of an outcast than you already felt in your small town just outside of Seattle. Mar. You could call Mar. She could come over, and you could tell her about Bruce. That would be a good icebreaker. Open up to her about why you'd been so MIA, about your mother's cancer, about why you left and why you came back. You needed someone to talk to.

An hour later you and her were sitting on the hotel bed eating takeout noodles. "So you're saying you stayed in Bruce Wayne's HOUSE, then he helped you pack up your apartment, then dropped you off at the airport," Her face was scrunched together, deep in thought as she recounted the last hour of conversation. Some broth from the noodles was on the top of her lip. "Then he was the commencement speaker at your graduation, he talked to your parents after, then later that night he found you again and talked to you?"

"When you say it like that it sounds like stalking." You shrugged and took another chomp of noodles. Mar stared at you. "If it sounds like stalking,"

"It's coincidence, I promise." You hadn't completely kept out the part where you two hated each other, you made sure that was clear, but you sure as hell kept out the why. Mar was trustworthy, sure, but you didn't even want to remember he was Batman. It made you anxious and nervous to think about him in the suit. Then you would've had to explain that you and Bruce were now circling each other with ammo pointed at the other's chest if one of you stepped out of line.

"I don't know, it sounds creepy. What if he shows up here in the middle of the night..." Mar trailed off when she saw you look away. You hadn't told Mar about your mom yet, and didn't know if you wanted to for fear of it becoming more real. You wanted to leave that out of Gotham. Leave the trauma, leave the guilt, leave it for the weekends when you would fly back. You shrugged and made a joke about getting to be associated with a billionaire. "Maybe it wouldn't be so bad if he got papped here. Might boost my journalistic impact." The conversation moved away from Bruce after that, and you and Mar spent the rest of the evening talking, eventually laying in bed scrolling Scypher on your respective phones. The second you loaded the app, however, you saw a Dior ad everyone in Gotham was swooning over, and couldn't hold back your gasp.

He had not only been photographed often by paparazzi, it seemed, going on regular walks to downtown shops and local charity events, but this was his first official campaign. Mar leaned over and nodded, saying 'everyone' was talking about the photo. "I thought you'd already seen it, that's why you brought him up."

"No, I haven't." You scrolled through the comments trying to hold back a cringe.

He can top me

BARK BARK BARK

y did he keep his BEAUTY FROM US FOR SO LONG???????????

daddy

when is the rest of the campaign dropping asking for a friend

You turned your phone off and rolled over in bed. You told Mar goodnight (she decided to spend the night since she hadn't seen you in so long), murmuring something about having to be up the next day for your orientation. Bruce Wayne. Billionaire playboy. What the fuck happened with him?

[thoughtportal]

mRNA vaccines have gained widespread attention for their crucial role in fighting the COVID-19 pandemic. Yet, even before the pandemic, researchers at Memorial Sloan Kettering Cancer Center were investigating the potential of mRNA vaccine technology in the fight against cancer.

Leading this innovative research is Dr. Vinod Balachandran, a physician-scientist associated with the David M. Rubenstein Center for Pancreatic Cancer Research, the Human Oncology and Pathogenesis Program, and the Parker Institute for Cancer Immunotherapy.

Dr. Balachandran's groundbreaking efforts have paved the way for a clinical trial focused on using mRNA vaccines to treat pancreatic cancer, offering new hope to patients confronting this challenging disease.

Neoantigens in Pancreatic Tumors

At the heart of this innovative approach lies the concept of neoantigens, proteins found within pancreatic tumors that serve as alarm bells, alerting the immune system to the presence of cancer cells. These neoantigens play a pivotal role in rallying the immune response to keep pancreatic cancer at bay.

Unlike traditional vaccines, which are one-size-fits-all, these mRNA vaccines are tailored to each individual, with the aim of stimulating the production of specific immune cells known as T cells. These T cells are trained to recognize and target pancreatic cancer cells, reducing the risk of cancer recurrence following surgical removal of the primary tumor.

Intriguingly, the results of this groundbreaking research have shown remarkable promise. Among the 16 patients studied, eight experienced activation of T cells that recognized their own pancreatic cancers.

Importantly, these patients demonstrated delayed recurrence of their pancreatic cancers, providing tantalizing evidence that the T cells activated by the vaccines may be effectively holding the cancer at bay.

Dr. Balachandran's work in pioneering mRNA vaccines for pancreatic cancer received a significant boost through collaboration with BioNTech, the company responsible for developing the Pfizer-BioNTech COVID-19 vaccine.

When asked about the inspiration behind using a vaccine to combat pancreatic cancer, Dr. Balachandran explained, "There has been great interest in using immunotherapy for pancreatic cancer because nothing else has worked very well. We thought immunotherapy held promise because of research we began about seven years ago."

This research, spanning seven years, revealed that a select group of pancreatic cancer patients managed to defy the odds and survive after tumor removal surgery. Upon close examination, it was observed that these tumors harbored an unusually high number of immune cells, particularly T cells.

These immune cells were drawn to the tumors by signals emitted from within. These signals, as it turned out, were neoantigens—proteins that T cells recognize as foreign invaders, prompting an immune system assault on the cancer.

Even more intriguing was the discovery that T cells recognizing these neoantigens persisted in the bloodstream of these fortunate patients for up to 12 years after tumor removal.

This sustained immune response resembled an autovaccination, with T cells retaining a memory of the neoantigens as a threat, akin to the way vaccines confer long-term protection against pathogens. This finding sparked the idea of artificially inducing a similar effect in other pancreatic cancer patients.

Unlocking the Potential of mRNA Vaccines

To understand how mRNA vaccines can combat pancreatic cancer, one must delve into their intricate mechanisms. Dr. Balachandran and his team published their findings on immune protection in long-term pancreatic cancer survivors in the prestigious journal Nature in November 2017. During this time, they were also exploring methods to deliver neoantigens to patients in the form of vaccines, with a particular focus on mRNA vaccines.

Unlike traditional vaccines, which introduce weakened or inactivated pathogens into the body, mRNA vaccines leverage a piece of genetic code known as messenger RNA (mRNA).

This genetic code instructs cells in the body to produce a specific protein, thus triggering an immune response. Coincidentally, BioNTech's co-founder and CEO, Uğur Şahin, expressed interest in the research conducted by Dr. Balachandran's team, initiating a collaboration that would prove pivotal.

In late 2017, Dr. Balachandran and his team journeyed to Mainz, Germany, where BioNTech is headquartered. Over dinner, they discussed the potential of mRNA vaccines in the context of pancreatic cancer treatment. This marked the beginning of a journey that held immense promise for cancer patients worldwide.Scientist, CEO and co-founder of BioNTech Ugur Sahin. (CREDIT: BERND VON JUTRCZENKA/POOL/AFP via Getty Images)

The intricacies of designing an effective cancer vaccine are manifold. Given that cancer arises from the body's own cells, distinguishing proteins in cancer cells as foreign entities is a formidable challenge for the immune system. Nevertheless, advances in cancer biology and genomic sequencing have paved the way for the design of vaccines capable of discerning the difference.

Dr. Balachandran's team, in conjunction with BioNTech and Genentech, capitalized on these advances, recognizing the critical role played by tumor mutations in triggering immune responses. Their optimism in the potential of mRNA vaccines for pancreatic cancer was well-founded, setting the stage for their groundbreaking research.

Personalized mRNA Vaccines: A Tailored Approach

The personalized nature of mRNA vaccines for pancreatic cancer is a testament to their efficacy. After a patient undergoes surgical removal of a pancreatic tumor, the tumor is genetically sequenced to identify mutations that generate optimal neoantigen proteins—those that appear most foreign to the immune system.

Subsequently, an mRNA vaccine is meticulously crafted, containing the genetic code specific to these neoantigens present in the individual's tumor.

During the vaccine production process, patients receive a single dose of a checkpoint inhibitor drug. This combination is intended to enhance the immune response to tumors. Once the mRNA vaccine is administered into the bloodstream, it prompts dendritic cells—an essential component of the immune system—to produce the neoantigen proteins.

These dendritic cells simultaneously educate other immune system components, including T cells, to recognize and attack tumor cells bearing the same neoantigen proteins. With T cells primed to seek out and destroy cells displaying these proteins, the chances of cancer recurrence are diminished.

Overcoming Challenges: The Road to Success

The road to realizing personalized mRNA vaccines for pancreatic cancer was fraught with challenges, not least of which was the complexity of the manufacturing process. Unlike mass-produced vaccines like those for COVID-19, the mRNA cancer vaccine had to be custom-made for each patient based on the unique characteristics of their tumor.Neoantigens are an important feature of cancer cells and help to stimulate anti-cancer immune responses. (CREDIT: Technology Networks)

This necessitated an intricate series of steps, including the surgical removal of the tumor, shipping the tumor sample to Germany for sequencing, manufacturing the vaccine, and returning it to New York—all within a tight timeframe.

Thankfully, Dr. Balachandran's team and their collaborators rose to the occasion, successfully enrolling the target total of 20 patients nearly a year ahead of schedule. Their unwavering dedication and meticulous planning ensured that the personalized mRNA vaccines could be provided to those in dire need.

As if the hurdles of personalized vaccine production weren't enough, the emergence of the COVID-19 pandemic added an unprecedented layer of complexity to the clinical trial. Dr. Balachandran and his team recognized the urgency of adapting swiftly to ensure that patients were not adversely affected.

Under the leadership of Cristina Olcese and with the unwavering support of individuals such as Department of Surgery Chair Jeffrey Drebin and Hepatopancreatobiliary Service Chief William Jarnagin, the team orchestrated the logistics required to maintain the trial's momentum.

Remarkably, what was initially estimated as a two-and-a-half-year trial was completed in a mere 18 months. The tireless efforts of Dr. Drebin, Medical Oncologist Eileen O'Reilly, Physician-Scientist Jedd Wolchok, Biologist Taha Merghoub, Computational Biologist Ben Greenbaum, and the support from Stand Up 2 Cancer/Lustgarten Foundation were instrumental in making this trial a reality amidst the challenges posed by the pandemic.

A Bright Future for mRNA Vaccines in Pancreatic Cancer Treatment

The recent findings from this pioneering research offer a beacon of hope for patients grappling with pancreatic cancer. Dr. Balachandran affirms that "an mRNA vaccine can trigger the production of T cells that recognize pancreatic cancer cells."

The prospect of personalized vaccines enlisting the immune system in the fight against pancreatic cancer—a disease in dire need of improved treatments—holds tremendous promise. Moreover, these developments may extend their impact to other forms of cancer as well.

Looking ahead, Dr. Balachandran and his team are committed to further analyzing the data obtained from the clinical trial. This analysis will provide valuable insights into the factors that facilitate the vaccine's efficacy in patients. Armed with this knowledge, they aim to refine the vaccines to make them more effective and applicable to a broader spectrum of pancreatic cancer patients.

In a testament to the forward-thinking vision of the Memorial Sloan Kettering Cancer Center, this pioneering work exemplifies their commitment to bringing cutting-edge treatments to cancer patients.

Through their partnership with BioNTech and Genentech, and with the support of Stand Up 2 Cancer/Lustgarten Foundation, a larger study is already in the pipeline, aiming to test personalized mRNA vaccines in a more extensive cohort of pancreatic cancer patients.

As Dr. Balachandran notes, they were at the forefront of mRNA vaccines before their popularity surged, leveraging scientific discoveries to make a tangible impact on patients' lives. The future indeed looks brighter for those facing the formidable challenge of pancreatic cancer, thanks to the relentless pursuit of innovation in the field of mRNA vaccines.

Key Takeaways

Some people with pancreatic cancer survive many years after diagnosis.

In these patients, the immune system keeps the cancer from returning.

A messenger RNA vaccine based on this concept is being tested in combination with another type of immunotherapy.

Early results suggest the vaccine is having the desired effect on the immune system.