Cardiology

Applications of Nanotechnology in the Field of Cardiology – Cureus

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Applications of Nanotechnology in the Field of Cardiology - Cureus

Cardiology

TAVR Found Non-Inferior to SAVR for Low-Risk Patients – Diagnostic and Interventional Cardiology

April 11, 2024 Transcatheter aortic valve replacement (TAVR) was found to bring no increased risks and was associated with substantial decreased rates of death or stroke at one year in lowrisk patients, compared with surgical aortic valve replacement (SAVR), according to findings presented at the American College of Cardiologys Annual Scientific Session.

TAVR and SAVR are procedures to replace a damaged aortic valve that is not functioning properly. U.S. guidelines recommend TAVR, a catheter-based approach in which the new valve is threaded to the heart through a blood vessel in the groin or chest, over open-heart SAVR for older patients and those with high cardiovascular risk. However, previous studies and different countries guidelines have varied when it comes to determining the optimal approach for younger and lower-risk patients.

We can now provide strong data that in this low-risk patient population, you could very safely offer TAVR vs. SAVR, said Moritz Seiffert, MD, professor of cardiology at BG University Hospital Bergmannsheil, Ruhr University Bochum in Bochum, Germany, and one of the study authors. TAVR is less invasive; its usually performed under local anesthesia, lasting 30-60 minutes, and the convalescence is shorter than with open chest surgery. [These findings offer] a strong argument toward catheter-based treatment, at least for the one-year timeframe of this study, in these patients.

The DEDICATE-DZHK6 trial compared TAVR vs. SAVR in 1,414 patients who underwent valve replacement procedures at 38 centers in Germany.

All patients enrolled in the trial were eligible for either TAVR or SAVR and had similar characteristics in terms of the severity of aortic stenosis (narrowing of the valve which makes it harder for blood to flow efficiently) and a similar balance of risks and benefits expected with either type of procedure. Patients with bicuspid valves, previous heart surgery or additional coronary or valvular diseases requiring further treatment were excluded. The average age of participants was 74 years and 43% were women.

Researchers randomly assigned half of the participants to undergo TAVR and the other half to SAVR. Since the trial was intended to mirror real-world conditions, many decisions were left to the local heart teams at each study site, rather than strict predetermined study protocols. Local interdisciplinary heart teams determined which patients were eligible to participate in the study based on broad inclusion criteria. Operators selected which replacement valve to use and followed their own centers standard practices for performing the procedures.

The co-primary safety endpoint was designed to assess whether TAVR was non-inferior to SAVR as indicated by an absolute increase of no more than 1% in the composite rate of death or stroke at one year. The trial met this endpoint, showing that people who underwent TAVR were 47% less likely than those undergoing SAVR to experience death or stroke at one year. Event rates for several secondary endpoints, including all-cause death or disabling stroke, were also significantly lower in patients undergoing TAVR compared with those undergoing SAVR at one year.

Although we primarily tested for non-inferiority, the magnitude of the difference surprised us, Seiffert said. Valve prosthesis selection based on individual patients anatomical and medical considerations may have played a role. In addition, the COVID-19 pandemic might have amplified the surgical risk. In fact, the relative difference was comparable to previous studies, but the overall higher event rates and larger patient population may have led to these significant results.

Researchers plan to further investigate some factors that set the trial apart from previous studies and may have contributed to the substantially reduced risk in the TAVR group, including the relatively high proportion of females in the study group. The data were consistent among the subgroups tested so far.

Overall, researchers said that the findings are likely generalizable to patient populations and health care environments across many developed countries.

What it really adds to previous trials is that it mirrors clinical routine, Seiffert said. Its completely industry independent, not focused on one particular device but comparing a catheter-based strategy to a surgical strategy overall. That makes it more applicable and aligned with the types of decisions physicians are making in their daily medical work.

The researchers will continue to track outcomes for at least five years. Future analyses will include additional metrics for assessing clinical superiority as well as quality of life outcomes. In addition, researchers plan to examine whether certain subgroups appear to derive specific risks or benefits from one approach or the other.

The study was funded by German Center for Cardiovascular Research with financial support by the German Heart Foundation. This study was simultaneously published online in the New England Journal of Medicine at the time of presentation.

For more information:www.acc.org

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TAVR Found Non-Inferior to SAVR for Low-Risk Patients - Diagnostic and Interventional Cardiology

Cardiology

Global Interventional Cardiology Devices Market Projected to Reach $21.9 Billion by 2030 – GlobeNewswire

Dublin, April 08, 2024 (GLOBE NEWSWIRE) -- The "Global Interventional Cardiology Devices Market Size, Share & Industry Trends Analysis Report By End-use (Hospitals & Clinics, Ambulatory Surgical Centers & Others), By Product, By Regional Outlook and Forecast, 2023 - 2030" report has been added to ResearchAndMarkets.com's offering.

Market Dynamics and Growth Factors

The global interventional cardiology devices market is expected to achieve significant growth, with projections estimating a reach of $21.9 billion by 2030. This growth is anticipated to occur at a CAGR of 7.4% during the forecast period. Technology advancements, strategic collaborations, and an increasing burden of cardiovascular diseases serve as major catalysts for this expansion.

Unified by the common objective to combat cardiovascular diseases (CVDs) and improve patient outcomes, industry leaders are reinforcing their market positions through strategic partnerships and collaborations. The integration of cutting-edge technologies in the treatment of heart conditions is a key component driving the global market forward.

Product Innovations and Strategic Alliances

Pioneering products such as drug-eluting stents (DES) are playing a crucial role in shaping the future of cardiovascular care, offering new avenues for treatment with lower restenosis rates. Additionally, the ability of DES to reduce the risk of stent thrombosis marks a significant technological milestone. Furthermore, notable collaborations among top industry players are set to enhance the range of cardiovascular devices available, thereby augmenting the scope of patient care.

COVID-19 Impact and Resilience

The onset of the COVID-19 pandemic initially disrupted the interventional cardiology devices sector due to postponed elective procedures and a shift in healthcare priorities. Despite this, the market demonstrated resilience with the continued necessity for acute cardiovascular interventions and adoption of remote monitoring practices. The market is now recovering and showing a return to pre-pandemic activity levels.

Market Outlook by End-use and Product

The hospitals & clinics segment continues to lead the interventional cardiology devices market, given their comprehensive cardiac care offerings. Nevertheless, ambulatory surgical centers are steadily gaining ground, proving themselves as efficient venues for interventional cardiology procedures. The product landscape remains diverse, with coronary stents, PTCA balloon catheters, and accessory devices shaping the interventional approach to cardiovascular care.

Regional Market Insights

From a regional perspective, the Asia Pacific market is displaying robust growth, underpinned by an increasing prevalence of cardiovascular diseases and rising healthcare investments. This mirrors the global concern for advanced solutions to address the surging incidence of heart-related ailments, reinforcing the need for sophisticated interventional cardiology devices across diverse healthcare settings.

The report provides an in-depth analysis of market dynamics, product segments, and regional trends that are influencing the growth trajectory of the interventional cardiology devices industry. The insights are dedicated to fostering a comprehensive understanding of market forces and strategic imperatives in the healthcare sector.

Future Outlook

Looking ahead, the interventional cardiology devices market is poised for sustained growth, drawing from an expanding patient pool and continuous innovation in medical technologies. The focus on improving cardiovascular treatments and mitigating disease impact stands as a testament to the healthcare industry's commitment to enhancing the quality of life for patients globally.

Companies Featured

For more information about this report visit https://www.researchandmarkets.com/r/sdy5ts

About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

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Global Interventional Cardiology Devices Market Projected to Reach $21.9 Billion by 2030 - GlobeNewswire

Cardiology

Telemedicine Strategy After MI Scores a Win in TELE-ACS – TCTMD

ATLANTA, GAA telemedicine-based approach to care after acute coronary syndromes can reduce readmissions to the hospital, visits to the emergency department (ED), and the rates of stroke and MI, according to results from the randomized TELE-ACS trial. Notably, use of the management strategy also was linked a reduction in patient-reported symptoms.

MI remains one of the leading causes of mortality in the UK despite cutting-edge medical and interventional therapies, said Nasser S. Alshahrani, MSc (Imperial College London, England, and King Khalid University, Abha, Saudi Arabia), presenting the data at the recent American College of Cardiology (ACC) 2024 Scientific Session. Moreover, around 10% of patients return to the hospital within 30 days of their event.

TELE-ACS, said Alshahrani, was designed to see if a novel telemonitoring system-based algorithm would reduce hospital readmissions for patients post-ACS by using well-validated technologies coupled with an urgent remote consultation with a cardiologist.

One question at the outset was whether the remote monitoring would provide enough information to guarantee clinicians could effectively assess patients without necessitating a face-to-face encounter, he said. The results, simultaneously published in the Journal of the American College of Cardiology, suggest the answer to that is yes.

ACC President Cathleen Biga, MSN, RN (Cardiovascular Management of Illinois, Woodridge), said she was struck by this trial and others at the meeting that focused on transformation of care delivery. So much of medicine has evolved, yet our quality hasnt gotten better, Biga commented. We have got to figure out a different way of caring for our patients because our MI readmission rate, our 30-day mortality after an acute coronary syndrome, the needle isnt moving. So what are we going to do differently to help move that needle?

Biga said the TELE-ACS trial speaks to the possibilities that a remote approach could continue to offer MI patients in todays practice.

The COVID-19 pandemic abruptly upended care back in 2020, Biga pointed out. We went completely telehealth in 12 hours, . . . before we opened our office that Monday. We changed in a nanosecond. Then, as the world grew more used to the virus, we went right back to packed waiting rooms [and] in-person visits, she noted.

Telemedicine vs Usual Care

Alshahrani and colleagues analyzed data for 337 patients (mean age 58.1 years; 86% male; 46% white) with at least one cardiovascular risk factor who had been hospitalized with ACS between January 2022 and April 2023. Three-quarters had hypercholesterolemia, nearly 60% were smokers or had a history of smoking, around half had hypertension, four in 10 had a family history of CAD, and a little more than a quarter had diabetes.

Prior to discharge, the patients were randomized to receive either telemedicine-based or standard care; to participate, they had to have access to a smartphone or other smart device.

In the intervention group, patients received a telemonitoring package consisting of a 12-lead ECG belt (SHL SmartHeart; SHL Telemedicine), an automated blood-pressure monitor (Omron Basic M2; Omron Corporation), and a pulse oximeter (Kinetik Wellbeing), as well as training in how to use the devices. They also received follow-up phone calls for training at 2, 4, and 8 weeks.

When these patients felt symptoms they thought were potentially cardiac, they used their telemonitoring tools, with the details transmitted to a cardiologist. The cardiologist performed remote clinical assessment and then triaged patients to receive either reassurance with clinical follow-up as previously planned or advice to contact their general practitioner, go to the ED for further testing, or call emergency services. Cardiologists based their decision-making on an algorithm that categorized symptoms and clinical parameters. Remote consultations were available from 7 AM to 11 PM on weekdays; outside of these time frames, or if they didnt hear from a cardiologist within 15 minutes of reporting their symptoms, patients were meant to seek medical advice through the usual clinical pathways.

In the control arm, patients sought medical advice through the usual pathways and received standard routine clinical care, with remote, phone-based follow-up at 3, 6, and 9 months.

We have got to figure out a different way of caring for our patients, because . . . the needle isnt moving. Cathleen Biga

Study participants made a total of 169 calls, 64% of them during the active hours on weekdays. Reported symptoms were most often chest pain/discomfort, followed by palpitations and general weakness.

Of the 108 calls during the active hours, 54.6% resulted in patients receiving reassurance. Another 26.9% were advised to visit their general practitioner, 13.9% told to visit the ED, and 4.62% recommended to call emergency services.

By 6-month follow-up, there were 20 readmissions with telemedicine and 50 with standard care. Thus, the time to readmission (primary endpoint) was reduced with the remote strategy, as were visits to the ED and MIs. Stroke trended lower, though the rate of all-cause death was identical in the two groups.

Six-Month Outcomes in ACS Patients

Telemedicine

Control

HR (95% CI)

Readmission

8%

29%

0.24 (0.13-0.44)

ED Visit

24%

37%

0.59 (0.40-0.89)

MI

7%

22%

0.27 (0.14-0.53)

Stroke

2%

5%

0.38 (0.10-1.42)

All-Cause Death

1.2%

1.2%

1.03 (0.15-7.31)

Moreover, patients in the telemedicine group had fewer unplanned coronary revascularizations than did controls (3% vs 9%) and were less likely to report chest pain (9% vs 24%), breathlessness (21% vs 39%), and dizziness (6% vs 18%).

Telemonitoring in the active study arm ceased at 6 months. Notably, though, the initial effect between 0 to 6 [months] was large enough to leave a legacy effect up to 9 months, Alshahrani said.

At 9-month follow-up, hospital readmissions still were less common with the intervention than with usual care (HR 0.35; 95% CI 0.21-0.59). So, too, were visits to the emergency department (HR 0.66; 95% CI 0.46-0.94) and the rate of invasive coronary angiography and/or angioplasty (4% vs 10%; P= 0.03). However, there was no longer a difference in symptoms between the two groups.

Alshahrani, in his presentation, cited several limitations to their study. Among them were its predominately male population, the potential for recall bias due to retrospective collection of symptom data, and the fact that participants were required to have access to a smartphone.

Additionally, the high level of support for the telemedicine group, with prompt cardiology responses, may be challenging to replicate outside a trial setting, requiring significant investment and training, he continued, while technological barriers and infrastructure requirements may pose some obstacles to implementation. . . . Further studies need to establish the feasibility of implementation in different healthcare systems.

We were surprised by the large effect. Nasser S. Alshahrani

Malissa Wood, MD (Lee Health Heart Institute, Fort Myers, FL), discussant for the TELE-ACS results, highlighted the decrease in MI with monitoring. Do you think the intervention was related to that, as far as the patients knowing that they were being monitored or that they could reach out to someone? Did you look at any psychosocial variables to see if that reduced stress, anxiety, or depression in that population that may have been related to that reduction in myocardial infarction?

We were surprised by the large effect, and it could be because of the high level of support that we delivered and also the patient education on symptoms at the point of contact and then at regular intervals thereafter, Alshahrani explained. It could be the Hawthorne effect: when the patient is monitored, they tend to change their behavior.

For ease of use, Wood suggested that going forward it would be good to have a device that incorporates all three measurementsoxygen saturation, blood pressure, and ECG readingsso you dont have the patient having to [use] all these different devices to transmit data.

Biga, speaking with TCTMD, said that much of the positive impact in TELE-ACS may come from the fact that telemedicine offered a way to connect regularly with a human touch, albeit remote, that was reassuring but also offered practical advice and constant education. This can be valuable for patients feeling overwhelmed by the intricacies of their care after discharge, she said.

As Biga noted, the challenge lies in how to implement the strategy. Patients may prefer to call their own doctors office over a less-familiar hotline, and any added personnel or other resources to handle these calls must be paid for. The most convenient, cost-effective option going forward might be third-party companies to streamline remote monitoring, she added, so the practices dont carry the burden, because the payment from [Medicare for] remote patient monitoring isnt going to begin to cover the cost of that: you have the equipment and the intellectual property.

Scaling up is tricky, especially with the tsunami of data, Biga stressed. In just one of her practices, Biga said, 900 patients are seen a daymore than five times the number of participants in the intervention arm of TELE-ACS. The real-world math is daunting, she pointed out. How many MIs do I have a month? Can I get them all hooked up and compliant and have the staff to analyze that data?

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Telemedicine Strategy After MI Scores a Win in TELE-ACS - TCTMD

Neuroscience

Unlocking Flow: The Neuroscience of Creative Bliss – Neuroscience News

Summary: A new study involving Philadelphia-area jazz guitarists, has explored the brain processes that enable creative flow. The research reveals that achieving flow requires a solid foundation of expertise, after which one must learn to relax conscious control to allow creativity to flourish.

By measuring brain activity and performance quality during improvisation, the study shows that experienced musicians entering flow exhibit less frontal lobe activity, which is associated with executive functions, and more in sensory processing areas. These findings suggest that mastering and then mentally releasing ones craft is key to achieving the high creativity and productivity associated with flow states.

Key Facts:

Source: The Conversation

Flow, or being in the zone, is a state of amped-up creativity, enhanced productivity and blissful consciousness that, some psychologists believe, is also thesecret to happiness. Its considered thebrains fast track to successin business, the arts or any other field.

But in order to achieve flow, a person must first develop a strong foundation of expertise in their craft. Thats according to anew neuroimaging studyfrom Drexel Universitys Creativity Research Lab, which recruited Philly-area jazz guitarists to better understand the key brain processes that underlie flow. Once expertise is attained, the study found, this knowledge must be unleashed and not overthought in order for flow to be reached.

As acognitive neuroscientistwho is senior author of this study, and a university writing instructor, we are a husband-and-wife team who collaborated on abook about the science of creative insight. We believe that this new neuroscience research reveals practical strategies for enhancing, as well as elucidating, innovative thinking.

The concept of flow has fascinated creative people ever since pioneeringpsychological scientist Mihly Cskszentmihlyibegan investigating the phenomenon in the 1970s.

Yet, a half-century of behavioral research has not answered many basic questions about the brain mechanisms associated with the feeling of effortless attention that exemplifies flow.

The Drexel experiment pitted two conflicting theories of flow against each other to see which better reflects what happens in peoples brains when they generate ideas. One theory proposes that flow is a state ofintensive hyperfocuson a task. The other theory hypothesizes that flow involvesrelaxing ones focusor conscious control.

The team recruited 32 jazz guitarists from the Philadelphia area. Their level of experience ranged from novice to veteran, as quantified by the number of public performances they had given. The researchers placed electrode caps on their heads to record their EEG brain waves while they improvised to chord sequences and rhythms that were provided to them.

Jazz improvisationis a favorite vehicle for cognitive psychologists and neuroscientists who study creativity because it is a measurable real-world task that allows fordivergent thinking the generation of multiple ideas over time.

The musicians themselves rated the degree of flow that they experienced during each performance, and those recordings were later played for expert judges who rated them for creativity.

As jazz greatCharlie Parker is said to have advised, Youve got to learn your instrument, then, you practice, practice, practice. And then, when you finally get up there on the bandstand, forget all that and just wail.

This sentiment aligns with the Drexel study findings. The performances that the musicians self-rated as high in flow were also judged by the outside experts as more creative. Furthermore, the most experienced musicians rated themselves as being in flow more than the novices, suggesting that experience is a precondition for flow. Their brain activity revealed why.

The musicians who were experiencing flow while performing showed reduced activity in parts of their frontal lobes known to be involved inexecutive functionorcognitive control. In other words, flow was associated with relaxing conscious control or supervision over other parts of the brain.

And when the most experienced musicians performed while in a state of flow, their brains showed greater activity in areas known to be involved in hearing and vision, which makes sense given that they were improvising while reading the chord progressions and listening to rhythms provided to them.

In contrast, the least experienced musicians showed very little flow-related brain activity.

We were surprised to learn that flow-state creativity is very different from nonflow creativity.

Previous neuroimaging studies suggested that ideas are usually produced by thedefault-mode network, a group of brain areas involved in introspection, daydreaming and imagining the future. The default-mode network spews ideas like an unattended garden hose spouts water, without direction.

The aim is provided by the executive-control network, residing primarily in the brains frontal lobe, which acts like a gardener who points the hose to direct the water where it is needed.

Creative flow is different: no hose, no gardener. The default-mode and executive-control networks are tamped down so that they cannot interfere with the separate brain network that highly experienced people have built up for producing ideas in their field of expertise.

For example, knowledgeable but relatively inexperienced computer programmers may have to reason their way through every line of code. Veteran coders, however, tapping their specialized brain network for computer programming, may just start writing code fluently without overthinking it until they complete perhaps in one sitting a first-draft program.

The findings that expertise and the ability to surrender cognitive control are key to reaching flow are supported by a2019 studyfrom the Creativity Research Lab. For that study, jazz musicians were asked to play more creatively. Given that direction, the nonexpert musicians were indeed able to improvise more creatively.

That is apparently because their improvisation was largely under conscious control and could therefore be adjusted to meet the demand. For example, during debriefing, one of the novice performers said, I wouldnt use these techniques instinctively, so I had to actively choose to play more creatively.

On the other hand, the expert musicians, whose creative process was baked in through decades of experience, were not able to perform more creatively after being asked to do so. As one of the experts put it, I felt boxed-in, and trying to think more creatively was a hindrance.

The takeaway for musicians, writers, designers, inventors and other creatives who want to tap into flow is that training should involve intensive practice followed by learning to step back and let ones skill take over. Future research may develop possible methods for releasing control once sufficient expertise has been achieved.

Author: John Kounios and Yvette Kounios Source: The Conversation Contact: John Kounios and Yvette Kounios The Conversation Image: The image is credited to Neuroscience News

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Unlocking Flow: The Neuroscience of Creative Bliss - Neuroscience News

Neuroscience

Decoding spontaneous thoughts from the brain via machine learning – EurekAlert

image:

First, the data was independently segmented into quintiles (5 levels) for self-relevance and valence based on participants ratings. Next, time points (TRs) were assigned according to the levels of these two dimensions, resulting in a total of 55 quantized TR indices. Utilizing these indices, exemplified by level 2 for self-relevance and level 5 for valence highlighted as red-shaded TRs in the figure, each index's fMRI and rating data were averaged, thereby generating 25 fMRI images and corresponding rating data for each participant. Subsequently, employing these orthogonalized data, whole-brain pattern-based predictive models were developed using principal component regression (PCR) along with leave-one-subject-out cross-validation (LOSO-CV) and random-split cross-validation (RS-CV).

Credit: Institute for Basic Science

A team of researchers led by KIM Hong Ji and WOO Choong-Wan at the Center for Neuroscience Imaging Research (CNIR) within the Institute for Basic Science (IBS), in collaboration with Emily FINN at Dartmouth College, has unlocked a new realm of understanding within the human brain. The team demonstrated the possibility of using functional Magnetic Resonance Imaging (fMRI) and machine learning algorithms to predict subjective feelings in peoples thoughts while reading stories or in a freely thinking state.

The brain is constantly active, and spontaneous thoughts occur even during rest or sleep. These thoughts can be anything ranging from memories of the past to aspirations for the future, and they are often intertwined with emotions and personal concerns. However, because spontaneous thought typically occurs without any constraint of consciousness, researching them poses challenges - even simply asking individuals what they are currently thinking can change the nature of their thoughts.

New research suggests that it may be possible to develop predictive models of affective contents during spontaneous thought by combining personal narratives with fMRI. Narratives and spontaneous thoughts share similar characteristics, including rich semantic information and temporally unfolding nature. To capture a diverse range of thought patterns, participants engaged in one-on-one interviews to craft personalized narrative stimuli, reflecting their past experiences and emotions. While participants read their stories inside the MRI scanner, their brain activity was recorded.

After the fMRI scan, the participants were asked to read the stories again and report perceived self-relevance (i.e., how much this content is related to themselves) and valence (i.e., how much this content is positive or negative) at each moment. Using a quintile (five levels) from each participant's self-relevance and valence ratings, 25 (5 levels of self-relevance rating 5 levels of valence rating) possible segments of fMRI and rating data were created. The team then harnessed machine learning techniques to train predictive models, combining these data with the fMRI brain scans from 49 individuals to decode the emotional dimensions of thoughts in real time.

To interpret the brain representations of the predictive models, the research team employed multiple approaches, such as virtual lesion and virtual isolation analyses at both region and network levels. Through these analyses, they discovered the significance of the default mode, ventral attention, and frontoparietal networks in both self-relevance and valence predictions. Specifically, they identified the involvement of the anterior insula and midcingulate cortex in self-relevance prediction, while the left temporoparietal junction and dorsomedial prefrontal cortex played important roles in valence prediction.

Moreover, the predictive models showed their capacity to predict both self-relevance and valence not only during story reading but also when applied to data from 199 individuals engaging in spontaneous, task-free thinking or even during resting. These findings show the promise of daydream decoding.

Several tech companies and research teams are currently endeavoring to decode words or images directly from brain activity, but there are limited initiatives aimed at decoding intimate emotions underlying these thoughts, stated Dr. WOO Choong-Wan, associate director of IBS, who led the study. Our research is centered on human emotions, with the aim of decoding emotions within the natural flow of thoughts to obtain information that can benefit peoples mental health.

KIM Hongji, a doctoral candidate and the first author of this study, emphasized, "This study holds significance as we decoded the emotional state associated with general thoughts, rather than targeting emotions limited to specific tasks," adding, "These findings advance our understanding of the internal states and contexts influencing subjective experiences, potentially shedding light on individual differences in thoughts and emotions, and aiding in the evaluation of mental well-being."

Video abstract can be found at: https://youtu.be/wUr6apaRuAE

Proceedings of the National Academy of Sciences

Experimental study

People

Brain decoding of spontaneous thought: predictive modeling of self-relevance and valence using personal narratives

28-Mar-2024

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Neuroscience

Revolutionizing Glioblastoma Treatment – Neuroscience News

Summary: Researchers demonstrated significant initial success using CAR-T therapy for glioblastoma, a notoriously deadly brain cancer. They detailed the outcomes of the first three patients in a Phase 1 clinical trial who experienced dramatic tumor reductions shortly after treatment.

This innovative approach combines CAR-T cells with bispecific antibodies to more effectively target the heterogeneous cell populations within solid tumors. While the initial results show promise, the team is exploring ways to enhance the longevity of the therapys effectiveness.

Key Facts:

Source: Harvard

A collaborative project to bring the promise of cell therapy to patients with a deadly form of brain cancer has shown dramatic results among the first patients to receive the novel treatment.

In apaperpublished Wednesday in The New England Journal of Medicine, researchers fromMass General Cancer Centershared the results for the first three patient cases from a Phase 1 clinical trial evaluating a new approach to CAR-T therapy for glioblastoma.

Just days after a single treatment, patients experienced dramatic reductions in their tumors, with one patient achieving near-complete tumor regression. In time, the researchers observed tumor progression in these patients, but given the strategys promising preliminary results, the team will pursue strategies to extend the durability of response.

This is a story of bench-to-bedside therapy, with a novel cell therapy designed in the laboratories of Massachusetts General Hospital and translated for patient use within five years, to meet an urgent need, said co-authorBryan Choi, a neurosurgeon at Harvard-affiliated Mass General and an assistant professor at Harvard Medical School.

The CAR-T platform has revolutionized how we think about treating patients with cancer, but solid tumors like glioblastoma have remained challenging to treat because not all cancer cells are exactly alike and cells within the tumor vary.

Our approach combines two forms of therapy, allowing us to treat glioblastoma in a broader, potentially more effective way.

The new approach is a result of years of collaboration and innovation springing from the lab ofMarcela Maus, director of the Cellular Immunotherapy Program and an associate professor at the Medical School.

Maus lab has set up a team of collaborating scientists and expert personnel to rapidly bring next-generation genetically modified T cells from the bench to clinical trials in patients with cancer.

Weve made an investment in developing the team to enable translation of our innovations in immunotherapy from our lab to the clinic, to transform care for patients with cancer, said Maus.

These results are exciting, but they are also just the beginning they tell us that we are on the right track in pursuing a therapy that has the potential to change the outlook for this intractable disease. We havent cured patients yet, but that is our audacious goal.

CAR-T (chimeric antigen receptor T-cell) therapy works by using a patients own cells to fight cancer it is known as the most personalized way to treat the disease. A patients cells are extracted, modified to produce proteins on their surface called chimeric antigen receptors, and then injected back into the body to target the tumor directly.

Cells used in this study were manufactured by the Connell and OReilly Families Cell Manipulation Core Facility of the Dana-Farber/Harvard Cancer Center.

CAR-T therapies have been approved for the treatment of blood cancers, but the therapys use for solid tumors is limited. Solid tumors contain mixed populations of cells, allowing some malignant cells to continue to evade the immune systems detection even after treatment with CAR-T. Maus team is working to overcome this challenge by combining two previously separate strategies: CAR-T and bispecific antibodies, known as T-cell engaging antibody molecules.

The version of CAR-TEAM for glioblastoma is designed to be directly injected into a patients brain.

In the new study, the three patients T cells were collected and transformed into the new version of CAR-TEAM cells, which were then infused back into each patient. Patients were monitored for toxicity throughout the duration of the study. All patients had been treated with standard-of-care radiation and temozolomide chemotherapy and were enrolled in the trial after disease recurrence.

The authors note that despite the remarkable responses among the first three patients, they observed eventual tumor progression in all the cases, though in one case, there was no progression for over six months.

Progression corresponded in part with the limited persistence of the CAR-TEAM cells over the weeks following infusion. As a next step, the team is considering serial infusions or preconditioning with chemotherapy to prolong the response.

We report a dramatic and rapid response in these three patients. Our work to date shows signs that we are making progress, but there is more to do, said co-author Elizabeth Gerstner, a Mass General neuro-oncologist.

In addition to Choi, Maus, and Gerstner, other authors are Matthew J. Frigault, Mark B. Leick. Christopher W. Mount, Leonora Balaj, Sarah Nikiforow, Bob S. Carter, William T. Curry, and Kathleen Gallagher.

Funding: The study was supported in part by the National Gene Vector Biorepository at Indiana University, which is funded under a National Cancer Institute contract.

Author: Haley Bridger Source: Harvard Contact: Haley Bridger Harvard Image: The image is credited to Neuroscience News

Original Research: Closed access. Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma by Bryan D.Choi et al. NJEM

Abstract

Intraventricular CARv3-TEAM-E T Cells in Recurrent Glioblastoma

In this first-in-human, investigator-initiated, open-label study, three participants with recurrent glioblastoma were treated with CARv3-TEAM-E T cells, which are chimeric antigen receptor (CAR) T cells engineered to target the epidermal growth factor receptor (EGFR) variant III tumor-specific antigen, as well as the wild-type EGFR protein, through secretion of a T-cellengaging antibody molecule (TEAM).

Treatment with CARv3-TEAM-E T cells did not result in adverse events greater than grade 3 or dose-limiting toxic effects.

Radiographic tumor regression was dramatic and rapid, occurring within days after receipt of a single intraventricular infusion, but the responses were transient in two of the three participants.

(Funded by Gateway for Cancer Research and others; INCIPIENT ClinicalTrials.gov number,NCT05660369.)

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Revolutionizing Glioblastoma Treatment - Neuroscience News

Neuroscience

Reducing Toxic AI Responses – Neuroscience News

Summary: Researchers developed a new machine learning technique to improve red-teaming, a process used to test AI models for safety by identifying prompts that trigger toxic responses. By employing a curiosity-driven exploration method, their approach encourages a red-team model to generate diverse and novel prompts that reveal potential weaknesses in AI systems.

This method has proven more effective than traditional techniques, producing a broader range of toxic responses and enhancing the robustness of AI safety measures. The research, set to be presented at the International Conference on Learning Representations, marks a significant step toward ensuring that AI behaviors align with desired outcomes in real-world applications.

Key Facts:

Source: MIT

A user could ask ChatGPT to write a computer program or summarize an article, and the AI chatbot would likely be able to generate useful code or write a cogent synopsis. However, someone could also ask for instructions to build a bomb, and the chatbot might be able to provide those, too.

To prevent this and other safety issues, companies that build large language models typically safeguard them using a process called red-teaming. Teams of human testers write prompts aimed at triggering unsafe or toxic text from the model being tested. These prompts are used to teach the chatbot to avoid such responses.

But this only works effectively if engineers know which toxic prompts to use. If human testers miss some prompts, which is likely given the number of possibilities, a chatbot regarded as safe might still be capable of generating unsafe answers.

Researchers from Improbable AI Lab at MIT and the MIT-IBM Watson AI Lab used machine learning to improve red-teaming. They developed a technique to train a red-team large language model to automatically generate diverse prompts that trigger a wider range of undesirable responses from the chatbot being tested.

They do this by teaching the red-team model to be curious when it writes prompts, and to focus on novel prompts that evoke toxic responses from the target model.

The technique outperformed human testers and other machine-learning approaches by generating more distinct prompts that elicited increasingly toxic responses. Not only does their method significantly improve the coverage of inputs being tested compared to other automated methods, but it can also draw out toxic responses from a chatbot that had safeguards built into it by human experts.

Right now, every large language model has to undergo a very lengthy period of red-teaming to ensure its safety. That is not going to be sustainable if we want to update these models in rapidly changing environments.

Our method provides a faster and more effective way to do this quality assurance, says Zhang-Wei Hong, an electrical engineering and computer science (EECS) graduate student in the Improbable AI lab and lead author of apaper on this red-teaming approach.

Hongs co-authors include EECS graduate students Idan Shenfield, Tsun-Hsuan Wang, and Yung-Sung Chuang; Aldo Pareja and Akash Srivastava, research scientists at the MIT-IBM Watson AI Lab; James Glass, senior research scientist and head of the Spoken Language Systems Group in the Computer Science and Artificial Intelligence Laboratory (CSAIL); and senior author Pulkit Agrawal, director of Improbable AI Lab and an assistant professor in CSAIL. The research will be presented at the International Conference on Learning Representations.

Automated red-teaming

Large language models, like those that power AI chatbots, are often trained by showing them enormous amounts of text from billions of public websites. So, not only can they learn to generate toxic words or describe illegal activities, the models could also leak personal information they may have picked up.

The tedious and costly nature of human red-teaming, which is often ineffective at generating a wide enough variety of prompts to fully safeguard a model, has encouraged researchers to automate the process using machine learning.

Such techniques often train a red-team model using reinforcement learning. This trial-and-error process rewards the red-team model for generating prompts that trigger toxic responses from the chatbot being tested.

But due to the way reinforcement learning works, the red-team model will often keep generating a few similar prompts that are highly toxic to maximize its reward.

For their reinforcement learning approach, the MIT researchers utilized a technique called curiosity-driven exploration. The red-team model is incentivized to be curious about the consequences of each prompt it generates, so it will try prompts with different words, sentence patterns, or meanings.

If the red-team model has already seen a specific prompt, then reproducing it will not generate any curiosity in the red-team model, so it will be pushed to create new prompts, Hong says.

During its training process, the red-team model generates a prompt and interacts with the chatbot. The chatbot responds, and a safety classifier rates the toxicity of its response, rewarding the red-team model based on that rating.

Rewarding curiosity

The red-team models objective is to maximize its reward by eliciting an even more toxic response with a novel prompt. The researchers enable curiosity in the red-team model by modifying the reward signal in the reinforcement learning set up.

First, in addition to maximizing toxicity, they include an entropy bonus that encourages the red-team model to be more random as it explores different prompts. Second, to make the agent curious they include two novelty rewards.

One rewards the model based on the similarity of words in its prompts, and the other rewards the model based on semantic similarity. (Less similarity yields a higher reward.)

To prevent the red-team model from generating random, nonsensical text, which can trick the classifier into awarding a high toxicity score, the researchers also added a naturalistic language bonus to the training objective.

With these additions in place, the researchers compared the toxicity and diversity of responses their red-team model generated with other automated techniques. Their model outperformed the baselines on both metrics.

They also used their red-team model to test a chatbot that had been fine-tuned with human feedback so it would not give toxic replies. Their curiosity-driven approach was able to quickly produce 196 prompts that elicited toxic responses from this safe chatbot.

We are seeing a surge of models, which is only expected to rise. Imagine thousands of models or even more and companies/labs pushing model updates frequently. These models are going to be an integral part of our lives and its important that they are verified before released for public consumption.

Manual verification of models is simply not scalable, and our work is an attempt to reduce the human effort to ensure a safer and trustworthy AI future, says Agrawal.

In the future, the researchers want to enable the red-team model to generate prompts about a wider variety of topics. They also want to explore the use of a large language model as the toxicity classifier. In this way, a user could train the toxicity classifier using a company policy document, for instance, so a red-team model could test a chatbot for company policy violations.

If you are releasing a new AI model and are concerned about whether it will behave as expected, consider using curiosity-driven red-teaming, says Agrawal.

Funding: This research is funded, in part, by Hyundai Motor Company, Quanta Computer Inc., the MIT-IBM Watson AI Lab, an Amazon Web Services MLRA research grant, the U.S. Army Research Office, the U.S. Defense Advanced Research Projects Agency Machine Common Sense Program, the U.S. Office of Naval Research, the U.S. Air Force Research Laboratory, and the U.S. Air Force Artificial Intelligence Accelerator.

Author: Adam Zewe Source: MIT Contact: Adam Zewe MIT Image: The image is credited to Neuroscience News

Original Research: The findings will be presented at the International Conference on Learning Representations

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Reducing Toxic AI Responses - Neuroscience News

Neuroscience

Angela Bryan Awarded Hazel Barnes Prize | Psychology and Neuroscience – University of Colorado Boulder

Published: April 10, 2024

CU Psychology and Neuroscience ProfessorAngela Bryan(Social) was awarded the Hazel Barnes Prize for 2024. From the Office the Chancellor's website: This is "the largest and most prestigious single faculy award funded by the University of Colorado Boulder.It was established in 1991 by former Chancellor James Corbridge in honor of Philosophy Professor Emerita Hazel Barnes to recognize 'the enriching interrelationship between teaching and research'.

"Nominees are regionally and nationally recognized, tenured faculty members who are not only outstanding teachers, but who also have distinguished records in research and scholarship. The Hazel Barnes Prize selection committee is comprised of past recipients."

Read more about the prize and check out thelist of past recipients on the chancellor's website.

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Angela Bryan Awarded Hazel Barnes Prize | Psychology and Neuroscience - University of Colorado Boulder