Tag: Academic research

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FDA Clears First AI Algorithm to Diagnose Cardiac Amyloidosis

Anumana has received FDA approval for its ECG-AI algorithm designed to support the diagnosis of cardiac amyloidosis at the point of care. This makes it the first and only AI algorithm cleared by the FDA for this severe heart condition, which is often missed by the human eye when looking at electrocardiogram (ECG) data.  

“Cardiac amyloidosis can be challenging to detect early, especially when its signs overlap with more common heart conditions,” said Martha Grogan, MD, consultant in cardiovascular medicine at Mayo Clinic and co-principal investigator of the clinical study that supported the approval. “A tool that helps clinicians recognize suspicion of amyloidosis from a routine ECG could support earlier diagnosis and more timely next steps in care.”

Caused by abnormal protein deposits in the heart, cardiac amyloidosis is a life-threatening condition that can lead to heart failure if missed. Early diagnosis is critical to ensure a timely intervention, which can significantly improve patient outcomes, but the condition is often underdiagnosed due to unspecific symptoms that can be easily mistaken for other, more common heart conditions. 

Symptoms of cardiac amyloidosis are evaluated using a routine ECG. However, diagnosis requires identifying a combination of subtle features found in ECG data, meaning human interpretation can often miss the condition. 

Anumana’s ECG-AI algorithm can analyze ECG waveform to detect these subtle patterns in the data and support the diagnosis process. In a validation study involving more than 15,000 adults presenting signs, symptoms, or comorbidities of cardiac amyloidosis, the AI model detected the condition with 78.9% sensitivity and 91.2% specificity. 

“What makes this work especially meaningful is the rigor of the validation,” said Angela Dispenzieri, MD, hematologist at Mayo Clinic and co-principal investigator of the clinical study. “This ECG-AI algorithm was validated in a large multicenter study that included both ATTR and AL cardiac amyloidosis at major referral centers with deep expertise in amyloidosis diagnosis, supporting its potential to help identify patients earlier.”

Because the algorithm leverages ECGs obtained in routine clinical practice, it can be directly integrated into existing workflows without requiring clinicians to conduct any additional testing, helping them identify patients at risk and informing treatment decisions. 

Anumana previously received FDA clearance for two other ECG-AI algorithms, one for the diagnosis of low ejection fraction and another for pulmonary hypertension. All of these heart conditions are characterized by complex diagnoses that are often delayed or missed; for these patients, early diagnosis and treatment can significantly increase their outcomes and life expectancy.

“Each of our FDA-cleared algorithms addresses a specific and frequently missed cardiovascular condition, and cardiac amyloidosis represents an important addition to that portfolio,” said Maulik Nanavaty, CEO of Anumana. “The more conditions we can identify from a single ECG, the more valuable the test becomes in clinical practice. That’s what Anumana is working toward with each new clearance as we continue to advance our rigorous clinical evidence approach.”

The post FDA Clears First AI Algorithm to Diagnose Cardiac Amyloidosis appeared first on Inside Precision Medicine.

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Metabolic Driver of Radiation Resistance in Lung Cancer Identified

Radiation therapy remains a cornerstone of lung cancer treatment, yet its long-term effectiveness is often undermined by a persistent challenge: tumors adapt and become resistant. Understanding, and overcoming, this resistance is a major priority in oncology.

A new study from researchers at The University of Texas MD Anderson Cancer Center, published in Cancer Research, identifies a metabolic mechanism that allows lung cancer cells to evade radiation-induced death and proposes a clinically actionable strategy to counter it.

A hidden driver of resistance

Radiotherapy works by damaging cancer cells in multiple ways, including triggering ferroptosis—an iron-dependent form of cell death driven by oxidative stress. However, many tumors develop the ability to suppress this process, allowing them to survive treatment.

The new study pinpoints a key player in this resistance: the mitochondrial enzyme dihydroorotate dehydrogenase (DHODH). Researchers found that radiation exposure increases DHODH activity in lung cancer cells, enabling them to withstand ferroptosis and continue growing.

“This is an important finding because of the immediate translational opportunity,” said Boyi Gan, PhD, senior author of the study. “By understanding how DHODH is preventing cell death in radioresistant cancer cells, we were able to develop a strategy to overcome radiation therapy resistance in tumor models.”

A metabolic shield against cell death

DHODH is best known for its role in nucleotide synthesis, helping cells produce the building blocks needed for DNA repair and replication. But the study highlights an additional function that is particularly relevant in cancer.

The enzyme also supports the production of ubiquinol, a molecule that protects cells from oxidative damage. In the context of radiation therapy, this acts as a shield, preventing the lipid damage required to trigger ferroptosis.

By simultaneously promoting DNA repair and suppressing ferroptosis, DHODH enables cancer cells to survive what would otherwise be lethal radiation-induced stress.

Repurposing an existing drug

Rather than developing a new inhibitor from scratch, the researchers turned to leflunomide—an FDA-approved drug currently used to treat rheumatoid arthritis, which is known to inhibit DHODH.

In preclinical models, blocking DHODH alone modestly increased sensitivity to radiation. However, the most striking results emerged when the team combined three treatment modalities: radiation therapy, immune checkpoint blockade, and DHODH inhibition.

Radiation plus immunotherapy alone was insufficient to control tumor growth. But when leflunomide was added, the combination restored ferroptosis and led to a marked reduction in tumor progression.

“DHODH inhibition alone had some effect on sensitization to radiation therapy, but it was really this triple combination that had a marked effect,” Gan said.

Leveraging the immune response

A key aspect of the strategy lies in its interaction with the immune system. Immunotherapy, specifically anti–PD-1 checkpoint blockade, stimulates the production of interferon-gamma (IFN-γ), a signaling molecule that can enhance ferroptosis.

However, in resistant tumors, this signal alone is not enough to overcome the protective effects of DHODH. By inhibiting the enzyme, the researchers effectively remove this metabolic barrier, allowing IFN-γ–driven ferroptosis to proceed.

The result is a coordinated therapeutic effect in which radiation induces stress, immunotherapy amplifies cell death signals, and DHODH inhibition prevents tumor cells from escaping.

Toward clinical translation

One of the most compelling aspects of the study is its translational potential. Leflunomide is already widely used in clinical practice, with a well-characterized safety profile, potentially accelerating its evaluation in oncology settings.

“These findings provide a good rationale for testing this combination in clinical studies,” Gan said in a press release.

If validated in patients, this approach could offer a new strategy for overcoming resistance not only in lung cancer but potentially in other solid tumors treated with radiotherapy.

A broader shift in cancer therapy

The findings also reflect a broader trend in cancer research: targeting metabolic pathways that enable tumor survival under stress. While traditional therapies focus on directly damaging cancer cells, emerging approaches aim to disrupt the adaptive mechanisms that allow tumors to recover.

By linking metabolism, immune signaling, and cell death pathways, the study provides a more integrated view of how resistance develops—and how it can be reversed.

Although the results are based on preclinical models, they offer a clear path forward. Future clinical trials will be needed to determine whether the triple combination strategy can improve outcomes in patients with radioresistant lung cancer.

More broadly, the work highlights the importance of identifying “druggable” vulnerabilities within resistance pathways, especially those that can be targeted with existing therapies.

In this case, a drug originally developed for autoimmune disease may help solve one of the most persistent challenges in cancer treatment: restoring the effectiveness of radiation therapy when it begins to fail.

The post Metabolic Driver of Radiation Resistance in Lung Cancer Identified appeared first on Inside Precision Medicine.

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STAT+: Replimune skin cancer drug that became FDA flashpoint is rejected again

The Food and Drug Administration on Friday rejected — again — an experimental treatment for advanced skin cancer developed by Replimune Group. 

Replimune’s treatment, an engineered virus designed to rev up the immune system against melanoma, has been a flashpoint in a simmering debate over shifting standards at the agency.

The drug was initially rejected in July, just two months after Vinay Prasad was appointed the FDA’s head of biologics. As an academic oncologist, Prasad criticized regulators for approving drugs with limited data, and the Replimune decision was viewed as a possible sign of the stricter stance he might take at the agency.

Continue to STAT+ to read the full story…

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What’s in a name? Moderna’s “vaccine” vs. “therapy” dilemma

Is it the Department of Defense or the Department of War? The Gulf of Mexico or the Gulf of America? A vaccine—or an “individualized neoantigen treatment”?

That’s the Trump-era vocabulary paradox facing Moderna, the covid-19 shot maker whose plans for next-generation mRNA vaccines against flus and emerging pathogens have been dashed by vaccine skeptics in the federal government. Canceled contracts and unfriendly regulators have pushed the Massachusetts-based biotech firm to a breaking point. Last year, Robert F. Kennedy Jr., head of the Department of Health and Human Services, zeroed in on mRNA, unwinding support for dozens of projects—including a $776 million award to Moderna for a bird flu vaccine. By January, the company was warning it might have to stop late-stage programs to develop vaccines against infections altogether.

That raises the stakes for a second area of Moderna’s research. In a partnership with Merck, it’s been using its mRNA technology to destroy tumors through a very, very promising technique known as a cancer vacc—

“It’s not a vaccine,” a spokesperson for Merck jumped in before the V-word could leave my mouth. “It’s an individualized neoantigen therapy.”

Oh, but it is a vaccine. And here’s how it works. Moderna sequences a patient’s cancer cells to find the ugliest, most peculiar molecules on their surface. Then it packages the genetic code for those same molecules, called neoantigens, into a shot. The patient’s immune system has its orders: Kill any cells with those yucky surface markers.

Mechanistically, it’s similar to the covid-19 vaccines. What’s different, of course, is that the patient is being immunized against a cancer, not a virus.

And it looks like a possible breakthrough. This year, Moderna and Merck showed that such shots halved the chance that patients with the deadliest form of skin cancer would die from a recurrence after surgery.

In its formal communications, like regulatory filings, Moderna hasn’t called the shot a cancer vaccine since 2023. That’s when it partnered up with Merck and rebranded the tech as individualized neoantigen therapy, or INT. Moderna’s CEO said at the time that the renaming was to “better describe the goal of the program.” (BioNTech, the European vaccine maker that’s also working in cancer, has shifted its language too, moving from “neoantigen vaccine” in 2021 to “mRNA cancer immunotherapies” in its latest report.)

The logic of casting it as a therapy is that patients already have cancer—so it’s a treatment as opposed to a preventive measure. But it’s no secret what the other goal is: to distance important innovation from vaccine fearmongering, which has been inflamed by high-ranking US officials. “Vaccines are maybe a dirty word nowadays, but we still believe in the science and harnessing our immune system to not only fight infections, but hopefully to also fight … cancers,” Kyle Holen, head of Moderna’s cancer program, said last summer during BIO 2025, a big biotech event in Boston.

Not everyone is happy with the word games. Take Ryan Sullivan, a physician at Massachusetts General Hospital who has enrolled patients in Moderna’s trials. He says the change raises questions over whether trial volunteers are being properly informed. “There is some concern that there will be patients who decline to treat their cancer because it is a vaccine,” Sullivan told me. “But I also felt it was important, as many of my colleagues did, that you have to call it what it is.”

But is it worth going to the mat for a word? Lillian Siu, a medical oncologist at the Princess Margaret Cancer Centre, in Toronto, who has played a role in safety testing for the new shots, watches US politics from a distance. She believes name change is acceptable “if it allows the research to continue.”

Holen told me the doctors complaining to Moderna were basically motivated by a desire to defend vaccines—which are, of course, among the greatest public health interventions of all time. They wanted the company to stand strong. 

But that’s not what’s happening. When Moderna’s latest results were published in February, the paper’s main text didn’t use the word “vaccine” at all. It was only in the footnotes that you could see the term—in the titles of old papers and patents.

All this could be a sign that Kennedy’s strategy is working. His agencies often appear to make mRNA vaccines a focus of people’s worries, impede their reach, devalue them for companies, and sideline their defenders. 

Still, Moderna’s strategy may be working too. So far, at least, the government hasn’t had much to say about the company’s cancer vacc— I mean, its individualized neoantigen therapy.

This article first appeared in The Checkup, MIT Technology Review’s weekly biotech newsletter. To receive it in your inbox every Thursday, and read articles like this first, sign up here.

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How blindness shapes personality: a neuro-ecological account

IntroductionThe established link between personality and psychological well-being underscores the need to understand how major life changes, such as vision loss, reshape an individual’s disposition. While previous research has produced inconsistent findings, the roles of concurrent environmental factors and underlying neural mechanisms have remained largely unexplored.MethodsThis study employed an integrated neuro-ecological framework to investigate how blindness influences personality. We recruited 46 blind participants and 41 sighted controls, who completed comprehensive assessments including the NEO-Five-Factor Inventory, social and lifestyle questionnaires, and multimodal neuroimaging, including structural magnetic resonance imaging (MRI), diffusion MRI, and resting-state functional MRI.ResultsBlind participants showed higher agreeableness, extraversion, and conscientiousness, while reduced neuroticism compared to sighted controls, and these personality trait differences were attenuated after accounting for trait anxiety. These differences were partially mediated by increased perceived social support from friends. Furthermore, mobile phone usage habits showed an interaction with blindness on personality traits. Neuroimaging identified both shared and vision-specific neural correlates of personality. For instance, blindness-related changes in white matter integrity of the anterior thalamic radiation and forceps minor mediated the reduction in neuroticism. Moderated mediation models further revealed that the strength of these neural pathways was regulated by environmental factors, such as social support and mobile phone self-control.DiscussionCollectively, these results indicate that personality patterns in blindness are a dynamic process involving the interplay of neural plasticity and environmental modulation, rather than a direct consequence of sensory loss alone.
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Zingerone alleviates acute seizures by reducing intrinsic hippocampal neuronal excitability in a rat model of temporal lobe epilepsy

BackgroundEpilepsy is a complex neurological disorder characterized by recurrent seizures. Neuroinflammation and excessive neuronal excitation are key pathogenic factors, but current therapies fail to target these mechanisms effectively, highlighting the need for novel therapeutic agents. Zingerone, a bioactive compound derived from ginger (Zingiber officinale Roscoe), exhibits anti-inflammatory, antioxidant, and neuroprotective properties. However, its acute anticonvulsant efficacy and underlying mechanism in temporal lobe epilepsy (TLE) remain unclear. This study aimed to investigate whether zingerone exerts anticonvulsant effects by modulating neuronal excitability.MethodsA lithium chloride-pilocarpine-induced acute TLE rat model was established. Rats were randomly assigned to control, pilocarpine, and zingerone treatment groups (75, 150, and 300 mg/kg, i.p.). Seizure activity was evaluated via behavioral scoring (Racine scale) and electroencephalography (EEG). Immunohistochemistry (IHC), hematoxylin-eosin (HE) staining, and immunofluorescence were used to assess hippocampal microglial/astrocytic activation and neuronal damage. Whole-cell patch-clamp recordings were performed to analyze intrinsic neuronal excitability and synaptic transmission in hippocampal CA1 pyramidal neurons.ResultsAcute administration of zingerone (150 and 300 mg/kg) significantly reduced the number and duration of Racine stage IV/V generalized seizures. Zingerone dose-dependently inhibited microglial (IBA1+) and astrocytic (GFAP+) activation (p < 0.01 for 150 mg/kg; p < 0.001 for 300 mg/kg) and preserved neuronal integrity in the hippocampal CA1 region, as evidenced by reduced neuronal shrinkage, pyknosis, and increased NeuN+ neuron density. Electrophysiological recordings revealed that zingerone (10 μM) decreased the firing frequency of CA1 pyramidal neurons (p < 0.05), prolonged the inter-spike interval (p = 0.0026), reduced the action potential peak (p = 0.041), increased the rheobase current (p = 0.042), and increased afterhyperpolarization amplitude (p = 0.0001). Furthermore, Zingerone also modulated excitatory synaptic transmission onto CA1 neurons.ConclusionZingerone exerts acute anticonvulsant and neuroprotective effects in a TLE rat model by suppressing hippocampal neuroinflammation and reducing the intrinsic excitability of pyramidal neurons. These findings highlight zingerone as a promising natural compound for developing novel adjuvant therapies for drug-resistant TLE.
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Exploratory assessment of cerebrospinal fluid-related microdynamics after mild traumatic brain injury using intravoxel incoherent motion magnetic resonance imaging

AimThis study aimed to characterize regional alterations in cerebrospinal fluid (CSF) microdynamics following mild traumatic brain injury (TBI) using intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and compare f-value–based CSF motion between patients with TBI and healthy controls.MethodsIn this prospective observational study, 14 patients with mild TBI and 14 healthy volunteers underwent IVIM MRI using a 3-Tesla scanner. The f-value, reflecting incoherent CSF-related microfluidic motion, was quantified across predefined supratentorial and infratentorial regions of interest. Group differences in mean f-values were evaluated, and longitudinal changes were assessed in three patients who underwent follow-up MRI.ResultsThe TBI group exhibited a significantly higher mean f-value in the left cerebellopontine angle (CPA) compared with controls. Exploratory trends toward lower f-values were also observed in several supratentorial regions, including the left lateral ventricle and right frontal subarachnoid space. Longitudinal analysis revealed increasing f-values in supratentorial regions over time—suggesting partial recovery—whereas infratentorial regions demonstrated decreasing or stable trajectories.ConclusionMild TBI may be associated with region-specific alterations in CSF microdynamics, characterized by increased motion in the CPA and exploratory reductions in selected supratentorial regions. Although preliminary, these findings highlight the potential of IVIM MRI as a complementary tool for investigating post-traumatic abnormalities in CSF motion.
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A survey on data augmentation for EEG-based emotion recognition and cognitive workload decoding

Electroencephalography (EEG) is extensively employed in emotion recognition and cognitive workload decoding. However, signal characteristics and inter-subject variability pose significant challenges for deep learning models, particularly due to data scarcity and limited generalization. Although data augmentation (DA) is a critical approach to addressing data scarcity, a notable paucity of systematic reviews exists within deep learning frameworks focused exclusively on these two tasks. Through a systematic review of relevant literature, we summarize commonly used public EEG datasets, input representations, and deep learning classifiers. Subsequently, we focus on analyzing the specific applications and effectiveness of seven categories of DA methods in emotion recognition and cognitive workload decoding. The investigation identifies current challenges in this field, explores future research directions, and provides valuable references for researchers seeking to select and apply DA techniques to enhance model performance.
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Effect of transcranial magnetic stimulation on prognosis in patients with postherpetic neuralgia and comorbid depression undergoing interventional neuromodulation therapy: protocol for a randomized double-blind placebo-controlled trial

BackgroundPostherpetic neuralgia (PHN) is often accompanied by depression, creating a vicious cycle that exacerbates symptoms and contributes to suboptimal treatment outcomes, even with interventional therapies. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated potential in alleviating both pain and mood disturbances. However, its efficacy in enhancing prognosis when used alongside interventional neuromodulation therapy for PHN accompanied by depression remains inadequately explored and requires further investigation.ObjectiveThis study aims to generate preliminary evidence on the efficacy and safety of rTMS in enhancing prognosis and alleviating pain in patients with PHN and mild to moderate depression undergoing interventional neuromodulation therapy.MethodsThis study is a single-center, randomized, double-blind, placebo-controlled trial involving 174 adult patients with PHN. Participants will be randomly assigned, stratified by interventional neuromodulation therapy, to either the rTMS group (n=87) or the control group (n=87). Both groups will undergo either 10 Hz rTMS or sham stimulation for five consecutive days. The primary outcome is the incidence of poor prognosis at 3 months post-discharge. Secondary outcomes include the incidence of poor prognosis at 6 months post-discharge; Visual Analog Scale (VAS) sleep scores; short-form McGill Pain Questionnaire (SF-MPQ) scores; Self-Rating Depression Scale (SDS) scores; patient satisfaction; Pain Disability Index (PDI) scores; Multidimensional Fatigue Inventory-20 (MFI-20) scores; pregabalin oral doses; and the need for tramadol or antidepressants. Safety outcomes will include assessments of headache, pain at the stimulation site, neck pain, insomnia, muscle soreness, dizziness, nausea, tinnitus, irritability, tachycardia (heart rate > 100 bpm), and epilepsy. Data will be analyzed using a modified intention-to-treat approach.DiscussionThis study aims to provide preliminary evidence on the efficacy and safety of 10 Hz rTMS in improving prognosis and alleviating pain in PHN patients with mild to moderate depression undergoing interventional pain management.Trial registrationhttps://www.chictr.org.cn/bin/project/edit?pid=261070, identifier ChiCTR2500096978.
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From work-related trauma to suicidal ideation: a serial mediation model of posttraumatic stress and depression in rescue workers

ObjectivesRescue workers face frequent occupational trauma, increasing their risk for posttraumatic stress symptoms (PTSS), depression, and suicidal ideation. However, pathways linking trauma to suicidality remain poorly understood. This study investigated these mechanisms by testing a serial mediation model.MethodsFrom a larger survey of Swiss rescue workers, participants reporting suicidal ideation (n = 44) were matched by age, sex, and profession with a control group without suicidal ideation (n = 44). Symptomatology was assessed using validated questionnaires such as the Posttraumatic Stress Scale-10 (PTSS-10) for posttraumatic stress and the Brief Symptom Inventory (BSI) for depressive symptoms. Structural Equation Modeling (SEM) was employed to test a serial two-mediator model: Trauma Exposure – PTSS – Depressive Symptoms – Suicidal Ideation.ResultsParticipants with suicidal ideation had significantly higher levels of trauma, PTSS, and depressive symptoms. SEM confirmed an excellent model fit (χ² = 1.925, CFI = 1.000, RMSEA <.001) and a full mediation effect: trauma exposure was associated with PTSS, which in turn related to depressive symptoms, which were subsequently linked to suicidal ideation. The specific serial indirect pathway was significant (B = 0.143, p = .011), while the direct path from trauma to suicidal ideation was non-significant. The model explained 69.4% of the variance in suicidal ideation.ConclusionThe findings suggest a developmental pathway in which trauma exposure is associated with suicidal ideation through the sequential roles of PTSS and depressive symptoms. Consequently, suicide prevention for rescue workers should prioritize the management of post-traumatic and depressive symptoms to potentially disrupt this symptomatic progression.