Libertarian Group Sues To Block Biden Student Loan Forgiveness

 A California libertarian group has sued the Biden administration over its plan to cancel student debt, calling it an illegal overreach which will end up taxing some Americans whose debt is forgiven.

"Congress did not authorize the executive branch to unilaterally cancel student debt," said attorney Caleb Kruckenberg of the Pacific Legal Foundation, which filed the lawsuit - believed to be the first targeting Biden's plan, AP reports. The Sacramento-based legal advocacy group filed the suit in Indiana, which is one of several states that plans to tax those whose debt is canceled by Biden's plan.

Kruckenberg says that it's illegal for the executive branch to create such policy "by press release, and without statutory authority."

(Meanwhile, Biden is yanking student loan forgiveness for more than 750,000 borrowers who took federal government loans that were issued and managed by private lenders)

The suit’s plaintiff is Frank Garrison, described as a public interest attorney who lives in Indiana and is employed by the libertarian group.

Garrison is on track to get his student debt erased through a separate federal program for public servants. Although most borrowers will need to apply for Biden’s plan, Garrison and many others in that program will automatically get the relief because the Education Department has their income information on file. -AP

Garrison, the plaintiff, says that Biden's plan would automatically cancel up to $20,000 of his debt, which would trigger an "immediate tax liability" owed to the state of Indiana.

"Mr. Garrison and millions of others similarly situated in the six relevant states will receive no additional benefit from the cancellation — just a one-time additional penalty," read the suit.

Other states which plan to debt forgiven debt under the Biden plan are; Arkansas, California, Minnesota, Mississippi, North Carolina and Wisconsin, unless lawmakers act to change their current laws.

When asked how people could opt out of the debt forgiveness, White House press secretary Karine Jean-Pierre, who said 'anyone can opt-out' had no answers, after previously saying that roughly 8 million Americans would automatically receive the debt relief.

"The bottom line is this — no one who does not want debt relief will have to get that debt relief," she said.

The White House has called the lawsuit "baseless," suggesting that it's nothing more than political opponents who "are trying anything they can to stop this program that will provide needed relief to working families."

Biden's plan will cancel $10,000 in federal student debt for those making $125,000 per year or less, and $250,000 per household. Pell Grant recipients are set to receive an additional $10,000 benefit. 

Conservative groups have called Biden's plan legally questionable, and point out that the debt forgiveness unfairly cancels student debt at the expense of Americans who didn't attend college - or paid off their loans.

The Biden administration has repeatedly argued that the plan is on solid legal ground.

In its legal justification for debt cancellation, the Biden administration invoked the HEROES Act of 2003, which aimed to provide help to members of the military. The law gives the administration “sweeping authority” to reduce or eliminate student debt during a national emergency, the Justice Department said in an August legal opinion.

Education Secretary Miguel Cardona has said he has the legal authority to cancel debt for people who faced hardship during the pandemic. Cardona says Biden’s plan will ensure borrowers aren’t worse off after the pandemic than they were before. -AP

"Nothing about loan cancellation is lawful or appropriate," reads the lawsuit. "In an end-run around Congress, the administration threatens to enact a profound and transformational policy that will have untold economic impacts."

https://www.zerohedge.com/political/libertarian-group-sues-block-biden-student-loan-forgiveness

Gene loss enhances metastasis and cancer progression

 Investigators have discovered that the loss of the gene SLIT2 in circulating tumor cells regulates metastasis of prostate cancer tumors, according to a Northwestern Medicine study published in Science Advances.

Metastasis accounts for most cancer-related deaths, yet its underlying mechanisms have remained poorly understood despite recent advances in cancer treatments and care.

Circulating tumor cells (CTCs) drive cancer metastasis by breaking off from primary tumors and traveling through the bloodstream to seed new tumors. However, identifying the genetic factors that regulate CTCs and help them enter the bloodstream has remained a major roadblock due to CTCs' rarity and heterogeneous nature.

"If we could turn off metastasis, cancer would not be deadly. Understanding why CTCs enter the blood is a critical step," said Shana Kelley, Ph.D., professor of Biochemistry and Molecular Genetics, the Neena B. Schwartz Professor of Chemistry and Biomedical Engineering at the McCormick School of Engineering and senior author of the study.

To uncover the mechanisms driving CTC migration, the investigators used CRISPR gene editing to knock out genes in tumor-forming prostate cancer cells implanted in mice, with each cell having loss of function of one gene in the human genome. CTCs were collected using a first-of-its-kind approach developed by Kelley's laboratory that efficiently isolates CTCs from blood cells.

From this screening, the investigators identified SLIT2 as the most common gene associated with CTCs. The gene encodes the SLIT2 protein, which in turn influences cellular migration. When SLIT2 knockout CTCs were inserted back into the mouse model, the investigators found that the number of CTCs increased in the bloodstream of mice.

The findings suggest that SLIT2 loss in circulating tumor cells promotes metastasis and enhances cancer progression. According to Kelley, next steps will involve screening genes that are activated, rather than knocked out, to identify new drug targets that could potentially slow or prevent metastasis.

"We know that in patients if there's a loss of SLIT2, there are poorer outcomes, so this suggests that if we could bring back SLIT2 function we could keep metastasis from happening," said Kelley, who is a member of the Robert H. Lurie Comprehensive Cancer Center of Northwestern University.

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How tumor cells 'camouflage' themselves in the bloodstream to avoid being detected

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More information: Fan Xia et al, Genome-wide in vivo screen of circulating tumor cells identifies SLIT2 as a regulator of metastasis, Science Advances (2022). DOI: 10.1126/sciadv.abo7792

https://medicalxpress.com/news/2022-09-gene-loss-metastasis-cancer.html

Non-opioid compounds squelch pain without sedation

 A newly identified set of molecules alleviated pain in mice while avoiding the sedating affect that limits the use of opiates, according to a new study led by researchers at UC San Francisco. The molecules act on the same receptor as clonidine and dexmedetomidine—drugs commonly used in hospitals as sedatives—but are chemically unrelated to them and may not be addictive.

Clonidine and dexmedetomidine are also both effective pain killers but so sedating that they are rarely used for pain relief outside of the hospital.

"We showed that it's possible to separate the analgesic and sedative effects related to this receptor, said Brian Shoichet, Ph.D., professor in the School of Pharmacy, and one of four senior authors of the study, which appears in the Sept. 30, 2022, issue of Science. "That makes it a very promising target for drug development."

The research began shortly before the COVID-19 pandemic, with the aim of finding effective painkillers that can be used together or in conjunction with opioids.

The work brings together researchers from a variety of disciplines; Shoichet's co-authors include UCSF anatomy chair Allan Basbaum, Ph.D., chemist Peter Gmeiner of Freidrichs Alexander University in Germany, structural biologist Yang Du, Ph.D., of the Chinese University of Hong Kong, and molecular biologist Michel Bouvier, Ph.D., of the University of Montreal.

"Together, we were able to take this from the most fundamental level to identifying new molecules that might be relevant, and then to demonstrating that, in fact, they are relevant," said Basbaum. "That doesn't happen very often."

6 Molecules Out of 300 Million

Shoichet was encouraged to look for substances that would activate this adrenergic receptor, called alpha2a, by Basbaum, who had studied it in his lab and showed that it is tied to pain relief.

To start the search for molecules that would bind firmly to the receptor, Shoichet computationally combed through a virtual library of over 300 million molecules, eliminating those that were too bulky for the small receptor. The remaining thousands were virtually "docked," one by one, on a computer model of the receptor.

Through a series of tests, Shoichet narrowed the field from an initial 48 candidates to six, based on how they bound to the receptor in cultured human and mouse cells. Each of the final six was tested on three different mouse models for acute and chronic pain, and successfully alleviated pain in all three instances.

The pain-relieving molecules, which were from chemically different families, are also entirely novel. None of them had previously been synthesized.

Whereas the older drugs, like dexmedetomidine, activate a broad spectrum of neuronal pathways, the new molecules trigger only a selective subset of these, Shoichet said. The molecules also concentrate in the brain, and bind tightly to the receptor, making them good candidates for further development.

Hope for 1 in 5 Americans

Basbaum cautions that it may take several years of research before any of the compounds could be tested in clinical trials. The researchers don't yet understand possible side effects of the new molecules, and whether there might be unintended consequences from long-term use.

He believes, however, that it's unlikely the compound is addictive. "Substance abuse happens when the drug generates a reward, which we didn't see any evidence of," he said.

While opioids clearly help patients with pain from surgery or cancer, Basbaum noted that the majority of the 50 million Americans with chronic pain have other conditions, like back injuries, joint pain, and inflammatory disease, that often aren't helped by the drugs. New analgesics could completely change the outlook for these patients.

"If we can create a drug that works in combination with a much lower dose of opiate, that would be the dream," he said. "The need for that is huge."

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Body's natural pain killers can be enhanced

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More information: Elissa A. Fink et al, Structure-based discovery of nonopioid analgesics acting through the α2A-adrenergic receptor, Science (2022). DOI: 10.1126/science.abn7065

https://medicalxpress.com/news/2022-09-non-opioid-compounds-squelch-pain-sedation.html

Another monkey virus could be poised for spillover to humans

 An obscure family of viruses, already endemic in wild African primates and known to cause fatal Ebola-like symptoms in some monkeys, is "poised for spillover" to humans, according to new University of Colorado Boulder research published online Sept. 30 in the journal Cell.

While such arteriviruses are already considered a critical threat to macaque monkeys, no human infections have been reported to date. And it is uncertain what impact the virus would have on people should it jump species.

But the authors, evoking parallels to HIV (the precursor of which originated in African monkeys), are calling for vigilance nonetheless: By watching for arteriviruses now, in both animals and humans, the global health community could potentially avoid another pandemic, they said.

"This animal virus has figured out how to gain access to human cells, multiply itself, and escape some of the important immune mechanisms we would expect to protect us from an animal virus. That's pretty rare," said senior author Sara Sawyer, a professor of molecular, cellular and developmental biology at CU Boulder. "We should be paying attention to it."

There are thousands of unique viruses circulating among animals around the globe, most of them causing no symptoms. In recent decades, increasing numbers have jumped to humans, wreaking havoc on naïve immune systems with no experience fighting them off: That includes Middle Eastern Respiratory Syndrome (MERS) in 2012, Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) in 2003, and SARS-CoV-2 (the virus that causes COVID-19) in 2020.

For 15 years, Sawyer's lab has used laboratory techniques and tissue samples from wildlife from around the globe to explore which animal viruses may be prone to jump to humans.

For the latest study, she and first author Cody Warren, then a postdoctoral fellow at the BioFrontiers Institute at CU, zeroed in on arteriviruses, which are common among pigs and horses but understudied among nonhuman primates. They looked specifically at simian hemorrhagic fever virus (SHFV), which causes a lethal disease similar to Ebola virus disease and has caused deadly outbreaks in captive macaque colonies dating back to the 1960s.

The study demonstrates that a molecule, or receptor, called CD163, plays a key role in the biology of simian arteriviruses, enabling the virus to invade and cause infection of target cells. Through a series of laboratory experiments, the researchers discovered, to their surprise, that the virus was also remarkably adept at latching on to the human version of CD163, getting inside human cells and swiftly making copies of itself.

Like human immunodeficiency virus (HIV) and its precursor simian immunodeficiency virus (SIV), simian arteriviruses also appear to attack immune cells, disabling key defense mechanisms and taking hold in the body long-term.

"The similarities are profound between this virus and the simian viruses that gave rise to the HIV pandemic," said Warren, now an assistant professor in the College of Veterinary Medicine at The Ohio State University.

The authors stress that another pandemic is not imminent, and the public need not be alarmed.

But they do suggest that the global health community prioritize further study of simian arteriviruses, develop blood antibody tests for them, and consider surveillance of human populations with close contact to animal carriers.

A broad range of African monkeys already carries high viral loads of diverse arteriviruses, often without symptoms, and some species interact frequently with humans and are known to bite and scratch people.

"Just because we haven't diagnosed a human arterivirus infection yet doesn't mean that no human has been exposed. We haven't been looking," said Warren.

Warren and Sawyer note that in the 1970s, no one had heard of HIV either.

Researchers now know that HIV likely originated from SIVs infecting nonhuman primates in Africa, likely jumping to humans sometime in the early 1900s.

When it began killing young men in the 1980s in the United States, no serology test existed, and no treatments were in the works.

Sawyer said there is no guarantee that these simian arteriviruses will jump to humans. But one thing is for sure: More viruses will jump to humans, and they will cause disease.

"COVID is just the latest in a long string of spillover events from animals to humans, some of which have erupted into global catastrophes," Sawyer said. "Our hope is that by raising awareness of the viruses that we should be looking out for, we can get ahead of this so that if human infections begin to occur, we're on it quickly."

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How do diseases jump from one species to another?

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More information: Sara L. Sawyer, Primate hemorrhagic fever-causing arteriviruses are poised for spillover to humans, Cell (2022). DOI: 10.1016/j.cell.2022.09.022. www.cell.com/cell/fulltext/S0092-8674(22)01194-1

https://medicalxpress.com/news/2022-09-monkey-virus-poised-spillover-humans.html

Human Brain Project researchers identify new marker of ALS outcome

 A study by Human Brain Project (HBP) researchers has identified a new marker for predicting the clinical outcome of patients with Amyotrophic Lateral Sclerosis (ALS) through magnetoencephalography. This marker can be measured in the brain during its resting state and highlights the importance of brain flexibility for ALS patients. The study has been led by the Institut de Neurosciences des Systèmes in Marseille, in collaboration with Consiglio Nazionale delle Ricerche, Parthenope University of Naples and Institute of Diagnosis and Care Hermitage Capodimonte in Naples, and the Monash University in Melbourne. It was published online on Sept. 30, 2022, in Neurology.

ALS is a neurodegenerative disease of the brain and spinal cord that causes loss of muscle control. The ability of moving, speaking and, eventually, breathing is progressively impaired. There is no known cure but treatments to improve symptoms, including magnetic stimulation, are being tested.

"The behavior of the brain of an ALS patient is often hard to understand. The impairments can be caused by neuronal dysfunction of a small area of the brain that influences a much larger area, meaning you need whole brain scans to make predictions of the clinical outcome," explains Pierpaolo Sorrentino from the INS, the last author of the study. "Patients can struggle with motor tasks during the scans. This new method, instead, can be applied to the brain at rest, making it easier for the patients and more consistent."

The researchers collected magnetoencephalography data on 42 ALS patients and 42 healthy controls at the University Parthenope in Naples, whose MEG facilities have recently become part of EBRAINS—a digital research infrastructure developed as part of the HBP. The new study builds on previous work by the same group, which applied the methodology to Parkinson's disease.

"A healthy brain is a flexible one, capable of reconfiguring itself to respond to stimuli, triggering neuronal avalanches across different areas," adds Sorrentino. "Think of it as a goalkeeper waiting for a penalty kick. If you are fast enough, constantly moving rather than standing in the same place is a better strategy for being ready for most possible trajectories."

"The neuronal avalanches spread in patterns which we can monitor with whole-brain scans," explains Arianna Polverino of the Institute of Diagnosis and Care Hermitage Capodimonte, lead author of the study. "We call the collection of all unique patterns the 'functional repertoire,' a measurement of the flexibility of the brain."

The researchers focused on quantifying the functional repertoire of ALS brains, even when the patient is unprompted and the brain is in a resting state. "We found that a restriction of the functional repertoire corresponded to a more severe functional impairment. The more flexible the brain, the better the clinical outcome: the functional repertoire can be used as a reliable predictor of how the clinical outlook of a patient will likely evolve."

"It is often difficult to tell how a particular therapy is working—now we might have a strong marker to predict its outcome," says Sorrentino.

The next step, according to the scientists, is to use this non-invasive readout in a longitudinal study that tracks the evolution of the disease in a patient-specific way and adjust treatment accordingly. "The ultimate goal is to apply the predictive power of the functional repertoire in personalized medicine, perhaps extending the same approach to brain dynamics to other, large-scale applications," concludes Polverino.

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Study explores mechanisms that underlie disorders of consciousness

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More information: Flexibility of Fast Brain Dynamics and Disease Severity in Amyotrophic Lateral Sclerosis, Neurology (2022). DOI: 10.1212/WNL.0000000000201200

https://medicalxpress.com/news/2022-09-human-brain-marker-als-outcome.html

Analysts positive on AtriCure following Converge AFib procedure update

 Analysts have a positive outlook on AtriCure (Nasdaq:ATRC) following an investor webinar discussing the company’s Convergent procedure.

Convergent uses the company’s EPi-Sense system. Its epicardial-sensing electrodes allow both electrophysiologists (EPs) and cardiothoracic surgeons to sense and record cardiac signals. It can be used for the coagulation of cardiac tissue using radiofrequency (RF) energy.

According to BTIG analyst Marie Thibault, both EPs on Wednesday’s webinar — Dr. Zayd Eldadah from MedStar Heart & Vascular Institute in Washington, D.C. and Dr. Eric Buch from UCLA Health — believe the patient population for the procedure is large and can extend beyond its current use for long-standing persistent AFib. The FDA approved EPi-Sense for treating long-standing persistent AFib in April 2021.

Thibault said it may take time to start and ramp a program but the EPs expect volume to increase “significantly.” Dr. Buch is performing around four procedures per month and expects a four-fold increase in the next two years, she wrote.

“Increasing awareness, overcoming skepticism, and building referral networks are all key factors for a successful program,” Thibault said.

Both doctors said their own Convergent clinical outcomes come in stronger than “already-impressive” results from the Converge trial. Thibault continues to consider AtriCure a “Buy” option.

“While we acknowledge Convergent adoption has been gradual, this discussion underscored the enthusiasm of current users,” she wrote. “We continue to expect an acceleration in Convergent revenue later this year and in 2023.”

EPi-Sense demonstrated superiority compared to endocardial catheter ablation alone in the Converge clinical trial. It demonstrated a 29% absolute difference in efficacy at 12 months (78% relative improvement). The therapy produced an absolute difference of 35% at 18 months (110% relative improvement).

Afib burden decreased by 33% in the EPi-Sense group at 12 months and fell to 37% at 18 months. The Converge trial proved that AtriCure’s Hybrid AF therapy offers durable, sustained efficacy, the company said in 2021.

Needham analyst Mike Matson said investors had been “frustrated” by the slow initial uptake for EPi-Sense. However, he called the webinar “enlightening.”

“[The webinar] shed light on why growth has been slow and why it’s premature in our view to write off Convergent,” Matson wrote.

He added that AtriCure shares “would react favorably” to strong sequential minimally invasive ablation growth over a quarter or two.

https://www.massdevice.com/analysts-atricure-converge-procedure-afib/

Metabolite-driven antitumor immunity

 JAMES A. NATHAN

DOI: 10.1126/science.ade3697

Abstract

Otto Warburg’s observations that solid organ tumors preferentially use aerobic glycolysis, metabolizing glucose to lactate, to facilitate growth paved the way for our understanding of how nutrient availability and metabolism can promote cancer. A common theme is that proliferating tumor cells use a diverse array of mechanisms to acquire nutrients to grow rather than to simply support adenosine triphosphate (ATP) production (1). However, promoting cell growth is generally not sufficient for solid-organ tumors to develop because they must also evade cytotoxic T cells, raising the question of whether this immune evasion is linked to metabolism. On page 1519 of this issue, Notarangelo et al. (2) show that D-2-hydroxyglutarate (D-2HG), a metabolite secreted by tumors with mutations in isocitrate dehydrogenase (IDH) (3), functions within the tumor microenvironment (TME) to impair CD8+ T cell–mediated tumor cell killing. These findings highlight the potential for metabolites within the TME to alter antitumor immune responses.

https://www.science.org/doi/10.1126/science.ade3697