Background: Speech sound disorders are common in children and are associated with an increased risk of academic reading difficulties. The COVID-19 pandemic further highlighted the need for remote and digitalized assessment tools. In South Korea, standardized instruments such as the Urimal Test of Articulation and Phonation and Assessment of Phonology and Articulation for children are widely used but have limitations, including reliance on face-to-face evaluation, and the absence of automated scoring. Objective: This study aimed to develop and establish the content validity of an articulation assessment tool that can overcome these limitations and be integrated into digital therapeutics (DTx). Methods: A 3-round modified Delphi survey was conducted between July and September 2025 with 92% (23/25) of the invited experts, including 52.2% (12/23) physiatrists and 47.8% (11/23) speech-language pathologists, with a mean professional experience of 10.69 (SD 5.09) years. All participants (23/23, 100%) completed all rounds. Panelists evaluated the appropriateness of word lists, phonological environments, and scoring criteria. Quantitative analyses, including calculations of content validity ratio (CVR), content validity index (CVI), and median and IQR, were performed. Consensus thresholds were set at a CVR of ≥0.39, a CVI of ≥0.78, a median of ≥3.5, and an IQR of ≤1.0. Items were retained only when all 4 criteria were satisfied. While formal qualitative analysis was not performed, the research team internally reviewed and synthesized core keywords and themes from the experts’ open-ended responses to guide the refinement of items. Results: These findings were summarized into four key areas: (1) modernization of word stimuli, (2) expansion of phonological coverage, (3) refinement of scoring criteria to reduce ambiguity, and (4) enhancement of result interpretability through visualization. In round 2, a revised 35-word list was evaluated across 25 items, of which 20 (80%) met all consensus criteria. In total, 20% (5/25) of the items failed to meet at least one threshold, including phonological environment adequacy (CVR=0.48; CVI=0.74), scoring redundancy (CVR=0.13; CVI=0.57), usefulness of proportion of whole-word correctness or percentage of word proximity (CVR=0.39; CVI=0.70), contribution of mean phonological length (CVR=0.22; CVI=0.61), and usefulness of feature-based indexes (CVR=0.30; CVI=0.65; IQR 2). Items that reached consensus showed CVR values of 0.57 to 0.91, CVI values of 0.78 to 0.96, a median score of 4, and IQR values of 0 to 1. In round 3, all remaining items achieved consensus. Conclusions: This Delphi study developed a novel articulation assessment tool with robust content validity. This tool includes updated word stimuli, diverse analysis indexes, and visualization features, thereby enhancing its clinical utility and suitability for integration into artificial intelligence–based DTx. By standardizing and digitalizing articulation assessments, this tool has the potential to support personalized and accessible interventions for children with speech sound disorders.
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Exploring the Cultural Adaptation of an Ongoing Evidence-Based Intervention for Chinese and Korean American Dementia Caregivers: Descriptive Study
Background: The aging and caregiving population is becoming increasingly diverse in the United States, leading to a growing need for culturally adapted interventions to address the unique needs of underrepresented groups, such as Asian Americans. However, interventions targeting Asian Americans and exploring cultural adaptation strategies remain limited in dementia caregiving research. Objective: This study aimed to describe the cultural adaptation process of an evidence-based intervention for Chinese and Korean American dementia caregivers, called the New York University Caregiver Intervention–Enhanced Support. Methods: We conducted a deductive content analysis and categorized our adaptation strategies into 5 elements: content, context, relationship fidelity and core elements, engagement, and cultural competence. Timing and types of responses to each adaptation strategy were also observed. Two authors conducted the initial analysis, and additional team members finalized the synthesis through discussion. The Template for Intervention Description and Replication (TIDieR) checklist was used to guide the methodological rigor. Results: Twenty-four major adaptations were identified and categorized. For content, we translated materials, used culturally relevant terms, incorporated ethnic-specific surveys and resources, created social media support groups on platforms widely used by the targeted population, and extended the time allocated to complete the 6 counseling sessions. Context adaptation included expanding the range of individuals eligible for family counseling sessions to include fictive kin, using online and social media apps for communication, cultural matching and training of staff, and partnerships with relevant community organizations. Relationship fidelity and core elements involved consulting with community experts, conducting focus group interviews with caregivers, having regular meetings with the developer of the original intervention and an experienced New York University Caregiver Intervention–Enhanced Support clinician as well as experts in Chinese and Korean culture, and continuing regular counseling supervision. To enhance engagement, we provided clear explanations of the study procedure, which emphasized the benefits in participants’ native languages and matched participants with social workers who shared the same cultural backgrounds. We also used a step-by-step contact approach and prolonged communication, explained staff roles to build rapport, and offered participant compensation. Finally, cultural competence was reflected in tailoring counseling techniques with respect for cultural beliefs, the use of euphemistic language for taboo subjects, and culturally appropriate refreshments to show respect and build interpersonal relationships. Conclusions: We systematically adjusted a counseling-based intervention, an approach less familiar among Asian Americans, to fit the cultural characteristics of the target population. A contribution of this study is using an integrated, theory-driven approach that combines 2 cultural adaptation frameworks while also capturing real-time adaptations informed by external feedback and self-reflection. This work provides a practical model for adapting evidence-based interventions to serve Chinese and Korean American dementia caregivers and may inform future adaptations for other East Asian populations. Trial Registration: ClinicalTrial.gov NCT05461495; https://clinicaltrials.gov/study/NCT05461495
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Expected Competencies and Personal Attributes of Digital Health Navigators to Support Digital Mental Health Care: Focus Group and Interview Study With Patients and Health Care Professionals
Background: Digital mental health apps (DMHAs), and in particular digital therapeutics (DTx), offer promising opportunities to support mental health care. However, their effective use in outpatient settings in Germany remains limited. To overcome this gap, the role of digital health navigators (DHNs) has been introduced. DHNs are trained individuals who support patients and health care professionals in selecting, using, and integrating DMHAs into care. Despite increasing interest in this role, there is limited evidence on the competencies, knowledge, and personal attributes required for DHNs to work effectively in mental health settings. Objective: The study aims to explore the expected competencies, knowledge areas, and personal attributes that DHNs need to effectively support the implementation and use of DTx in outpatient mental health care. Methods: As part of the prestudy of the Digital Navigators for Acceptance and Competence Development with Mental Health Apps (DigiNavi) study, a qualitative study was conducted involving 35 participants (7 general practitioners, 8 patients in general practice, 11 outpatient psychiatrists/psychologists, and 9 patients in psychiatric outpatient clinics) from different general practices and psychiatric outpatient clinics in Germany. A total of 17 semistructured interviews and 4 focus groups were conducted to explore expectations of DHNs. Data were analyzed using qualitative content analysis. Results: Participants emphasized that DHNs should combine strong interpersonal skills (empathy, patience, and sensitive communication) with technical and basic clinical competencies. Most favored DHNs as integrated clinical team members (eg, medical assistants), citing their existing patient relationships, but noted time and training constraints. Key expectations included the ability to support patients with DTx use, adapt communication to individual needs, and convey data privacy information clearly. Foundational knowledge of mental health conditions and sensitivity to crises were considered important for identifying warning signs and escalating concerns. While DHNs were seen as essential intermediaries between patients, health care professionals, and DTx, participants highlighted the necessity for clearly defined roles, structured training, and realistic expectations to prevent role overload and enable sustainable implementation in outpatient mental health care. Conclusions: DHNs require a specialized skill set that bridges clinical understanding, digital expertise, and interpersonal competence. Our results lay the groundwork for developing training curricula and implementation strategies that align with real-world expectations for the DHN role. Defining these core competencies is essential for supporting the sustainable and effective integration of DMHAs into mental health care. Trial Registration: German Clinical Trials Register DRKS00034327; https://drks.de/search/en/trial/DRKS00034327 and ClinicalTrials.gov NCT06575582; https://clinicaltrials.gov/study/NCT06575582 International Registered Report Identifier (IRRID): RR2-10.2196/67655
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Enabling In Vivo Lentiviral Therapies: Manufacturing Strategies to Improve Purity, Scalability, and Clinical Readiness
Lentiviral vectors are gaining momentum not just as ex vivo tools but as potential in vivo therapeutic platforms. But with that shift comes a number of manufacturing challenges, including higher doses, tighter control of impurities, greater batch consistency, and scalable processes to meet both clinical and commercial needs.
In this GEN Podcast, two experts from SK pharmteco, a global CMO, address these challenges and lay out some best practices that guide the manufacture of lentiviral vectors with the requisite purity, robustness, and economic feasibility required for widespread clinical adoption..
Podcast Guests:

Tatiana Nanda, PhD
CTO, Cell and Gene Therapy
SK pharmteco

Mardhani Aparajithan
Director of Manufacturing,
Science and Technology
SK pharmteco
Produced with support from:
The post Enabling <i>In Vivo</i> Lentiviral Therapies: Manufacturing Strategies to Improve Purity, Scalability, and Clinical Readiness appeared first on GEN – Genetic Engineering and Biotechnology News.
STAT+: Trump celebrates closing first round of drug pricing deals, promises more ahead
WASHINGTON — President Trump heralded a drug pricing agreement with Regeneron on Thursday, closing the last of 17 deals initially sought by the White House last year.
Regeneron, as part of the private deal, will reduce prices on drugs to Medicaid, provide cholesterol medicine Praluent on TrumpRx for $225, and invest $27 billion in drug development in the United States.
On the same day, Regeneron also announced Food and Drug Administration approval of Otarmeni, the first gene therapy to be greenlit under the agency’s new National Priority Voucher program. In early trials, the drug provided modest hearing gains for people with a rare type of hearing loss, though its development has received pushback from parts of the Deaf community. Regeneron plans to offer the drug at no cost to American patients.
How to De-Escalate an Autistic Meltdown
A common misconception about tantrums and meltdowns is that they’re interchangeable. But while they share some similarities in their initial expression — crying, screaming, door slamming, harsh words — they’re actually quite different. Dealing with a meltdown requires a more specialized approach, especially with kids on the autism spectrum.
What is a tantrum vs a meltdown?
The two events happen for different reasons. A child throws a tantrum when they’re angry or frustrated, acting out because they feel an injustice has been done to them. They are aware of what they’re doing and still have some sense of control. And if a child’s tantrum is ignored by their parent or caregiver, it will likely subside quickly.
Meltdowns, on the other hand, happen involuntarily and seemingly out of nowhere. They also tend to become much more intense than a typical tantrum and may involve violent behavior such as head banging, hitting others, and damaging property. Once a meltdown has started, intervention is needed to stop it, whether it’s self-imposed (e.g., removing oneself from the trigger) or external (e.g., support from the parent or caregiver). The event can last between a few minutes and several hours.
Tantrums are common among all children, but kids with autism are more likely to experience meltdowns of varying degrees, says Conner Black, PhD, associate director of the Autism Center at the Child Mind Institute.
What are the stages of an autistic meltdown?
For a child with autism, a meltdown is triggered when they become overwhelmed, whether it’s by stress, powerful emotions, sensory input, change, or something else. Their sympathetic nervous system — the network in the body responsible for our “fight-or-flight” response — goes into overdrive and they lose control.
There are several stages to an autistic meltdown and understanding them can help you know how to respond effectively. The duration and intensity of the meltdown depend on whether intervention, including learned coping skills, can stop the child from reaching a crisis point, Dr. Black explains. “Certain skills may not work every time, and that’s really no one’s fault,” he says, but once a child reaches that crisis stage, intervention is no longer useful. He describes the course of a meltdown via the phases of the behavior escalation cycle:
- Calm: “This is basically the valley or plain on the side of mountain, which is considered the baseline, when the child is happy, relaxed, and at their best,” Dr. Black says. For instance, in a classroom setting, a student’s behavior might be described as cooperative and responsive to instruction. These behaviors are specific to the individual, so it helps to recognize what that looks like in your child.
- Trigger: While triggers can vary, Dr. Black says, there are some common ones that he typically encounters in kids with autism. “They’re often related to the misunderstanding of social situations, a lack of time to engage with their preferred interests, a sudden change in their schedule, or a transition that was unexpected,” he says. “It could also be certain sensory aversion, so things like loud noises or loud conversations. It could even sometimes be as simple as how food is presented on someone’s plate.” The child’s response to that trigger can vary depending on their current internal state or outside environmental factors. But if the trigger isn’t removed or is strong enough to dysregulate the child, they’re going to enter the next phase: agitation.
- Agitation: At this point, the child will begin to display behaviors that indicate they are no longer in their calm phase. They might start fidgeting, darting their eyes back and forth, or tapping their hands. For other kids, it could look like total disengagement or staring into space. While removing the trigger might still work at the start of this phase, attempts at problem-solving may backfire and push the child to escalate their behaviors.
- Acceleration/Escalation: “This is really when you start seeing a ramping up of behaviors,” Dr. Black says. “Anything from screaming to throwing toys to aggressing toward the caregiver or whoever’s in the room. Or they could turn that aggression on themselves, whether that’s head banging or hitting themselves repeatedly.” The child may become resistant to intervention and argumentative.
- Peak/Crisis: At this phase, the child hasn’t responded to attempts to de-escalate and will continue to engage in potentially dangerous behaviors. “When thinking about the crisis point, I think about behaviors that are often going to require a higher level of care. So that could be violence, self-injurious behaviors, or even intense suicidal ideation,” says Dr. Black. To be able to distinguish between escalation and crisis, he adds, it’s important to know what the top level of your child’s behaviors look like. “Throwing things could be the escalation stage, and then the next stage is actually when they’re destroying property,” Dr. Black explains.
- De-escalation: Finally, the intensity of the behavior begins to subside. The child may appear disoriented, confused, and tired. They will gradually become calmer.
- Recovery: The child is officially in this phase when they’re fully back at their baseline, Dr. Black says. The behaviors you’ll see at this phase are the same ones you see when they’re in their calm phase.
How to prevent meltdown escalation
Once a child has started to experience a meltdown, it’s hard to get them back to baseline. Depending on the phase, certain interventions may help while others might make things worse.
First, you want to avoid triggers, Dr. Black advises. “Autistic individuals can have a lot of difficulty talking about or even understanding what their emotions are. So, it’s typically up to the parents or caregivers to identify what things can trigger them in a certain way,” he says.
For instance, some kids with autism really thrive with routine and can become agitated when there are unexpected changes. Having a visual schedule of exactly what’s going to happen during the day can help prevent that, says Dr. Black. “If you know there’s going to be a change, you can pick a time, maybe a couple of days in advance, where you talk to them about what that difference is going to be.”
And if your child is known to have meltdowns in public spaces, says Dr. Black, think about what those outside triggers are and how to prepare ahead of time. If they tend to get upset by loud noises, for example, a pair of headphones can be an item — along with phone, wallet, keys! — that you never leave the house without. If possible, work with a mental health professional to identify triggers and develop an escalation plan.
What to do in the agitation phase
If your child has reached the agitation phase, says Dr. Black, you can try to intervene with coping skills that you’ve learned in therapy, whether it’s something as simple as removing a trigger or giving them a preferred activity in that moment to help prevent their behaviors from escalating.
Sometimes kids encounter an environment, like school, that is beyond your control but contains a wide range of potential triggers and pushes them into the agitation phase. Because their house is a more comfortable environment, kids with autism may keep themselves together at school and then quickly melt down once they get home.
“In that case, for that first hour, let them have their alone time where they can just chill,” Dr. Black suggests. “It could be eating snacks, watching a TV show, or even just sitting quietly in their room. Maybe it’s engaging in some sort of self-stimming behavior.” This can give them the space to cool down and take some time away from any sort of outside stimuli that could push them to move from the agitation phase into the escalation point of a meltdown.
What to do in the acceleration/escalation phase
It can be hard to anticipate every possible trigger, especially when there might be multiple at once on any given day. And sometimes coping strategies aren’t enough to keep a child from escalating or the trigger is too strong. Still, there are some things that Dr. Black suggests you can do to try to keep them from reaching that crisis point.
Keep communication short and concrete
Too much talking can be overwhelming for the child at this stage and might push them to crisis, Dr. Black explains, so the less communication the better. “A simple instruction looks like using just a short sentence. Say there’s a loud noise, for example. You can just say, ‘Go get your headphones,’” he says.
Use visual prompts
Instead of trying to communicate verbally, you can hold up a visual prompt. “If your child has already been working with a therapist or if they’ve learned some coping skills, it would be helpful to have a laminated sheet readily available with their name and pictures of four different coping skill options — like headphones, deep breathing, coloring, sitting alone in their room.”
Dr. Black advises only giving a few options, as it’s already difficult for the child to focus while they’re upset. Additionally, if they don’t choose one right away and you want to try again, he recommends that you “let there be silence for 60 seconds at minimum between prompts, because you don’t want to over-prompt and exacerbate the situation even more.” But providing these choices allows them to maintain their autonomy, which is important during escalation.
What to do in the peak/crisis phase
“Once they get to that apex, they’ve reached the point of no return and just need to go through the process,” says Dr. Black. He stresses that at this point, communication needs to be very minimal or nonexistent.
When maintaining safety is the focus
“The goal switches to really being able to maintain safety for both the individual as well as the family members in the area,” Dr. Black explains. “If they’re harming themselves, such as head banging, move them to their bed so at least it’s on something that’s softer and not going to potentially cause significant injury.”
Efforts to make sure the child is as safe as possible can put you in harm’s way. “If there’s aggression, you can be watching and making sure they’re safe but not getting too close where you could get aggressed upon,” says Dr. Black.
If there are other children in the house, Dr. Black advises that you make plans for how to keep them safe. “Maybe they can go to their room and lock the door while it’s happening,” he says. “Some families have the other kids go to the car and sit and wait until their parents come out to get them.”
When you need emergency services
If the crisis phase goes on for a long period of time, says Dr. Black, “this is when you’d have to think about calling 911. And as kids become adolescents, the response is going to look a lot different. Because of size alone, it’s a little bit easier to manage the situation in a 5-year-old than it would be in a 15-year-old.”
Dr. Black advises that you get in touch with your local police department or EMT service in advance to let them know you have a child with autism in the home, so if you call during an emergency, they are already familiar with your family.
What to do in the de-escalation and recovery phases
Watch for signs that the child is beginning to de-escalate, Dr. Black says. “All you’re doing at this point is maintaining safety until you’re really able to see a lessening of the intensity of the behavior or the frequency decreases a little bit.” Then, he says, you can start to slowly communicate with them again. You really need to be careful here, because it may look like they’re calming down, but if they’re pushed too hard and they’re not ready to talk, they might go right back into crisis phase.
At the recovery phase, “the whole family is recovering,” Dr. Black says. It’s at this point where you can all debrief and work through what may have triggered this escalation and how to possibly prevent it in the future.
“Make sure you’re also debriefing separately with the other siblings in the home after it happens,” Dr. Black adds. “They’ve just witnessed something that may have been traumatic and really stressful for them. There’s often so much focus given to the child with the big behaviors in the moment.”
Medication treatment
Sometimes, a child or teen may suffer from frequent meltdowns to the point that it’s interfering with their quality of life and their ability to attend school. At that time, a mental health professional may recommend working with a psychiatrist to add medication to their treatment.
The type of medication depends on the underlying mechanisms contributing to the behaviors, Dr. Black says. “For instance, if it’s coming from significant anxiety, psychiatrists may prescribe an SSRI like Prozac or Zoloft. If a child has co-occurring ADHD, which is very common, stimulant or non-stimulant ADHD medication might be recommended. And if the behavior stems from irritability or some kind of rigidity, antipsychotic medications like Abilify or risperidone can be useful.”
Improvement is possible
Dr. Black notes that when kids receive the support they need, their quality of life really improves. “I’ve seen that when families work with therapists to come up with different behavioral plans and figure out a proper medication regimen, there’s a lot of improvement in behavior challenges,” he says. “The duration, frequency, and intensity of the meltdowns decrease as the child learns how to handle strong emotions and parents learn how to respond to them. And the medication can help to increase their likelihood of being able to use coping skills or regulation techniques to calm back down when they start to get really frustrated.”
The post How to De-Escalate an Autistic Meltdown appeared first on Child Mind Institute.
Medical Students and Clinicians’ Perceptions of Social Media Direct-to-Consumer Advertising and Medication Requests
This study examines how medical students and clinicians report experiencing patient medication requests associated with prescription drug direct-to-consumer advertising on social media; survey data from 98 respondents indicate that those providing both in-person and virtual care encounter more frequent requests for medications advertised online, particularly branded glucagon-like peptide-1 (GLP-1) weight loss drugs.
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CRISPR Base Editing Repairs Hard-to-Treat Cystic Fibrosis Mutation in Cell Models
Affecting an estimated 100,000 people globally, cystic fibrosis (CF) cases stem from mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. In the past several decades, scientists have successfully engineered various small-molecule therapies that lessen the severity of the disease. However there are still treatment challenges. Now, data from a new study in a cell model demonstrates that a gene therapy can successfully repair an “untreatable” mutation associated with a particularly severe form of the disease. Details of the potential therapy are published in a new Science Translational Medicine paper titled “Functional correction of the untreatable CFTR 1717-IG>A mutation through mRNA- and sgRNA-optimized base editing.”
Many current therapies benefit patients with the most common disease-associated mutation, F508del. However they often have little effect on patients who harbor other types of mutations. For example, some patients have a mutation named 1717-1G>A, which is relatively common but doesn’t have any approved therapies due to being a splicing mutation that results in little to no protein production. In fact, “about 10% of people with CF do not qualify for any of the available CFTR modulator therapies, particularly those people with severe splicing mutations that result in frameshifts and the formation of premature termination codons.”
The 1717-1G>A mutation is the target of the therapy described in the paper, which was written by scientists from the University of Trento and their collaborators elsewhere. Specifically, the team developed an “adenine base editing strategy to efficiently correct the 1717-1G>A mutation,” they wrote in Science Translational Medicine. “By harnessing the SpRY- ABE9 system, which we delivered as optimized RNAs for both the base editor and single guide RNA (sgRNA), we achieved functional correction in patient-derived models.”
Furthermore, the scientists note that they opted to use base editing rather than strategies like base editing because it has the advantage of “typically higher nucleotide modification efficiencies and a streamlined system requiring only the editor and an sgRNA” and because it has been used in other CF studies.
Using their ABE9 base editor and modified CRISPR-Cas9 tool, the scientists report successfully editing up to 30% of target DNA in human embryonic kidney cell lines and patient-derived airway epithelial cells with minimal off-target effects. It also corrected the mutation in intestinal organoids derived from CF patients as evidenced by restored CFTR activity.
Additional studies are needed, especially in animals, to fully assess the effectiveness of potential therapy but early results are promising. Overall, the approach achieved an editing efficiency of 13%. Prior studies showed that 10% efficiency may be enough for functional recovery. The results suggest that the therapy could benefit the subset of patients whose disease is caused by 1717-1G>A.
The post CRISPR Base Editing Repairs Hard-to-Treat Cystic Fibrosis Mutation in Cell Models appeared first on GEN – Genetic Engineering and Biotechnology News.
Heart’s Constant Beating Suppresses Tumor Growth in Cardiac Tissues
The results of a study by researchers at the International Centre for Genetic Engineering and Biotechnology (ICGEB) suggest that the heart’s constant beating may actively suppress tumor growth in cardiac tissues. The collective findings from the team’s research in mouse models and in engineered heart tissues (EHT) suggests that this is because cellular pathways in these tissues alter gene regulation in cancer cells to keep them from proliferating.
Headed by Giulio Ciucci, PhD, and Serena Zacchigna, MD, PhD, at the ICGEB Cardiovascular Biology Laboratory, the scientists say the findings shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to new cancer therapies based on mechanical stimulation. First author Ciucci, together with senior author Zacchigna and colleagues reported on their findings in Science, in a paper titled “Mechanical load inhibits cancer growth in mouse and human hearts.” In their report the authors concluded “Collectively, the data presented in this work provide evidence that mechanical load in the heart inhibits cancer cell proliferation, likely explaining the low incidence of cardiac tumors.”
Heart cancer is very rare in mammals, but as the authors noted, “The mechanisms that protect the heart remain elusive.” The adult human heart in addition has a limited capacity for self-renewal, with cardiomyocytes regenerating at roughly 1% per year. “This suggests that the same mechanisms that halt the proliferation of cardiac cells could also inhibit the growth of cancer cells in the adult heart,” the authors continued. One proposed explanation for this loss of cardiomyocyte proliferative capacity lies in the intense mechanical demands placed on heart tissues, which must continuously pump blood against significant resistance. “We hypothesized that it could similarly hamper the proliferation of cancer cells in the heart,” the investigators reported.
Using a genetically engineered mouse model, Ciucci et al. first showed that the heart is remarkably resistant to cancer-causing mutations, even when potent oncogenic changes were introduced. To understand why, the authors developed a transplantation model in which the heart’s mechanical workload could be reduced. By grafting a donor heart into the neck of a compatible mouse, they created a “mechanically unloaded” organ, one that remained perfused with blood but did not bear physiological strain. “To assess the contribution of mechanical load to the low incidence and growth of cancer in the heart, we used a model of in vivo cardiac unloading by heterotopically transplanting a donor heart into the neck of a recipient syngeneic mouse,” they explained.
![Image of lung cancer cells (in green) growing in a heart, in which cardiomyocytes are stained in red. Nuclei are stained in blue. [Ciucci et al., Science 2026]](https://www.genengnews.com/wp-content/uploads/2026/04/low-res-4-300x300.jpeg)
After injecting human cancer cells directly into the heart muscle, they compared tumor behavior in the unloaded transplanted heart versus the animal’s native, mechanically active heart. Across their experiments, Ciucci et al. found that mechanical load consistently suppressed the growth of various cancer types, while unloading the heart promoted tumor cell proliferation within cardiac tissue.
According to the study findings, mechanical forces within the tissue reshape the cancer cell genome’s regulatory landscape, influencing whether cells can proliferate. Central to this process is Nesprin-2, a protein that transmits mechanical signals from the cell surface to the nucleus. “Nesprin-2, a protein known to mediate mechanotransduction from the cytoplasm to the nucleus, emerged as a key molecule sensing mechanical forces operating in beating hearts and translating them into reduced cell proliferation,” the scientists reported.
Nesprin-2, a component of the LINC complex, senses the mechanical microenvironment of the heart and functionally alters chromatin structure and histone methylation, reducing gene activity linked to tumor cell proliferation. When Nesprin-2 was silenced in cancer cells, those cells regained the ability to grow in the mechanically active environment of the heart, forming tumors. “Silencing of Nesprin-2 in lung cancer cells prior to their implantation in the heart in vivo restored the capacity of the cells to proliferate in the presence of physiological mechanical load, resulting in the formation of large tumors,” the authors stated.
The team noted that their collective results shed light on the role of mechanical forces in protecting the heart from cancer and may pave the way to new approaches to cancer therapy. “This offers fundamental insights into the biology of cell proliferation within the myocardium, and additionally, the mechanical stimuli that operate in a beating heart could be exploited for the development of a mechanical therapy for cancer.”
The post Heart’s Constant Beating Suppresses Tumor Growth in Cardiac Tissues appeared first on GEN – Genetic Engineering and Biotechnology News.
New Markers of Diabetes and Heart Disease Revealed via Genetic Study in Indians
A study in 3,000 Punjabi Sikhs has identified previously unreported molecular pathways that contribute to cardiometabolic disease. Published today in PLOS Medicine, these findings highlight the benefits of including diverse participants in these types of studies, which have historically centered on individuals of European ancestry.
“Genetic mechanisms that predispose people to type 2 diabetes and cardiovascular disease remain poorly understood, partly because of a lack of sufficient data on non-European ethnic groups,” write the authors of the study, who were led by Dharambir K. Sanghera, PhD, director of the Genetic Epidemiology Laboratory at the University of Oklahoma Health Sciences Center. “Extending these evaluations to diverse cohorts is essential for gaining insights into the molecular pathways involved in disease.”
Sanghera and colleagues conducted a metabolite genome-wide association study to look for links between the human lipidome and cardiometabolic disorders in a Punjabi population originating from Northern India. Epidemiological studies have repeatedly shown that South Asians living abroad experience a higher incidence of type 2 diabetes and are more susceptible to cardiovascular disease compared to other ethnic groups. However, the exact mechanism responsible for this increased risk remains unknown and lipidomic and genome-wide data is lacking for Indian populations.
“Genome-wide studies have shown that genes influencing blood lipid metabolites are often linked to different diseases,” write the study authors. “However, most of this research has been done on people of European ancestry. Studying more diverse populations is important to better understand how these genetic pathways contribute to disease in different ethnic groups.”
The study looked at genetic influences on 516 lipids in 3,000 Punjabi Sikh individuals and then validated the results in larger cohorts, with both European and non-European ancestry, using data from UK Biobank, GeneRISK, DIAMANT, PROMIS, and other studies. After multiple rounds of testing and correction, results showed strong associations in 36 pairs of lipid metabolites and single nucleotide polymorphisms (SNPs). Among them, 33 had not been reported before, and three were confirmed to be ancestry-specific.
Further investigation identified a causal association between type 2 diabetes and the metabolite LPC O-16:0, which was paired with a genetic variant in the gene encoding for CD45, a key regulator of immune signaling. Another possible causal relationship was found with PC 38:4, a metabolite shown to protect against coronary artery disease in Indian populations that was paired with a genetic variant in an untranslated region of the FADS1/2 genes.
“Our study has discovered new metabolite markers and genes that intersect with pathways of inflammation and immuno-vascular diseases, which have not been reported in previous European studies, specifically emphasizing how immune system signaling affects metabolic health,” state the authors. “By identifying unique genetic signatures in Asian Indians, the research advocates for ancestry-specific medical approaches to address chronic immuno-vascular conditions in cardiometabolic disease. These advances could be beneficial in clinical practice, enabling effective personalized therapies and preventive strategies.”
The post New Markers of Diabetes and Heart Disease Revealed via Genetic Study in Indians appeared first on Inside Precision Medicine.


